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Other Publications (200)

Articles by Wei Lin in JoVE

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Collection, Isolation and Enrichment of Naturally Occurring Magnetotactic Bacteria from the Environment

1School of Earth Sciences, The Ohio State University, 2School of Environment & Natural Resources, The Ohio State University, 3Institute of Geology and Geophysics, Chinese Academy of Sciences


JoVE 50123

We demonstrate a method to collect magnetotactic bacteria (MTB) that can be applied to natural waters. MTB can be isolated and enriched from sediment samples using a relatively simple setup that takes advantage of the bacteria's natural magnetism. Isolated MTB can then be examined in detail using both light and electron microscopy.

Other articles by Wei Lin on PubMed

[Effects of Chronic Intermittent Hypobaric Hypoxia on Immune Function in Rat]

To elucidate the effect of CIHH on cellular immunity and humoral immunity in rat by using flow cytometry method, immunohistochemistry method and electron microscopy techniques.

Effect of Serotypes on Clinical Manifestations of Dengue Fever in Adults

Dengue fever (DF) is a major public health issue. However, it is unclear whether different dengue virus serotypes (DENV) are associated with different clinical manifestations and outcomes. This study investigated the association between viral serotype and clinical manifestations of DF.

[Protective Effect of Tert-butylhydroquinone on PC12 Cells from Neurotoxicity Induced by Manganese in Vitro]

To investigate the protective effect of the tert-butylhydroquinone (tBHQ) on PC12 cells from neurotoxicity induced by manganese.

Specific Primers for the Detection of Freshwater Alphaproteobacterial Magnetotactic Cocci

Freshwater magnetotactic cocci within Alphaproteobacteria are of ecological interest due to their ubiquitous distribution in aquatic environments as well as their potential roles in iron cycling and the bulk magnetism of sediment. To effectively investigate the diversity and distribution of these cocci, specific primers (FMTCf and FMTCr) were developed. Their specificity, applicability, and effectiveness were then evaluated theoretically and empirically.

[Clinical Analysis of Donor Hepatectomy in Living Donor Liver Transplantation: Report of 74 Cases]

To evaluate the living donor selection, donor hepatectomy technique, and surgical complication in living donor liver transplantation.

[Repair of Soft Tissue Defect Caused by Resection of Sacral Tumors]

To study the therapeutic effect of combining vacuum sealing drainage (VSD) with gluteus maximus myocutaneous flap on the repair of soft tissue defect caused by the resection of sacral tumors.

[Evaluation of the Implant Sites of Palatal Implants Using Cone Beam Computed Tomography]

To investigate the vertical bone height and the bone density of the palate for implants placement using cone beam CT(CBCT) and to provide references to the safe and stable placement of palatal implants.

Effect of Catalyst Shape and Etchant Composition on Etching Direction in Metal-assisted Chemical Etching of Silicon to Fabricate 3D Nanostructures

Metal-assisted chemical etching (MaCE) of silicon in conjunction with shaped catalysts was used to fabricate 3D nanostructures such as sloping channels, cycloids, and spirals along with traditional vertical channels. The investigation used silver nanorods, nanodonuts along with electron beam lithography (EBL)-patterned gold nanodiscs, nanolines, squares, grids, and star-shaped catalysts to show how catalyst shape and line width directly influence etching direction. Feature sizes ranging from micrometers down to 25 nm were achieved with aspect ratios of at least 10:1 and wall roughness of 10 nm or less. This research demonstrates the potential of MaCE as a new, maskless nanofabrication technology.

[Middle Hepatic Treatment Algorithm in Right Lobe Living Donor Liver Transplantation for Donor Recipient Safety]

The treatment algorithm of donor middle hepatic vein (MHV) was made depending on the remnant liver volume of the total donor liver volume as calculated by computer tomography, estimated graft-to-recipient weight ratio and also anatomy. The present study was to analyze the influence of this algorithm upon the safety of donors and recipients in right lobe living donor liver transplantation (LDLT) and to provide references for our future clinical practices.

Errors of Phases and Group Delays in SAW RFID Tags with Phase Modulation

To achieve high-volume code capacity for SAW-based radio frequency identification(RFID) tags, it is very important to improve the delay time resolution. An efficient encoding method is to use the phase delay of the carrier wave in the pulses, but one has to solve the issues of the phase ambiguity at unknown temperatures and the location of reflectors to exact positions. In this paper, a method is proposed to obtain a high-phase delay resolution by measuring group delays and constructing a certain restriction on the exact positions of reflectors. To define the restriction parameter for a SAW RFID system with large code capacity, it is imperative to have a priori knowledge of the errors of the phases and group delays. The experimental and simulation errors for both the phases and the group delays, originated from the design procedure, the temperature effect, the fabrication process and the measurement, are presented. The error probability distribution curves in simulation and experiments are plotted. The maximum error of phase delay is about +/- 14 degrees, and the maximum error of group delay is about +/- 4 periods. The temperature range in investigation is from -5 to 45 degrees C.

Polarization Effects on Quantum Levels in InN/GaN Quantum Wells

Polarization effects on quantum states in InN/GaN quantum wells have been investigated by means of ab initio calculation and spectroscopic ellipsometry. Through the position-dependent partial densities of states, our results show that the polarization modified by the strain with different well thickness leads to an asymmetry band bending of the quantum well. The quantum levels are identified via the band structures and their square wave function distributions are analyzed by the partial charge densities. Further theoretical and experimental comparison of the imaginary part of the dielectric function show that the overall transition probability increases under larger polarization fields, which can be attributable to the fact that the excited quantum states of 2h have a greater overlap with 1e states and enhance other hole quantum states in the well by a hybridization. These results would provide a new approach to improve the transition probability and light emission by enhancing the polarization fields in a proper way.

Experimental Evidence for the All-up Reactive Conformation of Chiral Rhodium(II) Carboxylate Catalysts: Enantioselective Synthesis of Cis-cyclopropane Alpha-amino Acids

Useful empirical insights onto the enantioinduction process of chiral Rh(II)-carboxylate catalysts are described in the first catalytic asymmetric cyclopropanation of alkenes with alpha-nitro diazoacetophenones. X-ray, solution NMR, and reactivity studies made on these complexes suggest that the level of asymmetric induction strongly depends on their active symmetry, which in turn relies on the nature of the chiral ligands' substituents. The catalyst's 'All Up' reactive conformation resulted in being necessary to obtain good stereoselectivity, and the resulting products are shown to be key intermediates in a concise synthesis of highly enantioenriched cis-cyclopropane alpha-amino acids.

Improved Signal Spoiling in Fast Radial Gradient-echo Imaging: Applied to Accurate T(1) Mapping and Flip Angle Correction

In conventional spoiled gradient echo imaging utilizing quadratic radio frequency (RF) spoiling, nonideal signal intensities are often generated, particularly when repetition time is short and/or excitation flip angle (FA) becomes larger. This translates to significant errors in various quantitative applications based on T(1)-weighted image intensities. In this work, a novel spoiling scheme is proposed, based on random gradient moments and RF phases. This scheme results in a non-steady-state condition, but achieves ideal mean signal intensity. In order to suppress artifacts created by the inter-TR signal variations and at the same time attain the ideal signal intensity, radial data acquisition is utilized. The proposed method achieves ideal spoiling for a wide range of T(1), T(2), TR, and FAs. Phantom and in vivo experiments demonstrate improved performance for T(1) mapping and FA correction when compared with conventional RF spoiling methods.

Partial Fourier Reconstruction Through Data Fitting and Convolution in K-space

A partial Fourier acquisition scheme has been widely adopted for fast imaging. There are two problems associated with the existing techniques. First, the majority of the existing techniques demodulate the phase information and cannot provide improved phase information over zero-padding. Second, serious artifacts can be observed in reconstruction when the phase changes rapidly because the low-resolution phase estimate in the image space is prone to error. To tackle these two problems, a novel and robust method is introduced for partial Fourier reconstruction, using k-space convolution. In this method, the phase information is implicitly estimated in k-space through data fitting; the approximated phase information is applied to recover the unacquired k-space data through Hermitian operation and convolution in k-space. In both spin echo and gradient echo imaging experiments, the proposed method consistently produced images with the lowest error level when compared to Cuppen's algorithm, projection onto convex sets-based iterative algorithm, and Homodyne algorithm. Significant improvements are observed in images with rapid phase change. Besides the improvement on magnitude, the phase map of the images reconstructed by the proposed method also has significantly lower error level than conventional methods.

Asymptotic Behavior of Periodic Cohen-Grossberg Neural Networks with Delays

Without assuming the positivity of the amplification functions, we prove some M-matrix criteria for the R(n)(+)-global asymptotic stability of periodic Cohen-Grossberg neural networks with delays. By an extension of the Lyapunov method, we are able to include neural systems with multiple nonnegative periodic solutions and nonexponential convergence rate in our model and also include the Lotka-Volterra system, an important prototype of competitive neural networks, as a special case. The stability criteria for autonomous systems then follow as a corollary. Two numerical examples are provided to show that the limiting equilibrium or periodic solution need not be positive.

Contextual Extracellular Cues Promote Tumor Cell EMT and Metastasis by Regulating MiR-200 Family Expression

Metastatic disease is a primary cause of cancer-related death, and factors governing tumor cell metastasis have not been fully elucidated. Here, we address this question by using tumor cell lines derived from mice that develop metastatic lung adenocarcinoma owing to expression of mutant K-ras and p53. Despite having widespread somatic genetic alterations, the metastasis-prone tumor cells retained a marked plasticity. They transited reversibly between epithelial and mesenchymal states, forming highly polarized epithelial spheres in three-dimensional culture that underwent epithelial-to-mesenchymal transition (EMT) following treatment with transforming growth factor-beta or injection into syngeneic mice. This transition was entirely dependent on the microRNA (miR)-200 family, which decreased during EMT. Forced expression of miR-200 abrogated the capacity of these tumor cells to undergo EMT, invade, and metastasize, and conferred transcriptional features of metastasis-incompetent tumor cells. We conclude that tumor cell metastasis is regulated by miR-200 expression, which changes in response to contextual extracellular cues.

[Transition of Studying on Shen Deficiency Syndrome and Aging from Holistic Concept to Systematic Biologic Viewpoint]

Holistic concept is a characteristic contribution of Chinese medicine to medical science. Based on holistic concept, we investigated the correlation of Shenyang deficiency syndrome with the hypothalamus-pituitary-target gland axis; and revealed by gene chip technique the molecular network regulatory rule of intervention with Chinese drugs on hypothalamus-pituitary-adrenal-thymus axis in aged rats as a model for Shen deficiency syndrome; also the two major gene regulation pathways, namely, the neuro-endocrine-immune pathway and the neuro-endocrine-bone metabolic pathway, in hypothalamus, pituitary, adrenal, lymphocytes, kidney, liver, bone of aged rats, so as to advance the holistic research on Chinese medicine syndromes. Recently, based on the dynamic, intervention and multi-layer integration requirement of systematic biology, the common rule of aging was found at three different levels, the whole genomic transcription level, the metabolic level and the single ageing signaling pathway level. Meanwhile, it was demonstrated that the temporal and spatial association of genes will be weakened gradually along with aging. And Epimedium Flavonoids (EF), an extracts from Epimedium have been proved to be capable of effectively reversing both of these systemic changes. Thus, the transition of study from holistic concept to systematic biologic viewpoint could surely promote the progression of Chinese medicine to modern life science.

Seasonal Changes in Supercooling Points and Glycerol Content in Overwintering Larvae of the Asiatic Rice Borer from Rice and Water-oat Plants

The Asiatic rice borer Chilo suppressalis (Walker) occurs mainly on rice Oryza sativa L. and water-oat Zizania latifolia (Turcz). Certain ecological and physiological differentiations between rice and water-oat populations have been shown. To determine whether there is host-associated differentiation in supercooling capacity, seasonal changes in supercooling points, glycerol content, and other physiological parameters of naturally occurring C. suppressalis larvae overwintering in rice and water-oat plants were compared over the winter. Supercooling points were low in the winter (November and December), significantly higher in March, and significantly lower in the water-oat population than in the rice population in the winter. Larvae from the water-oat population experienced a significant weight loss from December to March and were heavier than those from the rice population in the winter. Body water content (percentage of fresh weight) was low in the winter and increased significantly in March; no population differences were detected. Hemolymph glycerol content was high in the winter and dropped significantly in March; interpopulation differences were significant in December. Hemolymph trehalose content increased in the winter, and no population differences were detected. Whole body glucose and lipid content varied differently between the rice and the water-oat populations over the winter. It was found that variations in hemolymph glycerol content were responsible for the host-associated seasonal changes in supercooling capacity of overwintering larvae of the Asiatic rice borer.

Reduced Efficiency of Magnetotaxis in Magnetotactic Coccoid Bacteria in Higher Than Geomagnetic Fields

Magnetotactic bacteria are microorganisms that orient and migrate along magnetic field lines. The classical model of polar magnetotaxis predicts that the field-parallel migration velocity of magnetotactic bacteria increases monotonically with the strength of an applied magnetic field. We here test this model experimentally on magnetotactic coccoid bacteria that swim along helical trajectories. It turns out that the contribution of the field-parallel migration velocity decreases with increasing field strength from 0.1 to 1.5 mT. This unexpected observation can be explained and reproduced in a mathematical model under the assumption that the magnetosome chain is inclined with respect to the flagellar propulsion axis. The magnetic disadvantage, however, becomes apparent only in stronger than geomagnetic fields, which suggests that magnetotaxis is optimized under geomagnetic field conditions. It is therefore not beneficial for these bacteria to increase their intracellular magnetic dipole moment beyond the value needed to overcome Brownian motion in geomagnetic field conditions.

Adaptive Identification of Time Delays in Nonlinear Dynamical Models

This paper develops an adaptive synchronization strategy to identify both discrete and distributed time delays in nonlinear dynamical models. In contrast with adaptive techniques for parameter estimation in the literature, the adaptive strategy developed here for time-delay identification invites more precise results that have physical and dynamical importance. It is analytically and numerically found that distributed time delays in a model with an asymptotically stable steady state can be adaptively identified, and which is different from the case of discrete time-delays identification. Other aspects of the strategy developed here, for time-delay identification, are illustrated by several representative dynamical models. Aside from illustrations for toy models and their generated data, the strategy developed is used with experimental data, to identify a time delay, called transcriptional delay, in a model describing the transcription of messenger RNAs (mRNAs) for Notch signaling molecules.

Locating Unstable Periodic Orbits: when Adaptation Integrates into Delayed Feedback Control

Finding unstable periodic orbits (UPOs) is always a challenging demand in biophysics and computational biology, which needs efficient algorithms. To meet this need, an approach to locating unstable periodic orbits in chaotic dynamical system is presented. The uniqueness of the approach lies in the introduction of adaptive rules for both feedback gain and time delay in the system without requiring any information of the targeted UPO periods a priori. This approach is theoretically validated under some mild conditions and successfully tested with some practical strategies in several typical chaotic systems with or without significant time delays.

Association of Toll-like Receptor 4 Gene Polymorphism and Expression with Urinary Tract Infection Types in Adults

Innate immunity of which Toll-like receptor (TLR) 4 and CXCR1 are key elements plays a central role in the development of urinary tract infection (UTI). Although the relation between the genetics of TLR4 and CXCR1 and UTI is investigated partly, the polymorphisms and expression of TLR4 and CXCR1 in different types of UTI in adults are not extremely clear.

A Three-dimensional Framework in 2,2'-biimidazolium Bis(2,2'-biimidazole-κ(2)N,N')bis(biphenyl-2,4'-dicarboxylato-κO)manganese(II) Hexahydrate

In the title salt, (C(6)H(8)N(4))[Mn(C(14)H(8)O(4))(2)(C(6)H(6)N(4))(2)]·6H(2)O, the Mn(II) atom lies on an inversion centre and is coordinated by four N atoms from two 2,2'-biimidazole (biim) ligands and two O atoms from two biphenyl-2,4'-dicarboxylate (bpdc) anions to give a slightly distorted octahedral coordination, while the cation lies about another inversion centre. Adjacent [Mn(bpdc)(2)(biim)(2)](2-) anions are linked via two pairs of N-H...O hydrogen bonds, leading to an infinite chain along the [100] direction. The protonated [H(2)biim](2+) moiety acts as a charge-compensating cation and space-filling structural subunit. It bridges two [Mn(bpdc)(2)(biim)(2)](2-) anions through two pairs of N-H...O hydrogen bonds, constructing two R(2)(2)(9) rings, leading to a zigzag chain in the [2-1-1] direction, which gives rise to a ruffled set of [H(2)biim](2+)[Mn(bpdc)(2)(biim)(2)](2-) moieties in the [01-1] plane. The water molecules give rise to a chain structure in which O-H...O hydrogen bonds generate a chain of alternating four- and six-membered water-oxygen R(4)(2)(8) and R(6)(6)(12) rings, each lying about independent inversion centres giving rise to a chain along the [100] direction. Within the water chain, the (H(2)O)(6) water rings are hydrogen bonded to two O atoms from two [Mn(bpdc)(2)(biim)(2)](2-) anions, giving rise to a three-dimensional framework.

[Effects of High-frequency Electromagnetic Field on Morphology of Hippocampal Cells in Female Rats]

To analyze the effects of high-frequency electromagnetic field (HF-EMF, 30 MHz, 0-1600 V/m) on the apoptosis and ultramicrostructure of the hippocamp and demonstrate the cytotoxicity of hippocamp.

CE-ESI-MS Coupled with Dynamic PH Junction Online Concentration for Analysis of Peptides in Human Urine Samples

In this article, an approach has been developed for the analysis of some small peptides with similar pI values by CE-ESI-MS based on the online concentration strategy of dynamic pH junction. The factors affected on the separation, detection and online enrichment, such as BGE, injection pressure, sheath flow liquid and separation voltage have been investigated in detail. Under the optimum conditions, i.e. using 0.5 mol/L formic acid (pH 2.15) as the BGE, preparing the sample in 50 mM ammonium acetate solution (pH 7.5), 50 mbar of injection pressure for 300 s, using 7.5 mM of acetic acid in methanol-water (80% v/v) solution as the sheath flow liquid and 20 kV as the separation voltage, four peptides with similar pI values, such as L-Ala-L-Ala (pI = 5.57), L-Leu-D-Leu (pI = 5.52), Gly-D-Phe (pI = 5.52) and Gly-Gly-L-Leu (pI = 5.52) achieved baseline separation within 18.3 min with detection limits in the range of 0.2-2.0 nmol/L. RSDs of peak migration time and peak area were in the range of 1.45-3.57 and 4.93-6.32%, respectively. This method has been applied to the analysis of the four peptides in the spiked urine sample with satisfactory results.

Selective Electrodiffusion of Zinc Ions in a Zrt-, Irt-like Protein, ZIPB

All living cells need zinc ions to support cell growth. Zrt-, Irt-like proteins (ZIPs) represent a major route for entry of zinc ions into cells, but how ZIPs promote zinc uptake has been unclear. Here we report the molecular characterization of ZIPB from Bordetella bronchiseptica, the first ZIP homolog to be purified and functionally reconstituted into proteoliposomes. Zinc flux through ZIPB was found to be nonsaturable and electrogenic, yielding membrane potentials as predicted by the Nernst equation. Conversely, membrane potentials drove zinc fluxes with a linear voltage-flux relationship. Direct measurements of metal uptake by inductively coupled plasma mass spectroscopy demonstrated that ZIPB is selective for two group 12 transition metal ions, Zn(2+) and Cd(2+), whereas rejecting transition metal ions in groups 7 through 11. Our results provide the molecular basis for cellular zinc acquisition by a zinc-selective channel that exploits in vivo zinc concentration gradients to move zinc ions into the cytoplasm.

"Organic Aqua Regia"--powerful Liquids for Dissolving Noble Metals

Preparation of Iron-impregnated Granular Activated Carbon for Arsenic Removal from Drinking Water

Granular activated carbon (GAC) was impregnated with iron through a new multi-step procedure using ferrous chloride as the precursor for removing arsenic from drinking water. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis demonstrated that the impregnated iron was distributed evenly on the internal surface of the GAC. Impregnated iron formed nano-size particles, and existed in both crystalline (akaganeite) and amorphous iron forms. Iron-impregnated GACs (Fe-GACs) were treated with sodium hydroxide to stabilize iron in GAC and impregnated iron was found very stable at the common pH range in water treatments. Synthetic arsenate-contaminated drinking water was used in isotherm tests to evaluate arsenic adsorption capacities and iron use efficiencies of Fe-GACs with iron contents ranging from 1.64% to 12.13% (by weight). Nonlinear regression was used to obtain unbiased estimates of Langmuir model parameters. The arsenic adsorption capacity of Fe-GAC increased significantly with impregnated iron up to 4.22% and then decreased with more impregnated iron. Fe-GACs synthesized in this study exhibited higher affinity for arsenate as compared with references in literature and shows great potential for real implementations.

[Preparation and Characterization of Zirconium Hydroxide Powder for Fluoride Adsorption]

The method co-precipitation was applied to preparation the zirconium hydroxide as a type drinking-water defluoridation adsorbent. The effect of the preparation conditions on the adsorptive capacity was studied. The optimization of preparation condition for zirconium hydroxide concludes that co-precipitation time is 10 h, pH value is 7.0, drying time is 72 h, calcination temperature is below 100 degrees C. Also, the adsorbent samples were characterized. SEM measurements reveal that zirconium hydroxide powder are constructed by several small particles, with a diameter about 20-30 microm. XRD and TG/DTA measurements show that the zirconium hydroxide samples have amorphous phase and converse to tetragonal phase when calcined at 600 degrees C. Nitrogen adsorption/desorption measurements show that samples have large surface areas of 138.4 m2/g and a 2 nm average pore size distribution in the mesopore region. The performance of zirconium hydroxide regeneration process was investigated. The results show that the regeneration techniques are very suitable to restore the fluorine-removal ability for zirconium hydroxide.

GRAPPA Operator for Wider Radial Bands (GROWL) with Optimally Regularized Self-calibration

A self-calibrated parallel imaging reconstruction method is proposed for azimuthally undersampled radial dataset. A generalized auto-calibrating partially parallel acquisition (GRAPPA) operator is used to widen each radial view into a band consisting of several parallel lines, followed by a standard regridding procedure. Self-calibration is achieved by regridding the central k-space region, where Nyquist criterion is satisfied, to a rotated Cartesian grid. During the calibration process, an optimal Tikhonov regularization factor is introduced to reduce the error caused by the small k-space area of the self-calibration region. The method was applied to phantom and in vivo datasets acquired with an eight-element coil array, using 32-64 radial views with 256 readout samples. When compared with previous radial parallel imaging techniques, GRAPPA operator for wider radial bands (GROWL) provides a significant speed advantage since calibration is carried out using the fully sampled k-space center. A further advantage of GROWL is its applicability to arbitrary-view angle ordering schemes.

Applied Anatomic Site Study of Palatal Anchorage Implants Using Cone Beam Computed Tomography

The purpose of this study was to conduct quantitative research on bone height and bone mineral density of palatal implant sites for implantation, and to provide reference sites for safe and stable palatal implants.

