The common approach in fluorescence molecular tomography (FMT) assumes homogeneous distributions of the optical properties and normally results in reconstructions of low sensitivity. A natural enhancement is to incorporate diffuse optical tomography (DOT) to FMT. However, the traditional voxel-based DOT has been a severely ill-posed inverse problem and cannot retrieve the optical property distributions accurately. We present a structural-prior-based DOT method to effectively acquire the heterogeneous optical background with the aid of some imperfect structural priors from x-ray computed tomography and/or magnetic resonance imaging anatomical imaging modalities, and quantitatively compare its hard- and soft-prior schemes for achieving an improved recovery of the fluorescence distribution. Numerical simulations are conducted on a region-labeled three-dimensional (3D) digital mouse model to investigate the performance of this method. Physical experiments on a cylindrical phantom are also conducted to assess this methodology. Our simulated and experimental reconstruction results indicate that the structural-prior-based DOT guided FMT approach can significantly improve the sensitivity of FMT reconstruction, as well as its imaging resolution and quantitative accuracy.
Disodium edetate (EDTA-Na), a popular hexadentate ligand in analytical chemistry, was successfully introduced in organic solar cells (OSCs) as cathode interfacial layer. The inverted OSCs with EDTA-Na showed superior performance both in power conversion efficiency and devices stability compared with conventional devices. Interestingly, we found that the performance of devices with EDTA-Na could be optimised through external bias treatment. After optimisation, the efficiency of inverted OSCs with device structure of ITO/EDTA-Na/polymer thieno[3,4-b]thiophene/benzodithiophene (PTB7):PC71BM/MoO3/Al was significantly increased to 8.33% from an initial value of 6.75%. This work introduces a new class of interlayer materials, small molecule electrolytes, for organic solar cells.
A temperature compensated magnetic field strength optical fiber sensor has been proposed and experimentally demonstrated. A fiber Bragg grating (FBG) is cascaded to modal interferometer (MI), which is fabricated by dual S-bend splicing between thin fiber (TF) and single mode fiber (SMF) with intentionally controlled misalignment between cores. We established a modified numerical model to describe the multi-mode interference of this exceptional S-bend and misalignment structure, together with the simulation based on beam propagation method to gain insight into its operation mechanism. The FBG is used to interrogate the temperature change, and then compensate the perturbation of temperature on transmission of the MI. Thanks to the proposed dual S-bend structure and the diameter-thinned TF used here; we have obtained high magnetic sensitivity of -0.0678 dB/Oe using only 4 mm TF after the elimination of ambient temperature change.
The International Agency for Research on Cancer has recently reclassified diesel engine exhaust (DEE) as a Group 1 carcinogen. Micronucleus (MN), nucleoplasmic bridge (NPB), and nuclear bud (NBUD) frequencies in peripheral blood lymphocytes (PBLs) are associated with cancer risk. However, the impact of DEE exposure on MN frequency has not been thoroughly elucidated due to mixed exposure and its impact on NPB and NBUD frequencies has never been explored in humans. We recruited 117 diesel engine testing workers with exclusive exposure to DEE and 112 non-DEE-exposed workers, and then we measured urinary levels of four mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) using high performance liquid chromatography-mass spectrometry as well as MN, NPB, and NBUD frequencies in PBLs using cytokinesis-block micronucleus assay. The DEE-exposed workers exhibited significantly higher MN, NPB, and NBUD frequencies than the non-DEE-exposed workers (p<0.05). Among all study subjects, increasing levels of all four urinary OH-PAHs, on both quartile and continuous scales, were associated with increased MN, NPB, and NBUD frequencies (all p<0.05). When the associations were analyzed separately in DEE-exposed and non-DEE-exposed workers, we found that the association between increasing quartiles of urinary 9-hydroxyphenanthrene (9-OHPh) and MN frequencies persisted in DEE-exposed workers (p=0.001). The percent of MN frequencies increased, on average, by 23.99% (95% confidential interval, 9.64-39.93) per 1-unit increase in ln-transformed 9-OHPh. Our results clearly show that exposure to DEE can induce increases in MN, NPB, and NBUD frequencies in PBLs and suggest that DEE exposure level is associated with MN frequencies.
To study the mechanisms of death following a single lethal dose of thoracic radiation, WAG/RijCmcr (Wistar) rats were treated with 15 Gy to the whole thorax and followed until they were morbid or sacrificed for invasive assays at 6 weeks. Lung function was assessed by breathing rate and arterial oxygen saturation. Lung structure was evaluated histologically. Cardiac structure and function were examined by echocardiography. The frequency and characteristics of pleural effusions were determined. Morbidity from 15 Gy radiation occurred in all rats 5 to 8 weeks after exposure, coincident with histological pneumonitis. Increases in breathing frequencies peaked at 6 weeks, when profound arterial hypoxia was also recorded. Echocardiography analysis at 6 weeks showed pulmonary hypertension and severe right ventricular enlargement with impaired left ventricular function and cardiac output. Histologic sections of the heart revealed only rare foci of lymphocytic infiltration. Total lung weight more than doubled. Pleural effusions were present in the majority of the irradiated rats and contained elevated protein, but low lactate dehydrogenase, when compared with serum from the same animal. Pleural effusions had a higher percentage of macrophages and large monocytes than neutrophils and contained mast cells that are rarely present in other pathological states. Lethal irradiation to rat lungs leads to hypoxia with infiltration of immune cells, edema and pleural effusion. These changes may contribute to pulmonary vascular and parenchymal injury that result in secondary changes in heart structure and function. We report that conditions resembling congestive heart failure contribute to death during radiation pneumonitis, which indicates new targets for therapy.
Orosomucoid 2 (ORM2) or alpha-1-acid glycoprotein 2 is associated with intestinal system disease and cancers, including stage II colorectal cancer (CRC). The highly heterogeneous characteristics of CRC have made the application of adjuvant therapies in patients with stage II CRC controversial. This study aimed to validate the prognostic significance of plasma ORM2 in patients with stage II CRC.
The NIH/NIAID initiated a countermeasure program to develop mitigators for radiation-induced injuries from a radiological attack or nuclear accident. We have previously characterized and demonstrated mitigation of single organ injuries, such as radiation pneumonitis, pulmonary fibrosis or nephropathy by angiotensin converting enzyme (ACE) inhibitors. Our current work extends this research to examine the potential for mitigating multiple organ dysfunctions occurring in the same irradiated rats. Using total body irradiation (TBI) followed by bone marrow transplant, we tested four doses of X radiation (11, 11.25, 11.5 and 12 Gy) to develop lethal late effects. We identified three of these doses (11, 11.25 and 11.5 Gy TBI) that were lethal to all irradiated rats by 160 days to test mitigation by ACE inhibitors of injury to the lungs and kidneys. In this study we tested three ACE inhibitors at doses: captopril (88 and 176 mg/m(2)/day), enalapril (18, 24 and 36 mg/m(2)/day) and fosinopril (60 mg/m(2)/day) for mitigation. Our primary end point was survival or criteria for euthanization of morbid animals. Secondary end points included breathing intervals, other assays for lung structure and function and blood urea nitrogen (BUN) to assess renal damage. We found that captopril at 176 mg/m(2)/day increased survival after 11 or 11.5 Gy TBI. Enalapril at 18-36 mg/m(2)/day improved survival at all three doses (TBI). Fosinopril at 60 mg/m(2)/day enhanced survival at a dose of 11 Gy, although no improvement was observed for pneumonitis. These results demonstrate the use of a single countermeasure to mitigate the lethal late effects in the same animal after TBI.
