Ab initio computations are carried out to explore the structure and stability of FNgEF3 and FNgEF (E = Sn, Pb; Ng = Kr-Rn) compounds. They are the first reported systems to possess Ng-Sn and Ng-Pb bonds. Except for FKrEF3, the dissociations of FNgSnF3 and FNgEF, producing Ng and SnF4 or EF2, are only exergonic in nature at room temperature, whereas FNgPbF3 has a thermochemical instability with respect to two two-body dissociation channels. However, they are kinetically stable, having positive activation barriers (ranging from 2.2 to 49.9 kcal mol(-1)) with respect to those dissociations. The kinetic stability gradually improves in moving from the Kr to Rn analogues. The remaining possible dissociation channels for these compounds are found to be endergonic in nature. The nature of the bonding is analyzed by natural bond order, electron density, and energy decomposition analyses. Particularly, the natural population analysis reveals that they are best represented as F(-)(NgEF3)(+) and F(-)(NgEF)(+). All the Xe/Rn-E bonds in FNgEF3 and FNgEF are covalent in nature.
A taxonomic study was carried out on strain YN3T, which was isolated from a seaweed sample on the coast of Weihai, China. The bacterium was Gram-stain-negative, rod-shaped, and could grow at pH 5.0-10.0 and 4-32 °C in presence of 0-9.0 % (w/v) NaCl. Strain YN3T was positive for hydrolysis of polysaccharides, such as agar, starch and xylan. The predominant respiratory quinone was ubiquinone-8. The major fatty acids were C16:1?7c and/or iso-C15:0 2-OH, C16:0 and C18:1?7c. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine, and two unidentified glycolipids. The genomic DNA G + C content was 49.4 mol %. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain YN3T should be assigned to the genus Gilvimarinus. 'Gilvimarinus agarilyticus' KCTC 23325T and Gilvimarinus chinensis QM42T had the closest phylogenetic relationship with strain YN3T, and showed 97.9 % and 95.8 % sequence similarities, respectively. On the basis of phenotypic, chemotaxonomic and genotypic data and DNA-DNA hybridization studies, we propose that strain YN3T represents a novel species of the genus Gilvimarinus, for which the name Gilvimarinus polysaccharolyticus sp. nov. is proposed. The type strain is YN3T (= KCTC 32438T = JCM 19198T). An emended description of the genus Gilvimarinus is also presented.
A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity. Using fluorescently labeled CD47 antibody (anti-CD47) as molecular imaging agent, we demonstrated consistent identification of bladder cancer with clinical grade fluorescence imaging systems, confocal endomicroscopy, and blue light cystoscopy in fresh surgically removed human bladders. With blue light cystoscopy, the sensitivity and specificity for CD47-targeted imaging were 82.9 and 90.5%, respectively. We detected variants of bladder cancers, which are diagnostic challenges, including carcinoma in situ, residual carcinoma in tumor resection bed, recurrent carcinoma following prior intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), and excluded cancer from benign but suspicious-appearing mucosa. CD47-targeted molecular imaging could improve diagnosis and resection thoroughness for bladder cancer.
The widespread planting of genetically engineered cotton producing the Cry1Ac toxin has led to significantly reduced pesticide applications since 1997. However, consequently, the number of green mirid bug (GMB), Apolygus lucorum (Meyer-Dür) has increased. So far the GMB, instead of the cotton bollworm Helicoverpa armigera (Hübner), has become the major pest in transgenic Bt cotton field and influenced cotton yield. Disproportionately, only a few studies on GMB at a molecular level have been reported. Libraries from both third instar nymph and adult were sequenced using Illumina technology, producing more than 106 million short reads and assembled into 63 029 unigenes of mean length 597 nt and N50 813 nt, ranging from 300 nt to 9771 nt. BLASTx analysis against Nr, Swissprot, GO and COG was performed to annotate these unigenes. As a result, 26 478 unigenes (42.01%) matched to known proteins and 107 immune-related, 320 digestive-related and 53 metamorphosis-related genes were detected in these annotated unigenes. Additionally, we profiled gene expression using mapping based differentially expressed genes (DEGs) strategy between the two developmental stages: nymph and adult. The results demonstrated that thousands of genes were significantly differentially expressed at different developmental stages. The transcriptome and gene expression data provided comprehensive and global gene resources of GMB. This transcriptome would improve our understanding of the molecular mechanisms of various underlying biological characteristics, including development, digestion and immunity in GMB. Therefore, these findings could help elucidate the intrinsic factors of the GMB resurgence, offering novel pest management targets for future transgenic cotton breeding. This article is protected by copyright. All rights reserved.
With the help of the ligand-oriented method, we have successfully embedded independent copper-based units into the indium-organic framework system for the first time, in which the Cu4I4 clusters and In3O(CO2)6 clusters coexist. This heterometallic cluster-based framework has a large porosity with extra-open channels along the c-axis, and its sorption capacity has also been investigated.
We summarize the most recent research of the Georgia Tech Terabit Optical Networking Consortium and the state-of-the-art in fiber telecommunications. These results comprise high-capacity single-mode fiber systems with digital coherent receivers and shorter-reach multimode fiber links with vertical cavity surface emitting lasers. We strongly emphasize the capabilities that sophisticated digital signal processing and electronics add to these fiber-based data transport links.
A novel facultatively anaerobic, Gram-negative bacterium, designated strain HT7-2T, was isolated from Ulva prolifera collected from the intertidal zone of Qingdao sea area, China, during its bloom. Cells were rod-shaped (1.9-3.5 × 0.4-0.6 ?m), non-sporulating, and motile by gliding. Strain HT7-2T was able to grow at 4-50 °C (optimum 40-42 °C), pH 5.5-8.5 (optimum pH 7.0), 0-8% (w/v) NaCl (optimum 2-3%) and 0.5-10% (w/v) sea salts (optimum 2.5%). The genomic DNA G+C content was 38.8 mol%. The phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HT7-2T belonged to the genus Maribacter with sequence similarity values of 94.5-96.6%, and was most closely related to Maribacter aestuarii GY20T (96.6%). Chemotaxonomic analysis showed that the main isoprenoid quinone was MK-6 and the major fatty acids were iso-C15:0 and unknown ECL 13.565. The polar lipids of strain HT7-2T consisted of one phosphatidylethanolamine (PE), four unidentified lipids (L1~4) and one unidentified aminolipid (AL). On the basis of the phenotypic, phylogenetic and chemotaxonomic characteristics, strain HT7-2T (= CGMCC 1.12207T = JCM 18466T) is concluded to represent a novel species of the genus Maribacter, for which the name Maribacter thermophilus sp. nov. is proposed. An emended description of the genus Maribacter is also proposed.
Fluorescent-magnetic iron oxide coated fluoridated HAp/Ln(3+) (Ln = Eu or Tb) nanocomposites were prepared. After transforming hydrophobic fluoridated HAp/Ln(3+) nanorods into hydrophilic ones, iron oxide particles were coated on their surface via thermal decomposition of Fe(acac)3. Fluorescent-magnetic nanocomposites developed in this study demonstrate excellent fluorescent-magnetic properties and prominent biocompatibility.
