分类： 生物学 >> 生物物理学 >> 生物力学与生物流变学 提交时间： 2016-05-11
摘要： Influenza virus can rapidly change its antigenicity, via mutation in the hemagglutinin (HA) protein, to evade host immunity. The emergence of the novel human-infecting avian H7N9 virus in China has caused widespread concern. However, evolution of the antigenicity of this virus is not well understood. Here, we inferred the antigenic epitopes of the HA protein from all H7 viruses, based on the five well-characterized HA epitopes of the human H3N2 virus. By comparing the two major H7 phylogenetic lineages, i.e., the Eurasian lineage and the North American lineage, we found that epitopes A and B are more frequently mutated in the Eurasian lineage, while epitopes B and C are more frequently mutated in the North American lineage. Furthermore, we found that the novel H7N9 virus (derived from the Eurasian lineage) isolated in China in the year 2013, contains six frequently mutated sites on epitopes that include site 135, which is located in the receptor binding domain. This indicates that the novel H7N9 virus that infects human may already have been subjected to gradual immune pressure and receptor-binding variation. Our results not only provide insights into the antigenic evolution of the H7 virus but may also help in the selection of suitable vaccine strains.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-12
摘要： The oxygen-evolving center (OEC) in photosystem II catalyzes a water splitting reaction. Great efforts have already been made to artificially synthesize the OEC, in order to elucidate the structure-function relationship and the mechanism of the reaction. Now, a new synthetic model makes the best mimic yet of the OEC. This recent study opens up the possibility to study the mechanism of photosystem II and photosynthesis in general for applications in renewable energy and synthetic biology.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
摘要： Synthetic aperture radar (SAR) provides a powerful surveillance capability allowing the observation of target, independently from weather effects and from the day and night cycle. Unfortunately, the automatic interpretation of SAR images is often complicated and time consuming. In support of real-time vessel monitoring, a fast line-scanning detector designed for detecting ships from SAR imagery is proposed in this paper. The detector does not require any prior knowledge about ships and background observation. It uses a novel local gray-level gathering degree algorithm to detect potential targets and then a complementary filtering scheme to reject false alarms. The performance analysis over real SAR images confirms that the proposed detector works well in various circumstances with high detection rate, fast detection speed and perfect shape preservation.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Yuan, Shanshan
Zhang, Yang
Liu, Yalei
Yu, Nan
Zhang, Hong
Lu, Guizhi
Gao, Yanming
Gao, Ying
Guo, Xiaohui
Li, Qianqian
Huang, Chuncui
Wu, Hongmei
Li, Yan
摘要： Objective: Sera of Hashimoto's thyroiditis (HT) patients are known to exhibit elevated levels of anti-thyroglobulin IgG (TgAb IgG). Therefore, TgAb IgG represents a hallmark of this debilitating autoimmune disease. The aim of our study was to investigate the differential expression of specific glycosylation patterns of TgAb IgG from HT patients and healthy blood donors. Methods: HT patients (n = 32) were divided into two subgroups, medium level group (mHT, n = 15) and high level group (hHT, n = 17), according to the serum levels of TgAb detected by electrochemiluminescence immunoassay. TgAb IgG was purified by affinity chromatography from the sera of the HT group and control group (n = 15). MALDI-QIT-TOF-MS/MS spectrometry was performed to identify the glycosylation profiles of purified TgAb IgG. Lectin microarray technology was used to compare the abundance of different glycans found on TgAb IgG between HT patients and controls, and between the mHT and hHT groups. Results: The results by MALDI-QIT-TOF-MS/MS showed that the glycosylation profiles of TgAb IgG were similar between the mHT, hHT, and control groups. Furthermore, the lectin microarray showed that compared to the control group (all P < .001), there were higher levels present of (1) mannose (detected as lectin LCA, VFA, and MNA-M); (2) terminal sialic acid (detected as SNA-I and PSA); (3) core fucose (detected as LcH); and (4) Gal(beta 1-4) GlcNAc(beta 1-2) Man glycans (detected as PHA-L) on TgAb IgG from the HT group. A similar trend was observed between the hHT and mHT group, with elevated levels of mannose, terminal sialic acid, core fucose, and Gal(beta 1-4) GlcNAc(< 12) Man glycans on TgAb IgG found in the hHT group compared with the mHT group (all P < .05). Conclusions: TgAb IgG of HT patients exhibits higher glycosylation levels than those observed for TgAb IgG of healthy controls. Our results provide new clues for exploring the role of TgAb in the pathogenesis of HT.