By the reaction of chiral Mn(III) Schiff-base complexes with the dicyanoruthenate building block, [Ru(salen)(CN)2](-) (salen(2-) = N,N'-ethylenebis(salicylideneimine) dianion), two couples of enantiomerically pure chiral cyano-bridged heterobimetallic one-dimensional (1D) chain complexes, [Mn((R,R)-salcy)Ru(salen)(CN)2]n (-(RR)) and [Mn((S,S)-salcy)Ru(salen)(CN)2]n (-(SS)) (Salcy = N,N'-(1,2-cyclohexanediylethylene)bis(salicylideneiminato) dianion), [Mn((R,R)-salphen)Ru(salen)(CN)2]n (-(RR)) and [Mn((S,S)-salphen)Ru(salen)(CN)2]n (-(SS)) (salphen = N,N'-(1,2-diphenylethylene)bis(salicylideneiminato) dianion), were synthesized and structurally characterized. Circular dichroism (CD) and vibrational circular dichroism (VCD) spectra confirm the enantiomeric nature of the optically active complexes. Structural analyses reveal the formation of neutral cyano-bridged zigzag single chains in -(RR) and -(SS), and double chains in -(RR) and -(SS). Magnetic studies show that antiferromagnetic coupling is operative between Ru(III) and Mn(III) centers bridged by cyanide. Compounds -(RR) and -(SS) show metamagnetic behavior with a critical field of about 7.2 kOe at 1.9 K resulting from the intermolecular ?? interactions. Additionally, magnetostructural correlation for some typical cyano-bridged heterobimetallic Ru(III)-Mn(III) compounds is discussed.
The long term results of vertebral artery ostium (VAO) stenting remain uncertain. We sought to evaluate the incidence and risk factors for recurrent ischemic events on long term follow-up in patients who have undergone VAO stenting.
Objective: This study sought to use a meta-analysis approach to comprehensively evaluate correlations between the human leukocyte antigen-DR beta 1 (HLA-DRB1)*03 allele and chronic hepatitis B (CHB) in the Han Chinese population. Methods: The China Biomedical Literature database (CBMdisc), the Chongqing VIP database (VIP), and the PubMed database were searched. Using the inclusion and exclusion criteria of this study, all relevant case-control studies retrieved in these searches that satisfied the conditions of this investigation were collected. Review Manager (RevMan) 5.2 software was used to conduct a meta-analysis on the results of these studies. Results: There were 9 publications that satisfied the inclusion criteria. These publications included a total of 970 cases in the CHB group and 1185 cases in the normal control group. Egger's test revealed no significant publication bias. A comprehensive analysis indicated that the pooled odds ratio (OR) value was 1.94 with a 95% confidence interval (CI) of 1.23-3.06 (Z=2.84, p=0.004); these findings suggested that in the Han Chinese population, the HLA-DRB1*03 allele is a susceptibility allele related to the occurrence of CHB. Conclusion: There is a statistically significant correlation between the HLA-DRB1*03 allele and the occurrence of CHB in the Han Chinese population, and the HLA-DRB1*03 allele may be a susceptibility allele for this disease.
The modulation transfer function (MTF) of radiographic systems is frequently evaluated by the system's line spread function (LSF) using narrow slits. The conventional slit method requires LSF tail approximation, which is achieved by exponentially extrapolating the LSF tails beyond 1% of peak value. However, the estimated MTF at low frequencies from extrapolation may not reflect the true performance of the system. In this study, a monotone spline regression technique for LSF tail approximation is developed to improve the accuracy of MTF estimation at low frequencies. This technique is based on the underlying physical principles of the system response. The advantages of this technique are demonstrated with simulated examples of which the true MTFs are known. The application of this measurement technique is also demonstrated.
We present a spectral domain low-coherence interferometry (SD-LCI) method that is effective for applications in on-line surface inspection because it can obtain a surface profile in a single shot. It has an advantage over existing spectral interferometry techniques by using cylindrical lenses as the objective lenses in a Michelson interferometric configuration to enable the measurement of long profiles. Combined with a modern high-speed CCD camera, general-purpose graphics processing unit, and multicore processors computing technology, fast measurement can be achieved. By translating the tested sample during the measurement procedure, real-time surface inspection was implemented, which is proved by the large-scale 3D surface measurement in this paper. ZEMAX software is used to simulate the SD-LCI system and analyze the alignment errors. Two step height surfaces were measured, and the captured interferograms were analyzed using a fast Fourier transform algorithm. Both 2D profile results and 3D surface maps closely align with the calibrated specifications given by the manufacturer.
We report a highly sensitive fiber-optic sensor based on two cascaded intrinsic fiber Fabry-Perot interferometers (IFFPIs). The cascaded IFFPIs have different free spectral ranges (FSRs) and are formed by a short section of hollow core photonic crystal fiber sandwiched by two single mode fibers. With the superposition of reflective spectrum with different FSRs, the Vernier effect will be generated in the proposed sensor and we found that the strain sensitivity of the proposed sensor can be improved from 1.6 pm/?? for a single IFFPI sensor to 47.14 pm/?? by employing the Vernier effect. The sensor embed with a metglas ribbon can be also used to measure the magnetic field according to the similar principle. The sensitivity of the magnetic field measurement is achieved to be 71.57 pm/Oe that is significantly larger than the 2.5 pm/Oe for a single IFFPI sensor.
Gold nanocages (AuNCs), which have tunable near-infrared (NIR) absorption and intrinsically high photothermal conversion efficiency, have been actively investigated as photothermal conversion agents for photothermal therapy (PTT). The short blood circulation lifetime of AuNCs, however, limits their tumor uptake and thus in vivo applications. Here we show that such a limitation can be overcome by cloaking AuNCs with red blood cell (RBC) membranes, a natural stealth coating. The fusion of RBC membranes over AuNC surface does not alter the unique porous and hollow structures of AuNCs, and the resulting RBC-membrane-coated AuNCs (RBC-AuNCs) exhibit good colloidal stability. Upon NIR laser irradiation, the RBC-AuNCs demonstrate in vitro photothermal effects and selectively ablate cancerous cells within the irradiation zone as do the pristine biopolymer-stealth-coated AuNCs. Moreover, the RBC-AuNCs exhibit significantly enhanced in vivo blood retention and circulation lifetime compared to the biopolymer-stealth-coated counterparts, as demonstrated using a mouse model. With integrated advantages of photothermal effects from AuNCs and long blood circulation lifetime from RBCs, the RBC-AuNCs demonstrate drastically enhanced tumor uptake when administered systematically, and mice that received PPT cancer treatment modulated by RBC-AuNCs achieve 100% survival over a span of 45 days. Taken together, our results indicate that the long circulating RBC-AuNCs may facilitate the in vivo applications of AuNCs, and the RBC-membrane stealth coating technique may pave the way to improved efficacy of PPT modulated by noble metal nanoparticles.
The objective of this study was to determine the role of Hsp90? in regulating the migration of mesenchymal stem cells (MSCs) and to investigate the underlying mechanisms of this effect. MSCs migration was assessed by wound healing assay and transwell migration assay. Hsp90? expression was silenced in MSC by siRNA (sirHsp90?). The activity of secreted metalloproteases MMP-2 and MMP-9, and their expression levels in MSC were evaluated using gelatin zymography, Western blot analysis and real-time PCR. Gene expression of VCAM-1 and CXCR4 cytokines was evaluated by real-time PCR. Akt and ERK activity were analyzed by Western blotting using antibodies against phosphorylated forms of these proteins. Treatment with Hsp90? significantly enhanced MSC migration, and this effect was blocked by transfecting MSC with sirHsp90?. Treating the cells with recombinant human Hsp90? (rhHsp90?) enhanced gene expression and protein levels of MMP-2 and MMP-9, as well as their secretion and activity. MSC incubated with rhHsp90? exhibited increased gene expression of CXCR4 and VCAM-1. Finally, the levels of phosphorylated Akt and Erk were markedly increased by rhHsp90? treatment. These findings indicate that Hsp90? promotes MSCs migration via PI3K/Akt and ERK signaling pathways, and that this effect is possibly mediated by MMPs, SDF-1/CXCR4 pathway, and VCAM-1.