Fast Preparation of Printable Highly Conductive Polymer Nanocomposites by Thermal Decomposition of Silver Carboxylate and Sintering of Silver Nanoparticles

We show the fast preparation of printable highly conductive polymer nanocomposites for future low-cost electronics. Highly conductive polymer nanocomposites, consisting of an epoxy resin, silver flakes, and incorporated silver nanoparticles, have been prepared by fast sintering between silver flakes and the incorporated silver nanoparticles. The fast sintering is attributed to: 1) the thermal decomposition of silver carboxylate-which is present on the surface of the incorporated silver flakes-to form in situ highly reactive silver nanoparticles; 2) the surface activation of the incorporated silver nanoparticles by the removal of surface residues. As a result, polymer nanocomposites prepared at 230 °C for 5 min, at 260 °C for 10 min, and using a typical lead-free solder reflow process show electrical resistivities of 8.1×10(-5), 6.0×10(-6), and 6.3×10(-5) Ω cm, respectively. The correlation between the rheological properties of the adhesive paste and the noncontact printing process has been discussed. With the optimal rheological properties, the formulated highly viscous pastes (221 mPa s at 2500 s(-1)) can be non-contact-printed into dot arrays with a radius of 130 μm. The noncontact printable polymer nanocomposites with superior electrical conductivity and fast processing are promising for the future of printed electronics.

Relationships Among Adiponectin Gene Polymorphisms, Proteinuria and Increased Blood Pressure in the Context of Placental Diseases

The etiology and pathogenesis of preeclampsia remain unclear. Little is known about the possible impact of adiponectin gene polymorphisms on the pathogenesis of preeclampsia. In this study, we analyzed the association of two adiponectin single-nucleotide polymorphisms (SNPs) with preeclampsia. One hundred eighty-eight Han Chinese pregnant women were enrolled (81 normal-term, 20 mild preeclampsia and 87 severe cases). Serum adiponectin level, and adiponectin exon 2 SNP +45T/G (rs2241766) genotype and intron 2 SNP +276G/T genotype (rs1501299) and their allele distributions were tested with enzyme-linked immunosorbent assay and PCR-restriction-fragment length polymorphism, respectively. There were no significant differences among the three groups (P>0.05) in genotype distribution or allele frequencies of either SNP. Systolic pressure and 24-h urinary protein were lower in TT homozygotes than those in TG+GG patients at SNP +45T/G in the severe preeclamptic group (P<0.05). Furthermore, blood pressure, serum adiponectin level and 24-h urinary protein were lower in GG homozygotes than those in TG+TT patients at SNP +276G/T in the severe preeclamptic group (P<0.05). The risk of high blood pressure (≥160/110 mm Hg) and of high serum adiponectin in T-allele carriers at +276G/T in the severe preeclamptic group were 5.345 and 5.818 times higher, respectively, compared with GG patients. These data suggest that adiponectin +45T/G and +276G/T polymorphisms are associated with important clinical manifestations of preeclampsia and that polymorphism +276G/T is associated with serum adiponectin level. Taken together, these findings suggest that adiponectin gene polymorphism is involved in the pathogenesis of preeclampsia.

Adsorption of Nitrosamines by Mesoporous Zeolite

On the basis of a study of the adsorption of zeolite and mesoporous silica, we attempted to create a hierarchical structure in the new nitrosamines trapper. Thus, mesoporous HZSM-5 zeolite was fabricated through impregnating a structure-directing agent into the as-synthesized MCM-41 followed by dry-gel conversion to transform amorphous silica to zeolite crystal. The texture of mesoporous ZSM-5 was tailored by adjusting the Si/Al ratio in the MCM-41 source and the thermal treatment time. The resulting samples were characterized by N(2) adsorption to evaluate their textural properties. One volatile nitrosamine, N-nitrosopyrrolidine (NPYR), was used as probe molecule in instantaneous adsorption to survey the function of the resulting composites. Adsorptions of N'-nitrosonornicotine (NNN) in dichloromethane solution and tobacco-specific nitrosamines (TSNA) in tobacco-extract solution were also utilized for the same purpose. As expected, mesoporous zeolite exhibits a good adsorption capacity in laboratory tests, superior to either microporous zeolite or mesoporous silica, providing a valuable candidate for controlling nitrosamines in the environment.

Bat Head Contains Soft Magnetic Particles: Evidence from Magnetism

Recent behavioral observations have indicated that bats can sense the Earth's magnetic field. To unravel the magnetoreception mechanism, the present study has utilized magnetic measurements on three migratory species (Miniopterus fuliginosus, Chaerephon plicata, and Nyctalus plancyi) and three non-migratory species (Hipposideros armiger, Myotis ricketti, and Rhinolophus ferrumequinum). Room temperature isothermal remanent magnetization acquisition and alternating-field demagnetization showed that the bats' heads contain soft magnetic particles. Statistical analyses indicated that the saturation isothermal remanent magnetization of brains (SIRM(1T_brain)) of migratory species is higher than those of non-migratory species. Furthermore, the SIRM(1T_brain) of migratory bats is greater than their SIRM(1T_skull). Low-temperature magnetic measurements suggested that the magnetic particles are likely magnetite (Fe3O4). This new evidence supports the assumption that some bats use magnetite particles for sensing and orientation in the Earth's magnetic field.

MicroRNA-181a Modulates Gene Expression of Zinc Finger Family Members by Directly Targeting Their Coding Regions

MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that specifically bind to the 3' untranslated region (3'UTR) of target genes in animals. However, some recent studies have demonstrated that miRNAs also target the coding regions of mammalian genes. Here, we show that miRNA-181a downregulates the expression of a large number of zinc finger genes (ZNFs). Bioinformatics analysis revealed that these ZNFs contain many miR-181a seed-matched sites within their coding sequences (CDS). In particular, miR-181a 8-mer-matched sequences were mostly localized to the regions coding for the ZNF C2H2 domain. A series of reporter assays confirmed that miR-181a inhibits the expression of ZNFs by directly targeting their CDS. These inhibitory effects might be due to the multiple target sites located within the ZNF genes. In conclusion, our findings indicate that some miRNA species may regulate gene family by targeting their coding regions, thus providing an important and novel perspective for decoding the complex mechanism of miRNA/mRNA interplay.

Data Convolution and Combination Operation (COCOA) for Motion Ghost Artifacts Reduction

A novel method, data convolution and combination operation, is introduced for the reduction of ghost artifacts due to motion or flow during data acquisition. Since neighboring k-space data points from different coil elements have strong correlations, a new "synthetic" k-space with dispersed motion artifacts can be generated through convolution for each coil. The corresponding convolution kernel can be self-calibrated using the acquired k-space data. The synthetic and the acquired data sets can be checked for consistency to identify k-space areas that are motion corrupted. Subsequently, these two data sets can be combined appropriately to produce a k-space data set showing a reduced level of motion induced error. If the acquired k-space contains isolated error, the error can be completely eliminated through data convolution and combination operation. If the acquired k-space data contain widespread errors, the application of the convolution also significantly reduces the overall error. Results with simulated and in vivo data demonstrate that this self-calibrated method robustly reduces ghost artifacts due to swallowing, breathing, or blood flow, with a minimum impact on the image signal-to-noise ratio.

Single Molecule Biosensing Using Color Coded Plasmon Resonant Metal Nanoparticles

Plasmonic metal nanoparticles (NPs) exhibit size, shape, and composition-dependent optical properties and have been studied extensively in the field of biosensing, but wide applications so far are limited by a lack of both highly sensitive and quantitative yet cost-effective optical detection schemes. We present a single molecule biosensing method based on color differentiation of scattered light between single plasmonic NPs and DNA hybridization-induced NP aggregates. With a seed-mediated NP growth method and a fast DNA modification method, highly stable, spectrally uniform and monodisperse Au NP (40 nm) and Au/Ag/Au composite NP (33 nm) probes were successfully prepared. Through theoretical calculations, single NP spectral measurements, and real time single-NP tracking experiments, we show that binding of a single target molecule between two NP probes can be recognized without separation from the unbound NPs by simply using a darkfield microscope equipped with a conventional light source and a color charge coupled device (CCD) camera. The detection limit of this homogeneous assay reached 0.02 pM. As an initial demonstration of multiplexed sensing at the single NP level, we used Au NPs and Au/Ag/Au composite NPs as different color probes. This scheme could be potentially applied to other areas such as multiplexed immunoassay, single cell analysis, and real time biomolecule interaction studies.

Complete Genome Sequence of the Rifamycin SV-producing Amycolatopsis Mediterranei U32 Revealed Its Genetic Characteristics in Phylogeny and Metabolism

Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimycobacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10,236,715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9,228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel 'quasi-core' with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.

Affinity Capillary Electrophoresis Coupling with Partial Filling Technique and Field-amplified Sample Injection for Enantioseparation and Determination of DL-tetrahydropalmatine

A novel, simple and sensitive method for the enantioseparation and determination of DL-tetrahydropalmatine (DL-THP) was developed using ACE in combination with partial filling technique and field-amplified sample injection. A chiral selector, i.e. BSA, was used for the enantioseparation of DL-THP in ACE. Effects of BSA concentration, pH and separation voltage on the effectiveness of the enantiomer separation were evaluated. In an optimal condition, D- and L-THP were completely enantio-separated in less than 9 min by partially filling an electrophoretic capillary with 50 micromol/L BSA (50 mbar, 100 s) and carrying out an electrophoresis with 20 mmol/L phosphate buffer (pH 7.4) at 15 kV. The sensitivity was further improved by making use of field-amplified sample injection to lower the LOD (defined as S/N=3) down to 6 ng/mL. Real samples were also tested and promising results for the determination of DL-THP enantiomers were obtained.

A Rapid and Robust Numerical Algorithm for Sensitivity Encoding with Sparsity Constraints: Self-feeding Sparse SENSE

The method of enforcing sparsity during magnetic resonance imaging reconstruction has been successfully applied to partially parallel imaging (PPI) techniques to reduce noise and artifact levels and hence to achieve even higher acceleration factors. However, there are two major problems in the existing sparsity-constrained PPI techniques: speed and robustness. By introducing an auxiliary variable and decomposing the original minimization problem into two subproblems that are much easier to solve, a fast and robust numerical algorithm for sparsity-constrained PPI technique is developed in this work. The specific implementation for a conventional Cartesian trajectory data set is named self-feeding Sparse Sensitivity Encoding (SENSE). The computational cost for the proposed method is two conventional SENSE reconstructions plus one spatially adaptive image denoising procedure. With reconstruction time approximately doubled, images with a much lower root mean square error (RMSE) can be achieved at high acceleration factors. Using a standard eight-channel head coil, a net acceleration factor of 5 along one dimension can be achieved with low RMSE. Furthermore, the algorithm is insensitive to the choice of parameters. This work improves the clinical applicability of SENSE at high acceleration factors.

A Mouse Knockout Library for Secreted and Transmembrane Proteins

Large collections of knockout organisms facilitate the elucidation of gene functions. Here we used retroviral insertion or homologous recombination to disrupt 472 genes encoding secreted and membrane proteins in mice, providing a resource for studying a large fraction of this important class of drug target. The knockout mice were subjected to a systematic phenotypic screen designed to uncover alterations in embryonic development, metabolism, the immune system, the nervous system and the cardiovascular system. The majority of knockout lines exhibited altered phenotypes in at least one of these therapeutic areas. To our knowledge, a comprehensive phenotypic assessment of a large number of mouse mutants generated by a gene-specific approach has not been described previously.

The LysR-type Virulence Activator AphB Regulates the Expression of Genes in Vibrio Cholerae in Response to Low PH and Anaerobiosis

AphB is a LysR-type activator that initiates the expression of the virulence cascade in Vibrio cholerae by cooperating with the quorum-sensing-regulated activator AphA at the tcpPH promoter on the Vibrio pathogenicity island (VPI). To identify the ancestral chromosomal genes in V. cholerae regulated by AphB, we carried out a microarray analysis and show here that AphB influences the expression of a number of genes that are not associated with the VPI. One gene strongly activated by AphB is cadC, which encodes the ToxR-like transcriptional activator responsible for activating the expression of lysine decarboxylase, which plays an important role in survival at low pH. Other genes activated by AphB encode a Na(+)/H(+) antiporter, a carbonic anhydrase, a member of the ClC family of chloride channels, and a member of the Gpr1/Fun34/YaaH family. AphB influences each of these genes directly by recognizing a conserved binding site within their promoters, as determined by gel mobility shift assays. Transcriptional lacZ fusions indicate that AphB activates the expression of these genes under aerobic conditions in response to low pH and also under anaerobic conditions at neutral pH. Further experiments show that the regulation of cadC by AphB in response to low pH and anaerobiosis is mirrored in the heterologous organism Escherichia coli, is independent of the global regulators Fnr and ArcAB, and depends upon the region of the promoter that contains the AphB binding site. These results raise the possibility that the activity of AphB is influenced by the pH and oxygen tension of the environment.

Enhancement of the Innate Immune Response of Bladder Epithelial Cells by Astragalus Polysaccharides Through Upregulation of TLR4 Expression

The innate host defenses at mucosal surfaces are critical in the early stages of urinary tract bacterial infection. Recent studies have shown that uroepithelial cells aid innate immune cells in fighting off infection, although the exact mechanism by which the uroepithilium participates in immunity remains unclear. TLR4 has been implicated to possess antimicrobial activities specific for bladder epithelial cells (BECs). TLR4 promotes secretion of IL-6 and IL-8, mediates inhibition of bladder epithelial cell (BEC) bacterial invasion, and mediates expulsion of uropathogenic Escherichia coli from BECs. In this study, cultured 5637 cells and Balb/C mice were treated with Astragalus polysaccharides (APS) against invading E. coli. To determine the contribution of TLR4 upregulation to immune response, TLR4 expression and bacterial colony numbers were monitored. After 24 h incubation, only 5637 cells treated with 500 microg/ml APS expressed higher levels of TLR4 compared with the untreated group. However, after 48h, all 5637 cells treated by APS showed higher levels of TLR4 expression than the control cells. The TLR4 expression in the bladder and macrophages mice that received APS was higher than that in the controls. Bacterial colonization in 5637 cells and the bladders of mice treated with APS was significantly reduced compared with the controls. These results demonstrate that at certain concentrations, APS can induce increased TLR4 expression in vivo and in vitro. Further, TLR4 expression upregulation can enhance innate immunity during mucosal bacterial infection. The findings establish the use of APS to modulate the innate immune response of the urinary tract through TLR4 expression regulation as an alternative option for UTI treatment.

Human Gammadelta T Lymphocytes Induce Robust NK Cell-mediated Antitumor Cytotoxicity Through CD137 Engagement

Natural killer (NK) cells are innate effector lymphocytes that control the growth of major histocompatibility complex class I negative tumors. We show here that γδ T lymphocytes, expanded in vitro in the presence isopentenylpyrophosphate (IPP), induce NK cell-mediated killing of tumors that are usually resistant to NK cytolysis. The induction of cytotoxicity toward these resistant tumors requires priming of NK cells by immobilized human immunoglobulin G1 and costimulation through CD137L expressed on activated γδ T lymphocytes. This costimulation increases NKG2D expression on the NK-cell surface, which is directly responsible for tumor cell lysis. Moreover, culturing peripheral blood mononuclear cells with zoledronic acid, a γδ T lymphocyte activating agent, enhances NK-cell direct cytotoxicity and antibody-dependent cellular cytotoxicity against hematopoietic and nonhematopoietic tumors. Our data reveal a novel function of human γδ T lymphocytes in the regulation of NK cell-mediated cytotoxicity and provide rationale for the use of strategies to manipulate the CD137 pathway to augment innate antitumor immunity.

Nanocomposites of Carbon Nanotube Fibers Prepared by Polymer Crystallization

Nanocomposites of carbon nanotube fibers have been prepared using controlled polymer crystallization confined in nanotube aerogel fibers. The polyethylene nanocomposites have been investigated by means of polarized optical microscopy (POM), scanning electron microscopy (SEM) and wide-angle X-ray diffraction (WAXD). The individual nanotubes are periodically decorated with polyethylene nanocrystals, forming aligned hybrid shish-kebab nanostructures. After melting and recrystallization, transcrystalline lamellae connecting the adjacent aligned nanotubes develop. Microstructural analysis shows that the nanotubes can nucleate the growth of both orthorhombic and monoclinic crystals of polyethylene in the quiescent state. The tensile strength, modulus, and axial electrical conductivity of these polyethylene/CNT composite fibers are as high as 600 MPa, 60 GPa, and 5000 S/m, respectively.

The Immunopathological Spectrum of Crescentic Glomerulonephritis: a Survey of 106 Patients in a Single Chinese Center

Crescentic glomerulonephritis (CrGN) is a severe form of glomerular injury. We retrospectively analyzed data from Chinese patients with CrGN in our center to characterize the immunopathological spectrum of CrGN.

Expression of Macrophage Migration Inhibitory Factor in Human Endometriosis: Relation to Disease Stage, Menstrual Cycle and Infertility

The aim of the present study was to compare the expression of macrophage migration inhibitory factor (MIF) in eutopic and ectopic endometria of women with endometriosis and eutopic endometria of women without endometriosis, and to investigate whether such an expression varies according to disease stage, menstrual cycle and infertility status.

Radiological Diagnosis of Duodenocaval Fistula: a Case Report and Literature Review

Duodenocaval fistula (DCF) is an uncommon but lethal clinical entity. The high mortality has been attributed to the difficulty of diagnosis before attempts at definitive therapy. In this case report, we describe a patient with a series of computed tomography (CT) examinations over a 2-mo period in hospital. A low-density air bubble appeared in the inferior vena cava (IVC) on the second day in hospital and became clear on day 19, and gradually enlarged. Magnetic resonance imaging (MRI) also clearly demonstrated a high-signal enteric contrast medium or thrombus and signal-void air bubbles in the IVC. However, cavography did not show the filling defect. We suggest that noninvasive CT and MRI should be chosen as a first-line investigation, and IVC, including the surrounding structures, should be carefully reviewed on images if DCF is clinically considered.

Comment on "the Effect of Stress Transfer Within Double-walled Carbon Nanotubes Upon Their Ability to Reinforce Composites"

Hierarchical Functionalized MCM-22 Zeolite for Trapping Tobacco Specific Nitrosamines (TSNAs) in Solution

To enable zeolite to trap bulky environment pollutants such as tobacco specific nitrosamines (TSNAs), we tailored the porous structure of MCM-22 zeolite by desilication to obtain a sample with mesopores centered 3.5 nm, in order to promote the mass transport. The meso-MCM-22 was further functionalized with -SO(3)H group to enhance the efficiency in adsorption of TSNAs. The composites were characterized by XRD and BET methods, and their adsorptive function was assessed in both liquid adsorption of N'-nitrosonornicotine (NNN) and the adsorption of TSNAs in aqueous tobacco-extract solution. Grafting -SO(3)H group on alkaline-treated MCM-22 significantly elevated the adsorption toward nitrosamines, and the resulting composite could reduce above 70% of NNN in dichloromethane solution or 54% of TSNAs in tobacco-extract solution.

[Relationship Between Bacterial Biofilms and Chronic Rhinosinusitis by Scanning Electron Microscopic Study]

To determine the presence and the morphological features of bacterial biofilms in surgical specimens of patients with chronic rhinosinusitis (CRS) compared with control patients without CRS by scanning electron microscopy (SEM), and to evaluate the role of biofilm on the pathogenesis of CRS.

Comment on "Adaptive Steady-state Stabilization for Nonlinear Dynamical Systems"

Instead of the problematic reasoning presented in the work of D. J. Braun [Phys. Rev. E 78, 016213 (2008)], a rigorous argument is provided to show the validity of the adaptive controller proposed by Braun under some particular assumptions. Without these assumptions, this controller may be failed to stabilize the unsteady state, which is numerically shown by specific examples. Also, the choice of parameters to guarantee the validity of these assumptions is illustrated.

JNK Regulates Serotonin-mediated Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells

JNK is a member of the MAPK family and has essential roles in inflammation and cell differentiation and apoptosis. In recent years, there have been accumulating data indicating a novel role for JNK in cell growth and migration. In this report, we demonstrate that JNK activity is necessary for serotonin (5-HT)-induced proliferation and migration of bovine pulmonary artery smooth muscle cells (PASMCs). Stimulation with 5-HT was found to lead to activation of JNK with a maximal activation at 10 min. Inhibition of JNK with its specific inhibitor, SP-600125, or its dominant-negative form, DN-JNK, significantly reduced 5-HT-stimulated [(3)H]thymidine incorporation and cyclin D1 expression. A similar inhibitory effect on SMC migration produced by 5-HT, as detected by a wound healing assay, was observed with inhibition of JNK. Furthermore, inhibition of 5-HT receptors (1B) and (2A), but not inhibition of the 5-HT transporter, blocked 5-HT-induced JNK activation. Inhibition of phosphatidylinositol 3-kinase (PI3K) with LY-294002 and wortmannin had little or no effect on 5-HT-induced JNK phosphorylation, but JNK inhibitor SP-600125 and DN-JNK blocked 5-HT-stimulated phosphorylation of Akt and its downstream effectors, p70S6K1 and S6, indicating that Akt is a downstream effector of JNK. Activation of Akt by 5-HT was blocked only minimally, if at all, by inhibitors of ERK and p38 MAPK, indicating a uniqueness of JNK MAPK in this activation of Akt. Coimmunoprecipitation showed binding of Akt to JNK, further supporting the interaction of JNK and Akt. Thus JNK is a critical molecule in 5-HT-induced PASMC proliferation and migration and may act at an important point for cross talk of the MAPK and PI3K pathways. Its activation by 5-HT is initiated through 5-HT (1B) and (2A) receptors, and its stimulation of SMC proliferation and migration occurs through the Akt pathway.

The Protein Kinase Hal5p is the High-copy Suppressor of Lithium-sensitive Mutations of Genes Involved in the Sporulation and Meiosis As Well As the Ergosterol Biosynthesis in Saccharomyces Cerevisiae

From a genome-scale genetic screen, we have identified 114 lithium-sensitive and 6 lithium-tolerant gene mutations in Saccharomyces cerevisiae. Twenty-five of these identified lithium-sensitive mutations are of genes previously reported to be involved in sporulation and meiosis, whereas thirty-six of them are of genes involved in the vacuolar protein sorting (VPS) pathway, mainly functioning in the membrane docking and fusion. Accordingly, the lithium-sensitive phenotypes for one third of identified VPS mutants well correlate to their intracellular lithium contents in response to lithium stress. This indicates the integrity of the VPS pathway is critic for the ion homeostasis in yeast cells. The halotolerant protein kinase Hal5p, a regulator of the potassium transporter Trk1p, is shown to be the high-copy suppressor of nearly one third of identified lithium-sensitive mutations of genes involved in the sporulation and meiosis as well as in the biosynthesis of ergosterol. These results suggest that Hal5p-mediated ion homeostasis is important for these two biological processes.