In order to study the effect of conservation tillage on soil CO2 and N2O emissions in the following crop-growing season, field experiments were conducted in the winter wheat-growing season. Four treatments were conventional tillage (T), no-tillage with no straw cover (NT), no-tillage with straw cover (NTS), and conventional tillage with straw incorporation (TS), respectively. The CO2 and N2O fluxes were measured using a static chamber-gas chromatograph technique. The results showed that in the following winter wheat-growing season, conservation tillage did not change the seasonal pattern of CO2 and N2O emission fluxes from soil, and had no significant effect on crop biomass. Conservation tillage significantly reduced the accumulative amount of CO2 and N2O. Compared with the T treatment, the accumulative amount of CO2 under TS, NT, and NTS treatments were reduced by 5.95% (P = 0.132), 12.94% (P = 0.007), and 13.91% (P = 0.004), respectively, and the accumulative amount of N2O were significantly reduced by 31.23% (P = 0.000), 61.29% (P = 0.000), and 33.08% (P = 0.000), respectively. Our findings suggest that conservation tillage significantly reduced CO2 and N2O emission from soil in the following winter wheat-growing season.
Halomonas sp. FS-N4 is a bacterium, which can grow in the medium Marine Broth 2216 with 5M initial hydrogen peroxide concentration, shows a strong oxidation resistance, and the crude enzyme activity can reach as high as 13.33katal/mg. We reported the draft genome sequence of H. sp. FS-N4, showing that it contains 3434 protein-coding genes, including the genes putatively involved in the response to the oxidative stress, among which a phytochrome-like gene might be a key point to survive in the environment with high concentration of hydrogen peroxide and exhibit high catalase activity.
This study aims to investigate the feasibility of a novel lumbar approach named extraforaminal lumbar interbody fusion (ELIF), a newly emerging minimally invasive technique for treating degenerative lumbar disorders, using a digitalized simulation and a cadaveric study.
The immune compromised patients after treatment of oral cancer may have a chance of infection by drug-resistant opportunistic microbes. We investigated the occurrence of opportunistic microorganisms in aged individuals receiving follow-up examinations after treatment of oral cancer in China.
The stability of noble gas (Ng)-bound SiH3 (+) clusters is explored by ab initio computations. Owing to a high positive charge (+1.53 e(-) ), the Si center of SiH3 (+) can bind two Ng atoms. However, the Si?Ng dissociation energy for the first Ng atom is considerably larger than that for the second one. As we go down group 18, the dissociation energy gradually increases, and the largest value is observed for the case of Rn. For NgSiH3 (+) clusters, the Ar-Rn dissociation processes are endergonic at room temperature. For He and Ne, a much lower temperature is required for it to be viable. The formation of Ng2 SiH3 (+) clusters is also feasible, particularly for the heavier members and at low temperature. To shed light on the nature of Si?Ng bonding, natural population analysis, Wiberg bond indices computations, electron-density analysis, and energy-decomposition analysis were performed. Electron transfer from the Ng centers to the electropositive Si center occurs only to a small extent for the lighter Ng atoms and to a somewhat greater extent for the heavier analogues. The Si?Xe/Rn bonds can be termed covalent bonds, whereas the Si?He/Ne bonds are noncovalent. The Si?Ar/Kr bonds possess some degree of covalent character, as they are borderline cases. Contributions from polarization and charge transfer and exchange are key terms in forming Si?Ng bonds. We also studied the effect of substituting the H atoms of SiH3 (+) by halide groups (?X) on the Ng binding ability. SiF3 (+) showed enhanced Ng binding ability, whereas SiCl3 (+) and SiBr3 (+) showed a lower ability to bind Ng than SiH3 (+) . A compromise originates from the dual play of the inductive effect of the ?X groups and X?Si ? backbonding (pz -pz interaction).
BackgroundArterial calcification is an important pathological change of diabetic vascular complication. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) plays an important cytopathologic role in arterial calcification. The glucagon-like peptide-1 receptor agonists (GLP-1RA), a novel type of antidiabetic drugs, exert cardioprotective effects through the GLP-1 receptor (GLP-1R). However, the question of whether or not GLP-1RA regulates osteoblastic differentiation and calcification of VSMCs has not been answered, and the associated molecular mechanisms have not been examined.MethodsCalcifying VSMCs (CVSMCs) were isolated from cultured human arterial smooth muscle cells through limiting dilution and cloning. The extent of matrix mineralization was measured by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot. Gene expression of receptor activator of nuclear factor-¿B ligand (RANKL) was silenced by small interference RAN (siRNA).ResultsExenatide, an agonist of GLP-1 receptor, attenuated ß-glycerol phosphate (ß-GP) induced osteoblastic differentiation and calcification of human CVSMCs in a dose- and time-dependent manner. RANKL siRNA also inhibited osteoblastic differentiation and calcification. Exenatide decreased the expression of RANKL in a dose-dependent manner. 1,25 vitD3 (an activator of RANKL) upregulated, whereas BAY11-7082 (an inhibitor of NF-¿B) downregulated RANKL, alkaline phosphatase (ALP), osteocalcin (OC), and core binding factor ¿1 (Runx2) protein levels and reduced mineralization in human CVSMCs. Exenatide decreased p-NF-¿B and increased p-AMPK¿ levels in human CVSMCs 48 h after treatment. Significant decrease in p-NF-¿B (p-Ser276, p-Ser536) level was observed in cells treated with exenatide or exenatide¿+¿BAY11-7082.ConclusionGLP-1RA exenatide can inhibit human VSMCs calcification through NF-¿B/ RANKL signaling.
The objective of this study was to analyze the expression levels of IL-8 in serum and liver tissues from patients with chronic hepatitis B (CHB) infection and to investigate whether IL-8 may antagonize interferon-alpha (IFN-?) antiviral activity against HBV. IL-8 expression in serum was determined by enzyme linked immunosorbent assay (ELISA), and fluorescence-based quantitative real-time PCR (RT-qPCR) was used to measure IL-8 mRNA in peripheral blood mononuclear cells (PBMCs) in patients with CHB. IL-8 protein expression was detected in liver biopsy tissues by immunohistochemistry. In addition, the differences in serum IL-8 and PBMCs mRNA levels were also observed in patients with different anti-viral responses to IFN-?. Compared to normal controls, serum IL-8 protein and mRNA levels were increased in CHB patients, IL-8 levels were positively correlated with the severity of liver inflammation/fibrosis. Moreover, serum IL-8 protein and mRNA levels were positively correlated with serum alanine aminotransferase (ALT) level and negatively correlated with serum prealbumin (PA) level. IL-8 expression was mainly located in portal area of liver tissues and was increased with the severity of liver inflammation and fibrosis stage. The expression serum and mRNA levels of IL-8 in the CHB patients with a complete response to IFN-? are significantly lower than that of the patients with non-response to IFN-? treatment. It is suggested that IL-8 might play important roles in the pathogenesis of CHB. Moreover, interferon resistance may be related to the up-regulation of IL-8 expression in the patients did not respond to IFN-? treatment.