A fundamental approach to enhancing the sensitivity of the fluorescence molecular tomography (FMT) is to incorporate diffuse optical tomography (DOT) to modify the light propagation modeling. However, the traditional voxel-based DOT has been involving a severely ill-posed inverse problem and cannot retrieve the optical property distributions with the acceptable quantitative accuracy and spatial resolution. Although, with the aid of an anatomical imaging modality, the structural-prior-based DOT method with either the hard- or soft-prior scheme holds promise for in vivo acquiring the optical background of tissues, the low robustness of the hard-prior scheme to the segmentation error and inferior performance of the soft-prior one in the quantitative accuracy limit its further application. We propose in this paper a shape-parameterized DOT method for not only effectively determining the regional optical properties but potentially achieving reasonable structural amelioration, lending itself to FMT for comparably improved recovery of fluorescence distribution.
Guillain-Barré syndrome is the most common acute peripheral neuropathy in children in most countries. The cause and pathogenesis of the disease have yet to be clarified. There have been only a few reports of Guillain-Barré syndrome resulting from parasite infections worldwide, no cases of Guillain-Barré syndrome after lung fluke infection have been reported. We report a case of an 8-year-old male patient with Guillain-Barré syndrome after lung fluke infection. The child had a history of consumption of undercooked crabs. He was diagnosed with paragonimiasis. The patient experienced paralysis of and pain in the lower limbs about 3 weeks after symptom onset. Neurologic and electrophysiologic examination findings supported the diagnosis of Guillain-Barré syndrome. Parasitic infections should also be considered when determining which antecedent infection is associated with Guillain-Barré syndrome.
Molecular self-assembly, a process to design molecular entities to aggregate into desired structures, represents a promising bottom-up route towards precise construction of functional systems. Here we report a multifunctional, self-assembled system based on magnetic-graphitic-nanocapsule (MGN) templated diacetylene assembly and photopolymerization. The as-prepared assembly system maintains the unique color and fluorescence change properties of the polydiacetylene (PDA) polymers, while also pursues the superior Raman, NIR, magnetic and superconducting properties from the MGN template. Based on both fluorescence and magnetic resonance imaging (MRI) T2 relaxivity, the MGN@PDA system could efficiently monitor the pH variations which could be used as a pH sensor. The MGN@PDA system further demonstrates potential as unique ink for anti-counterfeiting applications. Reversible color change, strong and unique Raman scattering and fluorescence emission, sensitive NIR thermal response, and distinctive magnetic properties afford this assembly system with multicoded anti-counterfeiting capabilities.
The morphology, ontogeny and SSU rRNA gene-based phylogeny of Bistichella cystiformans spec. nov., isolated from the slightly saline soil of a mangrove wetland in Zhanjiang, southern China, were investigated. The new species is characterized by having five to eight buccal cirri arranged in a row, three to five transverse cirri, four macronuclear nodules and two long frontoventral rows V and VI, which start from the frontal area and terminate close to the transverse cirri. The main ontogenetic features of the new species are as follows: (1) parental adoral zone of membranelles is completely inherited by the proter; (2) frontoventral and transverse cirri are formed in six-anlagen mode; (3) basically frontal-ventral-transverse cirral anlagen II - V generate one transverse cirrus each at their posterior ends while anlage VI provides no transverse cirrus; (4) both marginal rows and dorsal kineties develop intrakinetally, no dorsal kinety fragment is formed; and (5) the macronuclear nodules fuse into a single mass at the middle stage. Phylogenetic analyses based on the SSU rRNA gene show that the new species groups with the clade containing B. variabilis, Parabistichella variabilis, Uroleptoides magnigranulosus and two species of Orthoamphisiella. Given the present state of knowledge, it is still too early to come to a final conclusion regarding the familial classification of Bistichella and further investigation of key taxa with additional molecular markers is required.
BackgroundA major immune evasion mechanism of HIV-1 is the accumulation of non-synonymous mutations in and around T cell epitopes, resulting in loss of T cell recognition and virus escape.ResultsHere we analyze primary CD8+ T cell responses and virus escape in a HLA B*81 expressing subject who was infected with two T/F viruses from a single donor. In addition to classic escape through non-synonymous mutation/s, we also observed rapid selection of multiple recombinant viruses that conferred escape from T cells specific for two epitopes in Nef.ConclusionsOur study shows that recombination between multiple T/F viruses provide greater options for acute escape from CD8+ T cell responses than seen in cases of single T/F virus infection. This process may contribute to the rapid disease progression in patients infected by multiple T/F viruses.
MicroRNAs are implicated in the regulation of various cellular processes, including proliferation, differentiation, cell death, and cell mobility, and can function either as oncogenes or tumor suppressors in tumor progression. The effects of the expression of miR-96 in non-small cell lung cancer (NSCLC) remain unclear. In our study, qRT-PCR (quantitative reverse transcription PCR) was performed to identify the miR-96 expression level in 68 paired NSCLC and adjacent normal lung tissues. Trans-well, cell counting kit-8, and apoptosis assays were used to evaluate the effects of miR-96 expression on cell invasion, proliferation, and apoptosis. Dual-luciferase reporter assay and Western blotting were used to verify whether FOXO3 was a potential major target gene of miR-96. Finally, the effect of FOXO3 on miR-96-induced cell survival was determined by transfection of the genes expressing FOXO3 lacking 3'UTR and miR-96. The expression level of miR-96 in NSCLC tissues was higher than that in adjacent normal lung tissues, and this increased expression was significantly associated with lymph node metastasis. In contrast to the cells in the blank and negative control groups, the number of cells migrating through the matrigel was significantly lower and the incidence of apoptosis was significantly higher in cells transfected with a miR-96 inhibitor. Western blotting and dual-luciferase reporter assays demonstrated that miR-96 can bind to the putative seed region in FOXO3 mRNA 3'UTR, and can significantly lower the expression of FOXO3. The introduction of FOXO3 cDNA without 3'UTR restored miR-96 induced cell apoptosis and invasion. MiR-96 is up-regulated in NSCLC tissues. Downregulation of miR-96 inhibits invasion and promotes apoptosis in NSCLC cells A549 and SPC-A-1 by targeting FOXO3. Therefore, our study improves our understanding of the mechanisms underlying NSCLC pathogenesis and may promote the development of novel targeted therapies.
Ni-, Cu-, and Zn-TMPyP are capable of binding to single-strand poly(A) RNA with high preference and affinity and inhibiting the reverse transcription of RNA by both M-MuLV and HIV-1 reverse transcriptase. With 10 nM azidothymidine, the IC50 value of M-TMPyP could be lowered to 10(-1) ?M order.
Escin, a natural mixture of triterpene saponins, is commonly utilized for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema. Escin Ia is the chief active ingredient in escin and plays key role in mediating its pharmacological effects. Adequate pharmacokinetic data are essential for proper application of escin agent in clinical practice. However, pharmacokinetic properties of escin Ia are still poorly understood and this conflicts with the growing use of escin agent over the years.