Microwave Makes Carbon Nanotubes Less Defective

An ultrafast microwave annealing process has been developed to reduce the defect density in vertically aligned carbon nanotubes (CNTs). Raman and thermogravimetric analyses have shown a distinct defect reduction in the CNTs annealed in microwave for 3 min. Fibers spun from the as-annealed CNTs, in comparison with those from the pristine CNTs, show increases of approximately 35% and approximately 65%, respectively, in tensile strength ( approximately 0.8 GPa) and modulus (approximately 90 GPa) during tensile testing; an approximately 20% improvement in electrical conductivity (approximately 80000 S m(-1)) was also reported. The mechanism of the microwave response of CNTs was discussed.

Suppression of Human MDA-MB-435S Tumor by U6 Promoter-driven Short Hairpin RNAs Targeting Focal Adhesion Kinase

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase implicated in cancer cell survival, proliferation, and in various steps in the metastatic cascade. In the present study, we took advantage of a cationic liposome as gene carrier and targeted FAK function through both in vitro and in vivo approaches.

Combustion Synthesis and Effect of LaMnO3 and La0.8Sr0.2MnO3 on RDX Thermal Decomposition

Perovskite-type LaMnO(3) and La(0.8)Sr(0.2)MnO(3) with high specific surface areas were prepared by stearic acid gel combustion method. The obtained powders were characterized by XRD, FT-IR, SEM and XPS techniques. Their catalytic activities were investigated on thermal decomposition of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by TG-DSC techniques. The experimental results show that LaMnO(3) is a more effective catalyst than La(0.8)Sr(0.2)MnO(3) for the sublimation and melting process of RDX because of its higher concentration ratio of surface-adsorbed species. And the catalytic activity of La(0.8)Sr(0.2)MnO(3) is higher than that of LaMnO(3) for thermal decomposition of liquid RDX. This could be attributed to its higher concentration ratios of surface oxygen and Mn(4+)/Mn(3+). In conclusion, the concentration ratios of surface oxygen and Mn(4+)/Mn(3+) could play key roles for RDX thermal decomposition. This study points out a potential way to develop new and more active perovskite-type catalysts for the RDX thermal decomposition.

Silica Gel-catalyzed One-pot Syntheses in Water and Fluorescence Properties Studies of 5-amino-2-aryl-3H-chromeno[4,3,2-de][1,6]naphthyridine-4-carbonitriles and 5-amino-2-aryl-3H-quinolino[4,3,2-de][1,6]naphthyridine-4-carbonitriles

The silica gel-catalyzed synthesis of 5-amino-2-aryl-3H-chromeno[4,3,2-de][1,6]naphthyridine-4-carbonitriles and 5-amino-2-aryl-3H-quinolino[4,3,2-de][1,6]naphthyridine-4-carbonitriles were simply achieved upon the one-pot cascade reaction of malononitrile with substituted 2-hydroxyacetophenone (or 2-aminoacetophenone) and aromatic aldehyde in aqueous media. The mechanistic investigation results based on electrospray ionization mass spectrometry (ESI-MS) indicated that malononitrile displayed a dual role during this transformation. Thirteen bonds were cleaved and 12 new bonds were constructed in the formation of 5-amino-2-aryl-3H-chromeno[4,3,2-de][1,6]naphthyridine-4-carbonitriles, while only 2 H(2)O molecules were removed. The fluorescence properties screening showed five new compounds have high fluorescence quantum yields.

Effective Nitrosamines Trap Derived from the in Situ Carbonized Mesoporous Silica MCM-41

A new route to modify the mesoporous silica MCM-41 with carbon, using the inherent surfactant template in the as-synthesized sample as the carbon precursor, is reported in this article. Apart from the advantage of omitting energy and time required for removal of template, the resulting silica-carbon composites exhibit a high efficiency in adsorption and catalytic decomposition of N-nitrosopyrrolidine (NPYR), the typical carcinogenic pollutant in environment. The influence of carbonization temperature on the structure and performance of the resulting carbon-silica composite was investigated by use of XRD, N(2) adsorption-desorption, FTIR and TG-DSC techniques, and the instantaneous adsorption and the temperature-programmed surface reaction (TPSR) of NPYR as well as the reduction of nitrosamines level of cigarette smoke were also utilized to assess the actual function of these composites. The carbonization performed in the range of 773-973 K enabled the resulting composites to possess a higher activity than parent MCM-41 in eliminating volatile nitrosamines, which is beneficial for controlling carcinogenic pollutants in environment.

CD137 Promotes Proliferation and Survival of Human B Cells

CD137 (4-1BB)-mediated costimulation plays an important role in directing the fate of Ag-stimulated T cells and NK cells, yet the role of CD137 in mediating B cell function is unknown. We found that CD137 is expressed in vitro on anti-Ig-stimulated peripheral blood B cells and in vivo on tonsillar B cells with an activated phenotype. In vitro CD137 expression is enhanced by CD40 stimulation and IFN-gamma and is inhibited by IL-4, -10, and -21. The expression of CD137 on activated human B cells is functionally relevant because engagement with its ligand at the time of activation stimulates B cell proliferation, enhances B cell survival, and induces secretion of TNF-alpha and -beta. Our study suggests that CD137 costimulation may play a role in defining the fate of Ag-stimulated human B cells.

Motion Correction Using an Enhanced Floating Navigator and GRAPPA Operations

A method for motion correction in multicoil imaging applications, involving both data collection and reconstruction, is presented. The floating navigator method, which acquires a readout line off center in the phase-encoding direction, is expanded to detect translation/rotation and inconsistent motion. This is done by comparing floating navigator data with a reference k-space region surrounding the floating navigator line, using a correlation measure. The technique of generalized autocalibrating partially parallel acquisition is further developed to correct for a fully sampled, motion-corrupted dataset. The flexibility of generalized autocalibrating partially parallel acquisition kernels is exploited by extrapolating readout lines to fill in missing "pie slices" of k-space caused by rotational motion and regenerating full k-space data from multiple interleaved datasets, facilitating subsequent rigid-body motion correction or proper weighting of inconsistent data (e.g., with through-plane and nonrigid motion). Phantom and in vivo imaging experiments with turbo spin-echo sequence demonstrate the correction of severe motion artifacts.

Temporal Variation of Magnetotactic Bacterial Communities in Two Freshwater Sediment Microcosms

Magnetotactic bacteria (MTB), which can mineralize nanosized magnetite or greigite crystals within cells, play important roles in biogeochemical processes, for example iron and sulfur cycling, and depositional remanent magnetization acquisitions. Despite decades of research, the knowledge of MTB distribution and ecology is still limited. In the present study, we investigated the temporal variation of MTB communities in freshwater sediment microcosms based on 16S rRNA genes and unifrac analyses. Two microcosms (MY8 and MY11) collected from two separate sites in Lake Miyun (Beijing, China) were analyzed. The majority of retrieved sequences belonged to alphaproteobacterial magnetotactic cocci in both microcosms (representing 64.29% of clones from MY8 and 100% of clones from MY11), whereas so-called 'Magnetobacterium bavaricum'-like MTB affiliated within Nitrospira phylum were exclusively found in microcosm MY8. Over a 3-month period, the temporal variation of MTB communities was evident in both microcosms. In addition, the phylogenetic discrepancy of MTB communities between two microcosms is more prominent than that of the same microcosm at different times, implying adaptation of MTB phylogenetic lineages to specific microenvironments. Among the physical-chemical parameters measured, a strong correlation was shown between nitrate and the main genetic variability of MTB communities, indicating that nitrate may influence the occurrence of MTB phylogenetic lineages in natural environments.

[Adult-to-adult Living Donor Liver Transplantation with 94 Cases Report]

To investigate the donor evaluation, surgical protocol, and the complication for the adult-to-adult living donor liver transplantation (AALDLT).

[Prediction of Potential Distribution Area of Erigeron Philadelphicus in China Based on MaxEnt Model]

Erigeron philadelphicus, an alien weed originated from North America, has already invaded in Shanghai, Jiangsu, Anhui, and some other places in China, caused harm on local ecosystem and demonstrated huge potential invasiveness. By using MaxEnt model and geographic information system (GIS), this paper analyzed the environmental variables affecting the distribution of E. philadelphicus, and intuitively and quantitatively predicted its potential distribution regions in China. The prediction was verified by the ROC curve, and the results showed that E. philadelphicus had a wide potential distribution range, with the main suitable distribution area in Shanghai, Jiangsu, Zhejiang, Anhui, Henan, Hubei, Hunan and Jiangxi. At present, the actual invasive range of E. philadelphicus was far narrower than its potential maximum invasive range, and likely to be continued to spread. The ROC curve test indicated that the prediction with MaxEnt model had a higher precision, and was credible. Air temperature and precipitation could be the main environmental variables affecting the potential distribution of E. philadelphicus. More attentions should be addressed to the harmfulness of the weed. To eradicate the existing E. philadelphicus populations and to strictly monitor the invasion of E. philadelphicus to its most suitable distribution area could be the effective measures to prevent and control the further invasion of the alien weed.

Reduced Expression of Chemerin is Associated with a Poor Prognosis and a Lowed Infiltration of Both Dendritic Cells and Natural Killer Cells in Human Hepatocellular Carcinoma

Chemerin has been suggested to chemoattract dendritic cells (DC) and natural killer (NK) cells which have the antitumor role. However, no study has been performed to determine the expression of chemerin in tumor tissues. The aim of our study is to investigate chemerin expression in hepatocellular carcinoma (HCC) tumor tissues and to correlate chemerin expression with clinicopathological parameters and prognosis.

[Preliminary Exploration of Gd-DTPA Enhanced Inner Ear Image of Guinea Pig Using Magnetic Resonance Scan]

To observe the distribution of Gd-DTPA in the inner ear of guinea pig by MRI at different time points after intratympanic administration, explore the optical time for observing the whole inner ear. To study the pharmacokinetic feature of Gd-DTPA in the inner ear, and find out whether discrimination of endolymph and perilymph can be obtained under current conditions.

[Comparison of Proteomics Between Acute Myeloid Leukemia and Acute Lymphoid Leukemia]

The aim of this study was to explore the distinct protein profiles of different subtype of acute myeloid leukemia (AML), including M(1), M(2), M(3) and acute lymphoid leukemia (ALL) by differential proteomic expression analysis. The proteins of bone marrow leukemia cells from AML and ALL patients were separated by two-dimensional electrophoresis (2-DE). 2-DE patterns were analyzed by PDQuest 7.4 software and the differentially expressed proteins were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and bioinformatics. The results indicated that 21 differentially expressed proteins were found by 2-DE and 15 were identified by MS to be significantly differentially expressed. In AML, seven proteins were highly expressed such as MPO, PRDX3, CALR and ECH1 and so on, and eight proteins were highly expressed in ALL, including ARHGDIB, PFN1 and ACTG1 and so on. It is concluded that the distinct protein profiles between AML and ALL have been proved. It may be helpful for the identification of new targets for specific treatment approaches and the molecular markers for the early diagnosis of leukemia.

Snapping Magnetosome Chains by Asymmetric Cell Division in Magnetotactic Bacteria

The mechanism by which prokaryotic cells organize and segregate their intracellular organelles during cell division has recently been the subject of substantial interest. Unlike other microorganisms, magnetotactic bacteria (MTB) form internal magnets (known as magnetosome chain) for magnetic orientation, and thus face an additional challenge of dividing and equipartitioning this magnetic receptor to their daughter cells. Although MTB have been investigated more than four decades, it is only recently that the basic mechanism of how MTB divide and segregate their magnetic organelles has been addressed. In this issue of Molecular Microbiology, the cell cycle of the model magnetotactic bacterium, Magnetospirillum gryphiswaldense is characterized by Katzmann and co-workers. The authors have found that M. gryphiswaldense undergoes an asymmetric cell division along two planes. A novel wedge-like type of cellular constriction is observed before separation of daughter cells and magnetosome chains, which is assumed to help cell cope with the magnetic force within the magnetosome chain. The data shows that the magnetosome chain becomes actively recruited to the cellular division site, in agreement with the previous suggestions described by Staniland et al. (2010), and the actin-like protein MamK is likely involved in this fast polar-to-midcell translocalization. With the use of cryo-electron tomography, an arc-shaped Z ring is observed near the division site, which is assumed to trigger the asymmetric septation of cell and magnetosome chain.

Sensitization of Glioma Cells to Tamoxifen-induced Apoptosis by Pl3-kinase Inhibitor Through the GSK-3β/β-catenin Signaling Pathway

Malignant gliomas represent one of the most aggressive types of cancers and their recurrence is closely linked to acquired therapeutic resistance. A combination of chemotherapy is considered a promising therapeutic model in overcoming therapeutic resistance and enhancing treatment efficacy. Herein, we show by colony formation, Hochest 33342 and TUNEL staining, as well as by flow cytometric analysis, that LY294002, a specific phosphatidylinositide-3-kinase (PI3K) inhibitor, enhanced significantly the sensitization of a traditional cytotoxic chemotherapeutic agent, tamoxifen-induced apoptosis in C6 glioma cells. Activation of PI3K signaling pathway by IGF-1 protected U251 cells from apoptosis induced by combination treatment of LY294002 and tamoxifen. Interference of PI3K signaling pathway by PI3K subunit P85 siRNA enhanced the sensitization of U251 glioma cells to tamoxifen -induced apoptosis. By Western blotting, we found that combination treatment showed lower levels of phosphorylated Akt(Ser473) and GSK-3β(Ser9) than a single treatment of LY294002. Further, we showed a significant decrease of nuclear β-catenin by combination treatment. In response to the inhibition of β-catenin signaling, mRNA and protein levels of Survivin and the other three antiapoptotic genes Bcl-2, Bcl-xL, and Mcl-1 were significantly decreased by combination treatment. Our results indicated that the synergistic cytotoxic effect of LY294002 and tamoxifen is achieved by the inhibition of GSK-3β/β-catenin signaling pathway.

Effects of Phase Cancellation and Receiver Aperture Size on Broadband Ultrasonic Attenuation for Trabecular Bone In vitro

Phase cancellation in ultrasound due to large receiver size has been proposed as a contributing factor to the inaccuracy of estimating broadband ultrasound attenuation (BUA), which is used to characterize bone quality. Transducers with aperture size ranging from 2 to 5 mm have been used in previous attempts to study the effect of phase cancellation. However, these receivers themselves are susceptible to phase cancellation because aperture size is close to one center wavelength (about 3 mm at 500 KHz in water). This study uses an ultra small receiver (aperture size: 0.2 mm) in conjunction with a newly developed two-dimensional (2-D) synthetic array system to investigate the effects of phase cancellation and receiver aperture size on BUA estimations of bone tissue. In vitro ultrasound measurements were conducted on 54 trabecular bone samples (harvested from sheep femurs) in a confocal configuration with a focused transmitter and synthesized focused receivers of different aperture sizes. Phase sensitive (PS) and phase insensitive (PI) detections were performed. The results show that phase cancellation does have a significant effect on BUA. The normalized BUA (nBUA) with PS is 8.1% higher than PI nBUA while PI BUA is well correlated with PS BUA. Receiver aperture size also influences the BUA reading for both PI and PS detection and smaller receiver aperture tends to result in higher BUA readings. The results also indicate that the receiver aperture size used in the confocal configuration with PI detection should at least equal the aperture of the transmitter to capture most of the energy redistributed by the interference and diffraction from the trabecular bone.

[The Application of Near-infrared Spectroscopy and Pattern Recognition to Quality Assessment of Toothpaste Samples of Different Brands]

The near-infrared spectroscopy (NIR) was combined with pattern recognitions method and applied to the quality assessment of toothpaste samples of four different brands. Several chemometrics approaches, such as principal component analysis (PCA), clustering analysis (CA), partial least squares (PLS), artificial neural networks (ANN) and K-nearest neighbor (kNN) were used to investigate the quality of toothpastes samples. The obtained results showed that the four clustering groups can be observed after the pretreatment of multiple scatter correction for the NIR data. It was also found that the quality of toothpastes of all the four brands was relatively stable, however, there is a significant difference in the quality between two brand kinds of toothpaste samples.

[Lateral Homodigital Flaps Pedicled with Cutaneous Branches of Digital Artery for Repairing Nail Bed Defects]

To investigate the effectiveness of using lateral homodigital flaps pedicled with cutaneous branches of digital artery for repairing nail bed defects.

Controlling the Primary Particle Evolution Process Towards Silica Monoliths with Tunable Hierarchical Structure

In order to establish the hierarchical structure in multiple levels on mesoporous silica, this article reports a new strategy to prepare the monolith with the pore configuration in nanometer scale, micro-morphology in micrometer level and macroscopic shape in millimeter or larger grade. These hierarchical monoliths are synthesized in a weak acidic condition by using triblock copolymer P123, hydroxyl carboxylic acid and tetramethyl orthosilicate (TMOS), and the textural properties of the mesostructure can be facilely adjusted by simply controlling the synthesis condition without any additive. During the synthesis, the primary particles can be selectively synthesized as monodispersed sphere, noodle, prism, straight rods with different size or irregular bars, and their connection plus arrangement in 3D directions can be also regulated. Therefore, various textural properties of mesopore are able to be altered including pore size (5.5-10.6 nm), total pore volume (0.48-1.2 cm(3) g(-1)), micropore surface area (47-334 m(2) g(-1)), and pore shape (from 2D or 3D straight channel to plugged channel). Moreover, these monoliths exhibit a considerable mechanical strength; they are also applied in eliminating particulate matters and tobacco special nitrosamines (TSNA) in tobacco smoke, exhibiting various morphology-assisted functions.

[Antagonism of Tert-butylhydroquinone on Neurotoxicity and Oxidative Stress Induced by Paraquat in PC12]

To investigate the protective effects of the tert-butylhydroquinone (tBHQ) pretreatment on neurotoxicity and oxidative stress induced by paraquat (PQ) in PC12 cells.

Fabrication of Phase-change Chalcogenide Ge2Sb2Te5 Patterns by Laser-induced Forward Transfer

Femtosecond laser pulses are focused on a thin film of Ge2Sb2Te5 phase-change material, and the transfer of the illuminated material to a nearby substrate is investigated. The size, shape, and phase-state of the fabricated pattern can be effectively controlled by the laser fluence and by the thickness of the Ge2Sb2Te5 film. Results show multi-level electrical and optical reflection states of the fabricated patterns, which may provide a simple and efficient foundation for patterning future phase-change devices.

Noise-free Dual-wavelength Difference Imaging of Plasmonic Resonant Nanoparticles in Living Cells

Herein, we demonstrated a new optical microscopy method to selectively image small-size gold nanoparticles (GNPs) inside noisy living cells through determination of the difference image between the probe beam (illuminated at the resonance wavelength of GNPs, 532 nm) and the reference beam (illuminated at 473 nm). From computer simulation and single-particle imaging experiments, we demonstrated that GNPs with a diameter of 45 nm could be selectively imaged in the GNPs/cell lysates mixture and inside living cells by dual-wavelength difference (DWD) imaging. The diffusion dynamics of nucleic acids functionalized GNPs on cell membranes and the internalization kinetics of these GNPs by living cells were explored with this method. Our real-time tracking experiments showed that statistically 80% of GNPs were under restricted diffusion on the cell membrane. The cell cytoskeleton fence effect, as observed in the single-particle tracking experiments, may be one of the main factors for the restricted diffusion mode.

Map2k4 Functions As a Tumor Suppressor in Lung Adenocarcinoma and Inhibits Tumor Cell Invasion by Decreasing Peroxisome Proliferator-activated Receptor γ2 Expression

MAP2K4 encodes a dual-specificity kinase (mitogen-activated protein kinase kinase 4, or MKK4) that is mutated in a variety of human malignancies, but the biochemical properties of the mutant kinases and their roles in tumorigenesis have not been fully elucidated. Here we showed that 8 out of 11 cancer-associated MAP2K4 mutations reduce MKK4 protein stability or impair its kinase activity. On the basis of findings from bioinformatic studies on human cancer cell lines with homozygous MAP2K4 loss, we posited that MKK4 functions as a tumor suppressor in lung adenocarcinomas that develop in mice owing to expression of mutant Kras and Tp53. Conditional Map2k4 inactivation in the bronchial epithelium of mice had no discernible effect alone but increased the multiplicity and accelerated the growth of incipient lung neoplasias induced by oncogenic Kras. MKK4 suppressed the invasion and metastasis of Kras-Tp53-mutant lung adenocarcinoma cells. MKK4 deficiency increased peroxisomal proliferator-activated receptor γ2 (PPARγ2) expression through noncanonical MKK4 substrates, and PPARγ2 enhanced tumor cell invasion. We conclude that Map2k4 functions as a tumor suppressor in lung adenocarcinoma and inhibits tumor cell invasion by decreasing PPARγ2 levels.

[Advances in Virus Modification with Macromolecule]

Intravitreal Homocysteine-thiolactone Injection Leads to the Degeneration of Multiple Retinal Cells, Including Photoreceptors

Hyperhomocysteinemia is known to cause degeneration of retinal ganglion cells, but its influence on photoreceptors remains largely unknown. In particular, the role of homocysteine-thiolactone (Hcy-T)--the physiologic metabolite of homocysteine that has been proven to be more cytotoxic than homocysteine itself--as a factor that causes retinopathy, has not been defined. This study aimed to investigate the toxic effects of excessive Hcy-T in a mouse model.

Changes of Photosynthetic Behaviors in Kappaphycus Alvarezii Infected by Epiphyte

Epiphytic filamentous algae (EFA) were noted as a serious problem to reduce the production and quality of K. alvarezii. The morphological studies revealed that the main epiphyte on K. alvarezii was Neosiphonia savatieri in China. Though the harmful effects of EFA on the production of K. alvarezii have been reported, the detailed mechanism of the N. savatieri in limiting the production of K. alvarezii has not been studied yet. The present paper studied the effects of N. savatieri infection on photosynthetic behaviors in K. alvarezii by detecting chlorophyll fluorescence transient in vivo. The results revealed that damage of oxygen-evolving complex (OEC), decrease of active reaction centers (RCs), and the plastoquinone (PQ) pool as well as significant reduction in the performance indexes (PI) of PSII were caused by the infection of N. savatieri. The influence of N. savatieri on photosynthetic activity of K. alvarezii should be one of the important reasons to reduce the production of K. alvarezii infected by N. savatieri.

Risk of Ovarian Cancer in Women with Pelvic Inflammatory Disease: a Population-based Study

Ovarian cancer is commonly fatal and incidence has persistently risen in Taiwan over the past 20 years. Prevention strategies, however, are limited. Pelvic inflammatory disease (PID) has been suggested to increase the risk of developing ovarian cancer, but the results of studies have been inconsistent. Therefore, we investigated whether PID increases the risk of developing ovarian cancer in a large, nationwide cohort.

Decreased Catalytic Function with Altered Sumoylation of DNA Topoisomerase I in the Nuclei of Scleroderma Fibroblasts

Sumoylation is involved in nucleolus-nucleoplasm transport of DNA topoisomerase I (topo I), which may associate with changes of cellular and topo I functions. Skin fibroblasts of patients with systemic sclerosis (SSc) exhibit profibrotic cellular changes. The aims of this study were to examine the catalytic function and sumoylation of topo I in the nuclei of SSc fibroblasts, a major cell type involved in the fibrotic process.