L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia and amyloid-beta (Abeta)-induced animal models by inhibiting oxidative injury, neuronal apoptosis and glial activation, regulating amyloid-beta protein precursor (AbetaPP) processing and reducing Abeta generation. The objective of this study was to investigate the effects of L-3-n-butylphthalide on memory impairment and the expression of brain neurotrophic derived factor (BNDF), kinaseB (TrkB), phosphatidylinositol 3 kinase (PI3K) and Akt in APP/PS1 double transgenic mouse models. APP/PS1 double transgenic mice were administered 30 mg/kg•d L-NBP and 10 mg/kg•d L-NBP for one month. The learning and memory ability were studied using the water maze test. Protein expression and transcript levels of genes in the mice hippocampus were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. The results demonstrated that both 30 mg/kg•d L-NBP and 10 mg/kg•d L-NBP doses of L-NBP significantly increased memory capability and the expression of hippocampal BDNF/TrkB/PI3K/AKT in mice The results suggested that L-NBP treatment may reverse memory impairment in APP/PS1 transgenic mice, and BDNF/TrkB/PI3K/AKT, may be involved in this process.
In normal lung, the predominant cytoplasmic carbonic anhydrase (CA) isozyme, CAII, is highly expressed in amine and peptide producing pulmonary neuroendocrine cells (PNEC) where its role involves CO2 sensing. Here we report robust cytoplasmic expression of CAII by immunohistochemistry in the tumor cells of different native neuroendocrine tumor (NET) types including typical and atypical carcinoids and small cell lung carcinomas, and in NET and non-NET tumor cell lines. Since, in both PNEC and related NETs the hypercapnia - induced secretion of bioactive serotonin (5-HT) is mediated by CAII, we investigated the role of CAII in the biological behavior of a carcinoid cell line H727 and the type II cell derived A549 using both in vitro clonogenicity and in vivo xenograft model. We show that shRNA mediated downregulation of CAII resulted in significant reduction in clonogenicity of H727 and A549 cells in vitro, and marked suppression of tumor growth in vivo. CAII-shRNA cell derived xenografts showed significantly reduced mitosis (phosphohistone H3 marker), proliferation (Ki67 marker) and significantly increased apoptosis by TUNEL assay. Using an apoptosis gene array we found no association with caspases 3 and 8 but with a novel association of CAII mediated apoptosis with specific mitochondrial apoptosis associated proteins. Furthermore, these xenografts showed a significantly reduced vascularization (CD31marker). Thus CAII may play a critical role in NET lung tumor growth, angiogenesis and survival, possibly via 5-HT, known to drive autocrine tumor growth. Thus CAII is a potential therapeutic target for the difficult to treat lung NETs.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be inversely related to Parkinson's disease and Alzheimer's disease, both of which may share common mechanisms with essential tremor (ET). Use of these medications has not been studied in ET cases vs. controls.
Inspired by their geometrical perfection, intrinsic beauty, and particular properties of polyhedranes, a series of carbo-cages is proposed in silico via density functional theory computations. The insertion of alkynyl units into the C-C bonds of polyhedranes results in a drastic lowering of the structural strain. The induced magnetic field shows a significant delocalization around the three-membered rings. For larger rings, the response is paratropic or close to zero, suggesting a nonaromatic behavior. In the carbo-counterparts, the values of the magnetic response are shifted with respect to their parent compounds, but the aromatic/nonaromatic character remains unaltered. Finally, Born-Oppenheimer molecular dynamics simulations at 900 K do not show any drastic structural changes up to 10 ps. In the particular case of a carbo-prismane, no structural change is perceived until 2400 K. Therefore, although carbo-cages have enthalpies of formation 1 order of magnitude higher than those of their parent compounds, their future preparation and isolation should not be discarded, because the systems are kinetically stable, explaining why the similar systems like carbo-cubane have already been synthesized.
A novel bacterial strain, NH131(T), was isolated from deep-sea sediment of South China Sea. Cells were strictly aerobic, Gram-stain negative, short rod-shaped and motile with a single lateral flagellum. Strain NH131(T) grew optimally at pH 6.5-7.0 and 25-30 °C. 16S rRNA gene sequence analysis revealed that strain NH131(T) belonged to the genus Devosia, sharing the highest sequence similarity with the type strain, Devosia geojensis BD-c194(T) (96.2%). The predominant fatty acids were C(18?:?1)?7c, 11-methyl C(18?:?1)?7c, C(18?:?0) and C(16?:?0). Ubiquinone 10 was the predominant ubiquinone. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phospholipid, three glycolipids and two unknown lipids. The DNA G+C content of strain NH131(T) was 63.0 mol%. On the basis of the results of polyphasic identification, it is suggested that strain NH131(T) represents a novel species of the genus Devosia for which the name Devosia pacifica sp. nov. is proposed. The type strain is NH131(T) (?=?JCM 19305(T)?=?KCTC 32437(T)).
A quasi-planar member of the so-called 'Wankel motor' family, B18(2-), is found. This boron cluster is an electronically stable dianion and a concentric doubly ?- and ?-aromatic system. The inner B6 unit in B18(2-) undergoes quasi-free rotation inside the perimeter of the B12 ring. The absence of any localized ?-bond between the inner ring and the peripheral boron atoms makes the system fluxional.
Strain CMB17(T) was a short rod-shaped bacterium isolated from marine sediment of the Pacific Ocean. Cells were Gram-stain-negative and non-motile. Optimal growth occurred at 25-30 °C, pH 6.5-7 and 0.5-1% (w/v) NaCl. The major fatty acid was C(18?:?1)?7c (87.59%), and ubiquinone-10 was detected as the only isoprenoid quinone. The DNA G+C content of the genomic DNA was 62.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CMB17(T) is most closely related to Paracoccus stylophorae KTW-16(T) (96.7%), P. solventivorans DSM 6637(T) (96.4%) and P. saliphilus YIM 90738(T) (96.4%). Based on phenotypic, genotypic and phylogenetic characteristics, strain CMB17(T) is proposed to represent a novel species, denominated Paracoccus sediminis sp. nov. (type strain CMB17(T)?=?JCM 18467(T)?=?DSM 26170(T)?=?CGMCC 1.12681(T)).
Microbulbifer elongatus strain HZ11, was a new strain of M. elongates DSM 6810(T), which has the ability to degrade brown seaweeds such as Laminaria japonica into single cell detritus particles. Here we report a high quality draft genome of M. elongatus strain HZ11, which comprises 4,223,108bp in 9 contigs with the G+C content of 56.70%. A total of 3293 protein-coding sequences were predicted, including nine alginate lyases (EC 18.104.22.168), five agarases (EC 22.214.171.124), 2-dehydro-3-deoxygluconate kinase (EC 126.96.36.199) and all enzymes involved in the Entner-Doudoroff pathway. Our results suggest that strain HZ11 has the potential ability to produce bioethanol from alginate with moderate genetic modification, which may significantly increase the yield of bioethanol from brown seaweed and the utilization rate of brown seaweeds.
The stability of Ngn@B12N12 and Ngn@B16N16 systems is assessed through a density functional study and ab initio simulation. Although they are found to be thermodynamically unstable with respect to the dissociation of individual Ng atoms and parent cages, ab initio simulation reveals that except Ne2@B12N12 they are kinetically stable to retain their structures intact throughout the simulation time (500 fs) at 298 K. The Ne2@B12N12 cage dissociates and the Ne atoms get separated as the simulation proceeds at this temperature but at a lower temperature (77 K) it is also found to be kinetically stable. He-He unit undergoes translation, rotation and vibration inside the cavity of B12N12 and B16N16 cages. Electron density analysis shows that the He-He interaction in He2@B16N16 is of closed-shell type whereas for the same in He2@B12N12 there may have some degree of covalent character. In few cases, especially for the heavier Ng atoms, the Ng-N/B bonds are also found to have some degree of covalent character. But the Wiberg bond indices show zero bond order in He-He bond and very low bond order in cases of Ng-N/B bonds. The energy decomposition analysis further shows that the ?Eorb term contributes 40.9% and 37.3% towards the total attraction in the He2 dimers having the same distances as in He2@B12N12 and He2@B16N16, respectively. Therefore, confinement causes some type of orbital interaction between two He atoms, which akins to some degree of covalent character.