The cellular protein quality control system in association with aggresome formation contributes to protecting cells against aggregation-prone protein-induced toxicity. p62/Sequestosome 1 (p62) is a multifunctional protein which plays an important role in protein degradation and aggregation. Although poly-ubiquitination is usually required for p62-mediated protein degradation and aggresome formation, several p62 substrates are processed to form aggregate in an ubiquitination-independent manner. In this study we demonstrate that p62 directly interacts with pathogenic Machado Joseph Disease (MJD)-associated protein ataxin-3 with polyglutamine (polyQ) expansion. Moreover, p62 could regulate the aggresome formation of pathogenic ataxin-3 and protect cells against pathogenic ataxin-3-induced cell death.
Microscopy has revealed tremendous diversity of bacterial and eukaryotic forms. Recent molecular analyses show discordance in estimates of biodiversity between morphological and molecular analyses. Moreover, phylogenetic analyses of the diversity of microbial forms reveal evidence of convergence at scales as deep as interdomain: morphologies shared between bacteria and eukaryotes. Here, we highlight examples of such discordance, focusing on exemplary lineages such as testate amoebae, ciliates, and cyanobacteria. These have long histories of morphological study, enabling deeper analyses on both the molecular and morphological sides. We discuss examples in two main categories: (i) morphologically identical (or highly similar) individuals that are genetically distinct and (ii) morphologically distinct individuals that are genetically the same. We argue that hypotheses about discordance can be tested using the concept of neutral morphologies, or more broadly neutral phenotypes, as a null hypothesis.
To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.
Neutralizing antibodies (nAbs) are a high priority for vaccines that aim to prevent the acquisition of HIV-1 infection. Vaccine effectiveness will depend on the extent to which induced antibodies neutralize the global diversity of circulating HIV-1 variants. Using large panels of genetically and geographically diverse HIV-1 Env-pseudotyped viruses and chronic infection plasma samples, we unambiguously show that cross-clade nAb responses are commonly induced in response to infection by any virus clade. Nonetheless, neutralization was significantly greater when the plasma clade matched the clade of the virus being tested. This within-clade advantage was diminished in older, more-diverse epidemics in southern Africa, the United States, and Europe compared to more recent epidemics in Asia. It was most pronounced for circulating recombinant form (CRF) 07_BC, which is common in China and is the least-divergent lineage studied; this was followed by the slightly more diverse Asian CRF01_AE. We found no evidence that transmitted/founder viruses are generally more susceptible to neutralization and are therefore easier targets for vaccination than chronic viruses. Features of the gp120 V1V2 loop, in particular, length, net charge, and number of N-linked glycans, were associated with Env susceptibility and plasma neutralization potency in a manner consistent with neutralization escape being a force that drives viral diversification and plasma neutralization breadth. The overall susceptibility of Envs and potencies of plasma samples were highly predictive of the neutralization outcome of any single virus-plasma combination. These findings highlight important considerations for the design and testing of candidate HIV-1 vaccines that aim to elicit effective nAbs.
Biodiversity research has shown that primary productivity increases with plant species number, especially in many experimental grassland systems. Here, we assessed the correlation between productivity and diversity of phytophages and natural enemy assemblages associated with planting date and intercropping in four cotton agroecosystems. Twenty-one pairs of data were used to determine Pearson correlations between species richness, total number of individuals, diversity indices and productivity for each assemblage every five days from 5 June to 15 September 2012. At the same trophic level, the productivity exhibited a significant positive correlation with species richness of the phytophage or predator assemblage. A significant correlation was found between productivity and total number of individuals in most cotton fields. However, no significant correlations were observed between productivity and diversity indices (including indices of energy flow diversity and numerical diversity) in most cotton fields for either the phytophage or the predator assemblages. Species richness of phytophage assemblage and total individual numbers were significantly correlated with primary productivity. Also, species richness of natural enemy assemblage and total number of individuals correlated with phytophage assemblage productivity. A negative but not significant correlation occurred between the indices of numerical diversity and energy flow diversity and lower trophic-level productivity in the cotton-phytophage and phytophage-predator assemblages for most intercropped cotton agroecosystems. Our results clearly showed that there were no correlations between diversity indices and productivity within the same or lower trophic levels within the phytophage and predator assemblages in cotton agroecosystems, and inter-cropped cotton fields had a stronger ability to support the natural enemy assemblage and potentially to reduce phytophages.
Adiponectin, an insulin-sensitizing adipokine, confers protection against type 2 diabetes. Although adiponectin is secreted exclusively from fat, contributions of visceral adipose tissue (VAT) versus subcutaneous adipose tissue (SAT) to adiponectin levels have not been fully understood. We aimed to examine correlations between changes in VAT and SAT volumes and changes in adiponectin levels.
The SAMMPRIS trial suggested that aggressive treatment was superior to endovascular stenting in patients with severe symptomatic intracranial atherosclerotic stenosis (ICAS) due to high complication rates in patients in the stenting group. Given that 12.2% patients failed aggressive medical therapy in the SAMMPRIS study, it is imperative to perform a multicentre prospective registry study of stenting for patients with ICAS in China. This study aims to evaluate the safety and efficacy of endovascular stenting for patients with symptomatic intracranial artery stenosis and poor collaterals in China and to identify the characteristics of the population that would benefit the most from endovascular stenting in Chinese patients.
Essential genes, those critical for the survival of an organism under certain conditions, play a significant role in pharmaceutics and synthetic biology. Knowledge of protein localization is invaluable for understanding their function as well as the interaction of different proteins. However, systematical examination of essential genes from the aspect of the localizations of proteins they encode has not been explored before. Here, a comprehensive protein localization analysis of essential genes in 27 prokaryotes including 24 bacteria, 2 mycoplasmas and 1 archaeon has been performed. Both statistical analysis of localization information in these genomes and GO (Gene Ontology) terms enriched in the essential genes show that proteins encoded by essential genes are enriched in internal location sites, while exist in cell envelope with a lower proportion compared with non-essential ones. Meanwhile, there are few essential proteins in the external subcellular location sites such as flagellum and fimbrium, and proteins encoded by non-essential genes tend to have diverse localizations. These results would provide further insights into the understanding of fundamental functions needed to support a cellular life and improve gene essentiality prediction by taking the protein localization and enriched GO terms into consideration.
Many plant viruses without 5' caps or 3' poly(A) tails contain 3' proximal, cap-independent translation enhancers (3'CITEs) that bind to ribosomal subunits or translation factors thought to assist in ribosome recruitment. Most 3'CITEs participate in a long-distance kissing-loop interaction with a 5' proximal hairpin to deliver ribosomal subunits to the 5' end for translation initiation. Pea Enation Mosaic Virus (PEMV) contains two adjacent 3'CITEs in the center of its 703-nucleotide 3' untranslated region (3'UTR), the ribosome-binding, kissing-loop T-shaped structure (kl-TSS) and eukaryotic translation initiation factor 4E-binding Panicum mosaic virus-like translation enhance (PTE). We now report that PEMV contains a third, independent 3'CITE located near the 3' terminus. This 3'CITE is composed of three hairpins and two pseudoknots, similar to the TSS 3'CITE of the carmovirus Turnip crinkle virus (TCV). As with the TCV TSS, the PEMV 3'TSS is predicted to fold into a T-shaped structure that binds to 80S ribosomes and 60S ribosomal subunits. A small hairpin (kl-H) upstream of the 3'TSS contains an apical loop capable of forming a kissing-loop interaction with a 5' proximal hairpin and is critical for the accumulation of full-length PEMV in protoplasts. Although the kl-H and 3'TSS are dispensable for the translation of a reporter construct containing the complete PEMV 3'UTR in vitro, deleting the normally required kl-TSS and PTE 3'CITEs and placing the kl-H and 3'TSS proximal to the reporter termination codon restores translation to near wild-type levels. This suggests that PEMV requires three 3'CITEs for proper translation and that additional translation enhancers may have been missed if reporter constructs were used in 3'CITE identification. Importance: The rapid life cycle of viruses requires efficient translation of viral-encoded proteins. Many plant RNA viruses contain 3' cap-independent translation enhancers (3'CITEs) to effectively compete with ongoing host translation. Since only single 3'CITEs have been identified for the vast majority of individual viruses, it is widely accepted that this is sufficient for a virus's translational needs. Pea Enation Mosaic Virus possesses a ribosome-binding 3'CITE that can connect to the 5' end through an RNA-RNA interaction and an adjacent eukaryotic translation initiation factor 4E-binding 3'CITE. We report the identification of a third 3'CITE that binds weakly to ribosomes and requires an upstream hairpin to form a bridge between the 3' and 5' ends. Although both ribosome-binding 3'CITEs are critical for virus accumulation in vivo, only the CITE closest to the termination codon of a reporter open reading frame is active, suggesting that artificial constructs used for 3'CITE identification may underestimate the number of CITEs that participate in translation.