A Dynamical Model Reveals Gene Co-localizations in Nucleus

Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the observed co-localization of genes within a defined subnuclear region. A simple standard Brownian motion model in two and three dimensions shows that preferential co-localization is possible for co-regulated genes without any direct interaction, and suggests the occurrence may be due to a limitation in the number of available transcription factors. Experimental data of chromatin movements demonstrates that fractional rather than standard Brownian motion is more appropriate to model gene mobilizations, and we tested our dynamical model against recent static experimental data, using a sub-diffusion process by which the genes tend to colocalize more easily. Moreover, in order to compare our model with recently obtained experimental data, we studied the association level between genes and factors, and presented data supporting the validation of this dynamic model. As further applications of our model, we applied it to test against more biological observations. We found that increasing transcription factor number, rather than factory number and nucleus size, might be the reason for decreasing gene co-localization. In the scenario of frequency- or amplitude-modulation of transcription factors, our model predicted that frequency-modulation may increase the co-localization between its targeted genes.

Application of Image Spectrometer to in Situ Infrared Broadband Optical Monitoring for Thin Film Deposition

A path-folded infrared image spectrometer with five sub-gratings and five linear-array detectors was applied to a broadband optical monitoring (BOM) system for thin film deposition. Through in situ BOM, we can simultaneously acquire the thickness and refractive index of each layer in real time by fitting the measured spectra, and modify the deposition parameters during deposition process according to the fitting results. An effective data processing method was proposed and applied in the BOM process, and it shortened the data processing time and improved the monitoring efficiency greatly. For demonstration, a narrow band-pass filter (NBF) at 1540 nm with ~10 nm full width at half-maximum (FWHM) had been manufactured using the developed BOM system, and the results showed that this BOM method was satisfying for monitoring deposition of thin film devices.

The Body Image, Weight Satisfaction, and Eating Disorder Tendency of School Children: the 2-year Follow-up Study

This 2-year follow-up study was conducted to enhance our understanding of changes and rates of disturbed eating attitudes/behaviors, weight satisfaction, and prevalence of obesity in elementary school students between the ages of 10 and 12 years.

Evaluation of Global DNA Hypomethylation in Human Prostate Cancer and Prostatic Intraepithelial Neoplasm Tissues by Immunohistochemistry

OBJECTIVE: To identify the differences of 5-methylcytosine (5-MC) level between primary prostate cancer tissues (PCTs), prostate cancer-adjacent benign tissues (PCABTs), low-grade prostatic intraepithelial neoplasia (LGPIN), and high-grade prostatic intraepithelial neoplasia (HGPIN), and further analysis the 5-MC alterations in prostate cancer with pathologic grade and clinical prognosis. MATERIALS AND METHODS: Immunohistochemistry method with a 5-MC monoclonal antibody was used to identify the 5-methylcytosine (5-MC) levels in PCTs, PCABTs, LGPIN, and HGPIN specimens in the present study. Statistical analysis with SPSS software (SPSS Inc., Chicago, IL) was used to compare differences of 5-MC levels in the four groups and evaluate the 5-MC alterations in prostate cancer with pathologic grade and clinical prognosis. RESULTS: We found that 38 of 48 (79.1%) patients studied showed a decrease in 5-MC staining of PCTs compared with PCABTs. The difference in the methylation levels for the PCTs and the PCABTs was highly statistically significant (P < 0.001). Spearman correlation showed there was no statistically significant association between the average score of 5-MC staining and Gleason score sum. Kaplan-Meier survival analysis showed that patient group with no or weak 5-MC staining compared with group with moderate and strong 5-MC staining was associated with better survival of patients, although there was no statistically significant difference between the 2 groups in predicating prognosis (P = 0.385). The average scores of 5-MC staining for LGPIN, HGPIN, PCABTs, and PCTs groups were 6.91, 1.58, 6.63, and 3.10, respectively. The methylation level of HGPIN group, as well as that of PCTs group, was significantly lower than those of LGPIN (P < 0.001; P < 0.001) and PCABTs groups (P < 0.001; P < 0.001), respectively, with the 5-MC levels of PCABTS group similar to that of LGPIN group (P = 0.476). 5-MC levels of HGPIN group was lower than that PCTs group (P = 0.004). CONCLUSIONS: We found that global DNA methylation was low in most prostate cancer compared with benign regions from the same patient's sections. None of the DNA hypomethylation changes in primary cancers were associated with pathologic grade and clinical prognosis. In addition, immunohistochemistry showed that the global methylation was lower in HGPIN compared with LGPIN and methylcytosine staining in HGPIN was lower than that of PCTs. The results suggest that global DNA hypomethylation might play an important role in the process of prostate cancer initiation rather than progression.

Survey on Eating Disorder-related Thoughts, Behaviors, and Their Relationship with Food Intake and Nutritional Status in Female High School Students in Taiwan

Eating disorders are now a global health problem for adolescents and young female adults. The level of eating disorders among young female adults is growing in Asian countries. Therefore, the purpose of this study was to investigate body image, weight concerns, eating attitudes, dietary intake, and nutritional status related to eating disorders of female high school students in Taiwan.

Genome-wide Copy Number Analyses Identified Novel Cancer Genes in Hepatocellular Carcinoma

A powerful way to identify driver genes with causal roles in carcinogenesis is to detect genomic regions that undergo frequent alterations in cancers. Here we identified 1,241 regions of somatic copy number alterations in 58 paired hepatocellular carcinoma (HCC) tumors and adjacent nontumor tissues using genome-wide single nucleotide polymorphism (SNP) 6.0 arrays. Subsequently, by integrating copy number profiles with gene expression signatures derived from the same HCC patients, we identified 362 differentially expressed genes within the aberrant regions. Among these, 20 candidate genes were chosen for further functional assessments. One novel tumor suppressor (tripartite motif-containing 35 [TRIM35]) and two putative oncogenes (hairy/enhancer-of-split related with YRPW motif 1 [HEY1] and small nuclear ribonucleoprotein polypeptide E [SNRPE]) were discovered by various in vitro and in vivo tumorigenicity experiments. Importantly, it was demonstrated that decreases of TRIM35 expression are a frequent event in HCC and the expression level of TRIM35 was negatively correlated with tumor size, histological grade, and serum alpha-fetoprotein concentration. CONCLUSION: These results showed that integration of genomic and transcriptional data offers powerful potential for identifying novel cancer genes in HCC pathogenesis.

2005-2008 Nutrition and Health Survey in Taiwan: the Nutrition Knowledge, Attitude and Behavior of 19-64 Year Old Adults

The purpose of this study is to understand nutrition knowledge, attitude, and behavior in Taiwanese adults. Results indicated that adults' knowledge on 'relationship between diet and disease' and 'comparison of foods in terms of specific nutrients' is acceptable. However, they lack knowledge on 'daily serving requirements' and 'weight and weight loss'. Although they recognize the importance of nutrition, nutrition was not the major concern of food selection. Significant differences were found among gender and age groups. Females of most age groups are better than males in many aspects of nutrition knowledge, attitude and behavior except emotional and external eating behavior. Young (age 19-30) and prime (age 31-44) adults have better knowledge than that of middle adults (age 45-64), while prime adults hold a more positive attitude than young adults. As for nutrition behavior, prime and middle adults are better than young adults. Nutrition knowledge and attitude of adults in urban areas is generally better than those in suburban and remote areas. However, adults in urban areas perform 'emotional and external cued eating' more frequently than those in suburban and remote areas. There are significantly positive correlations among nutrition knowledge, attitude and behavior; and attitude has stronger correlation (r=0.42) with behavior than knowledge does (r=0.27). Therefore, to achieve desirable eating behaviors, the adult nutrition education program should include knowledge of what constitutes a balanced diet and what constitutes being overweight. Proper strategies to enhance the behavioral motivation of healthy food selection must also not be neglected.

Proteins in Leaked Amniotic Fluid As Biomarkers Diagnostic for Prelabor Rupture of Membranes

Early diagnosis of prelabor rupture of membranes (PROM) is essential to protect mother and fetus from intra-uterus infection and preterm birth. A simple and rapid bedside test would help clinicians confirm the diagnosis for early treatment.

Two Antimicrobial and Nematicidal Peptides Derived from Sequences Encoded Picea Sitchensis

Two antimicrobial peptides (piceain 1 and 2) derived from sequences encoded Picea sitchensis are identified. Their amino acid sequences are KSLRPRCWIKIKFRCKSLKF and RPRCWIKIKFRCKSLKF, respectively. One intra-molecular disulfide bridge is formed by these two half-cysteines in both piceain 1 and 2. Antimicrobial activities of synthesized piceains against several kinds of microorganisms were tested. They showed antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and fungus Candida albicans but little antimicrobial activity against Bacillus subtilis. The results of nematicidal test showed they exerted strong nematicidal activities against Caenorhabditis elegans, following exposure for 5 h at concentrations as low as 10 µg/ml. They had weak hemolytic abilities against human and rabbit red cells. At the concentration of 250 µg/ml, they induced red cell hemolysis of less than 5%. Circular dichroism spectra of the two antimicrobial peptides were investigated in several solutions. Their main secondary structure components are β-sheet and random. The current work provides a novel family of antimicrobial and nematicidal peptides with unique disulfided loop containing nine amino acid residues.

AAV2-mediated Subretinal Gene Transfer of HIFN-α Attenuates Experimental Autoimmune Uveoretinitis in Mice

Recent reports show that gene therapy may provide a long-term, safe and effective intervention for human diseases. In this study, we investigated the effectiveness of adeno-associated virus 2 (AAV2) based human interferon-alpha (hIFN-α) gene therapy in experimental autoimmune uveoretinitis (EAU), a classic model for human uveitis.

Silver Nanowires: from Scalable Synthesis to Recyclable Foldable Electronics

Identification of Functional Peroxisome Proliferator-activated Receptor α Response Element in the Human Ppsig Gene

Peroxisome proliferator-activated receptor α (PPARα), one of the key ligand-activated nuclear receptors interacting with PPAR response elements (PPREs), may trigger the expression of PPAR-responsive genes and be involved in the transcriptional regulation of lipid metabolism, energy balance, and some diseases. Previous studies have demonstrated that the mouse Ppsig gene is a novel PPARα target gene taking a pivotal role in maintaining energy balance during fasting. Disparity between humans and rodents in their PPAR systems requires corroborating experiments to determine whether the hPpsig gene (Ppsig homologous gene in human) is also a PPARα target gene. In this work, eight putative PPREs in the promoter and first intron of hPpsig were identified. However, only one intronic PPRE could respond to PPARα by transient transfection. Furthermore, the binding activity of PPARα with this intronic PPRE was confirmed by electrophoretic mobility shift assay in vitro. This investigation might help to elucidate the transcriptional regulatory mechanisms of Ppsig in humans.

The Validation of the Standard Chinese Version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) in Pre-operative Patients with Brain Tumor in China

Health related quality of life (HRQOL) has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0) in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery.

Generalized GRAPPA Operators for Wider Spiral Bands: Rapid Self-calibrated Parallel Reconstruction for Variable Density Spiral MRI

A rapid and self-calibrated parallel imaging reconstruction method is proposed for undersampled variable density spiral datasets. A set of generalized GRAPPA for wider readout line operators are used to expand each acquired spiral line into a wider spiral band, therefore fulfilling Nyquist sampling criterion throughout the k-space. The calibration of generalized GRAPPA for wider readout line operators is performed using the fully sampled central k-space region. The resulting generalized GRAPPA for wider readout line operator weights are adaptively regularized to minimize the error in the newly-generated data at different k-space locations. Simulation and experimental results demonstrate that the technique can be used either to achieve a significant acceleration and/or to reduce off-resonance artifacts due to a shorten readout duration.

Low-cost and Effective Phenol and Basic Dyes Trapper Derived from the Porous Silica Coated with Hydrotalcite Gel

Novel low-cost and effective adsorbents of phenol and basic dyes were made by coating amorphous silica with hydrotalcite (HT) gel followed by soaking in alkaline solution, and the surface basic-acidic properties of resulting composites were evaluated by CO(2)-TPD, Hammett indicator method and NH(3)-TPD, respectively. Both BET surface area and microporous surface area of the composites were increased after they were soaked with alkaline solution; meanwhile the center of pore size distribution was changed from 9 to 3-4 nm. These composites efficiently captured phenol in gaseous and liquid phases, superior to mesoporous silica such as MCM-48 or SBA-15 and zeolite NaY, and the equilibrium data of gaseous adsorption could be well fitted to Freundlich model. These modified silicas also exhibited high adsorption capacity forward basic dyes such as crystal violet (CV) and leuco-crystal violet (LCV), reaching the adsorption equilibrium within 1 h and offering a new material for environment protection.

Novel Phenol Capturer Derived from the As-synthesized MCM-41

Novel phenol-capturer was prepared by modifying the as-synthesized mesoporous silica MCM-41 with tetraethylenepentamine (TEPA), not only saving the energy and time for removal of template, but also opening the way to utilize the micelles for adsorption. Once the organic modifier was distributed in the template micelle of MCM-41 to form a web within the mesoporous channel, the composite could adsorb more phenols in gas stream than activated carbon for the first time. With an unwanted high adsorption capacity, this mesoporous silica-amine composite represented potential application for trapping phenols, especially in tobacco smoke to protect environment.

Co-gasification of Hardwood Chips and Crude Glycerol in a Pilot Scale Downdraft Gasifier

Seeking appropriate approaches to utilize the crude glycerol produced in biodiesel production is very important for the economic viability and environmental impacts of biodiesel industry. Gasification may be one of options for addressing this issue. Co-gasification of hardwood chips blending with crude glycerol in various loading levels was undertaken in the study involving a pilot scale fixed-bed downdraft gasifier. The results indicated that crude glycerol loading levels affected the gasifier's performance and the quality of syngas produced. When crude glycerol loading level increased, the CO, CH(4), and tar concentrations of the syngas also increased but particle concentration decreased. Though further testing is suggested, downdraft gasifiers could be run well with hardwood chips blending with liquid crude glycerol up to 20 (wt%). The syngas produced had relatively good quality for fueling internal combustion engines. This study provides a considerable way to utilize crude glycerol.

The Notch Ligand Jagged2 Promotes Lung Adenocarcinoma Metastasis Through a MiR-200-dependent Pathway in Mice

Epithelial tumor cells transit to a mesenchymal state in response to extracellular cues, in a process known as epithelial-to-mesenchymal transition (EMT). The precise nature of these cues has not been fully defined, an important issue given that EMT is an early event in tumor metastasis. Here, we have found that a population of metastasis-prone mouse lung adenocarcinoma cells expresses Notch and Notch ligands and that the Notch ligand Jagged2 promotes metastasis. Mechanistically, Jagged2 was found to promote metastasis by increasing the expression of GATA-binding (Gata) factors, which suppressed expression of the microRNA-200 (miR-200) family of microRNAs that target the transcriptional repressors that drive EMT and thereby induced EMT. Reciprocally, miR-200 inhibited expression of Gata3, which reversed EMT and abrogated metastasis, suggesting that Gata3 and miR-200 are mutually inhibitory and have opposing effects on EMT and metastasis. Consistent with this, high levels of Gata3 expression correlated with EMT in primary tumors from 2 cohorts of lung adenocarcinoma patients. These findings reveal what we believe to be a novel Jagged2/miR-200-dependent pathway that mediates lung adenocarcinoma EMT and metastasis in mice and may have implications for the treatment of human epithelial tumors.

Synergistic Effects of Arsenic Trioxide and Radiation in Osteosarcoma Cells Through the Induction of Both Autophagy and Apoptosis

Osteosarcoma is the most common primary malignant bone tumor, occurring mainly in children and adolescents, and survival largely depends on their response to chemotherapy. However, the risk of relapse and adverse outcomes is still high. We investigated the synergistic anti-cancer effects of ionizing radiation combined with arsenic trioxide (ATO) and the mechanisms underlying apoptosis or autophagy induced by combined radiation and ATO treatment in human osteosarcoma cells. We found that exposure to radiation increased the population of HOS cells in the G(2)/M phase within 12 h in a time-dependent manner. Radiation combined with ATO induced a significantly prolonged G(2)/M arrest, consequently enhancing cell death. Furthermore, combined treatment resulted in enhanced ROS generation compared to treatment with ATO or radiation alone. The enhanced cytotoxic effect of combined treatment occurred from the increased induction of autophagy and apoptosis through inhibition of the PI3K/Akt signaling pathway in HOS cells. The combined treatment of HOS cells pretreated with Z-VAD, 3-MA or PEG-catalase resulted in a significant reduction of cytotoxicity. In addition, G(2)/M arrest and ROS generation could be involved in the underlying mechanisms. The data suggest that a combination of radiation and ATO could be a new potential therapeutic strategy for the treatment of osteosarcoma.

Preparation of Wafer-level Glass Cavities by a Low-cost Chemical Foaming Process (CFP)

A novel foaming process-chemical foaming process (CFP)-using foaming agents to fabricate wafer-level micro glass cavities including channels and bubbles was investigated. The process consists of the following steps sequentially: (1) shallow cavities were fabricated by a wet etching on a silicon wafer; (2) powders of a proper foaming agent were placed in a silicon cavity, named 'mother cavity', on the etched silicon surface; (3) the silicon cavities were sealed with a glass wafer by anodic bonding; (4) the bonded wafers were heated to above the softening point of the glass, and baked for several minutes, when the gas released by the decomposition of the foaming agent in the 'mother cavity' went into the other sealed interconnected silicon cavities to foam the softened glass into cylindrical channels named 'daughter channels', or spherical bubbles named 'son bubbles'. Results showed that wafer-level micro glass cavities with smooth wall surfaces were achieved successfully without contamination by the CFP. A model for the CFP was proposed to predict the final shape of the glass cavity. Experimental results corresponded with model predictions. The CFP provides a low-cost avenue to preparation of micro glass cavities of high quality for applications such as micro-reactors, micro total analysis systems (μTAS), analytical and bio-analytical applications, and MEMS packaging.

Nrf2/HO-1 Pathway Activation by Manganese is Associated with Reactive Oxygen Species and Ubiquitin-proteasome Pathway, Not MAPKs Signaling

Manganese has been known to induce neurological disorders similar to Parkinson's disease. One of the features of manganese-induced neurotoxicity is oxidative stress. Accumulating data implicate NF-E2-related factor 2 (Nrf2) as a key regulator in the adaptive survival response to oxidative stress. Recent studies suggest that the activation of Nrf2 is induced by manganese in PC12 cells. In the present study, we investigated possible links between reactive oxygen species (ROS), proteasome or mitogen-activated protein kinase (MAPK) signaling and Nrf2/HO-1 activation in manganese-treated PC12 cells. After MnCl(2) treatment, there was an increase in nuclear localization and subsequent binding of Nrf2 to the antioxidant-responsive element (ARE) and upregulation of heme oxygenase-1 (HO-1) protein in PC12 cells. Pretreatment with N-acetyl cysteine, a scavenger of reactive oxygen species, suppressed MnCl(2) -induced Nrf2 activation, increase in Nrf2-ARE binding and subsequent upregulation of HO-1 expression. However, pretreatment with lactacystin, an inhibitor of proteasome activity, enhanced MnCl(2) -induced Nrf2 activation, increase in Nrf2-ARE binding and subsequent upregulation of HO-1 expression. Pretreatment of cells with a pharmacological inhibitor of MAPK (ERK inhibitor PD 98059, P38 inhibitor SB203580 or JNK inhibitor SP600125) did not affect the MnCl(2) -induced Nrf2 activation, increase in Nrf2-ARE binding or subsequent upregulation of HO-1 expression. These results suggest that Nrf2/HO-1 activation by Mn in PC12 cells is associated with ROS and the ubiquitin-proteasome pathway, not MAPK signaling.

Analgesic and Anti-inflammatory Effects of the Amphibian Neurotoxin, Anntoxin

Anntoxin is the first gene-encoded neurotoxin identified from amphibians, which is a 60-residue neurotoxin peptide, acting as an inhibitor of tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel (VGSC). Sodium channels have been considered as therapeutic targets for pain. Several animal models of persistent inflammatory and neuropathic pain (tail-flick test, hot plate test, acetic acid-induced writhing test, formalin-induced paw licking, carrageenan-induced paw edema) were used to test analgesic functions of recombinant anntoxin (r-anntoxin). In all these animal models, r-anntoxin showed strong analgesic functions. R-anntoxin obviously inhibited secretions of both tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2). Histopathological study indicated that r-anntoxin reduced the edematous epidermis induced by carrageenan. All these results indicate that r-anntoxin has strong analgesic and anti-inflammatory activities.

Fast MR Image Reconstruction for Partially Parallel Imaging with Arbitrary K-space Trajectories

Both acquisition and reconstruction speed are crucial for magnetic resonance (MR) imaging in clinical applications. In this paper, we present a fast reconstruction algorithm for SENSE in partially parallel MR imaging with arbitrary k-space trajectories. The proposed method is a combination of variable splitting, the classical penalty technique and the optimal gradient method. Variable splitting and the penalty technique reformulate the SENSE model with sparsity regularization as an unconstrained minimization problem, which can be solved by alternating two simple minimizations: One is the total variation and wavelet based denoising that can be quickly solved by several recent numerical methods, whereas the other one involves a linear inversion which is solved by the optimal first order gradient method in our algorithm to significantly improve the performance. Comparisons with several recent parallel imaging algorithms indicate that the proposed method significantly improves the computation efficiency and achieves state-of-the-art reconstruction quality.

Molecular Mechanisms of Bladder Outlet Obstruction in Transgenic Male Mice Overexpressing Aromatase (Cyp19a1)

We investigated the etiology and molecular mechanisms of bladder outlet obstruction (BOO). Transgenic (Tg) male mice overexpressing aromatase (Cyp19a1) under the ubiquitin C promoter in the estrogen-susceptible C57Bl/6J genetic background (AROM+/6J) developed inguinal hernia by 2 months and severe BOO by 9 to 10 months, with 100% penetrance. These mice gradually developed uremia, renal failure, renal retention, and finally died. The BOO bladders were threefold larger than in age-matched wild-type (WT) males and were filled with urine on necropsy. Hypotrophic smooth muscle cells formed the thin detrusor urinae muscle, and collagen III accumulation contributed to the reduced compliance of the bladder. p-AKT and ERα expression were up-regulated and Pten expression was down-regulated in the BOO bladder urothelium. Expression of only ERα in the intradetrusor fibroblasts suggests a specific role of this estrogen receptor form in urothelial proliferation. Inactivation of Pten, which in turn activated the p-AKT pathway, was strictly related to the activation of the ERα pathway in the BOO bladders. Human relevance for these findings was provided by increased expression of p-AKT, PCNA, and ERα and decreased expression of PTEN in severe human BOO samples, compared with subnormal to mild samples. These findings clarify the involvement of estrogen excess and/or imbalance of the androgen/estrogen ratio in the molecular pathogenetic mechanisms of BOO and provide a novel lead into potential treatment strategies for BOO.