Hedgehog (Hh) pathway inhibitors are clinically effective in treatment of basal cell carcinoma and medulloblastoma, but fail therapeutically or accelerate progression in treatment of endodermally derived colon and pancreatic cancers. In bladder, another organ of endodermal origin, we find that despite its initial presence in the cancer cell of origin Sonic hedgehog (Shh) expression is invariably lost during progression to invasive urothelial carcinoma. Genetic blockade of stromal response to Shh furthermore dramatically accelerates progression and decreases survival time. This cancer-restraining effect of Hh pathway activity is associated with stromal expression of BMP signals, which stimulate urothelial differentiation. Progression is dramatically reduced by pharmacological activation of BMP pathway activity with low-dose FK506, suggesting an approach to management of human bladder cancer.
Photosynthesis powers life on our planet. The basic photosynthetic architecture consists of antenna complexes that harvest solar energy and reaction centres that convert the energy into stable separated charge. In oxygenic photosynthesis, the initial charge separation occurs in the photosystem II reaction centre, the only known natural enzyme that uses solar energy to split water. Both energy transfer and charge separation in photosynthesis are rapid events with high quantum efficiencies. In recent nonlinear spectroscopic experiments, long-lived coherences have been observed in photosynthetic antenna complexes, and theoretical work suggests that they reflect underlying electronic-vibrational resonances, which may play a functional role in enhancing energy transfer. Here, we report the observation of coherent dynamics persisting on a picosecond timescale at 77 K in the photosystem II reaction centre using two-dimensional electronic spectroscopy. Supporting simulations suggest that the coherences are of a mixed electronic-vibrational (vibronic) nature and may enhance the rate of charge separation in oxygenic photosynthesis.
Two Gram-staining-negative, aerobic, rod-shaped bacterial strains, designated Za6a-12(T) and Za6a-17, were isolated from seawater of the East China Sea. Cells of Za6a-12(T) and Za6a-17 were approximately 1.5-2.0 µm×0.5-0.7 µm and motile by a single polar flagellum. Strains grew optimally at pH 7.5-8.0, 28 °C, and in the presence of 2.5-3.0% (w/v) NaCl. Chemotaxonomic analysis showed that the predominant respiratory quinone of strains Za6a-12(T) and Za6a-17 was ubiquinone-8 (>97%), and the major fatty acids were C(14?:?0), C(16?:?1)?7c and/or iso-C(15?:?0) 2-OH, C(16?:?0) and C(17?:?1)?8c. Their DNA G+C contents were 42.7 mol% and 42.8 mol%, respectively. 16S rRNA gene sequence analysis revealed that the isolates belonged to the genus Thalassomonas and showed the highest sequence similarity to Thalassomonas loyana CBMAI 722(T) (95.9%). Strains Za6a-12(T) and Za6a-17 could be differentiated from T. loyana CBMAI 722(T) according to their phenotypic and chemotaxonomic features, DNA G+C contents and fatty acid composition. On the basis of these features, we propose strains Za6a-12(T) and Za6a-17 to be representatives of a novel species of the genus Thalassomonas with the name Thalassomonas eurytherma sp. nov. suggested. Strain Za6a-12(T) (?=?CGMCC 1.12115(T)?=?JCM 18482(T)) is the type strain of this novel species.
Transmigration of peripheral leukocytes to the brain is a major contributor to cerebral ischemic cell death mechanisms. Humanized partial major histocompatibility complex class II constructs (pMHC), covalently linked to myelin peptides, are effective for treating experimental stroke in males, but new evidence suggests that some inflammatory cell death mechanisms after brain injury are sex-specific. We here demonstrate that treatment with pMHC constructs also improves outcomes in female mice with middle cerebral artery occlusion (MCAO). HLA-DR2 transgenic female mice with MCAO were treated with RTL1000 (HLA-DR2 moiety linked to human MOG-35-55 peptide), HLA-DRa1-MOG-35-55, or vehicle (VEH) at 3, 24, 48, and 72 h after reperfusion and were recovered for 96 h or 2 weeks post-injury for measurement of histology (TTC staining) or behavioral testing. RTL1000- and DRa1-MOG-treated mice had profoundly reduced infarct volumes as compared to the VEH group, although higher doses of DRa1-MOG were needed for females vs. males evaluated previously. RTL1000-treated females also exhibited strongly improved functional recovery in a standard cylinder test. In novel studies of post-ischemic ultrasonic vocalization (USV), as measured by animal calls to their cage mates, we modeled in mice the post-stroke speech deficits common in human stroke survivors. The number of calls was reduced in injured animals relative to pre-MCAO baseline regardless of RTL1000 treatment status. However, call duration was significantly improved by RTL1000 treatment, suggesting benefit to the animal's recovery of vocalization capability. We conclude that both the parent RTL1000 molecule and the novel non-polymorphic DR?1-MOG-35-55 construct were highly effective immunotherapies for treatment of transient cerebral ischemia in females.
The global minima of Be2N2, Be3N2 and BeSiN2 clusters are identified using a modified stochastic kick methodology. The structure, stability and bonding nature of these clusters bound to noble gas (Ng) atoms are studied at the MP2/def2-QZVPPD level of theory. Positive Be-Ng bond dissociation energy, which gradually increases down Group 18 from He to Rn, indicates the bound nature of Ng atoms. All of the Ng-binding processes are exothermic in nature. The Xe and Rn binding to Be2N2 and Be3N2 clusters and Ar-Rn binding to BeSiN2 are exergonic processes at room temperature; however, for the lighter Ng atoms, lower temperatures are needed. Natural population analysis, Wiberg bond index computations, electron density analysis, and energy decomposition analysis are performed to better understand the nature of Be-Ng bonds.
Aging represents an important health issue not only for the individual, but also for society in general. Burdens associated with aging are expanding as longevity increases. This has led to an enhanced focus on issues related to aging and age-related diseases. Until recently, anti-aging endocrine-therapy has been largely limited to hormone-replacement therapy (HRT) that is associated with multiple side effects, including an increased risk of cancer. This has greatly limited the application of HRT in anti-aging therapy. Recently, the focus of anti-aging research has expanded from endocrine signaling pathways to effects on regulatory gene networks. In this regard, the GHRH-GH-IGF-1/Insulin, TOR-S6K1,NAD(+)-Sirtuin, P53, Klotho and APOE pathways have been linked to processes associated with age-related diseases, including cancer, cardiovascular disease, diabetes, osteoporosis, and neurodegenerative diseases, all of which directly influence health in aging, and represent key targets in anti-aging therapy.