The Mycobacterium tuberculosis (Mtb) proteasome has been established as a viable target for the development of anti-tuberculosis agents. In this study, the inhibitory activities of 100 plant-derived natural products on the Mtb proteasome were analyzed to identify novel potential inhibitors.
An efficient room-temperature palladium-catalyzed direct 2-arylation of benzoxazoles with aryl bromides is presented. The Pd(OAc)2/NiXantphos-based catalyst enables the introduction of various aryl and heteroaryl groups, via a deprotonative cross-coupling process (DCCP) in good to excellent yields (60-99%).
Compared with traditional semiconductor quantum dots (QDs) and organic dyes, photoluminescent carbon dots (CDs) are superior because of their high aqueous solubility, robust chemical inertness, facile functionalization, high resistance to photobleaching, low toxicity and good biocompatibility. Herein, a green, large-scale and high-output heterogeneous synthesis of N-doped CDs was developed by reacting calcium citrate and urea under microwave irradiation without the use of any capping agents. The obtained N-doped CDs with a uniform size distribution exhibit good aqueous solubility and yellowish-green fluorescence in the solid and aqueous states. These unique luminescence properties of N-doped CDs inspire new thoughts for applications as fluorescent powders, fluorescent inks, the growth of fluorescent bean sprouts, and fingerprint detection tools.
High-salt diet-induced cardiac hypertrophy and fibrosis are associated with increased reactive oxygen species production. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, exerts a protective role in cardiac remodeling that resulted from myocardial infarction, and peroxisome proliferation-activated receptors ? (PPAR-?) play an important role in metabolic myocardium remodeling. However, it remains unknown whether activation of TRPV1 could alleviate cardiac hypertrophy and fibrosis and the effect of cross-talk between TRPV1 and PPAR-? on suppressing high-salt diet-generated oxidative stress. In this study, high-salt diet-induced cardiac hypertrophy and fibrosis are characterized by significant enhancement of HW/BW%, LVEDD, and LVESD, decreased FS and EF, and increased collagen deposition. These alterations were associated with downregulation of PPAR-?, UCP2 expression, upregulation of iNOS production, and increased oxidative/nitrotyrosine stress. These adverse effects of long-term high-salt diet were attenuated by chronic treatment with capsaicin. However, this effect of capsaicin was absent in TRPV1(-/-) mice on a high-salt diet. Our finding suggests that chronic dietary capsaicin consumption attenuates long-term high-salt diet-induced cardiac hypertrophy and fibrosis. This benefit effect is likely to be caused by TRPV1 mediated upregulation of PPAR-? expression.
Lentivirus vectors encoding Wnt10b gene (LV-Wnt10b) or luciferase gene (LV-luc) were constructed to determine whether Wnt10b overexpression improved fracture healing in a rat atrophic non-union model. After fracture, rats were injected with LV-Wnt10b or LV-luc. Luciferase signals were clearly detected. At 2 and 4 weeks, LV-Wnt10b group had 107 and 98 % more proliferating cell nuclear antigen (PCNA) positive cells, respectively, and promoted expression of bone morphogenetic protein-2 (BMP-2) in the callus compared with controls. LV-Wnt10b injection significantly increased bone mass density and bone mineral content: 46-84 and 96-193 %, respectively, at the site of fracturein the LV-Wnt10b group compared with controls. At 8 weeks, fractured femora were healed in the LV-Wnt10b group compared with atrophic non-unions formed in controls. Thus, Wnt10b overexpression associated with lentiviral gene therapy is effective in healing atrophic non-unions in rats.
The mixed lineage leukemia 3 (MLL3), a member of the mixed lineage leukemia (MLL) family, has been reported to be mutated in multiple cancer types. However, its function in esophageal squamous cell carcinoma (ESCC) remains poorly understood. Here, we found that the expression of MLL3 was downregulated in ESCC tissues. Moreover, over-expression of MLL3 in ESCC cells inhibited cell proliferation and migration, while the knockdown expression of MLL3 promoted the tumorigenicity of ESCC cells. Mechanistically, MLL3 regulated the expression of multiple growth-related and migration-related genes. Taken together, our study suggested that downregulation of MLL3 was very important in the progression of ESCC.
Recently, in consideration of the rapidly increasing demand for meat products and the trend towards fast food consumption, the prepared boneless pork chop, as a new style of value-added product, is cut from pork loins and welcomed by consumers after marinating or further cooking. The effect of different tumbling marinade treatments (control group, CG; conventional static marinade, SM; vacuum continuous tumbling marinade, CT; vacuum intermittent tumbling marinade, IT) on the water status and protein properties of prepared pork chops was investigated.
EBV-encoded latent membrane protein 1 (EBV-LMP1) is an important oncogenic protein for nasopharyngeal carcinoma (NPC) and has been shown to engage a plethora of signaling pathways. Correspondingly, an LMP1-targeted DNAzyme was found to inhibit the growth of NPC cells both in vivo and in vitro by suppressing cell proliferation and inducing apoptosis. However, it remains unknown whether an LMP1-targeted DNAzyme would affect the vasculature of NPC. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been applied in the clinical trials of anti-angiogenic drugs for more than ten years, and Ktrans has been recommended as a primary endpoint. Therefore, the objective of the current study was to use DCE-MRI to longitudinally study the effect of an EBV-LMP1-targeted DNAzyme on the vasculature of patients with NPC.
The past 2 years have seen a number of basic and translational science advances in the quest for development of an effective HIV-1 vaccine. These advances include discovery of new envelope targets of potentially protective antibodies, demonstration that CD8(+) T cells can control HIV-1 infection, development of immunogens to overcome HIV-1 T-cell epitope diversity, identification of correlates of transmission risk in an HIV-1 efficacy trial, and mapping of the coevolution of HIV-1 founder envelope mutants in infected subjects with broad neutralizing antibodies, thereby defining broad neutralizing antibody developmental pathways. Despite these advances, a promising HIV-1 vaccine efficacy trial published in 2013 did not prevent infection, and the HIV-1 vaccine field is still years away from deployment of an effective vaccine. This review summarizes what some of the scientific advances have been, what roadblocks still remain, and what the most promising approaches are for progress in design of successful HIV-1 vaccine candidates.
BackgroundFitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses.ResultsThe T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, the fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations.ConclusionsOur results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.