Synergistic Effect of Bortezomib and Valproic Acid Treatment on the Proliferation and Apoptosis of Acute Myeloid Leukemia and Myelodysplastic Syndrome Cells

The synergistic effect of proteasome inhibitor bortezomib and valproic acid (VPA), a histone deacetylase inhibitor, were investigated in this study. Co-treatment with VPA and bortezomib on acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cell lines resulted in marked inhibition of proliferation and induction of apoptosis, including a striking increase in mitochondrial injury, caspase cascade activation, and altered expression of Bcl-2 family proteins. Moreover, combination treatment inhibited cyto-protective signaling pathways, including inactivation of nuclear factor κB (NF-κB), the extracellular signal-related kinase (ERK) and Akt pathways, and activated stress-related signaling pathway, including the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) pathways. In addition, this regimen significantly caused G2/M phase arrest, while downregulating the expression of phospho-CDC2 and CyclinD1 as well as increasing p21(cip1). Furthermore, combination treatment efficiently induced apoptosis in primary AML/MDS cells, with little effect on normal cells. In summary, these findings indicate that combination treatment with VPA and bortezomib may be a potent therapy for AML/MDS malignancies.

Extension of the Distributed Point Source Method for Ultrasonic Field Modeling

The distributed point source method (DPSM) was recently proposed for ultrasonic field modeling and other applications. This method uses distributed point sources, placed slightly behind transducer surface, to model the ultrasound field. The acoustic strength of each point source is obtained through matrix inversion that requires the number of target points on the transducer surface to be equal to the number of point sources. In this work, DPSM was extended and further developed to overcome the limitations of the original method and provide a solid mathematical explanation of the physical principle behind the method. With the extension, the acoustic strength of the point sources was calculated as the solution to the least squares minimization problem instead of using direct matrix inversion. As numerical examples, the ultrasound fields of circular and rectangular transducers were calculated using the extended and original DPSMs which were then systematically compared with the results calculated using the theoretical solution and the exact spatial impulse response method. The numerical results showed the extended method can model ultrasonic fields accurately without the scaling step required by the original method. The extended method has potential applications in ultrasonic field modeling, tissue characterization, nondestructive testing, and ultrasound system optimization.

14-3-3Zeta Positive Expression is Associated with a Poor Prognosis in Patients with Glioblastoma

When identifying clinical markers predicting clinical outcome, disease recurrence and resistance to therapies often determine the diagnosis and therapy of some cancer types.

A Novel Monoclonal Antibody Against FbaA Can Inhibit the Binding of the Complement Regulatory Protein Factor H to Group A Streptococcus

Some microbial pathogens utilize human complement regulatory proteins, such as factor H (FH) and factor H-like protein 1 (FHL-1), for immune evasion. FbaA is an FHL-1 and FH binding protein expressed on the surface of group A streptococcus (GAS), a common agent of pharyngeal, skin, and soft tissue infections. In this study, we prepared monoclonal antibodies (MAbs) against FbaA, assayed them for specificity, and located their binding domains in FbaA. We found an MAb called FbaA MAb2, which demonstrated the highest affinity to GAS among all of the MAbs. Based on the binding with component peptides, the detected epitope, which was specific for FbaA MAb2, was the amino acid residues 95 to 118 of FbaA; on the other hand, it did not bind with the truncated protein of the internally deleted residues of the segment from 95 to 118 of FbaA. Furthermore, the predominant amino acids specific for FbaA MAb2 screened by phage display epitope library were I, T, P, D, and L, corresponding to the amino acid residues 101, 103, 105, 106, and 110 of FbaA, respectively. The binding location of FbaA with FH and FHL-1 was a 16-amino-acid region corresponding to amino acid residues 97 to 112 of FbaA, which overlapped the FbaA MAb2 binding domain, as confirmed by competitive inhibition enzyme-linked immunosorbent assay and immunofluorescence microscopy. Based on the results of the invasion assay, FbaA MAb2 can inhibit the binding of FH to GAS.

Modification of Collagen with a Natural Cross-linker, Procyanidin

We have investigated the modification of collagen with a natural plant polyphenol, procyanidin under acidic conditions. Fourier transform infrared spectroscopy (FTIR) and Atomic force microscopy (AFM) studies demonstrate that the hydrogen bond interactions between collagen and procyanidin does not destroy the triple helix conformation of collagen, and the fibril aggregation occurs because of the cross-linking with procyanidin. The water contact angle (WCA) tests indicate that the hydrophobicity of the procyanidin modified collagen films can be improved. Whereas, the water vapor permeability (WVP) of the films decrease with the increasing procyanidin content due to the formation of denser structure. Moreover, differential scanning calorimetry (DSC) and thermogravimetric (TG) measurements reveal that the collagen/procyanidin films have improved thermal stability in comparison with pure collagen. The present study reveals that procyanidin stabilizes collagen as a cross-linker and preserves its triple helical structure.

Electrospun PLGA-silk Fibroin-collagen Nanofibrous Scaffolds for Nerve Tissue Engineering

Electrospun nanofibrous scaffolds varying different materials are fabricated for tissue engineering. PLGA, silk fibroin, and collagen-derived scaffolds have been proved on good biocompatibility with neurons. However, no systematic studies have been performed to examine the PLGA-silk fibroin-collagen (PLGA-SF-COL) biocomposite fiber matrices for nerve tissue engineering. In this study, different weight ratio PLGA-SF-COL (50:25:25, 30:35:35) scaffolds were produced via electrospinning. The physical and mechanical properties were tested. The average fiber diameter ranged from 280 + 26 to 168 + 21 nm with high porosity and hydrophilicity; the tensile strength was 1.76 ± 0.32 and 1.25 ± 0.20 Mpa, respectively. The results demonstrated that electrospinning polymer blending is a simple and effective approach for fabricating novel biocomposite nanofibrous scaffolds. The properties of the scaffolds can be strongly influenced by the concentration of collagen and silk fibroin in the biocomposite. To assay the cytocompatibility, Schwann cells were seeded on the scaffolds; cell attachment, growth morphology, and proliferation were studied. SEM and MTT results confirmed that PLGA-SF-COL scaffolds particularly the one that contains 50% PLGA, 25% silk fibroin, and 25% collagen is more suitable for nerve tissue engineering compared to PLGA nanofibrous scaffolds.

The Developmental Transcriptome of Drosophila Melanogaster

Drosophila melanogaster is one of the most well studied genetic model organisms; nonetheless, its genome still contains unannotated coding and non-coding genes, transcripts, exons and RNA editing sites. Full discovery and annotation are pre-requisites for understanding how the regulation of transcription, splicing and RNA editing directs the development of this complex organism. Here we used RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages. We identified 111,195 new elements, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events, and inferred protein isoforms that previously eluded discovery using established experimental, prediction and conservation-based approaches. These data substantially expand the number of known transcribed elements in the Drosophila genome and provide a high-resolution view of transcriptome dynamics throughout development.

The Transcriptional Diversity of 25 Drosophila Cell Lines

Drosophila melanogaster cell lines are important resources for cell biologists. Here, we catalog the expression of exons, genes, and unannotated transcriptional signals for 25 lines. Unannotated transcription is substantial (typically 19% of euchromatic signal). Conservatively, we identify 1405 novel transcribed regions; 684 of these appear to be new exons of neighboring, often distant, genes. Sixty-four percent of genes are expressed detectably in at least one line, but only 21% are detected in all lines. Each cell line expresses, on average, 5885 genes, including a common set of 3109. Expression levels vary over several orders of magnitude. Major signaling pathways are well represented: most differentiation pathways are "off" and survival/growth pathways "on." Roughly 50% of the genes expressed by each line are not part of the common set, and these show considerable individuality. Thirty-one percent are expressed at a higher level in at least one cell line than in any single developmental stage, suggesting that each line is enriched for genes characteristic of small sets of cells. Most remarkable is that imaginal disc-derived lines can generally be assigned, on the basis of expression, to small territories within developing discs. These mappings reveal unexpected stability of even fine-grained spatial determination. No two cell lines show identical transcription factor expression. We conclude that each line has retained features of an individual founder cell superimposed on a common "cell line" gene expression pattern.

Two Novel Antimicrobial Peptides from Skin Secretions of the Frog, Rana Nigrovittata

Two novel antimicrobial peptides with similarity to brevinin-2 family are purified and characterized from the skin secretions of the frog, Rana nigrovittata. Their amino acid sequences were determined as GAFGNFLKGVAKKAGLKILSIAQCKLSGTC (brevinin-2-RN1) and GAFGNFLKGVAKKAGLKILSIAQCKLFGTC (brevinin-2-RN2), respectively, by Edman degradation. Different from brevinin-2, which is composed of 33 amino acid residues (aa), both brevinin-2-RN1 and -RN2 contain 30 aa. Five cDNA sequences (Genbank accession numbers, EU136465-9) encoding precursors of brevinin-2-RN1 and -RN2 were screened from the skin cDNA library of R. nigrovittata. These precursors are composed of 72 aa including a predicted signal peptide, an acidic spacer peptide, and a mature brevinin-2-RN. Both brevinin-2-RN1 and -RN2 showed strong antimicrobial activities against gram-positive and gram-negative bacteria and fungi. The current work identified and characterized two novel antimicrobial peptides with unique primary structure.

NF-E2-related Factor 2 Activation in PC12 Cells: Its Protective Role in Manganese-induced Damage

Manganese neurotoxicity presents with Parkinson-like symptoms that are associated with the generation of reactive oxygen species. Thus, its occurrence and severity can be reduced by cellular antioxidants. The components of the transcription factor NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway are the central regulators of cellular antioxidant responses. In this study, we investigated the role of activation of Nrf2 in response to oxidative damage induced by manganese chloride (MnCl(2)) in rat adrenal pheochromocytoma (PC12) cells. Exposure of PC12 cells to MnCl(2) for 24 h promoted an increased cytosolic and nuclear accumulation of Nrf2 and enhanced the binding of Nrf2 to the HO-1 gene ARE, thereby inducing the expression of an Nrf2-regulated gene, HO-1. Pre-treatment with tert-butylhydroquinone (tBHQ), a known agent that activates the Nrf2/ARE-HO-1 pathway, for 16 h prior to the 24 h MnCl(2) exposure attenuated both the cytotoxicity and the apoptosis induced by MnCl(2). These protective effects of tBHQ indicated a protective role for Nrf2 against MnCl(2)-induced cell damage. Taken together, these findings suggest that Nrf2 may play an important role in the protection of PC12 cells against MnCl(2) neurotoxicity.

Foxa1 and Foxa2 Positively and Negatively Regulate Shh Signalling to Specify Ventral Midbrain Progenitor Identity

Foxa2, a member of the Foxa family of forkhead/winged helix family of transcription factors, has previously been shown to be an upstream positive regulator of Shh expression in many different tissues. Recent studies also strongly suggest that Foxa2 specify cell fate by inhibiting the expression of cell fate determinants such as Helt1 and Nkx2.2. In this paper, phenotypic analyses of Wnt1cre; Foxa2flox/flox embryos in the midbrain have demonstrated a novel role for Foxa2 and its related family member, Foxa1, to attenuate Shh signalling by inhibiting the expression of its intracellular transducer, Gli2, at the transcriptional level. Chromatin immunoprecipitation experiments indicate that Foxa2 binds to genomic regions of Gli2 and likely regulates its expression in a direct manner. Our studies, involving loss and gain of function studies in mice, also provided further insights into the gene regulatory interactions among Foxa1, Foxa2 and Shh in ventral midbrain progenitors that contribute to midbrain patterning. Altogether, these data indicate that Foxa1 and Foxa2 contribute to the specification of ventral midbrain progenitor identity by regulating Shh signalling in a positive and negative manner.

Metagenomic Analysis Reveals Unexpected Subgenomic Diversity of Magnetotactic Bacteria Within the Phylum Nitrospirae

A targeted metagenomic approach was applied to investigate magnetotactic bacteria (MTB) within the phylum Nitrospirae in Lake Miyun near Beijing, China. Five fosmids containing rRNA operons were identified. Comparative sequence analysis of a total of 172 kb provided new insights into their genome organization and revealed unexpected subgenomic diversity of uncultivated MTB in the phylum Nitrospirae. In addition, affiliation of two novel MTB with the phylum Nitrospirae was verified by fluorescence in situ hybridization. One of them was morphologically similar to "Candidatus Magnetobacterium bavaricum," but the other differed substantially in cell shape and magnetosome organization from all previously described "Ca. Magnetobacterium bavaricum"-like bacteria.

The Role of Cytokines and Chemokines in Severe Respiratory Syncytial Virus Infection and Subsequent Asthma

Respiratory syncytial virus (RSV) is the primary cause of serious lower respiratory tract illness in infants and young children worldwide. The mechanism is largely unknown. RSV stimulates airway epithelial cells and resident leukocytes to release cytokines. Cytokines and chemokines involved in host response to RSV infection are thought to play a central role in the pathogenesis. In addition, RSV infection early in life has been associated with the development of asthma in later childhood. It is likely that the persistence of cytokines and chemokines in fully recovered patients with RSV in the long term can provide a substratum for the development of subsequent asthma. This review describes the genetic factors in cytokines and chemokines associated with severity of RSV disease, cytokines and chemokines synthesis in RSV infection, and the role of these innate immune components in RSV-associated asthma.

A New Algorithm for Spatial Impulse Response of Rectangular Planar Transducers

Previous solutions for spatial impulse responses of rectangular planar transducers require either approximations or complex geometrical considerations. This paper describes a new, simplified and exact solution using only trigonometric functions and simple set operations. This solution, which can be numerically implemented with a straightforward algorithm, is an exact implementation of the Rayleigh integral without any far field or paraxial approximation. Additionally, a nonlinear relationship was also established for spatial impulse responses from two field points which share the same projection point on the transducer surface plane. By incorporating this relationship in the algorithm, the computational efficiency of spatial impulse responses and continuous fields is improved about 20-folds and 14-folds, respectively. This algorithm has practical applications in designing l-D linear/phased arrays, 1.5-D arrays and 2-D arrays, as demonstrated through numerical simulations with array transducers. Experiments were also conducted to verify the new solution and results show that the algorithm is both accurate and efficient. The application of this method may include development of ultrasound imaging system for hard and soft tissue nondestructive assessment.

Role of Protein Transamidation in Serotonin-induced Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells

Pulmonary hypertension is characterized by elevated pulmonary artery pressure and pulmonary artery smooth muscle cell (SMC) proliferation and migration. Clinical and experimental evidence suggests that serotonin (5-HT) is important in these responses. We previously demonstrated the participation of the 5-HT transporter and intracellular 5-HT (5-HTi) in the pulmonary vascular SMC-proliferative response to 5-HT. However, the mechanism underlying the intracellular actions of 5-HT is unknown. We speculated that 5-HTi activates SMC growth by post-translational transamidation of proteins via transglutaminase (TGase) activity, a process referred to as serotonylation. To test this hypothesis, serotonylation of pulmonary artery SMC proteins, and their role in 5-HT-induced proliferative and migratory responses, were assessed. 5-HT caused dose- and time-dependent increase in serotonylation of multiple proteins in both bovine and rat pulmonary artery SMCs. Inhibition of TGase with dansylcadaverin blocked this activity, as well as SMC-proliferative and migratory responses to 5-HT. Serotonylation of proteins also was blocked by 5-HT transporter inhibitors, and was enhanced by inhibition of monoamine oxidase, an enzyme known to degrade 5-HTi, indicating that 5-HTi levels regulate serotonylation. Immunoprecipitation assays and HPLC-mass spectral peptide sequencing revealed that a major protein serotonylated by TGase was fibronectin (FN). 5-HT-stimulated SMC serotonylation and proliferation were blocked by FN small interfering (si) RNA. These findings, together with previous observations that FN expression in the lung strongly correlates with the progression of pulmonary hypertension in both experimental animals and humans, suggest an important role of FN serotonylation in the pathogenesis of this disease.

Stromal Cell-Derived Factor-1α As a Novel Biomarker for Hyperlipidemia

Stromal cell-derived factor-1 (SDF-1) is expressed in a wide variety of organs, such as heart, and plays a pivotal role in the mobilization of hematopoietic stem and progenitor cells in bone marrow. SDF-1α, a common subtype of SDF-1, may control hematopoiesis and angiogenesis, but its role in the pathogenesis of hyperlipidemia is unknown. The aim of this study was to determine the role of SDF-1α in the pathogenesis of hyperlipidemia. First, log-transformed SDF-1α serum levels (logSDF-1α) were significantly higher in male patients with borderline high lipid profile (BHLP; n = 28; 2.15 ± 0.08 ng/ml) compared to control subjects (n = 37; 1.94 ± 0.06 ng/ml; P < 0.01). The logSDF-1α in male patients with high lipid profile (HLP; n = 33; 1.95 ± 0.08 ng/ml) were lower than BHLP patients (P < 0.01). The logSDF-1α was positively associated with HDL-C only in female patients (n = 125; r = 0.379, P = 0.016). These results suggest the different pathophysiology in male and female patients with hyperlipidemia. Moreover, flow cytometry analysis showed that expression of the SDF-1α receptor, CXC-chemokine receptor 4, was lower in peripheral blood mononuclear cells of patients with BHLP (n = 10) and HLP (n = 10), compared to control subjects (n = 10; P < 0.001). Lastly, peripheral blood leukocyte, neutrophil and lymphocyte counts were higher in BHLP patients (n = 62; P < 0.05). Taken together, we suggest SDF-1α as a biomarker of hyperlipidemia that may be helpful to uncover the pathogenesis of hyperlipidemia.

[Differentiation of Ectomesenchymal Stem Cells into Dendritic Cells in Vitro Induced by Cytokines]

To induce the differentiation of ectomesenchymal stem cells (EMSCs) into dentritic cells (DCs) in vitro.

An Efficient Synthesis of Novel Dispirooxindole Derivatives Via One-Pot Three-Component 1,3-Dipolar Cycloaddition Reactions

A series of novel dispirooxindoles have been synthesized through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the decarboxylative condensation of isatin and an α-amino acid with the dipolarophile 5-benzylidene-1,3-dimethylpyrimidine-2,4,6-trione. This method has the advantages of mild reaction conditions, high atom economy, excellent yields, and high regio- and stereo-selectivity.

Moderately Hypofractionated Conformal Radiation Treatment of Thoracic Esophageal Carcinoma

Aims: To prospectively assess the efficacy and safety of moderately hypofractionated conformal radiotherapy in patients with thoracic esophageal cancer. Methods and Materials: From Sept. 2002 to Oct. 2005, 150 eligible patients with T2-4N0-1M0 stage thoracic esophageal squamous cell cancers were enrolled to receive either conventional fractionated radiation (CFR) or moderately hypofractionated radiation (MHR) with a three- dimensional conformal radiation technique. Of the total, 74 received moderately hypofractionated radiation with total dose of 54-60Gy/18-20fractions for 3.5-4 weeks in the MHR arm, and 76 received conventional radiation with total dose of 60Gy/30 fractions for 6 weeks in the CFR arm. Concurrent chemotherapy comprised of paclitaxel and cisplatin. Safety was evaluated, and local control and overall survival rates were calculated. Results: Statistically significant differences between the CFR versus MHR arms were observed in local/regional failure rate (47.3% v 27.0%, P=0.034) and the percentage of patients with persistent local disease (26.3% v 10.8%, P=0.012). But 3 and 5-year overall survival rates (43.2%, 38.8% v 38.2%, 28.0%, respectively) were not different between the two arms (P=0.268). There were no significant differences in the incidences of grade 3 or higher acute toxicities (66.3% v 50.0%) and late complications rates (27.0% v 22.4%) between the MHR and CFR arms. Conclusions: Moderately hypofractionated, three-dimensional radiation treatment could improve the local control rate of esophageal cancer and potentially increase patient survival.

Trivalent Chromium and Aluminum Affect the Thermostability and Conformation of Collagen Very Differently

Ultrasensitive differential scanning calorimetry (US-DSC) was used to directly measure the thermal transition temperature and energy change of acid soluble collagen in the presence of Cr(3+) and Al(3+) sulfates. The behavior of Cr(3+) was analogous to kosmotropes in the cation Hofmeister series and increased the stability of collagen in dilute solutions. Meanwhile, the denaturational enthalpy change (ΔH) of collagen was substantially reduced with change to increasing Cr(3+) concentration. This is likely due to the uni-point binding of Cr(3+) with carboxyl groups of collagen side chains that could decrease the hydrogen-bonding in collagen and result in the increase of protein hydrophobicity. In the case of Al(3+), the interactions between the ions and collagen showed very different properties: at low and medium ion concentrations, the stability of the collagen was decreased; however, a further increase of Al(3+) concentration led to a salting-out effect of collagen, indicating the Al(3+) is a typical chaotropic ion. This striking difference of the two ions in the stabilization of collagen can be explained in terms of the different interactions between the cations and the carboxyl groups of collagen side chains. Additionally, we studied metal ion induced conformational change by the combination of circular dichroism (CD) and atomic force microscopy (AFM). CD measurements revealed that neither metal ion interactions of collagen with Cr(3+) nor Al(3+) ions destroyed the triple-helical backbone structure of collagen in the solution. AFM results further confirmed that the dehydration of collagen by Cr(3+) is more significant than Al(3+), thus inducing the aggregation of collagen fibrils.

A Randomized Controlled Study Comparing Omeprazole and Cimetidine for the Prophylaxis of Stress-related Upper Gastrointestinal Bleeding in Patients with Intracerebral Hemorrhage

Object Patients with intracerebral hemorrhage (ICH) are at high risk for severe stress-related upper gastrointestinal (UGI) bleeding, which is predictive of higher mortality. The aim of this study was to evaluate the effectiveness of omeprazole and cimetidine compared with a placebo in the prevention and management of stress-related UGI bleeding in patients with ICH. Methods In a single-center, randomized, placebo-controlled study, 184 surgically treated patients with CT-proven ICH within 72 hours of ictus and negative results for gastric occult blood testing were included. Of these patients, 165 who were qualified upon further evaluation were randomized into 3 groups: 58 patients received 40 mg intravenous omeprazole every 12 hours, 54 patients received 300 mg intravenous cimetidine every 6 hours, and 53 patients received a placebo. Patients whose gastric occult blood tests were positive at admission (n = 70) and during/after the prophylaxis procedure (n = 48) were treated with high-dose omeprazole at 80 mg bolus plus 8 mg/hr infusion for 3 days, followed by 40 mg intravenous omeprazole every 12 hours for 7 days. Results Of the 165 assessable patients, stress-related UGI bleeding occurred in 9 (15.5%) in the omeprazole group compared with 15 patients (27.8%) in the cimetidine group and 24 patients (45.3%) in the placebo group (p = 0.003). The occurrence of UGI bleeding was significantly related to death (p = 0.022). Nosocomial pneumonia occurred in 14 patients (24.1%) receiving omeprazole, 12 (22.2%) receiving cimetidine, and 8 (15.1%) receiving placebo (p > 0.05). In patients with UGI bleeding in which high-dose omeprazole was initiated, UGI bleeding arrested within the first 3 days in 103 patients (87.3%). Conclusions Omeprazole significantly reduced the morbidity of stress-related UGI bleeding in patients with ICH due to its effective prophylactic effect without increasing the risk of nosocomial pneumonia, but it did not reduce the 1-month mortality or ICU stay. Further evaluation of high-dose omeprazole as the drug of choice for patients presenting with UGI bleeding is warranted. Clinical trial registration no.: ChiCTR-TRC-12001871, registered at the Chinese clinical trial registry ( http://www.chictr.org/en/proj/show.aspx?proj=2384 ).