Vitamin D binding protein (DBP) may alter the biologic activity of 25-hydroxyvitamin D [25(OH)D]. The objective of our present study was to determine the joint effect of serum 25(OH)D and DBP on the risk of frailty. Five hundred sixteen male participants aged 70 years or older were recruited in Changsha city and its surrounding area in Hunan province of China. Frailty was defined as the presence of at least three of the five following criteria: weakness, low physical activity, slow walking speed, exhaustion, and weight loss. Multivariate linear regression analysis was performed to assess the relationship between 25(OH)D and DBP levels. Odds ratios (ORs) for frailty were evaluated across quartiles of 25(OH)D and DBP levels, adjusted age, education, and body mass index. The results showed that participants in the lowest quartile of 25(OH)D and the highest quartile of DBP levels, the lowest quartile of 25(OH)D and the lowest quartile of DBP levels, and those in the the lower quartile of 25(OH)D and lowest quartile of DBP levels had significantly higher OR of being frail compared with those in the highest quartile of 25(OH)D and lowest quartile of DBP, with OR of 3.18 (95% CI: 1.46-4.56, P < 0.05), 2.63 (95% CI: 1.31-3.68, P < 0.01), and 2.52 (95% CI: 1.22-3.52, P < 0.05), respectively. The results indicate that the joint effect of serum 25(OH)D and DBP levels is associated with the risk of frailty, and serum DBP levels affects 25(OH)D-frailty relationship in the older men.
Vascular calcification is a major risk factor for cardiovascular diseases. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is a key step in vascular calcification, but the molecular mechanisms driving the differentiation remain elusive. In this study, the involvement of mammalian target of rapamycin (mTOR) signalling in osteoblastic differentiation of VSMCs is investigated.
Fructose is a nutritional composition of fruits and honey. Its excess consumption induces insulin resistance-associated metabolic diseases. Hypothalamic insulin signaling plays a pivotal role in controlling whole-body insulin sensitivity and energy homeostasis. Quercetin, a natural flavonoid, has been reported to ameliorate high fructose-induced rat insulin resistance and hyperlipidemia. In this study, we investigated its regulatory effects on the hypothalamus of high fructose-fed rats. Rats were fed 10% fructose in drinking water for 10 weeks. After 4 weeks, these animals were orally treated with quercetin (50 and 100 mg/kg), allopurinol (5 mg/kg) and water daily for the next 6 weeks, respectively. Quercetin effectively restored high fructose-induced hypothalamic insulin signaling defect by up-regulating the phosphorylation of insulin receptor and protein kinase B. Furthermore, quercetin was found to reduce metabolic nutrient sensors adenosine monophosphate-activated protein kinase (AMPK) activation and thioredoxin-interacting protein (TXNIP) overexpression, as well as the glutamine-glutamate cycle dysfunction in the hypothalamus of high fructose-fed rats. Subsequently, it ameliorated high fructose-caused hypothalamic inflammatory lesions in rats by suppressing the activation of hypothalamic nuclear factor ?B (NF-?B) pathway and NOD-like receptor 3 (NLRP3) inflammasome with interleukin 1? maturation. Allopurinol had similar effects. These results provide in vivo evidence that quercetin-mediated down-regulation of AMPK/TXNIP and subsequent inhibition of NF-?B pathway/NLRP3 inflammasome activation in the hypothalamus of rats may be associated with the reduction of hypothalamic inflammatory lesions, contributing to the improvement of hypothalamic insulin signaling defect in this model. Thus, quercetin with the central activity may be a therapeutic for high fructose-induced insulin resistance and hyperlipidemia in humans.
Adenoid cystic carcinoma (ACC) is one of the most common malignant neoplasms in salivary glands. To evaluate the therapeutic effects of nanosecond pulsed electric field (nsPEF) combined with pingyangmycin (PYM) on salivary gland adenoid cystic carcinoma (SACC), ACC high metastatic cell line (SACC-LM) and low metastatic cell line (SACC?83) were tested by CCK-8 assay, cell clonogenic assay, flow cytometry and Transwell assay. Extracellular matrix metalloproteinase inducer (EMMPRIN) expression was tested by western blotting to verify the synergistic mechanism of nsPEF and PYM. The results showed that nsPEF inhibited the cell proliferation of both cell lines, and the inhibitory effect was strongly associated with time and electrical field strength. Moreover, PYM combined with nsPEF may enhance the suppression effect significantly, even at a very low dose (0.01 µg/ml). The synergistic effects may contribute to the downregulation of EMMPRIN expression resulting from the application of nsPEF. For SACC, nsPEF combined with chemotherapy agents may be a valuable strategy not only to improve the treatment effect and prognosis, but also to reduce the side-effects of chemotherapy.
Tumor necrosis factor alpha (TNF?) is an adipokine involved in the regulation of cell differentiation and lipid metabolism, but its specific role has not been clearly understood. We validated a hypothesis that loss of TNF? function would inhibit Wnt/?-catenin signaling and accelerate adipogenesis in adolescent genetic obese mice. Epididymal white adipose tissues (eWAT) from TNF? deficient (TNF?(-/-)), leptin receptor deficient (db/db) and double gene mutant (db/db/TNF?(-/-), DT) male mice were used for comparative analysis of key molecules in Wnt/?-catenin signaling and adipogenic markers by qRT-PCR and western blot techniques. Compared with TNF?(-/-) and WT mice of 28 days old, an obese trait was observed in both db/db and DT mice, while the latter showed more significant body weight gain and eWAT hypertrophy. The mRNA level of key molecules in Wnt/?-catenin pathway was reduced in both obese groups, while the DT group was the lowest. Expression of adipocyte-specific genes was up-regulated during obese development in the two obese groups, while the DT group revealed more correlation than that of db/db group. At the protein level, a down regulation of Wnt10b and ?-catenin in obese eWAT showed similar tendency with that of mRNA level. Compared with the lean groups, the levels of adiponectin and PPAR?2 for the obese groups were down-regulated at 21-day-old age, while they were elevated at older age. Our results suggested that deficiency in TNF? inhibited Wnt/?-catenin signaling of the obese eWAT and up-regulated expression of adipokines, and accelerated adipogenesis in genetic obese mice on a chow diet.
Vascular calcification is common in patients with peripheral artery diseases and coronary artery diseases. The osteoblastic differentiation of vascular smooth muscle cells (VSMCs) contributes significantly to vascular calcification. Adiponectin has been demonstrated to exert a protective effect in osteoblastic differentiation of VSMCs through regulating mTOR activity. However, the upstream and downstream signaling molecules of adiponectin-regulated mTOR signaling have not been identified in VSMCs with osteoblastic differentiation. In this study, the VSMC differentiation model was established by beta-glycerophosphate (?-GP) induction. The mineralization was identified by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot or immunofluorescence. Adiponectin attenuated osteoblastic differentiation and mineralization of ?-GP-treated VSMCs. Adiponectin inhibited osteoblastic differentiation of VSMCs through increasing the level of p-AMPK?. Pretreatment of VSMCs with AMPK inhibitor blocked while AMPK activator enhanced the effect of adiponectin on osteoblastic differentiation of VSMCs. Adiponectin upregulated TSC2 expression and downregulated mTOR and S6K1 phosphorylation in ?-GP-treated VSMCs. Adiponectin treatment significantly attenuates the osteoblastic differentiation and calcification of VSMCs through modulation of AMPK-TSC2-mTOR-S6K1 signal pathway.