Orf virus (ORFV) is a typical member of the genus Parapoxvirus. The parapoxvirus genome consists of highly variable terminal regions and relatively conserved central regions with a high G + C content. In our previous study, a novel ORFV strain, NA1/11, was isolated from northeastern China. To fully characterize this strain, we sequenced the entire genome of NA1/11 and conducted a comparative analysis using multiple parapoxviruses. The genomic sequence of NA1/11 was found to consist of 137,080 nucleotides with a G + C content of 63.6 %, but it did not contain the terminal hairpin sequence. Alignment of ORFs from NA1/11 with NZ2, IA82 and SA00 revealed several highly variable ORFs, while the most evident ones are ORFs 001, 103, 109-110, 116 and 132. An odd phenomenon in the region of ORFs 118-120 is that the non-coding fragments are almost as long as the coding fragments. By comparative analysis of inverted terminal repeats, we identified one repeat motif and a long conserved fragment. By comparing the ITRs of SA00 with those of three other ORFVs, more clues were obtained about the correlation between ITR sequence and host adaption. Comparison of the NA1/11 genome with the sequences of other strains of ORFV revealed highly variable regions, thus providing new insights into the genetic diversity of ORFV.
Compared with other insulin analogues, insulin detemir induces less weight gain. This study investigated whether this effect was achieved by influencing the hypothalamic appetite regulators neuropeptide Y (NPY) and galanin (GAL).
Endothelial dysfunction and hypertension is more common in individuals with diabetes than in the general population. This study was aimed to investigate the underlying mechanisms responsible for endothelial dysfunction of type 1 diabetic rats fed with high-salt diet.
The live morphology, infraciliature and morphogenesis of a new urostylid ciliate, Trichototaxis marina n. sp., collected from coastal water in Qingdao, China, were studied based on the observations of live and silver stained specimens. The new species is characterised as follows: body very flexible and contractile, slight to brick-reddish in colour due to irregularly-shaped, brick-red pigments; ca. 70 adoral membranelles; about 17 frontal cirri arranged in a bicorona; average 67 midventral pairs, the right base of each pair being conspicuously larger than the left base; five to seven transverse cirri; constantly two frontoterminal, one buccal and two pretransverse ventral cirri; two or three left marginal rows; right and innermost left marginal rows with 56-92 and 66-106 cirri, respectively; six bipolar dorsal kineties; more than 100 macronuclear nodules. The characteristic morphogenetic feature in T. marina is the development of the left marginal rows, that is, only one left marginal row is newly built the other one or two being retained from the parental cell. Phylogenetic analyses based on small subunit ribosomal gene sequence data reveal a close relationship of T. marina with members of family Pseudokeronopsidae.
Crizotinib was granted accelerated approval by the Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). To evaluate the efficacy and safety of crizotinib, we performed a meta-analysis of published clinical trials using the random effect model.
Self-assembly of functional compounds into a prerequisite nanostructure with desirable dimension and morphology by controlling and optimizing intermolecular interaction attracts an extensive research interest for chemists and material scientist. In this work, a new triple-decker sandwich-type lanthanide complex with phthalocyanine and redox-active Schiff base ligand including tetrathiafulvalene (TTF) units has been synthesized, and characterized by single crystal X-ray diffraction analysis, absorption spectra, electrochemical and magnetic measurements. Interestingly, the non-centrosymmetric target complex displays a bias dependent selective adsorption on a solid surface, as observed by scanning tunneling microscopy (STM) at the single molecule level. Density function theory (DFT) calculations are utilized to reveal the formation mechanism of the molecular assemblies, and show that such electrical field dependent selective adsorption is regulated by the interaction between the external electric field and intrinsic molecular properties. Our results suggest that this type of multi-decker complex involving TTF units shows intriguing multifunctional properties from the viewpoint of structure, electric and magnetic behaviors, and fabrication through self-assembly.
Hepatic ischemia-reperfusion injury (IRI), an innate immunity-driven inflammation response, occurs in multiple clinical settings including liver resection, transplantation, trauma, and shock. T-cell immunoglobulin and mucin (TIM)-4, the only TIM protein not expressed on T cells, is found on macrophages and dendritic cells. The regulatory function of macrophage TIM-4 in the engulfment of apoptotic/necrotic bodies in innate immunity-mediated disease states remains unknown. This study focuses on the putative role of TIM-4 signaling in a model of liver warm ischemia (90 minutes) and reperfusion. The ischemia insult triggered TIM-4 expression by stressed hepatocellular phosphatidylserine (PS) presentation, peaking at 6 hours of reperfusion, and coinciding with the maximal hepatocellular damage. TIM-4-deficient or wild-type WT mice treated with antagonistic TIM-4 monoclonal antibody (mAb) were resistant against liver IRI, evidenced by diminished serum alanine aminotransferase (sALT) levels and well-preserved hepatic architecture. Liver hepatoprotection rendered by TIM-4 deficiency was accompanied by diminished macrophage infiltration/chemoattraction, phagocytosis, and activation of Toll-like receptor (TLR)2/4/9-dependent signaling. Correlating with in vivo kinetics, the peak of TIM-4 induction in lipopolysaccharide (LPS)-activated bone marrow derived-macrophages (BMM) was detected in 6-hour cultures. To mimic liver IRI, we employed hydrogen peroxide-necrotic hepatocytes, which readily present PS. Indeed, necrotic hepatocytes were efficiently captured/engulfed by WT (TIM-4+) but not by TIM-4-deficient BMM. Finally, in a newly established model of liver IRI, adoptive transfer of WT but not TIM-4-deficient BMM readily recreated local inflammation response/hepatocellular damage in the CD11b-DTR mouse system. Conclusion: These findings document the importance of macrophage-specific TIM-4 activation in the mechanism of hepatic IRI. Macrophage TIM-4 may represent a therapeutic target to minimize innate inflammatory responses in IR-stressed organs. (Hepatology 2014).
Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Here, we study the B cell response in a bnAb-producing individual and report cooperation between two B cell lineages to drive bnAb development. We isolated a virus-neutralizing antibody lineage that targeted an envelope region (loop D) and selected virus escape mutants that resulted in both enhanced bnAb lineage envelope binding and escape mutant neutralization-traits associated with increased B cell antigen drive. Thus, in this individual, two B cell lineages cooperated to induce the development of bnAbs. Design of vaccine immunogens that simultaneously drive both helper and broadly neutralizing B cell lineages may be important for vaccine-induced recapitulation of events that transpire during the maturation of neutralizing antibodies in HIV-1-infected individuals.
Three trachelocercid ciliates, Trachelocerca orientalis spec. nov., Prototrachelocerca fasciolata (Sauerbrey, 1928) Foissner, 1996 and Tracheloraphis huangi Xu et al., 2011, isolated from marine coastal habitats at Qingdao, China, were taxonomically studied using observation in vivo and silver staining methods. The new species T. orientalis spec. nov. can be recognized by the combination of its size (600-1,200 ?m in vivo), 15-21 somatic kineties and about 13 groups of macronuclear nodules forming a strand and the colorless globular cortical granules. Together with the sequence data of the small subunit ribosomal RNA (SSU rRNA) gene, the information of a new isolate of P. fasciolata and three populations of T. huangi is also documented based on the present work. According to the molecular data, the phylogeny of three species is estimated and the analyses show that they are all found within the trachelocercid assemblage though T. huangi does not cluster with its congeners but with Trachelocerca species. Nonetheless, the monophyly of Trachelocerca is not rejected by the approximately unbiased test (p = 0.345 > 0.05), while that of Tracheloraphis is not confirmed (p = 0.0002 < 0.05).
The conserved protein Rv3705c from Mycobacterium tuberculosis has been cloned, expressed, purified and crystallized by the sitting-drop vapour-diffusion method using PEG 3350 as a precipitant. The Rv3705c crystals exhibited space group P6122 or P6522, with unit-cell parameters a = b = 198.0, c = 364.1?Å, ? = ? = 90, ? = 120°, and diffracted to a resolution of 3.3?Å.