Normal Saline Injection Via Lumbar Puncture for the Treatment of Acute Tonsillar Herniation: A Report of 45 Cases

OBJECTIVE: Current treatment of apnea attributable to acute tonsillar herniation often is inadequate. This study was undertaken to verify the clinical usefulness of normal saline injection via lumbar puncture for the treatment of apnea secondary to acute tonsillar herniation. METHODS: Between 1969 and 2009, 45 patients who had not regained spontaneous respiratory function after external ventricular drainage or removal of a supratentorial lesion via open craniotomy received an injection of normal saline via lumbar puncture. Patient data were retrospectively analyzed. RESULTS: Eleven of the 45 patients regained spontaneous breathing and recovered fully (24.4%). Sixteen patients regained spontaneous breathing but died later (35.6%), and 18 patients did not regain spontaneous respiration (40.0%). The overall rate of effectiveness of injected normal saline was therefore 60.0%. CONCLUSION: For patients with tonsillar hernia who did not regain spontaneous respiration after external ventricular drainage or removal of a supratentorial lesion, an aggressive approach may be considered. Injection of normal saline via lumbar puncture could improve outcome in some of these patients.

Open Structure ZnO/CdSe Core/shell Nanoneedle Arrays for Solar Cells

Open structure ZnO/CdSe core/shell nanoneedle arrays were prepared on a conducting glass (SnO2:F) substrate by solution deposition and electrochemical techniques. A uniform CdSe shell layer with a grain size of approximately several tens of nanometers was formed on the surface of ZnO nanoneedle cores after annealing at 400°C for 1.5 h. Fabricated solar cells based on these nanostructures exhibited a high short-circuit current density of about 10.5 mA/cm2 and an overall power conversion efficiency of 1.07% with solar illumination of 100 mW/cm2. Incident photo-to-current conversion efficiencies higher than 75% were also obtained.

Neuroprotective Effects of Tert-butylhydroquinone on Paraquat-induced Dopaminergic Cell Degeneration in C57BL/6 Mice and in PC12 Cells

The present study was aimed at determining the role of paraquat (PQ) in the activation of the NF-E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway and the possible neuroprotective effects of tert-butylhydroquinone (tBHQ) pretreatment on PQ-induced neurodegeneration in vivo and in vitro. 7 mg/kg PQ treatment of male C57BL/6 mice caused decreased spontaneous locomotor activity, decreased tyrosine hydroxylase (TH)-positive neurons, increased terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL)-positive cells in the substantia nigra, as well as increased protein levels of both nuclear Nrf2 and HO-1. In PQ-treated mice, pretreatment with 1 % tBHQ (w/w) significantly attenuated impairments in behavioral performance, decreased TH-positive neurons, and increased TUNEL-positive cells in the substantia nigra, as well as increased protein expression of both nuclear Nrf2 and HO-1. Pretreatment with 40 μM tBHQ protected PC12 cells against 100 and 300 μM PQ-mediated cytotoxicity. The dual-luciferase reporter gene also revealed that the transcriptional activation of HO-1 gene expression of the antioxidant responsive element via Nrf2 occurred as a consequence of 100 and 300 μM PQ exposure. Collectively, these results clearly indicated for the first time that the Nrf2/HO-1 pathway in the substantia nigra was activated by PQ, and pretreatment with tBHQ conferred neuroprotection against PQ-induced Parkinsonism presumably by increasing Nrf2 and HO-1 expression.

Downregulation of MSP58 Suppresses Cell Proliferation in Neuroblastoma Cell Lines

MSP58, a novel oncogene, shows transforming activity in mouse embryonic fibroblasts. However, the oncogenic role of MSP58 in tumor cells has not been fully characterized. To extend understanding of how this protein operates in tumorigenesis, we aimed to identify the effect of MSP58 on neuroblastoma cell proliferation. Here, we found that MSP58 was highly expressed in neuroblastoma tumor samples and cell lines. We found that the majority of MSP58 protein can be detected in the nucleus as reported in other cells. Moreover, MSP58-targeted shRNA lentivirus attenuated neuroblastoma cell proliferation. Knockdown of MSP58 resulted in S-phase cell accumulation, which was accompanied by changes in cell cycle-related molecules. These results indicate that MSP58 plays an oncogenic role in the proliferation of neuroblastoma cells and could be a novel target for the treatment of neuroblastoma.

Frequency Specific Ultrasound Attenuation is Sensitive to Trabecular Bone Structure

This study investigated the efficacy of frequency modulated ultrasound attenuation in the assessment of the trabecular structural properties. Four frequency modulated signals were created to represent four frequency bands centered at 500 kHz, 900 kHz, 1.3 MHz and 1.7 MHz with the bandwidth of 400 kHz. Five 1-cm trabecular cubes were harvested from fresh bovine distal femur. The cubes underwent four steps of demineralization process to expand the sample size to 25 with the greater variations of the structural properties for the better correlation study. Pearson correlation study was performed between the ultrasound attenuation in four frequency bands and the trabecular structural properties. The results showed that correlations of frequency modulated ultrasound attenuation to the trabecular structural properties are dependent on frequency bands. The attenuation in proximal-distal orientation had the highest correlation to BV/TV (R(2) = 0.73, p < 0.001) and trabecular thickness (R(2) = 0.50, p < 0.001) at the frequency band centered at 1.7 MHz. It was equivalent in the four frequency bands in correlation to the trabecular number (average R(2) = 0.80, p < 0.001) and to the trabecular separation (average R(2) = 0.83, p < 0.001). The attenuation in anterio-posterial orientation had the highest correlation to BV/TV (R(2) = 0.80, p < 0.001) and trabecular thickness (R(2) = 0.71, p < 0.001) at the frequency band centered at 1.3 MHz. The attenuation in the first frequency band was the most sensitive to the trabecular number (R(2) = 0.71, p < 0.001) and trabecular separation (R(2) = 0.80, p < 0.001). No significant correlation was observed for the attenuation in medial-lateral orientation across the four frequency bands.

Landscape of Transcription in Human Cells

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.

An Integrated Encyclopedia of DNA Elements in the Human Genome

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

Aberrant CD40-induced NF-κB Activation in Human Lupus B Lymphocytes

Auto-reactive B lymphocytes and its abnormal CD40 signaling play important roles in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we analyzed CD40 expression and CD40/CD154 induced activation of NF-κB signaling pathway in B cells from SLE patients. B cells from healthy volunteers and tonsilar B cells from chronic tonsillitis were used as negative and positive controls. Results showed CD40-induced NF-κB signaling was constitutively activated in B cells from active lupus patients, including decreased CD40 in raft portion, increased phosphorylation and degradation of IκBα, phosphorylation of P65, as well as increased nuclear translocation of P65, P50, c-Rel, which could be blocked by anti-CD154. CD154 stimulation could induce further phosphorylation and degradation of IκBα, as well as phosphorylation of P65 and nuclear translocation of P65. In addition, CD40-induced kinase activities in B cells from lupus patients mimicked that of tonsil B cells, in that IKKα/β were more activated compared to normal B cells. CD40-induced NF-κB activity was blocked by both IκB phosphorylation and proteosome degradation inhibitors in both lupus and normal B cells. All together, our findings revealed that canonical NF-κB signaling is constitutively activated in active lupus and is mediated by CD154/CD40. CD40 induced NF-κB activation is different in human lupus B lymphocytes compared with normal B cells.

Short-term Effects of Temperature on the Abundance and Diversity of Magnetotactic Cocci

Temperature is one of the most important climate factors that can regulate the activity and growth of organisms. However, it is so far unclear how temperature influences the abundance and community composition of magnetotactic bacteria (MTB) that mineralize intracellular magnetite and/or greigite magnetosomes and play significant roles in the global iron cycling and sediment magnetization. To address this specific problem, in this study we have assessed the impact of temperature on freshwater magnetotactic cocci through laboratory microcosm simulations. Microcosms containing MTB were exposed to four constant temperatures ranging from 9°C to 37°C. After 10 days and 28 days of incubation, no significant differences in abundance were detected in microcosms at 9°C, 15°C, and 26°C (Student's t-test, P > 0.05); however, microcosms exposed to 37°C exhibited a significant decrease of magnetotactic cocci abundance (P < 0.05). Dendrogram analysis of community-amplified ribosomal DNA restriction analysis (community ARDRA) banding patterns distinguished the 37°C samples from samples at lower temperatures regardless of incubation periods. Furthermore, clone library analysis revealed that most of the operational taxonomic units (OTUs) detected in samples from 9°C to 26°C were absent from the 37°C microcosms, whereas six OTUs were exclusively detected in the 37°C samples. Community compositions from four incubation temperatures were further compared using statistical phylogenetic methods (UniFrac and LIBSHUFF), which revealed that the 37°C samples harbored phylogenetically distinct MTB communities compared to those found in 9°C, 15°C, and 26°C samples. Taken together, our results indicate that elevated temperature can influence the abundance and diversity of dominant members of magnetotactic cocci. This linkage further infers that the abundance and diversity of MTB (e.g., based on the fossil magnetosomes) may be useful in reconstruction of paleotemperature.

Genetic Variation and Population Differentiation in a Medical Herb Houttuynia Cordata in China Revealed by Inter-Simple Sequence Repeats (ISSRs)

Houttuynia cordata is an important traditional Chinese herb with unresolved genetics and taxonomy, which lead to potential problems in the conservation and utilization of the resource. Inter-simple sequence repeat (ISSR) markers were used to assess the level and distribution of genetic diversity in 226 individuals from 15 populations of H. cordata in China. ISSR analysis revealed low genetic variations within populations but high genetic differentiations among populations. This genetic structure probably mainly reflects the historical association among populations. Genetic cluster analysis showed that the basal clade is composed of populations from Southwest China, and the other populations have continuous and eastward distributions. The structure of genetic diversity in H. cordata demonstrated that this species might have survived in Southwest China during the glacial age, and subsequently experienced an eastern postglacial expansion. Based on the results of genetic analysis, it was proposed that as many as possible targeted populations for conservation be included.

An Efficient Synthesis of Pyrrolo[2,3,4-kl]acridin-1-one Derivatives Catalyzed by L-proline

An efficient domino approach for the synthesis of novel pyrrolo[2,3,4-kl]acridin-1-one derivatives has been established. This reaction represents the first facile conversion of an isatin to a pyrrolo[2,3,4-kl]acridin-1-one via a C-N bond cleavage reaction without the need for a multistep reaction process.

Significance of Human Telomerase RNA Gene Amplification Detection for Cervical Cancer Screening

Liquid-based cytology is the most often used method for cervical cancer screening, but it is relatively insensitive and frequently gives equivocal results. Used as a complementary procedure, the high-risk human papillomavirus (HPV) DNA test is highly sensitive but not very specific. The human telomerase RNA gene (TERC) is the most often amplified oncogene that is observed in cervical precancerous lesions. We assessed genomic amplification of TERC in liquid-based cytological specimens to explore the optimal strategy of using this for cervical cancer screening.

Self-reported Chronic Diseases and Health Status and Health Service Utilization - Results from a Community Health Survey in Singapore

ABSTRACT:

An Encyclopedia of Mouse DNA Elements (Mouse ENCODE)

ABSTRACT: To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

Impacts of Amount of Impregnated Iron in Granular Activated Carbon on Arsenate Adsorption Capacities and Kinetics

Iron-impregnated granular activated carbons (Fe-GAC) can remove arsenic effectively from water. In this study, Fe-GACs with iron content of 1.64 to 28.90% were synthesized using a new multi-step procedure for the investigation of effects of iron amount on arsenic adsorption capacities and kinetics. Langmuir model satisfactorily fit arsenic adsorption on Fe-GACs. The maximum arsenic adsorption capacity (q(m)) increased significantly with iron impregnation and reached 1,867 to 1,912 microg/g with iron content of 9.96 to 13.59%. Further increase of iron content (> 13.59%) caused gradual decrease of q(m). It was found that the amount of impregnated iron showed little impact on the affinity for arsenate. Kinetic study showed that the amount of impregnated iron affected the arsenic intraparticle diffusion rate greatly. The pseudo-second-order kinetic model fit arsenic adsorption kinetics on Fe-GACs better than the pseudo-first-order model. The arsenic adsorption rate increased with increasing of iron content from 1.64% to 13.59%, and then decreased with more impregnated iron (13.59 to 28.90%).

Association Between Serum Endogenous Secretory Receptor for Advanced Glycation End Products and Risk of Type 2 Diabetes Mellitus with Combined Depression in the Chinese Population

Abstract Objective: The role of the endogenous secretory receptor for advanced glycation end products (esRAGE) in depression of diabetes patients and its clinical significance are unclear. This study investigated the role of serum esRAGE in patients with type 2 diabetes mellitus with depression in the Chinese population. Patients and Methods: One hundred nineteen hospitalized patients with type 2 diabetes were recruited at Fujian Provincial Hospital (Fuzhou, China) from February 2010 to January 2011. All selected subjects were assessed with the Hamilton Rating Scale for Depression (HAMD). Among them, 71 patients with both type 2 diabetes and depression were included. All selected subjects were examined for the following: esRAGE concentration, glycosylated hemoglobin (HbA1c), blood lipids, C-reactive protein, trace of albumin in urine, and carotid artery intima-media thickness (IMT). Association between serum esRAGE levels and risk of type 2 diabetes mellitus with depression was also analyzed. Results: There were statistically significant differences in gender, age, body mass index, waist circumference, and treatment methods between the group with depression and the group without depression (P<0.05). Multiple linear regression analysis showed that HAMD scores were negatively correlated with esRAGE levels (standard regression coefficient -0.270, P<0.01). HAMD-17 scores were positively correlated with IMT (standard regression coefficient 0.183, P<0.05) and with HbA1c (standard regression coefficient 0.314, P<0.01). Conclusions: Female gender, younger age, obesity, poor glycemic control, complications, and insulin therapy are all risk factors of type 2 diabetes mellitus with combined depression in the Chinese population. Inflammation and atherosclerosis play an important role in the pathogenesis of depression. esRAGE is a protective factor of depression among patients who have type 2 diabetes.

Sustained Release of Heparin on Enlarged-pore and Functionalized MCM-41

Mesoporous silica MCM-41 and SBA-15 were chosen to study the adsorption and release of bulky biomolecule heparin, in order to develop new heparin controlled delivery system and expand the application of mesoporous materials in life science. To explore how the structure of support such as pore size and surface state affects the accommodation and release of heparin, we used decane as swelling agent to enlarge pores of MCM-41, introduced amino groups for improving the biocompatibility of support, and controllably retained templates in the as-synthesized sample. The influence of modification on the structure of samples was investigated by XRD and N(2) adsorption-desorption, whereas their performance of adsorbing and releasing heparin was assessed with that of toluidine blue method. Both enlarged pore and organic modification significantly promoted the adsorption and prolonged the release of heparin in MCM-41, and the release was characterized with a three-stage release model. The mechanism of heparin release from mesoporous material was studied by fitting the release profiles to the theoretical equation. As expected, some mesoporous composites could release heparin in the long term with tuned dosage.

Ring-opening Polymerization of Genipin and Its Long-range Crosslinking Effect on Collagen Hydrogel

Polymeric genipin macromers, prepared by ring-opening polymerization at various pH values, are used as crosslinking agents to fix collagen hydrogels. The results indicate that as the dark color of polymeric genipin itself and the networks formed by long-range intermolecular crosslinking, the genipin-fixed collagen hydrogels displace darker color. The polymeric genipin prepared at higher pH value needs longer time to fully crosslink with collagen molecules. Moreover, polymerization of genipin reduces the yield of genipin-fixed collagen hydrogels due to low extent of crosslinking. Specially, the microscope photographs present the porous networks structures of genipin-fixed collagen hydrogels. The pore size increases with the increase in polymerization degree of genipin. The data of FTIR indicate the likely transition of -NH(2) groups in collagen chains into C=N. Owning to much more number of hydrophilic groups and more porous networks, collagen hydrogels fixed by genipin with higher polymerization degree have higher water absorption capacity. The equilibrium swelling of genipin-fixed collagen hydrogels is pH-responsive, which show "M" type changes with the pH values. The results obtained in the study suggest that the polymeric genipin prepared at various pH values lead to significant influence to the crosslinking characteristics and properties of collagen hydrogels. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

Antimicrobial Peptide Diversity in the Skin of the Torrent Frog, Amolops Jingdongensis

Antimicrobial peptide diversity has been found in some amphibians. The diversity of antimicrobial peptides may have resulted from the diversity of microorganisms encountered by amphibians. Peptidomics and genomics analyses were used to study antimicrobial peptide diversity in the skin secretions of the torrent frog, Amolops jingdongensis. Thirty-one antimicrobial peptides belonging to nine groups were identified in the skin secretions of this frog. Among them, there are two novel antimicrobial groups (jingdongin-1 and -2) with unique structural motifs. The other seven groups belong to known antimicrobial peptide families, namely brevinin-1, brevinin-2, odorranain-F, esculentin-2, temporin, amolopin-3, and ranacyclin. Combined with previous reports, more than 13 antimicrobial peptide groups have been identified from the genus Amolops. Most of these antimicrobial peptide groups are also found in amphibians belonging to the genus Rana or Odorrana which suggests a possible evolutionary connection among Amolops, Rana, and Odorrana. Two novel antimicrobial groups (jingdongin-1 and -2) were synthesized and their antimicrobial activities were assayed. Some of them showed strong antimicrobial abilities against microorganisms including Gram-negative and -positive bacteria, and fungi. The extreme diversity of antimicrobial peptides in the Amolops amphibians was demonstrated. In addition, several novel peptide templates were provided for antimicrobial agent design.

[FTIR Study on the Reduction of 1-benzyl-3-hydroxypyrrolidine-2,5-dione]

The title compound was synthesized by reducing (S)-1-benzyl-3-hydroxypyrrolidine-2, 5-dione with sodium borohydride-iodin. The raw material, intermediate, and the end product were characterized by IR spectra and the mechanism of reduction of imide by sodium borohydride-iodin was also studied by IR spectra. According to the IR spectra, it was concluded that the product was (S)-1-bezyl-3-hydroxypyrrolidine. The mechanism of the reduction is that borane, formed in situ by reacting sodium borohydride with iodine, partly was conjugated to carbonyl to form four-member-ring intermediate and partly conjugated to nitrogen. (S)-1-benzyl-3-hydroxypyrrolidine/BH3 complex was gained when the reduction finished. The title compound was obtained by removing borane from the complex in methanol.

Ultrasound-promoted One-pot, Three-component Synthesis of Spiro[indoline-3,1'-pyrazolo[1,2-b]phthalazine] Derivatives

A series of 3'-aminospiro[indoline-3,1'-pyrazolo[1,2-b]phthalazine]-2,5',10'-trione derivatives have been synthesized by a one-pot three-component reaction of isatin, malononitrile or ethyl cyanoacetate and phthalhydrazide catalyzed by piperidine under ultrasound irradiation. For comparison the reactions were carried out under both conventional and ultrasonic conditions. In general, improvement in rates and yields were observed when the reactions were carried out under sonication compared with classical conditions.

[Rapid Pore Cranial Drilling and Ventricular Drainage in the Treatment of Ventricular Hemorrhage Caused by Thalamic Hemorrhage: an Analysis of 401 Cases]

To summarize the clinical efficacies and experiences of using rapid pore cranial drilling and external ventricular drainage (EVD) in the treatment of ventricular hemorrhage caused by thalamic hemorrhage.

A Microarray Analysis of Angiogenesis Modulation Effect of Xuefu Zhuyu Decoction on Endothelial Cells

To study the angiogenesis modulation mechanism of Xuefu Zhuyu Decoction () on the endothelial cell line ECV304.

A Novel Frog Skin Peptide Containing Function to Induce Muscle Relaxation

A novel bioactive peptide (polypedarelaxin 1) was identified from the skin secretions of the tree frog, Polypedates pingbianensis. Polypedarelaxin 1 is composed of 21 amino acid residues with a sequence of QGGLLGKVSNLANDALGILPI. Its primary structure was further confirmed by cDNA cloning and mass spectrometry analysis. Polypedarelaxin 1 was found to elicit concentration-dependent relaxation effects on isolated rat ileum. It has no antimicrobial and serine protease inhibitory activities. BLAST search revealed that polypedarelaxin 1 did not show similarity to known proteins or peptides. Especially, polypedarelaxin 1 do not contain conserved structural motifs of other amphibian myotropic peptides, such as bradykinins, bombesins, cholecystokinin (CCK), and tachykinins, indicating that polypedarelaxin 1 belongs to a novel family of amphibian myotropic peptide.

Reversible Superhydrophobic-superhydrophilic Transition of ZnO Nanorod/epoxy Composite Films

Tuning the surface wettability is of great interest for both scientific research and practical applications. We demonstrated reversible transition between superhydrophobicity and superhydrophilicity on a ZnO nanorod/epoxy composite film. The epoxy resin serves as an adhesion and stress relief layer. The ZnO nanorods were exposed after oxygen reactive ion etching of the epoxy matrix. A subsequent chemcial treatment with fluoroalkyl and alkyl silanes resulted in a superhydrophobic surface with a water contact angle up to 158.4° and a hysteresis as low as 1.3°. Under UV irradiation, the water contact angle decreased gradually, and the surface eventually became superhydrophilic because of UV induced decomposition of alkyl silanes and hydroxyl absorption on ZnO surfaces. A reversible transition of surface wettability was realized by alternation of UV illumination and surface treatment. Such ZnO nanocomposite surface also showed improved mechanical robustness.

Inhibitory Effect of the Antimalarial Agent Artesunate on Collagen-induced Arthritis in Rats Through Nuclear Factor Kappa B and Mitogen-activated Protein Kinase Signaling Pathway

Recent evidence indicates that the antimalarial agent artesunate (ART) has immunomodulatory properties that may be useful for treating rheumatoid arthritis (RA). However, the effects of ART on the RA animal model have not been described. The current study aimed to evaluate the antiarthritic effect of ART and explore the potential mechanism on type II collagen-induced arthritis (CIA) in rats. From the day of arthritis onset, rats were treated daily by gavage with leflunomide (Lef) or ART at a dosage of 10 mg/kg/d or 5 mg/kg/d, respectively, for 16 days. The severity of arthritis and levels of pro- and anti-inflammatory cytokines in site were measured. The expression and activity of metalloproteinase (MMP)-2 and MMP-9 were determined. The activation of nuclear factor kappa B and mitogen-activated protein kinase signaling pathways was investigated in rats with CIA and in Raw264.7 cells. Our results showed that ART treatment significantly attenuated inflammation symptoms and prevented cartilage and bone destruction. ART decreased expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α, and interleukin-17α. Both expression and activity of MMP-9 were efficiently inhibited by ART. ART significantly inhibited the degradation of IκB and activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase in rats with CIA and in lipopolysaccharide-stimulated Raw264.7 cells. The present study demonstrated that ART ameliorated rat CIA. The antiarthritic effect might be achieved by inhibiting the action of proinflammatory cytokines and the activity of MMP-9 via suppression of nuclear factor kappa B and mitogen-activated protein kinase signaling pathway. These results show that ART may be used as an adjuvant therapy for patients with RA.