A safe and effective adjuvant plays an important role in the development of a vaccine. However, adjuvants licensed for administration in humans remain limited. Here, for the first time, we developed a novel combination adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities, consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2.
The power absorbed by the human brain has possible implications in the study of the central nervous system-related biological effects of electromagnetic fields. In order to determine the specific absorption rate (SAR) of radio frequency (RF) waves in the human brain, and to investigate the effects of geometry and polarisation on SAR value, the finite-difference time-domain method was applied for the SAR computation. An anatomically realistic model scaled to a height of 1.70 m and a mass of 63 kg was selected, which included 14 million voxels segmented into 39 tissue types. The results suggested that high SAR values were found in the brain, i.e. ?250 MHz for vertical polarisation and 900-1200 MHz both for vertical and horizontal polarisation, which may be the result of head resonance at these frequencies.
Inflammation is an important contributor to the development of Alzheimer's disease (AD). Anti-inflammatory medication may offer promising treatment for AD. Hydroxy-safflor yellow A (HSYA), a chemical component of the safflower yellow pigments, has been reported to exert potent immunosuppressive effects. This study examined the anti-inflammatory effects of HSYA in A?????-treated BV-2 microglia cells. The mRNA levels of IL-1?, IL-4, IL-10, TNF-?, COX-2 and iNOS were detected by real-time PCR. Western blotting was used to determine the protein expression of COX-2, TNF-?, iNOS, Janus Kinase 2 (JAK2), p-JAK2, signal transducers and activators of transcription 3 (STAT3) and p-STAT3. BV2-conditioned medium was used to treat SH-SY5Y cells and primary neuronal cells in indirect toxicity experiments. Cell viability and apoptosis were assessed using MTT assay and Annexin V/PI staining respectively. The results demonstrated that HSYA significantly reduced the expression of the pro-inflammatory mediators and inhibited A?????-induced neuroinflammation. Moreover, HSYA protected primary cortical neurons and SH-SY5Y cells against microglia-mediated neurotoxicity. HSYA also enhanced the phosphorylation of JAK2/STAT3 pathway and inhibition of JAK2 by AG 490 attenuated the anti-inflammatory effects of HSYA. Overall, our findings suggested that HSYA inhibited A?????-induced inflammation and conferred neuroprotection partially through JAK2/STAT3 pathway, indicating that HSYA could be a potential drug for the treatment of AD.
A highly porous metal-organic framework structurally consists of three topological kinds of 3-connected 1,3,5-benzenetricarboxylate ligands, Zn2(COO)4, Zn3O(COO)6 and Zn4O(COO)6 SBUs, featuring a new 3,3,3,4,4,6-c hexanodal topology. Sorption behaviour in this complicated microporous MOF material has also been investigated.
The pulmonary neuroepithelial bodies (NEBs) constitute polymodal airway chemosensors for monitoring and signaling ambient gas concentrations (pO2, pCO2/H+) via complex innervation to the brain stem controlling breathing. NEBs produce the bioactive amine, serotonin (5-HT), and a variety of peptides with multiple effects on lung physiology and other organ systems. NEBs in mammals appear prominent and numerous during fetal and neonatal periods, and decline in the post-natal period suggesting an important role during perinatal adaptation. The naked mole-rat (NMR), Heterocephalus glaber, has adapted to the extreme environmental conditions of living in subterranean burrows in large colonies (up to 300 colony mates). The crowded, unventilated burrows are environments of severe hypoxia and hypercapnia. However, NMRs adjust readily to above ground conditions. The chemosensory NEBs of this species were characterized and compared to those of the conventional Wistar rat (WR) to identify similarities and differences that could explain the NMR's adaptability to environments. A multilabel immunohistochemical analysis combined with confocal microscopy revealed that the expression patterns of amine, peptide, neuroendocrine, innervation markers and chemosensor component proteins in NEBs of NMR were similar to that of WR. However, we found the following differences: 1) NEBs in both neonatal and adult NMR lungs were significantly larger and more numerous as compared to WR; 2) NEBs in NMR had a more variable compact cell organization and exhibited significant differences in the expression of adhesion proteins; 3) NMR NEBs showed a significantly greater ratio of 5-HT positive cells with an abundance of 5-HT; 4) NEBs in NMR expressed the proliferating cell nuclear antigen (PCNA) and the neurogenic gene (MASH1) indicating active proliferation and a state of persistent differentiation. Taken together our findings suggest that NEBs in lungs of NMR are in a hyperactive, functional and developmental state, reminiscent of a persistent fetal state that extends postnatally.
The morphology and infraciliature of two hypotrichous ciliates, Urosoma salmastra and U. karinae sinense nov. sspec., were investigated for populations collected from the surface of intertidal gravel in the Huguang Mangrove Forest, Zhanjiang, China and the upper 10cm layer of soil in the Sangke Grass Land in the southern part of Gansu Province, China, respectively. Urosoma salmastra is characterized by its elongate-elliptical body with no tail-like structure; two macronuclear nodules; cortical granules colourless, less than 1?m across, and arranged in short rows; adoral zone occupying 25% of body length in vivo; paroral conspicuously short and located in front of endoral. Urosoma karinae sinense nov. sspec. is characterized by its elongate-elliptical body with no tail; 2-4 macronuclear nodules; cortical granules colourless, less than 1?m across, and arranged in short rows; adoral zone occupying 30% of body length in vivo; paroral shorter than, and located ahead of endoral. Phylogenetic analyses based on SSU rRNA gene sequence data suggest a close relationship between U. salmastra, U. karinae sinense nov. sspec. and Oxytricha granulifera within the Oxytrichinae assemblage.
Allicin is the main active constituent of Allium sativum L., which is characterized by broad antibacterial spectrum (MarkosN et al., 2008; Chen et al., 2008); it also has apparent inhibitory effects on a variety of tumors. The Objective of the paper is to study the inhibitory effect of allicin on human gastric cancer cell line SGC-7901.
A novel open helmetlike coordination cage has been synthesized based on Co4-calixarene shuttlecock-like secondary building units and in situ generated phosphate anions, where the opening of the cage comprises a large 16-membered ring. The above unprecedented Co20 nanocage presents the first pentameric calixarene coordination compound. Sorption behavior and magnetic properties are also investigated.
Betaine as a dietary alkaloid has attracted the attention of patients with kidney diseases. This study aimed to investigate the effects of betaine on serum uric acid levels and kidney function, and explore their underlying mechanisms in potassium oxonate-induced hyperuricemic mice. Betaine at 5, 10, 20, and 40?mg/kg was orally administered to hyperuricemic mice for 7 days and found to significantly reduce serum uric acid levels and increase fractional excretion of uric acid in hyperuricemic mice in a dose-dependent manner. It effectively restored renal protein level alterations of urate transport-related molecular proteins urate transporter 1, glucose transporter 9, organic anion transporter 1, and ATP-binding cassette subfamily G member 2 in this model, possibly resulting in the enhancement of kidney urate excretion. Moreover, betaine reduced serum creatinine and blood urea nitrogen levels and affected urinary levels of beta-2-microglobulin and N-acetyl-beta-D-glucosaminidase as well as upregulated renal protein levels of organic cation/carnitine transporters OCT1, OCTN1, and OCTN2, resulting in kidney function improvement in hyperuricemic mice. The findings from this study provide evidence that betaine has anti-hyperuricemic and nephroprotective actions by regulating protein levels of these renal organic ion transporters in hyperuricemic mice.