In the present work, a highly sensitive and specific fluorescent biosensor for blood glucose monitoring is developed based on hemin-functionalized graphene quantum dots (GQDs) and glucose oxidase (GOx) system. The GQDs which are simply prepared by pyrolyzing citric acid exhibit strong fluorescence and good water-solubility. Due to the noncovalent assembly between hemin and GQDs, the addition of hemin can make hydrogen peroxide (H2O2) to destroy the passivated surface of GQDs, leading to significant fluorescence quenching of GQDs. Based on this effect, a novel fluorescent platform is proposed for the sensing of glucose. Under the optimized conditions, the linear range of glucose is from 9 to 300?M, and the limit of detection is 0.1?M. As unique properties of GQDs, the proposed biosensor is green, simple, cost-efficient, and it is successfully applied to the determination of glucose in human serum. In addition, the proposed method provides a new pathway to further design the biosensors based on the assembly of GQDs with hemin for detection of biomolecules.
Purpose. The outcome of recanalization in patients with chronic symptomatic intracranial vertebral artery (ICVA) total occlusion is poor. This paper reports the technical feasibility and long-term outcome of ICVA stenting in patients with chronic symptomatic total occlusion. Methods. Retrospective review of our prospectively maintained intracranial intervention database to identify patients with symptomatic total occlusion of ICVA with revascularization attempted >1 month after index ischemic event. Results. Eight patients (mean age 58 years) were identified. One had stroke and 7 had recurrent transient ischemic attacks. Four had bilateral ICVA total occlusion and 4 had unilateral ICVA total occlusion with severe stenosis contralaterally. Seven of 8 patients underwent endovascular recanalization, which was achieved in 6. Periprocedural complications included cerebellum hemorrhage, arterial dissection, perforation, and subacute in-stent thrombosis which occurred in 3 patients. One patient died of cerebellum hemorrhage. The other patients improved clinically after endovascular therapy. Conclusions. Stent-supported recanalization of ICVA total occlusion is technically feasible, and may become a viable treatment option in selected patients.
MicroRNAs (miRNAs) are a conserved class of small, endogenous, non protein-coding RNA molecules that are capable of regulating gene expression at post-transcriptional levels and are involved in diverse cellular processes, including cancer pathogenesis. It has previously been reported that miRNA-96 (miR-96) is overexpressed in human colorectal cancer (CRC). However, the underlying mechanism of miR-96 regulation in CRC remains to be elucidated. In the present study, miR-96 was confirmed to be upregulated in CRC tissues by reverse transcription quantitative polymerase chain reaction. MTT assay, colony formation assay and cell cycle analysis revealed that miR-96 overexpression led to increased tumor cell viability, colony formation ability and cell cycle progression. By contrast, inhibition of miR-96 resulted in the suppression of cell proliferation. It was also demonstrated that miR-96 reduced the messenger RNA and protein expression levels of tumor protein p53 inducible nuclear protein 1 (TP53INP1), forkhead box protein O1 (FOXO1) and FOXO3a, which are closely associated with cell proliferation. A luciferase reporter assay indicated that miR-96 inhibited luciferase intensity controlled by the 3'UTRs of TP53INP1, FOXO1 and FOXO3a. In conclusion, the results of the present study demonstrated that miR-96 contributed to CRC cell growth and that TP53INP1, FOXO1 and FOXO3a were direct targets of miR-96, suggesting that miR-96 may have the potential to be used in the development of miRNA?based therapies for CRC patients.
Triple-negative breast cancer (TNBC) has a poorer prognosis compared with other sub-groups. In the current study, survival associated with locoregional treatment of females with TNBC was investigated. Specifically, 468 patients with stage I-III TNBC treated between 2002 and 2009 were identified. Data included patient and tumor characteristics, treatment received and survival. Data were compared using ?(2) and Fisher's exact tests, as well as MANOVA. Kaplan-Meier curves were generated. The study cohort had a mean age of 54±13 years old with a mean follow-up period of 51±21 months. Of 468 patients, 249 (53%) underwent lumpectomy, 63 (14%) underwent simple mastectomy (SM) and 156 (33%) underwent modified radical mastectomy (MRM). Overall, 263 (56%) received adjuvant radiation, including 178/249 (71%) following lumpectomy, 13/63 (21%) following SM and 72/156 (46%) following MRM (P<0.0001). Following control for potential confounders in univariate tests, adjuvant radiation was associated with improved overall survival in the total cohort (HR, 0.46; 95% CI, 0.31-0.68; P=0.0001). When comparing survival by surgical type, receipt of adjuvant radiation significantly improved survival in the lumpectomy group (HR, 0.30; 95% CI, 0.16-0.58; P=0.0004), but was not associated with improved survival in the SM group (HR, 0.38; 95% CI, 0.05-3.04; P=0.36) or in the MRM group (HR, 0.79; 95% CI, 0.46-1.34; P=0.38). The survival benefit of adjuvant radiation in these TNBC patients is attributed to those undergoing breast-conserving therapy. There was no benefit in either mastectomy group. These data warrant validation from prospective trials, in order to develop tailored locoregional treatment for patients with TNBC.
As the female reproductive part of a flower, the pistil consists of the ovary, style, and stigma, and is a critical organ for the process from pollen recognition to fertilization and seed formation. Previous studies on pollen-pistil interaction mainly focused on gene expression changes with comparative transcriptomics or proteomics method. However, studies on protein PTMs are still lacking. Here we report a phosphoproteomic study on mature pistil of rice. Using IMAC enrichment, hydrophilic interaction chromatography fraction and high-accuracy MS instrument (TripleTOF 5600), 2347 of high-confidence (Ascore ? 19, p ? 0.01), phosphorylation sites corresponding to 1588 phosphoproteins were identified. Among them, 1369 phosphorylation sites within 654 phosphoproteins were newly identified; 41 serine phosphorylation motifs, which belong to three groups: proline-directed, basophilic, and acidic motifs were identified after analysis by motif-X. Two hundred and one genes whose phosphopeptides were identified here showed tissue-specific expression in pistil based on information mining of previous microarray data. All MS data have been deposited in the ProteomeXchange with identifier PXD000923 (http://proteomecentral.proteomexchange.org/dataset/PXD000923). This study will help us to understand pistil development and pollination on the posttranslational level.
Hypertension leads to cardiac hypertrophy as an adaptive response to increased workload. While initial development of hypertrophy is compensatory when contractile function is maintained, persistent stress on heart leads to deteriorated cardiac function and onset of heart failure. Mitochondrial dysfunction develops in the failing heart; however, whether it presents in compensatory cardiac hypertrophy is controversial.