Determining the Full Three-dimensional Orientation of Single Anisotropic Nanoparticles by Differential Interference Contrast Microscopy

Keeping track: By combining differential interference contrast (DIC) image pattern recognition with DIC polarization anisotropy, the exact full three-dimensional angular information of individual tilted gold nanorods positioned in the focal plane of the objective lens can be readily determined. The angular rotational modes and kinetics of individual in-focus gold nanorods can thus be resolved dynamically.

Proteomics and Transcriptome Analysis Coupled with Pharmacological Test Reveals the Diversity of Anti-thrombosis Proteins from the Medicinal Insect, Eupolyphaga Sinensis

The insect of Eupolyphaga sinensis Walker has been used as traditional anti-thrombosis medicine without bleeding risk for several hundreds years in eastern countries. Our previous work has identified a bi-functional anti-thrombosis protein containing both direct-acting fibrin(ogen)olytic and plasminogen-activating activities from the insect. By proteomics and transcriptome analysis, 105 serine proteases belonging to four families were identified from the ground beetle, E. sinensis and the classification is for serine proteases of this organism. Pharmacological test indicated that 5 (eupolytin 1-5) of them have the abilities to hydrolyze fibrin(ogen) and/or activate plasminogen. The current work revealed the extreme diversity of anti-thrombosis components in E. sinensis and anti-thrombosis molecular mechanisms of the traditional medicinal insect, and provided many templates for the development of new thrombolytic agents. Especially, these proteins, which contain both plasmin- and PA (plasminogen-activating)-like activities, are excellent candidates for anti-thrombosis medicines.

Electrophysiology and Ultrastructural Changes in Mouse Sciatic Nerve Associated with Colistin Sulfate Exposure

To investigate the neurotoxicity of colistin, female mice received colistin sulfate (7.5 mg/kg/12 h) intravenously for 7 days successively, the behavioral changes, and the neuropathological and electrophysiological characterizations of sciatic nerves were determined prior to administration and at 1, 3, 7 and 15 days thereafter. At 1, 3, and 7 days, the compound action potential durations (CAPDs), compound muscle action potential amplitudes (CAPAs), conduction velocities of sciatic-tibial nerve (NCVs) showed progressively abnormal changes with the time prolonged. Compared to the control, these changes were significant at day 7 (p < 0.01, p < 0.05, p < 0.05, p < 0.01 and p < 0.05, respectively), but at day 15, only CAPAs were significantly different (p < 0.05), other indexes presented a recovery tendency. These functional damages were confirmed by the synchronous ultrastructural observations which expressed axonal degeneration and demyelination in the sciatic nerves. These results indicated that peripheral neurotoxicity occurred in mice treated intravenously with colistin sulfate and the electrophysiological and ultrastructural changes of their sciatic nerves exerted in time-dependent fashion.

Genome-wide Characterization of Foxa2 Targets Reveals Upregulation of Floor Plate Genes and Repression of Ventrolateral Genes in Midbrain Dopaminergic Progenitors

The transcription factors Foxa1 and Foxa2 promote the specification of midbrain dopaminergic (mDA) neurons and the floor plate. Whether their role is direct has remained unclear as they also regulate the expression of Shh, which has similar roles. We characterized the Foxa2 cis-regulatory network by chromatin immunoprecipitation followed by high-throughput sequencing of mDA progenitors. This identified 9160 high-quality Foxa2 binding sites associated with 5409 genes, providing mechanistic insights into Foxa2-mediated positive and negative regulatory events. Foxa2 regulates directly and positively key determinants of mDA neurons, including Lmx1a, Lmx1b, Msx1 and Ferd3l, while negatively inhibiting transcription factors expressed in ventrolateral midbrain such as Helt, Tle4, Otx1, Sox1 and Tal2. Furthermore, Foxa2 negatively regulates extrinsic and intrinsic components of the Shh signaling pathway, possibly by binding to the same enhancer regions of co-regulated genes as Gli1. Foxa2 also regulates the expression of floor plate factors that control axon trajectories around the midline of the embryo, thereby contributing to the axon guidance function of the floor plate. Finally, this study identified multiple Foxa2-regulated enhancers that are active in the floor plate of the midbrain or along the length of the embryo in mouse and chick. This work represents the first comprehensive characterization of Foxa2 targets in mDA progenitors and provides a framework for elaborating gene regulatory networks in a functionally important progenitor population.

Bifurcations of Emergent Bursting in a Neuronal Network

Complex neuronal networks are an important tool to help explain paradoxical phenomena observed in biological recordings. Here we present a general approach to mathematically tackle a complex neuronal network so that we can fully understand the underlying mechanisms. Using a previously developed network model of the milk-ejection reflex in oxytocin cells, we show how we can reduce a complex model with many variables and complex network topologies to a tractable model with two variables, while retaining all key qualitative features of the original model. The approach enables us to uncover how emergent synchronous bursting can arise from a neuronal network which embodies known biological features. Surprisingly, the bursting mechanisms are similar to those found in other systems reported in the literature, and illustrate a generic way to exhibit emergent and multiple time scale oscillations at the membrane potential level and the firing rate level.

AAV2-mediated Combined Subretinal Delivery of IFN-α and IL-4 Reduces the Severity of Experimental Autoimmune Uveoretinitis

We previously showed that adeno-associated virus 2 (AAV2) mediated subretinal delivery of human interferon-alpha (IFN-α) could effectively inhibit experimental autoimmune uveoretinitis (EAU). In this study we investigated whether subretinal injection of both AVV2.IFN-α and AAV2.IL-4 had a stronger inhibition on EAU activity. B10RIII mice were subretinally injected with AAV2.IFN-α alone (1.5×10(7) vg), AAV2.IL-4 alone (3.55×10(7) vg), and AAV2.IFN-α combined with AAV2.IL-4. PBS, AAV2 vector encoding green fluorescent protein (AAV2.GFP) (5×10(7) vg) was subretinally injected as a control. IFN-α and IL-4 were effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2 vectors either alone or following combined administration and significantly attenuated EAU activity clinically and histopathologically. AAV2.IL-4 showed a better therapeutic effect as compared to AAV2.IFN-α. The combination of AAV2.IL-4 and AAV2.IFN-α was not significantly different as compared to AAV2.IL-4 alone. There was no difference concerning DTH (delayed-type hypersensitivity) reaction, lymphocyte proliferation and IL-17 production among the investigated treatment groups, suggesting that local retinal gene delivery did not affect the systemic immune response.

The Proteasome is Responsible for Caspase-3-like Activity During Xylem Development

Xylem development is a process of xylem cell terminal differentiation that includes initial cell division, cell expansion, secondary cell wall formation and programmed cell death (PCD). PCD in plants and apoptosis in animals share many common characteristics. Caspase-3, which displays Asp-Glu-Val-Asp (DEVD) specificity, is a crucial executioner during animal cells apoptosis. Although a gene orthologous to caspase-3 is absent in plants, caspase-3-like activity is involved in many cases of PCD and developmental processes. However, there is no direct evidence that caspase-3-like activity exists in xylem cell death. In this study, we showed that caspase-3-like activity is present and is associated with secondary xylem development in Populus tomentosa. The protease responsible for the caspase-3-like activity was purified from poplar secondary xylem using hydrophobic interaction chromatography (HIC), Q anion exchange chromatography and gel filtration chromatography. After identification by liquid chromatography-tandem mass spectrometry (LC-MS/MS), it was revealed that the 20S proteasome (20SP) was responsible for the caspase-3-like activity in secondary xylem development. In poplar 20SP, there are seven α subunits encoded by 12 genes and seven β subunits encoded by 12 genes. Pharmacological assays showed that Ac-DEVD-CHO, a caspase-3 inhibitor, suppressed xylem differentiation in the veins of Arabidopsis cotyledons. Furthermore, clasto-lactacystin β-lactone, a proteasome inhibitor, inhibited PCD of tracheary element in a VND6-induced Arabidopsis xylogenic culture. In conclusion, the 20S proteasome is responsible for caspase-3-like activity and is involved in xylem development.

Deterministic Conversion Between Memory and Threshold Resistive Switching Via Tuning the Strong Electron Correlation

Intensive investigations have been launched worldwide on the resistive switching (RS) phenomena in transition metal oxides due to both fascinating science and potential applications in next generation nonvolatile resistive random access memory (RRAM) devices. It is noteworthy that most of these oxides are strongly correlated electron systems, and their electronic properties are critically affected by the electron-electron interactions. Here, using NiO as an example, we show that rationally adjusting the stoichiometry and the associated defect characteristics enables controlled room temperature conversions between two distinct RS modes, i.e., nonvolatile memory switching and volatile threshold switching, within a single device. Moreover, from first-principles calculations and x-ray absorption spectroscopy studies, we found that the strong electron correlations and the exchange interactions between Ni and O orbitals play deterministic roles in the RS operations.

A Combined Etching Process Toward Robust Superhydrophobic SiC Surfaces

Large-scale porous SiC was fabricated by a combination of Pt-assisted etching and reactive ion etching. It was found that the surface roughness of combined etchings increased dramatically in comparison with metal-assisted etching or reactive ion etching only. To reduce the surface energy, the porous SiC surface was functionalized with perfluorooctyl trichlorosilane, resulting in a superhydrophobic SiC surface with a contact angle of 169.2° and a hysteresis of 2.4°. The superhydrophobicity of the SiC surface showed a good long-term stability in an 85 °C/85% humidity chamber. Such superhydrophobicity was also stable in acidic or basic solutions, and the pH values showed little or no effect on the SiC surface status. In addition, enhancement of porosity-induced photoluminescence intensity was found in the superhydrophobic SiC samples. The robust superhydrophobic SiC surfaces may have a great potential for microfluid device, thermal ground plane, and biosensor applications.

AAV2-mediated Subretinal Gene Transfer of MIL-27p28 Attenuates Experimental Autoimmune Uveoretinitis in Mice

Advances in gene transfer techniques have provided long-term, safe and stable transduction of retinal cells following subretinal injection with adeno-associated viral (AAV) vectors. In this study we investigated whether subretinal injection of AAV2-murine IL-27p28 vector was effective in inhibiting experimental autoimmune uveoretinitis (EAU) induced in B10RIII mice.

Syndecan-1 Plays a Novel Role in Enteral Glutamine's Gut Protective Effects of the Post Ischemic Gut: Role of Syndecan-1 in Gut Protection by Glutamine

ABSTRACT: Syndecan-1 is the predominant heparan sulfate proteoglycan found on the surface of epithelial cells, and like glutamine, is essential in maintaining the intestinal epithelial barrier. We therefore hypothesized that loss of epithelial syndecan-1 would abrogate the gut protective effects of enteral glutamine. Both an in vitro and in vivo model of gut ischemia/reperfusion (I/R) was utilized. In vitro, intestinal epithelial cells underwent hypoxia/reoxygenation (H/R) to mimic gut I/R with 2mM (physiologic) or 10 mM glutamine supplementation. Permeability, caspase activity, cell growth, and cell surface and shed syndecan-1 were assessed. In vivo, wild type (WT) and syndecan-1 knockout (KO) mice received ± enteral glutamine followed by gut I/R. Intestinal injury was assessed by fluorescent dye clearance and histopathology, permeability as mucosal to serosal clearance ex vivo in everted sacs, and inflammation by myeloperoxidase (MPO) activity. In an in vitro model of gut I/R, glutamine supplementation reduced epithelial cell permeability and apoptosis and enhanced cell growth. Shed syndecan-1 was reduced by glutamine without an increase in syndecan-1 mRNA. In vivo, intestinal permeability, inflammation, and injury were increased after gut I/R in WT mice and further increased in syndecan-1 KO mice. Glutamine's attenuation of I/R-induced intestinal hyperpermeability, inflammation, and injury were abolished in syndecan-1 KO mice. These results suggest that syndecan-1 plays a novel role in the protective effects of enteral glutamine in the post ischemic gut.

Prediction of Trabecular Bone Principal Structural Orientation Using Quantitative Ultrasound Scanning

Bone has the ability to adapt its structure in response to the mechanical environment as defined as Wolff's Law. The alignment of trabecular structure is intended to adapt to the particular mechanical milieu applied to it. Due to the absence of normal mechanical loading, it will be extremely important to assess the anisotropic deterioration of bone during the extreme conditions, i.e., long term space mission and disease orientated disuse, to predict risk of fractures. The propagation of ultrasound wave in trabecular bone is substantially influenced by the anisotropy of the trabecular structure. Previous studies have shown that both ultrasound velocity and amplitude is dependent on the incident angle of the ultrasound signal into the bone sample. In this work, seven bovine trabecular bone balls were used for rotational ultrasound measurement around three anatomical axes to elucidate the ability of ultrasound to identify trabecular orientation. Both ultrasound attenuation (ATT) and fast wave velocity (UV) were used to calculate the principal orientation of the trabecular bone. By comparing to the mean intercept length (MIL) tensor obtained from μCT, the angle difference of the prediction by UV was 4.45°, while it resulted in 11.67° angle difference between direction predicted by μCT and the prediction by ATT. This result demonstrates the ability of ultrasound as a non-invasive measurement tool for the principal structural orientation of the trabecular bone.

The Fabrication of Vertically Aligned and Periodically Distributed Carbon Nanotube Bundles and Periodically Porous Carbon Nanotube Films Through a Combination of Laser Interference Ablation and Metal-catalyzed Chemical Vapor Deposition

Scalable fabrication of carbon nanotube (CNT) bundles is essential to future advances in several applications. Here, we report on the development of a simple, two-step method for fabricating vertically aligned and periodically distributed CNT bundles and periodically porous CNT films at the sub-micron scale. The method involves laser interference ablation (LIA) of an iron film followed by CNT growth via iron-catalyzed chemical vapor deposition. CNT bundles with square widths ranging from 0.5 to 1.5 µm in width, and 50-200 µm in length, are grown atop the patterned catalyst over areas spanning 8 cm(2). The CNT bundles exhibit a high degree of control over square width, orientation, uniformity, and periodicity. This simple scalable method of producing well-placed and oriented CNT bundles demonstrates a high application potential for wafer-scale integration of CNT structures into various device applications, including IC interconnects, field emitters, sensors, batteries, and optoelectronics, etc.

Fast Fabrication of a Ag Nanostructure Substrate Using the Femtosecond Laser for Broad-band and Tunable Plasmonic Enhancement

Using a femtosecond laser, we have transformed the laser-direct-writing technique into a highly efficient method that can process AgO(x) thin films into Ag nanostructures at a fast scanning rate of 2000 μm(2)/min. The processed AgO(x) thin films exhibit broad-band enhancement of optical absorption and effectively function as active SERS substrates. Probing of the plasmonic hotspots with dyed polymer beads indicates that these hotspots are uniformly distributed over the treated area.

A Novel Myotropic Peptide from the Skin Secretions of the Tree Frog, Polypedates Pingbianensis

A novel myotropic peptide, polypedatein, was purified and characterized from the skin secretions of the tree frog, Polypedates pingbianensis. Its primary structure, TLLCKYFAIC, was determined by Edman degradation and mass spectrometry. Polypedatein was subjected to bioassays including myotropic, antimicrobial, and serine protease inhibitory activities, which are related with many amphibian skin bioactive peptides. It was found to elicit concentration-dependent contractile effects on isolated rat ileum. cDNA clones encoding the precursor of polypedatein were isolated by screening a skin cDNA library of P. pingbianensis and then sequenced. The amino acid sequence deduced from the cDNA sequences matches well with the result from Edman degradation. BLAST search revealed that the sequence of polypedatein did not show similarity to known protein or peptide sequences. Especially, polypedatein does not contain conserved structural motifs of other amphibian myotropic peptides, such as bradykinins, bombesins, cholecystokinin (CCK), and tachykinins, indicating that polypedatein belongs to a novel amphibian myotropic peptide family. The signal peptide of the precursor encoding polypedatein shows significant sequence identity to that of other amphibian skin defensive peptides, such as antimicrobial peptides, bradykinins, lectins, and serine protease inhibitors, suggesting that polypedatein belongs to a novel amphibian myotropic peptide family. Polypedatein is also the first bioactive peptide from the genus of the frog, Polypedates.

Dysregulation of Cell Polarity Proteins Synergize with Oncogenes or the Microenvironment to Induce Invasive Behavior in Epithelial Cells

Changes in expression and localization of proteins that regulate cell and tissue polarity are frequently observed in carcinoma. However, the mechanisms by which changes in cell polarity proteins regulate carcinoma progression are not well understood. Here, we report that loss of polarity protein expression in epithelial cells primes them for cooperation with oncogenes or changes in tissue microenvironment to promote invasive behavior. Activation of ErbB2 in cells lacking the polarity regulators Scribble, Dlg1 or AF-6, induced invasive properties. This cooperation required the ability of ErbB2 to regulate the Par6/aPKC polarity complex. Inhibition of the ErbB2-Par6 pathway was sufficient to block ErbB2-induced invasion suggesting that two polarity hits may be needed for ErbB2 to promote invasion. Interestingly, in the absence of ErbB2 activation, either a combined loss of two polarity proteins, or exposure of cells lacking one polarity protein to cytokines IL-6 or TNFα induced invasive behavior in epithelial cells. We observed the invasive behavior only when cells were plated on a stiff matrix (Matrigel/Collagen-1) and not when plated on a soft matrix (Matrigel alone). Cells lacking two polarity proteins upregulated expression of EGFR and activated Akt. Inhibition of Akt activity blocked the invasive behavior identifying a mechanism by which loss of polarity promotes invasion of epithelial cells. Thus, we demonstrate that loss of polarity proteins confers phenotypic plasticity to epithelial cells such that they display normal behavior under normal culture conditions but display aggressive behavior in response to activation of oncogenes or exposure to cytokines.

Histidine Pairing at the Metal Transport Site of Mammalian ZnT Transporters Controls Zn2+ over Cd2+ Selectivity

Zinc and cadmium are similar metal ions, but though Zn(2+) is an essential nutrient, Cd(2+) is a toxic and common pollutant linked to multiple disorders. Faster body turnover and ubiquitous distribution of Zn(2+) vs. Cd(2+) suggest that a mammalian metal transporter distinguishes between these metal ions. We show that the mammalian metal transporters, ZnTs, mediate cytosolic and vesicular Zn(2+) transport, but reject Cd(2+), thus constituting the first mammalian metal transporter with a refined selectivity against Cd(2+). Remarkably, the bacterial ZnT ortholog, YiiP, does not discriminate between Zn(2+) and Cd(2+). A phylogenetic comparison between the tetrahedral metal transport motif of YiiP and ZnTs identifies a histidine at the mammalian site that is critical for metal selectivity. Residue swapping at this position abolished metal selectivity of ZnTs, and fully reconstituted selective Zn(2+) transport of YiiP. Finally, we show that metal selectivity evolves through a reduction in binding but not the translocation of Cd(2+) by the transporter. Thus, our results identify a unique class of mammalian transporters and the structural motif required to discriminate between Zn(2+) and Cd(2+), and show that metal selectivity is tuned by a coordination-based mechanism that raises the thermodynamic barrier to Cd(2+) binding.

Serotonylated Fibronectin is Elevated in Pulmonary Hypertension

Serotonin (5-HT) and fibronectin (FN) have been associated with pulmonary hypertension (PH). We previously reported that FN is posttranslationally modified by tissue transglutaminase (TGase) to form serotonylated FN (s-FN) in pulmonary artery smooth muscle cells and that serotonylation stimulates their proliferation and migration, hallmarks of PH. We hypothesized that s-FN and its binding to TGase are elevated in human and experimental PH. To assess this hypothesis, FN isolation and electrophoretic, immunoblotting, and densitometric techniques were used. Mean ratio of serum s-FN to total FN level (s-FN/FN) was elevated in 19 consecutive pulmonary arterial hypertension (PAH) patients compared with 25 controls (0.3 ± 0.18 vs. 0.05 ± 0.07, P < 0.001). s-FN/FN also was increased in lungs of mice and rats with hypoxia-induced PH and in rats with monocrotaline-induced PH. In mice, the increase was detected at 1 wk of hypoxia, preceding the development of PH. Hypoxic rats had elevated serum s-FN/FN. Enhanced binding of TGase to its substrate FN occurred in serum from patients with PAH (mean 0.50 ± 0.51 vs. 0.063 ± 0.11, P = 0.002) and s-FN/FN and TGase-bound FN were highly correlated (R(2) = 0.77). TGase-bound FN also was increased in experimental PH. We conclude that increased serotonylation of FN occurs in human and experimental PH and may provide a biomarker for the disease.

Promoting Immobilization and Catalytic Activity of Horseradish Peroxidase on Mesoporous Silica Through Template Micelles

New concept on the promotion of immobilization and catalytic activity of enzyme on mesoporous silica through template micelles is proposed and realized in this paper. Proper P123 templates are controllable retained in the as-synthesized SBA-15, not only to anchor the horseradish peroxidase (HRP) guest, but also to establish the crowding-like microenvironment around the enzyme. The influence of retaining templates on the pore structure of SBA-15, immobilization, and catalytic activity of HRP is studied, and the possible process of template removal is proposed. Ethanol refluxing of 6 h is conformable to prepare the optimal mesoporous support characterized with the retained templates of about 8%. With the assistance of retained templates in SBA-15, up to 49 mg g(-1) of HRP can be immobilized, 100% more than that on calcined SBA-15. Furthermore, the thermal stability, the resistance of pH variation and denaturing agent urea, and the recycle usage of HRP immobilized are obviously elevated, paving a novel and low-cost route to develop enzyme catalysts.

[Clinical Experiences of Normal Saline Pressed Injection Via Lumbar Puncture in the Treatment of Apnea Due to Acute Tonsillar Hernia]

To summarize the clinical experiences of normal saline pressed injection via lumbar puncture in the treatment of acute tonsillar hernia induced apnea. This procedure was routinely carried out after external ventricular drainage and/or lesion removal via open craniotomy.

Accurate Identification of Human Alu and Non-Alu RNA Editing Sites

We developed a computational framework to robustly identify RNA editing sites using transcriptome and genome deep-sequencing data from the same individual. As compared with previous methods, our approach identified a large number of Alu and non-Alu RNA editing sites with high specificity. We also found that editing of non-Alu sites appears to be dependent on nearby edited Alu sites, possibly through the locally formed double-stranded RNA structure.

Structural Basis for the Dual Recognition of Helical Cytokines IL-34 and CSF-1 by CSF-1R

Lacking any discernible sequence similarity, interleukin-34 (IL-34) and colony stimulating factor 1 (CSF-1) signal through a common receptor CSF-1R on cells of mononuclear phagocyte lineage. Here, the crystal structure of dimeric IL-34 reveals a helical cytokine fold homologous to CSF-1, and we further show that the complex architecture of IL-34 bound to the N-terminal immunoglobulin domains of CSF-1R is similar to the CSF-1/CSF-1R assembly. However, unique conformational adaptations in the receptor domain geometry and intermolecular interface explain the cross-reactivity of CSF-1R for two such distantly related ligands. The docking adaptations of the IL-34 and CSF-1 quaternary complexes, when compared to the stem cell factor assembly, draw a common evolutionary theme for transmembrane signaling. In addition, the structure of IL-34 engaged by a Fab fragment reveals the mechanism of a neutralizing antibody that can help deconvolute IL-34 from CSF-1 biology, with implications for therapeutic intervention in diseases with myeloid pathogenic mechanisms.