The global minimum geometries of BeCN2 and BeNBO are linear BeN-CN and BeN-BO, respectively. The Be center of BeCN2 binds He with the highest Be-He dissociation energy among the studied neutral He-Be complexes. In addition, BeCN2 can be further tuned as a better noble gas trapper by attaching it with any electron-withdrawing group. Taking BeO, BeS, BeNH, BeNBO, and BeCN2 systems, the study at the CCSD(T)/def2-TZVP level of theory also shows that both BeCN2 and BeNBO systems have higher noble gas binding ability than those related reported systems. ?G values for the formation of NgBeCN2/NgBeNBO (Ng = Ar-Rn) are negative at room temperature (298 K), whereas the same becomes negative at low temperature for Ng = He and Ne. The polarization plus the charge transfer is the dominating term in the interaction energy.
Ubiquitin C-terminal hydrolase L1 (UCH-L1) is abundantly expressed in the brain and is critical for the normal function of synapses. cAMP response element binding protein (CREB) is a transcription factor which initiates the expression of proteins that related to the regulation of synaptic plasticity and memory function. Studies have shown that UCH-L1 can influence the expression and activity of CREB, but the underlying mechanisms remain unclear. In this study, we used UCH-L1 inhibitor LDN to treat mice hippocampal slices and found that UCH-L1 inhibition caused the dephosphorylation of CREB at Ser133 site. Meanwhile, hyperphosphorylation of microtubule-associated protein tau; increased expression of synaptic protein components of PSD-95 and synapsin-1, and decreased activity of tyrosine kinase Fyn were observed after UCH-L1 inhibition. Moreover, all these alternations have an influence on the normal function of N-methyl-D-aspartate (NMDA) receptor NR2B subunit which is likely to result in the dephosphorylation of CREB. We also found that LDN treatment mediated protein kinase A (PKA) deactivation was involved in the dephosphorylation of CREB. Thus, our study introduces a novel possible mechanism for elaborating the effects of UCH-L1 inhibition on the CREB activity and the implicated signaling pathways.
The Apolipoprotein (Apo) family is implicated in lipid metabolism. There are five types of Apo: Apoa, Apob, Apoc, Apod, and Apoe. Apoe has been demonstrated to play a central role in lipoprotein metabolism and to be essential for efficient receptor-mediated plasma clearance of chylomicron remnants and VLDL remnant particles by the liver. Apoe-deficient (Apoe(-/-)) mice develop atherosclerotic plaques spontaneously, followed by obesity. In this study, we investigated whether lipid deposition caused by Apoe knockout affects reproduction in female mice. The results demonstrated that Apoe(-/-) mice were severely hypercholesterolemic, with their cholesterol metabolism disordered, and lipid accumulating in the ovaries causing the ovaries to be heavier compared with the WT counterparts. In addition, estrogen and progesterone decreased significantly at D 100. Quantitative PCR analysis demonstrated that at D 100 the expression of cytochromeP450 aromatase (Cyp19a1), 3?-hydroxysteroid dehydrogenase (Hsd3b), mechanistic target of rapamycin (Mtor), and nuclear factor-?B (Nfkb) decreased significantly, while that of BCL2-associated agonist of cell death (Bad) and tuberous sclerosis complex 2 (Tsc2) increased significantly in the Apoe(-/-) mice. However, there was no difference in the fertility rates of the Apoe(-/-) and WT mice; that is, obesity induced by Apoe knockout has no significant effect on reproduction. However, the deletion of Apoe increased the number of ovarian follicles and the ratio of ovarian follicle atresia and apoptosis. We believe that this work will augment our understanding of the role of Apoe in reproduction.
The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro, ex vivo and in vivo methods. Five G?s-coupled receptors efficiently stimulated ghrelin secretion: as expected the ?1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of G?i/o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both G?i/o- and G?q/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive G?i/o pathway: FFAR2 (short chain fatty acid receptor; GPR43), FFAR4 (long chain fatty acid receptor; GPR120) and CasR (calcium sensing receptor). In addition to the common G? subunits three non-common G?i/o subunits were highly enriched in ghrelin cells: G?oA, G?oB and G?z. Inhibition of G?i/o signaling via ghrelin cell-selective pertussis toxin expression markedly enhanced circulating ghrelin. These 7TM receptors and associated G? subunits constitute a major part of the molecular machinery directly mediating neuronal and endocrine stimulation versus metabolite and somatostatin inhibition of ghrelin secretion including a series of novel receptor targets not previously identified on the ghrelin cell.
The Zn-BChl-containing reaction center (RC) produced in a bchD (magnesium chelatase) mutant of Rhodobacter sphaeroides assembles with six Zn-bacteriochlorophylls (Zn-BChls) in place of four Mg-containing bacteriochlorophylls (BChls) and two bacteriopheophytins (BPhes). This protein presents unique opportunities for studying biological electron transfer, as Zn-containing chlorins can exist in 4-, 5-, and (theoretically) 6-coordinate states within the RC. In this paper, the electron transfer perturbations attributed exclusively to coordination state effects are separated from those attributed to the presence, absence, or type of metal in the bacteriochlorin at the HA pocket of the RC. The presence of a 4-coordinate Zn(2+) ion in the HA bacteriochlorin instead of BPhe results in a small decrease in the rates of the P*?P(+)HA(-)?P(+)QA(-) electron transfer, and the charge separation yield is not greatly perturbed; however coordination of the Zn(2+) by a fifth ligand provided by a histidine residue results in a larger rate decrease and yield loss. We also report the first crystal structure of a Zn-BChl-containing RC, confirming that the HA Zn-BChl was either 4- or 5-coordinate in the two types of Zn-BChl-containing RCs studied here. Interestingly, a large degree of disorder, in combination with a relatively weak anomalous difference electron density was found in the HB pocket. These data, in combination with spectroscopic results, indicate partial occupancy of this binding pocket. These findings provide insights into the use of BPhe as the bacteriochlorin pigment of choice at HA in both BChl- and Zn-BChl-containing RCs found in nature.
Multiple sclerosis (MS) is an irreversible and demyelinating disease of the central nervous system, in part influenced by chronic inflammation. There is no proven effective therapy to stop the pathological progression of MS, although suppressing the immune system to control the inflammatory response may improve the clinical performance acutely. Here, we found that mesenchymal stem cells from human umbilical cord (hUC-MSCs) could restore behavioral functions and attenuate the histopathological deficits of experimental autoimmune encephalomyelitis mice over the long term (i.e., 50 days) by suppression of perivascular immune cell infiltrations and reduction in both demyelination and axonal injury in the spinal cord. These findings suggest that transplantation of hUC-MSCs may be a potential therapy for MS.