L-Glutamate is a major oxidative fuel for the small intestine. However, few studies have demonstrated the effect of L-glutamate on the intestinal architecture and signaling of amino acids in the small intestine. The aim of this study was to investigate the effects of dietary L-glutamate supplementation on the intestinal architecture and expressions of jejunal mucosa amino acid receptors and transporters in weaning piglets. A total of 120 weaning piglets aged 35±1 days with an average body weight at 8.91±0.45 kg were randomly allocated to two treatments with six replicates of ten piglets each, fed with diets containing 1.21% alanine, or 2% L-glutamate. L-Glutamate supplementation increased the activity of glutamate oxaloacetate transaminase (GOT) in the jejunal mucosa. Also, the mRNA expression level of jejunal mucosa glutamine synthetase (GS) was increased by L-glutamate supplementation. The height of villi in duodenal and jejunal segments, and the relative mRNA expression of occludin and zonula occludens protein-1 (ZO-1) in jejunal mucosa were increased by dietary L-glutamate supplementation. L-Glutamate supplementation increased plasma concentrations of glutamate, arginine, histidine, isoleucine, leucine, methionine, phenylalanine and threonine. L-Glutamate supplementation also increased the relative mRNA expression of the jejunal mucosa Ca2+-sensing receptor (CaR), metabotropic glutamate receptor 1 (mGluR1) and metabotropic glutamate receptor 4 (mGluR4), and neutral amino acid transporter B0-like (SLC1A5) in the jejunal mucosa. These findings suggest that dietary addition of 2% L-glutamate improves the intestinal integrity and influences the expression of amino acid receptors and transporters in the jejunum of weaning, which is beneficial for the improvement of jejunal nutrients for digestion and absorption.
Seed dormancy is a mechanism underlying the inability of viable seeds to germinate under optimal environmental conditions. To achieve rapid and uniform germination, wheat and other cereal crops have been selected against dormancy. As a result, most of the modern commercial cultivars have low level of seed dormancy and are susceptible to preharvest sprouting when wet and moist conditions occur prior to harvest. As it causes substantial loss in grain yield and quality, preharvest sprouting is an ever-present major constraint to the production of wheat. The significance of the problem emphasizes the need to incorporate an intermediate level of dormancy into elite wheat cultivars, and this requires detailed dissection of the mechanisms underlying the regulation of seed dormancy and preharvest sprouting. Seed dormancy research in wheat often involves after-ripening, a period of dry storage during which seeds lose dormancy, or comparative analysis of seeds derived from dormant and non-dormant cultivars. The increasing development in wheat genomic resources along with the application of transcriptomics, proteomics, and metabolomics approaches in studying wheat seed dormancy have extended our knowledge of the mechanisms acting at transcriptional and post-transcriptional levels. Recent progresses indicate that some of the molecular mechanisms are associated with hormonal pathways, epigenetic regulations, targeted oxidative modifications of seed mRNAs and proteins, redox regulation of seed protein thiols, and modulation of translational activities. Given that preharvest sprouting is closely associated with seed dormancy, these findings will significantly contribute to the designing of efficient strategies for breeding preharvest sprouting tolerant wheat.
DNA replication is one of the most basic processes in all three domains of cellular life. With the advent of the post-genomic era, the increasing number of complete archaeal genomes has created an opportunity for exploration of the molecular mechanisms for initiating cellular DNA replication by in vivo experiments as well as in silico analysis. However, the location of replication origins (oriCs) in many sequenced archaeal genomes remains unknown. We present a web-based tool Ori-Finder 2 to predict oriCs in the archaeal genomes automatically, based on the integrated method comprising the analysis of base composition asymmetry using the Z-curve method, the distribution of origin recognition boxes identified by FIMO tool, and the occurrence of genes frequently close to oriCs. The web server is also able to analyze the unannotated genome sequences by integrating with gene prediction pipelines and BLAST software for gene identification and function annotation. The result of the predicted oriCs is displayed as an HTML table, which offers an intuitive way to browse the result in graphical and tabular form. The software presented here is accurate for the genomes with single oriC, but it does not necessarily find all the origins of replication for the genomes with multiple oriCs. Ori-Finder 2 aims to become a useful platform for the identification and analysis of oriCs in the archaeal genomes, which would provide insight into the replication mechanisms in archaea. The web server is freely available at http://tubic.tju.edu.cn/Ori-Finder2/.
Artificial recombinants can be generated during PCR when more than two genetically distinct templates coexist in a single PCR reaction. These recombinant amplicons can lead to the false interpretation of genetic diversity and incorrect identification of biological phenotypes that do not exist in vivo. We investigated how recombination between 2 or 35 genetically distinct HIV-1 genomes was affected by different PCR conditions using the parallel allele-specific sequencing (PASS) assay and the next generation sequencing method. In a standard PCR condition, about 40% of amplicons in a PCR reaction were recombinants. The high recombination frequency could be significantly reduced if the number of amplicons in a PCR reaction was below a threshold of 10(13)-10(14) using low thermal cycles, fewer input templates, and longer extension time. Heteroduplexes (each DNA strand from a distinct template) were present at a large proportion in the PCR products when more thermal cycles, more templates, and shorter extension time were used. Importantly, the majority of recombinants were identified in heteroduplexes, indicating that the recombinants were mainly generated through heteroduplexes. Since prematurely terminated extension fragments can form heteroduplexes by annealing to different templates during PCR amplification, recombination has a better chance to occur with samples containing different genomes when the number of amplicons accumulate over the threshold. New technologies are warranted to accurately characterize complex quasispecies gene populations.
Human populations have experienced dramatic growth since the Neolithic revolution. Recent studies that sequenced a very large number of individuals observed an extreme excess of rare variants and provided clear evidence of recent rapid growth in effective population size, although estimates have varied greatly among studies. All these studies were based on protein-coding genes, in which variants are also impacted by natural selection. In this study, we introduce targeted sequencing data for studying recent human history with minimal confounding by natural selection. We sequenced loci far from genes that meet a wide array of additional criteria such that mutations in these loci are putatively neutral. As population structure also skews allele frequencies, we sequenced 500 individuals of relatively homogeneous ancestry by first analyzing the population structure of 9,716 European Americans. We used very high coverage sequencing to reliably call rare variants and fit an extensive array of models of recent European demographic history to the site frequency spectrum. The best-fit model estimates ?3.4% growth per generation during the last ?140 generations, resulting in a population size increase of two orders of magnitude. This model fits the data very well, largely due to our observation that assumptions of more ancient demography can impact estimates of recent growth. This observation and results also shed light on the discrepancy in demographic estimates among recent studies.
Clinical trials on early stage Alzheimers disease (AD) are reaching a bottleneck because none of the current disease markers changes appreciably early in the disease process and therefore a huge sample is required to adequately power such trials. We propose a method to combine multiple markers so that the longitudinal rate of progression can be improved. The criterion is to maximize the probability that the combined marker will be decreased over time (assuming a negative mean slope for each marker). We propose estimates to the weights of markers in the optimum combination and a confidence interval estimate to the combined rate of progression through the maximum likelihood estimates and a bootstrap procedure. We conduct simulations to assess the performance of our estimates and compare our approach with the first principal component from a principal component analysis. The proposed method is applied to a real world sample of individuals with preclinical AD to combine measures from two cognitive domains. The combined cognitive marker is finally used to design future clinical trials on preclinical AD, demonstrating a significant improvement in reducing the sample sizes needed to power such trials when compared with individual markers alone.
Two Dexiotricha species (D. elliptica and D. cf. granulosa) isolated from soil in northwest of Riyadh, Saudi Arabia and freshwater in Shanghai, eastern China, respectively, were investigated using standard methods. The species Loxocephalus ellipticus Kahl, 1931 was combined to the genus Dexiotricha and was characterized mainly by having constantly 16 somatic kineties, three post oral kineties with the middle one shortened, contractile vacuole sub-caudally located with excretory pore near posterior end of somatic kinety 2 and single caudal cilia. An organism of Dexiotricha granulosa-like having a sub-caudally located contractile vacuole and fewer somatic kineties was designated as D. cf. granulosa. The small subunit rRNA gene (SSU-rDNA) sequences of these two species were characterized and their phylogenetic position based on SSU-rDNA sequences were revealed by means of Bayesian inference and Maximum likelihood. Phylogenetic analyses confirmed Dexiotricha as a monophyletic genus and its assignment to the order Loxocephalida. However, its family assignment is still unsupported.
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