[Clinical Characteristics of Drug-induced Liver Injury in 31 Pediatric Cases]

To investigate the clinical characteristics and responsible agents of drug-induced liver injury (DILI) in pediatric patients.

VEGF Upregulates Homer 1a Gene Expression Via the Mitogen-activated Protein Kinase Cascade in Cultured Cortex Neurons

In alternative splice variants of Homer 1 transcripts, Homer 1a messenger RNA (mRNA) has been shown to be upregulated selectively and rapidly by neural stimulation and represents a member of the immediate early gene (IEG) family. In our study, Homer 1 variants were expressed in cultured neurons as investigated by RT-PCR and Western blot analysis. After stimulation of VEGF, neurons selectively upregulated Homer 1a mRNA via Flk-1. The induction of Homer 1a mRNA peaked at 2h and sustained to 8h, while no significant change was observed of Homer 1b/c mRNA levels. Inhibitor analysis as well as Western blot analysis has indicated that the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascade plays an important role in VEGF-stimulated induction of Homer 1a mRNA. These results demonstrate that MAPK is a key mediator that links distinct extracellular VEGF stimuli to the transcriptional activation of Homer 1a mRNA.

Unsynchronized Translational and Rotational Diffusion of Nanocargo on a Living Cell Membrane

Comment on "Widespread RNA and DNA Sequence Differences in the Human Transcriptome"

Li et al. (Research Articles, 1 July 2011, p. 53; published online 19 May 2011) reported widespread differences between the RNA and DNA sequences of the same human cells, including all 12 possible mismatch types. Before accepting such a fundamental claim, a deeper analysis of the sequencing data is required to discern true differences between RNA and DNA from potential artifacts.

Design of a Wireless Anchoring and Extending Micro Robot System for Gastrointestinal Tract

BACKGROUND: Diagnosis and treatment using a conventional endoscope in the gastrointestinal (GI) tract are very common nowadays. However, endoscopy has some disadvantages. METHODS: This paper describes a wireless micro-robot for active locomotion in the GI tract. After design and analysis of the anchoring-extending gait, two mechanisms were developed to meet the gait requirements. These actuation and transmission mechanisms were demonstrated in detail to explain the gait implementation. The mechanisms were driven by a micro-brush direct current motor with a micro-normal module (m = 0.2 mm) gearbox. The force of the mechanisms was tested to guarantee the sufficiency of the gait and the safety of the robot. After mounting a dedicated video capture unit and wireless power receiving coils, in vitro experiments were conducted to show the feasibility of locomotion by wireless power supply. RESULTS: The assembled micro-robot was 13 mm in diameter and 90 mm in length, with a velocity of 1 mm/s at 500 mW power consumption. CONCLUSIONS: The proposed anchoring and extending intestinal micro-robot met the requirements of intestinal disease diagnosis and treatment. Copyright © 2012 John Wiley & Sons, Ltd.

Associated Factors of Brachial-ankle Pulse Wave Velocity in Hypertensive Patients Aged 80 and Over

IL-27 Inhibits Vaccine-enhanced Pulmonary Disease Following Respiratory Syncytial Virus Infection by Regulating Cellular Memory Responses

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract disease in young children. In the 1960s, infants vaccinated with formalin-inactivated RSV developed a more severe disease characterized by excessive inflammatory immunopathology in lungs upon natural RSV infection. The fear of causing the vaccine-enhanced disease (VED) is an important obstacle for development of safe and effective RSV vaccines. The recombinant vaccine candidate G1F/M2 immunization also leaded to VED. It has been proved that cellular memory induced by RSV vaccines contributed to VED. IL-27 and IL-23 regulate Th1, Th17 and/or Th2 cellular immune responses. In this study, mice co-immunized with pcDNA3-IL-27 and G1F/M2 were fully protected, importantly, did not develop vaccine-enhanced inflammatory responses and immunopathology in lungs after RSV challenge, which was correlated with moderate Th1-, suppressed Th2- and Th17-like memory responses activated by RSV. In contrast, G1F/M2- or pcDNA3-IL-23+G1F/M2-immunized mice, in which robust Th2- and Th17-like memory responses were induced, developed enhanced pulmonary inflammation and severe immunopathology. Mice co-immunized with G1F/M2 and the two cytokine plasmids exhibited mild inflammatory responses as well as remarkable Th1-, suppressed Th2- and Th17-like memory responses. These results suggested that Th1-, Th2-, and Th17-like memory responses, and particularly, excessive Th2- and Th17-like memory responses were closely associated with VED; IL-27 may inhibit VED following respiratory syncytial virus infection by regulating cellular memory responses.

Chondroitin Sulfate Synthase 1 (Chsy1) is Required for Bone Development and Digit Patterning

Joint and skeletal development is highly regulated by extracellular matrix (ECM) proteoglycans, of which chondroitin sulfate proteoglycans (CSPGs) are a major class. Despite the requirement of joint CSPGs for skeletal flexibility and structure, relatively little is understood regarding their role in establishing joint positioning or in modulating signaling and cell behavior during joint formation. Chondroitin sulfate synthase 1 (Chsy1) is one of a family of enzymes that catalyze the extension of chondroitin and dermatan sulfate glycosaminoglycans. Recently, human syndromic brachydactylies have been described to have loss-of-function mutations at the CHSY1 locus. In concordance with these observations, we demonstrate that mice lacking Chsy1, though viable, display chondrodysplasia and decreased bone density. Notably, Chsy1(-/-) mice show a profound limb patterning defect in which orthogonally shifted ectopic joints form in the distal digits. Associated with the digit-patterning defect is a shift in cell orientation and an imbalance in chondroitin sulfation. Our results place Chsy1 as an essential regulator of joint patterning and provide a mouse model of human brachydactylies caused by mutations in CHSY1.

Tumour-derived IL-10 Within Tumour Microenvironment Represses the Antitumour Immunity of Socs1-silenced and Sustained Antigen Expressing DCs

It has been shown that silencing of suppressor of cytokine signalling 1 (Socs1) or stably expressing transgenic protein Ags in antigen-presenting dentritic cells (DCs) strongly enhances antigen-specific anti-tumour immunity. However, whether the strong and long-lasting T cell responses induced by the modified DCs could modulate the immunosuppressive tumour microenvironment has not been clarified. In this study, we explored the anti-tumour immunity of DCs modified by Socs1-shRNA lentiviral transduction combined with sustained expression of TRP2 in different tumour models. We showed that transfer Socs1-silenced or tumour antigen TRP2 persistent expressed DCs, or DCs modified by combination of Socs1-silencing and sustaining TRP2 expression prior to inoculation of tumour cells delayed B16 tumour cell growth, prolonged mouse survival and increased the ratio of CD8+ T/Treg as well as the CTL activity in tumours. However, there was no significant effect on tumour growth and mouse survival rate upon tumour established. Further, we showed that tumour cell secreted IL-10 counteracted the immunity of modified DCs in established tumour model, injection of Socs1-shRNA and TRP2 antigen modified significantly inhibited growth of the established B16-IL-10(-/-) tumours. These data indicated that the high level of IL-10 within tumour microenvironment is one of factors that compromise DC vaccine functions.

Pien Tze Huang Inhibits Tumor Cell Proliferation and Promotes Apoptosis Via Suppressing the STAT3 Pathway in a Colorectal Cancer Mouse Model

Signal transducer and activator of transcription 3 (STAT3) plays a critical role in cell survival and proliferation. Constitutive activation of STAT3 is strongly correlated with pathogenesis of various types of malignant tumors including colorectal cancer (CRC), and therefore is a major focus in the development of anti-cancer agents. Pien Tze Huang (PZH), a well-known traditional Chinese formula prescribed already in the Ming Dynasty, has been demonstrated to be clinically effective in the treatment of CRC. However, the precise mechanism of its anti-cancer activity remains largely unknown. In the present study we evaluated the efficacy of PZH against tumor growth in vivo in the CRC mouse xenograft model, and investigated the underlying molecular mechanisms. We found that administration of PZH reduced tumor volume and tumor weight but had no effect on body weight gain in CRC mice, demonstrating that PZH can inhibit colon cancer growth in vivo without apparent adverse effect. We also observed that PZH treatment inhibited the phosphorylation level of STAT3 in tumor tissues. Consequently, the inhibitory effect of PZH on STAT3 activation resulted in the up-regulation of Bax/Bcl-2 ratio as well as down-regulation of Cyclin D1 and CDK4 expression, leading to the induction of apoptosis as well as the inhibition of cell proliferation. These results suggest that promotion of cancer cell apoptosis and inhibition of proliferation via suppression of STAT3 pathway might be one of the mechanisms by which PZH treats colorectal cancer.

Preparation of Electrospun PLGA-silk Fibroin Nanofibers-based Nerve Conduits and Evaluation in Vivo

With advances in technical methodology, the grafting of biocompatible conduits may become a viable alternative for the reconstruction of nerve gaps. In this study, electrospinning was used to fabricate nerve conduits (NCs) from poly(L-lactide-coglycolide)-silk fibroin. Conduits or autograft nerves were employed to bridge 10 mm defects in the sciatic nerves of Sprague-Dawley rats. Six weeks after the operation, morphological and functional assessment showed that nerve conduits from PLGA-silk fibroin grafts promoted the regeneration of peripheral nerves. The effects were similar to those obtained using nerve autografts. This method offers a promising alternative to the use of nerve autografts.

K-t Sparse GROWL: Sequential Combination of Partially Parallel Imaging and Compressed Sensing in K-t Space Using Flexible Virtual Coil

Because dynamic MR images are often sparse in x-f domain, k-t space compressed sensing (k-t CS) has been proposed for highly accelerated dynamic MRI. When a multichannel coil is used for acquisition, the combination of partially parallel imaging and k-t CS can improve the accuracy of reconstruction. In this work, an efficient combination method is presented, which is called k-t sparse Generalized GRAPPA fOr Wider readout Line. One fundamental aspect of this work is to apply partially parallel imaging and k-t CS sequentially. A partially parallel imaging technique using a Generalized GRAPPA fOr Wider readout Line operator is adopted before k-t CS reconstruction to decrease the reduction factor in a computationally efficient way while preserving temporal resolution. Channel combination and relative sensitivity maps are used in the flexible virtual coil scheme to alleviate the k-t CS computational load with increasing number of channels. Using k-t FOCUSS as a specific example of k-t CS, the experiments with Cartesian and radial data sets demonstrate that k-t sparse Generalized GRAPPA fOr Wider readout Line can produce results with two times lower root-mean-square error than conventional channel-by-channel k-t CS while consuming up to seven times less computational cost.

Neuroprotective Effects of Osthole Pretreatment Against Traumatic Brain Injury in Rats

Osthole, a coumarin compound isolated from the plant-derived herb Cnidium monnieri, has been the subject of considerable interest because of its broad spectrum of pharmacological properties. The aim of this study was to investigate the potential protective effects of osthole in adult rats in the setting of traumatic brain injury (TBI). We employed Feeney's weight-drop model to ascertain whether intraperitoneal administration of osthole (10mg/kg, 20mg/kg and 40 mg/kg) 30 min before TBI could reduce the severity of neurological deficits, cerebral edema, and hippocampal neuron loss. The levels of malondialdehyde (MDA) and glutathione (GSH), the activity of superoxide dismutase (SOD), the expressions of Bcl-2, Bax, and active caspase-3, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells were also measured to characterize the antioxidative and antiapoptotic properties. A significant reduction of neurological deficits, cerebral edema and hippocampal neuron loss was observed in the osthole pretreatment groups (20mg/kg and 40 mg/kg, but not 10mg/kg) by 24h after TBI compared with the TBI group. Furthermore, pretreatment with osthole (40 mg/kg) significantly increased the activity of SOD, the level of GSH, and the ratio of Bcl-2/Bax, and also reduced the level of MDA, the expression of active caspase-3, and the number of apoptotic cells at 24h after TBI. In summary, these results suggested that osthole had a neuroprotective effect against TBI, and the protection may be associated with its antioxidative and antiapoptotic functions.

Newly Isolated but Uncultivated Magnetotactic Bacterium of the Phylum Nitrospirae from Beijing, China

Magnetotactic bacteria (MTB) in the phylum Nitrospirae synthesize up to hundreds of intracellular bullet-shaped magnetite magnetosomes. In the present study, a watermelon-shaped magnetotactic bacterium (designated MWB-1) from Lake Beihai in Beijing, China, was characterized. This uncultivated microbe was identified as a member of the phylum Nitrospirae and represents a novel phylogenetic lineage with ≥6% 16S rRNA gene sequence divergence from all currently described MTB. MWB-1 contained 200 to 300 intracellular bullet-shaped magnetite magnetosomes and showed a helical swimming trajectory under homogeneous magnetic fields; its magnetotactic velocity decreased with increasing field strength, and vice versa. A robust phylogenetic framework for MWB-1 and all currently known MTB in the phylum Nitrospirae was constructed utilizing maximum-likelihood and Bayesian algorithms, which yielded strong evidence that the Nitrospirae MTB could be divided into four well-supported groups. Considering its population densities in sediment and its high numbers of magnetosomes, MWB-1 was estimated to account for more than 10% of the natural remanent magnetization of the surface sediment. Taken together, the results of this study suggest that MTB in the phylum Nitrospirae are more diverse than previously realized and can make important contributions to the sedimentary magnetization in particular environments.

A Refined MS-EVB Model for Proton Transport in Aqueous Environments

In order to improve the description of proton mobility in aqueous environments, a revised multistate empirical valence bond model (aMS-EVB3) is developed. The new aMS-EVB3 model is built upon an anharmonic water force field (aSPC/Fw) in which the OH bond potential is described through a quartic approximation to a Morse potential. First, it is shown that the aSPC/Fw anharmonic water model provides an accurate description of water at ambient conditions and reproduces the available experimental data for several structural, thermodynamic, and dynamical properties. Second, it is shown that, when applied to the study of proton solvation and transport in bulk water, the new aMS-EVB3 model accurately describes the solvation structure around the excess proton. Importantly, the new aMS-EVB3 model predicts a significantly larger proton diffusion coefficient than previous models, which largely improves the agreement with the available experimental data.

Induction of Cell Cycle Arrest by the Carbazole Alkaloid Clauszoline-I from Clausena Vestita D. D. Tao Via Inhibition of the PKCδ Phosphorylation

Sixteen carbazole alkaloids from Clausena vestita D. D. Tao were extracted, and their anti-tumor activities were evaluated. Among the extracts, Clauszoline-I exhibited an obvious growth inhibitory activity against several cancer cell lines through its ability to induce cell cycle arrest in the S and G2/M phases. A dramatic morphologic change with decreased F-actin staining and RhoA activity was found in Clauszoline-I treated HepG2 cells, in which the phosphorylation of PKCδ (Ser643) was inhibited. Our results indicated that induction cell cycle arrest by Clauszoline-I might be achieved by decreasing the RhoA activity via the inhibition of PKCδ phosphorylation.

Vascular Endothelial Growth Factor-D Promotes Growth, Lymphangiogenesis and Lymphatic Metastasis in Gallbladder Cancer

Lymph node metastasis is a major prognostic factor for patients with gallbladder cancer (GBC), and greater understanding of the molecule mechanism of lymph node metastasis in GBC is needed to improve prognosis. VEGF-D has been implicated in the control of lymphangiogenesis in many carcinomas, but the biological function of VEGF-D in human GBC remains unclear. In this study, we analyzed the role of the VEGF-D in human GBC cells and addressed the functional role of VEGF-D using a xenograft mouse model. We examined the expression of VEGF-D in three human gallbladder cancer cell lines. A lentivirus-based effective VEGF-D siRNA vector was infected into GBC NOZ cells. The effect of VEGF-D siRNA on GBC NOZ cells was investigated by cell proliferation assay and invasion assay. Furthermore, we examined the role of VEGF-D-SiRNA on GBC NOZ cells in the mice of subcutaneous and orthotopic xenograft tumor. Our results are as follows: VEGF-D mRNA and protein were expressed in all three GBC cell lines (GBC-SD, NOZ, and SGC-996). We successfully selected D-3/siRNA as the most effective siRNA to silence VEGF-D expression after four VEGF-D siRNA plasmid transfection in NOZ cells. VEGF-D mRNA and protein expression were suppressed by lentivirus-mediated D-3/siRNA. D-3-RNAi-LV inhibited NOZ cells proliferation and invasion ability in vitro. D-3-RNAi-LV inhibited tumor growth and lymphangiogenesis in the NOZ cell subcutaneous xenograft model. D-3-RNAi-LV inhibited lymphangiogenesis and lymphatic metastasis in the NOZ cell orthotopic xenograft model. Furthermore, D-3-RNAi-LV inhibited tumor ascites and hepatic invasion in the NOZ cell orthotopic xenograft model. In conclusion, VEGF-D is involved and plays an important role in GBC progression, suggesting that VEGF-D may be a potential molecular target in the treatment of GBC.

The Crystal Structure of AphB, a Virulence Gene Activator from Vibrio Cholerae, Reveals Residues That Influence Its Response to Oxygen and PH

Expression of the two critical virulence factors of Vibrio cholerae, toxin-coregulated pilus and cholera toxin, is initiated at the tcpPH promoter by the regulators AphA and AphB. AphA is a winged helix DNA-binding protein that enhances the ability of AphB, a LysR-type transcriptional regulator, to activate tcpPH expression. We present here the 2.2 Å X-ray crystal structure of full-length AphB. As reported for other LysR-type proteins, AphB is a tetramer with two distinct subunit conformations. Unlike other family members, AphB must undergo a significant conformational change in order to bind to DNA. We have found five independent mutations in the putative ligand-binding pocket region that allow AphB to constitutively activate tcpPH expression at the non-permissive pH of 8.5 and in the presence of oxygen. These findings indicate that AphB is responsive to intracellular pH as well as to anaerobiosis and that residues in the ligand-binding pocket of the protein influence its ability to respond to both of these signals. We have solved the structure of one of the constitutive mutants, and observe conformational changes that would allow DNA binding. Taken together, these results describe a pathway of conformational changes allowing communication between the ligand and DNA binding regions of AphB.

Arginine Decreases Peroxisome Proliferator-activated Receptor-γ Activity Via C-Jun

We have previously shown in the post ischemic gut that enteral arginine enhanced injury and inflammation via c-Jun/AP-1 and abrogated peroxisome proliferator-activated receptor (PPAR) γ activity. In the current study, we investigated the mechanism by which arginine inhibited PPARγ in vitro in rat small bowel epithelial IEC-6 cells. Arginine repressed PPARγ transcriptional activity in a time and dose-dependent fashion. Furthermore, downregulation of PPARγ by arginine involved phosphorylation of c-Jun that occurred before to changes in PPARγ transcriptional activity. Silencing of c-Jun increased PPARγ beyond that of nonsilenced cells and was not mitigated by arginine. Using a series of blocking studies, we found no relationship between arginine and the ligand-dependent binding site of PPARγ. In conclusion, arginine decreased PPARγ transcriptional activity in small bowel intestinal epithelial cells. These changes are due, in part, to phosphorylation of c-Jun and may explain the deleterious effects of enteral arginine in the post ischemic gut.

Off-resonance Artifacts Correction with Convolution in K-space (ORACLE)

Off-resonance artifacts hinder the wider applicability of echo-planar imaging and non-Cartesian MRI methods such as radial and spiral. In this work, a general and rapid method is proposed for off-resonance artifacts correction based on data convolution in k-space. The acquired k-space is divided into multiple segments based on their acquisition times. Off-resonance-induced artifact within each segment is removed by applying a convolution kernel, which is the Fourier transform of an off-resonance correcting spatial phase modulation term. The field map is determined from the inverse Fourier transform of a basis kernel, which is calibrated from data fitting in k-space. The technique was demonstrated in phantom and in vivo studies for radial, spiral and echo-planar imaging datasets. For radial acquisitions, the proposed method allows the self-calibration of the field map from the imaging data, when an alternating view-angle ordering scheme is used. An additional advantage for off-resonance artifacts correction based on data convolution in k-space is the reusability of convolution kernels to images acquired with the same sequence but different contrasts.

A Biogeographic Distribution of Magnetotactic Bacteria Influenced by Salinity

Magnetotactic bacteria (MTB), which synthesize intracellular ferromagnetic magnetite and/or greigite magnetosomes, have significant roles in global iron cycling in aquatic systems, as well as sedimentary magnetism. The occurrence of MTB has been reported in aquatic environments from freshwater to marine ecosystems; however, the distribution of MTB across heterogeneous habitats remains unclear. Here we examined the MTB communities from diverse habitats across northern and southern China, using comprehensive transmission electron microscopy and comparison of 16S rRNA gene analyses. A total of 334 16S rRNA gene sequences were analyzed, representing the most comprehensive analysis on the diversity and distribution of MTB to date. The majority (95%) of sequences belong to the Alphaproteobacteria, whereas a population of giant magnetotactic rod is affiliated with the Nitrospirae phylum. By a statistical comparison of these sequence data and publicly available MTB sequences, we infer for the first time that the composition of MTB communities represents a biogeographic distribution across globally heterogeneous environments, which is influenced by salinity.

High Temporal Resolution Retrospective Motion Correction with Radial Parallel Imaging

A method for motion correction in multicoil imaging applications, involving both data collection and reconstruction, is presented. A bit-reversed radial acquisition scheme, in conjunction with a rapid self-calibrated parallel imaging method, Generalized auto-calibrating partial parallel acquisition (GRAPPA) operator for wider radial bands (GROWL), is used to achieve motion correction at a high temporal resolution. View-by-view in-plane motion correction is achieved in 2D imaging, while 3D motion correction is achieved for every two consecutive slice-encoding planes in 3D imaging. In the proposed technique, GROWL contributes in two aspects: First, a central k-space circle/cylinder used as the motion-free reference is generated from a small number of radial lines/planes; Second, undersampled k-space regions resulting from rotation and inconsistent (e.g. intraview and nonrigid body) motion can be filled in. When compared with navigator-based motion correction methods, the proposed method does not prolong scan time and can be applied to short-TR sequences. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.

A Hybrid Method for More Efficient Channel-by-channel Reconstruction with Many Channels

In MRI, imaging using receiving coil arrays with a large number of elements is an area of growing interest. With increasing channel numbers for parallel acquisition, longer reconstruction times have become a significant concern. Channel reduction techniques have been proposed to reduce the processing time of channel-by-channel reconstruction algorithms. In this article, two schemes are combined to enable faster and more accurate reconstruction than existing channel reduction techniques. One scheme use two stages of channel reduction instead of one. The other scheme is to incorporate all acquired data into the final reconstruction. The combination of these two schemes is called flexible virtual coil. Applications of flexible virtual coil for partially parallel imaging, motion compensation, and compressed sensing are presented as specific examples. Theoretical analysis and experimental results demonstrate that the proposed method has a major impact in reducing computation cost in reconstruction with high-channel count coil elements.

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