A Gram-negative, non-motile and aerobic bacterium, designed CF17T, was isolated from coastal planktonic seaweeds, East China Sea. The isolate grew at 18-37 °C (optimum 25-28 °C), pH 6.5-9.0 (optimum 7.0-8.0), NaCl 0-5% (optimum 1-2%, w/v) and sea salts 0.5-10% (optimum 2-3%, w/v). Growth of strain CF17T could be prominently stimulated by supplementing the autoclaved supernatant of the culture of strain CF5, which was isolated from the same sample in company with strain CF17T. The cell morphology of strain CF17T was bean-shaped rod consisting of a swollen end and a long prosthecae. The phylogenetic analysis of 16S rRNA gene sequences indicated that strain CF17T clustered with Gemmobacter nectariphilus DSM 15620T within the lineage of genus Gemmobacter. The DNA G+C content of strain CF17T was 61.4 mol%. The respiratory quinone was ubiquinone Q-10. The major fatty acids included C18:1 ?7c and C18:0. The polar lipids of strain CF17T consisted of one phosphatidylethanolamine (PE), one phosphatidylglycerol (PG), one phosphatidylcholine (PC), two uncharacterized phospholipids (PL1~2), one uncharacterized aminolipids (AL1), three uncharacterized glycolipids (GL1~3) and one uncharacterized lipids (L1). On the basis of phenotypic, phylogenetic and chemotaxonomic data, strain CF17T (=CGMCC 1.11024T =JCM 18498T) is considered to represent a novel species of genus Gemmobacter, for which the name Gemmobacter megaterium sp. nov. is proposed.
The performance of a sound barrier is usually degraded if a large reflecting surface is placed on the source side. A wave-trapping barrier (WTB), with its inner surface covered by wedge-shaped structures, has been proposed to confine waves within the area between the barrier and the reflecting surface, and thus improve the performance. In this paper, the deterioration in performance of a conventional sound barrier due to the reflecting surface is first explained in terms of the resonance effect of the trapped modes. At each resonance frequency, a strong and mode-controlled sound field is generated by the noise source both within and in the vicinity outside the region bounded by the sound barrier and the reflecting surface. It is found that the peak sound pressures in the barriers shadow zone, which correspond to the minimum values in the barriers insertion loss, are largely determined by the resonance frequencies and by the shapes and losses of the trapped modes. These peak pressures usually result in high sound intensity component impinging normal to the barrier surface near the top. The WTB can alter the sound wave diffraction at the top of the barrier if the wavelengths of the sound wave are comparable or smaller than the dimensions of the wedge. In this case, the modified barrier profile is capable of re-organizing the pressure distribution within the bounded domain and altering the acoustic properties near the top of the sound barrier.
In this Letter, a proof is provided for the reciprocity between modal scattering coefficients of the acoustic waveguides connected by a junction enclosure. The result holds for all waveguide modes and for junction enclosures with locally reactive boundary conditions away from the interfaces between the junction and waveguides. Also provided is a physical interpretation of the reciprocity of the modal scattering coefficients. The scattering of two-dimensional waveguide modes by a right-angled bend in a rectangular duct is used as an illustrating example.
Human soluble guanylate cyclase (hsGC), a NO sensor/NO receptor of a heterodimeric hemoprotein, plays a critical role in the NO-sGC-cGMP signaling pathway, and also reveals a novel nitrite reductase activity. This indicates that hsGC could activate itself by catalytic reduction of nitrite to NO instead of receiving NO from nitric oxide synthase (NOS), which provides valuable insight into the physiological function of the homodimeric hsGC.
A method for determining the complete higher-order scattering matrix of an acoustic discontinuity is developed. The method is demonstrated for a right-angled waveguide bend, and the magnitude and phase of the reflection and transmission coefficients are extracted precisely. The procedure is straightforward and based on the solutions to the Helmholtz equation by the finite element method (FEM). The consistency of the scattering coefficients found by this method is verified by their properties of symmetry, and their accuracy is established by the conservation of energy. The reliability of the new technique is further proved by means of an arbitrary sound source and by comparing the direct FEM response to the reflection matrix calculation. Some features of the scattering matrix as a function of frequency are surprising, such as the steps and reversion of the phase evolution or the complete loss of transmission of the incoming wave. The methodology detailed in this paper can be extended to other multiport junctions, such as T-junctions or size discontinuities in ducts.
Genome-wide association studies (GWASs) in identifying the disease-associated genetic variants have been proved to be a great pioneering work. Two-stage design and analysis are often adopted in GWASs. Considering the genetic model uncertainty, many robust procedures have been proposed and applied in GWASs. However, the existing approaches mostly focused on binary traits, and few work has been done on continuous (quantitative) traits, since the statistical significance of these robust tests is difficult to calculate. In this paper, we develop a powerful F-statistic-based robust joint analysis method for quantitative traits using the combined raw data from both stages in the framework of two-staged GWASs. Explicit expressions are obtained to calculate the statistical significance and power. We show using simulations that the proposed method is substantially more robust than the F-test based on the additive model when the underlying genetic model is unknown. An example for rheumatic arthritis (RA) is used for illustration.
In high-throughput ultrasonication enhanced hollow-fiber liquid-phase microextraction (H-U-HF-LPME), ultrasonication was introduced into HF-LPME to enhance the mass transfer rate of the analytes in the two immiscible liquid phases, which resulted in a very short time for extraction equilibrium and a high-throughput analysis. Several parameters were investigated and optimized (such as extraction solvent, temperature of sample, frequency and intensity of ultrasonication, volume of extractant, extraction time, ionic strength of the sample and sample concentration). Based on the results of this study, nicotine was first extracted from a 1.5 mL sample solution under the optimum conditions (ultrasonic power of 50 W with a frequency of 60 kHz, extraction time of 10 min, sodium chloride concentration of 5 mol/L and temperature of 37°C). Next, 0.5 µL of acceptor solution inside the hollow fiber was automatically injected into a gas chromatograph with a flame ionization detector. The results of this study illustrated that the limit of detection, relative standard deviation (n = 6), relative recovery and enrichment factor of nicotine were 0.06 µg/L, 3%, 99.8% and 16.6, respectively. Finally, H-U-HF-LPME was successfully applied for the determination of nicotine in plasma.
The kinetics and pathway of electron transfer has been explored in a series of reaction center mutants from Rhodobacter sphaeroides, in which the leucine residue at M214 near the bacteriopheophytin cofactor in the A-branch has been replaced with methionine, cysteine, alanine, and glycine. These amino acids have substantially different volumes, both from each other and, except for methionine, from the native leucine. Though the mutation site of M214 is close to the bacteriopheophytin cofactor, which is involved in the electron transfer, none of the mutations alter the cofactor composition of the reaction center and the primary charge separation reaction is essentially undisturbed. However, the kinetics of electron transfer from HA(-) ? QA becomes both slower and substantially heterogeneous in three of the four mutants. The decreased HA(-) ? QA electron transfer rate allows charge recombination between P(+) and HA(-) to compete with the forward reaction, resulting in a drop in the overall yield of charge separation. Both the yield change and the variation in kinetics correlate well with the volume of the mutant amino acid side chains. Analysis of the kinetics suggests that the introduction of a smaller side chain at M214 results in greater protein structural heterogeneity and dynamics on multiple time scales, resulting in perturbation of the electronic environment and its evolution in the vicinity of the early charge-separated radical pair, P(+)HA(-), and the subsequent acceptor QA, affecting both the extent and time scale of dielectric relaxation. It appears that the reaction center has been optimized not only in terms of its static structure-function relationships, but also finely tuned to favor particular reaction pathways on particular time scales by adjusting protein dynamics.
We examined the whole genome expression profile in advanced colorectal cancer (ACC) patients who had received FOLFOX4 chemotherapy to establish a genetic biomarker model predicting chemotherapy sensitivity.
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