分类： 生物学 >> 生物物理学 >> 生物力学与生物流变学 提交时间： 2016-05-11
摘要： A natural biomaterial has been discovered with bactericidal activities, which is mainly attributed to its nanopatterned surface structure. The surface of Clanger cicada (Psaltoda claripennis) wings has been identified as a natural bactericidal material, which has lead to the emergence of research on the development of novel antibacterial surfaces. From the interactions between bacterial biofilms and nanopatterned surface structures, a new mechanical model is proposed that investigates the rupture of bacterial cells within the framework of the "stretching" theory. The effect of surface nanoroughness on the survival of bacterial cells is evaluated by determining the stretching ability of their cell walls. The results, calculated using Gram-positive and Gram-negative bacteria as examples, show a correlation between the stretching of the cell wall and the geometric parameters of the surface structures. The theoretical results indicate that for a given cell rigidity, the bactericidal nature of the surface is determined by the geometric parameters of the surface structures. (C) 2015 Elsevier Ltd. All rights reserved.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-05
摘要： Autofocusing is a fundamental step towards automated microscopic screening of Caenorhabditis elegans. Determining the optimal focus in an optical microscope is based on a clarity-evaluation function that is applied to images acquired from different focuses of the same field. The maximum value of the function is considered as the point of optimal focus. In this paper, 16 autofocus algorithms which were collected from well-known algorithms as well as the most recently proposed focusing algorithms have been evaluated. Through these evaluations, an optimal algorithm was found for C. elegants lipid droplets to set up an automatic screening system. Many features were assessed in this paper, for instance accuracy, computational time, addition of noise, and focusing curve. Our results have shown that most of the algorithms show an overall high performance for this type of image, and absolute Tenengrad algorithm will be our first choice for its best performance considering accuracy.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-12
摘要： The homeostasis of magnesium (Mg2+), an abundant divalent cation indispensable for many biological processes including mitochondrial functions, is underexplored. Previously, two mitochondrial Mg2+ importers, Mrs2 and Lpe10, were characterized for mitochondrial Mg2+ uptake. We now show that mitochondrial Mg2+ homeostasis is accurately controlled through the combined effects of previously known importers and a novel exporter, Mme1 (mitochondrial magnesium exporter 1). Mme1 belongs to the mitochondrial carrier family and was isolated for its mutation that is able to suppress the mrs2 Delta respiration defect. Deletion of MME1 significantly increased steady-state mitochondrial Mg2+ concentration, while overexpression decreased it. Measurements of Mg2+ exit from proteoliposomes reconstituted with purified Mme1 provided definite evidence for Mme1 as an Mg2+ exporter. Our studies identified, for the first time, a mitochondrial Mg2+ exporter that works together with mitochondrial importers to ensure the precise control of mitochondrial Mg2+ homeostasis. (C) 2015 Elsevier B.V. All rights reserved.
分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-12
摘要： Mitochondrial calcium uniporter (MCU) is a conserved Ca2+ transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress-induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial localized in both HeLa and primary cerebellar granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial Ca2+ uptake following histamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca2+ uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-11
Xue Peng
Zhou Yue
Ding Xiang
Wang Jun
Xie Zhen-Sheng
Yang Fu-Quan
Xue Peng
Zhou Yue
Wang Jun
Zhou Yue
摘要： Glycosylation is one of the most common and important post-translational modifications of proteins. Identification of large-scale N-linked glycoprotein is a very important aspect in glycoproteomics research. The N-glycopeptide enrichment is a key step in high-throughput identification of N-glycosylation site. Lectin enrichment and hydrazide chemistry are the two widely used N-glycopeptides enrichment methods. Each method can only enrich certain types of glycopeptides. It has been reported that the two methods are highly complementary, but few studies compared overlaps of glycosties from the two methods. In this paper, using HepG2 cells, we systematically compared the performance of hydrazide chemistry and lectins enrichment methods. The results showed that although the hydrazide method with glycopeptides enrichment efficiency of 76.7%, far higher than the 54.6% lectin enrichment method, 825 glycoprotein and 1 879 N-glycosylation sites identified with the lectin method was significantly more than 522 glycoprotein and 1 014 glycosylation sites enriched by the hydrazide method. Moreover, the two methods did not show significant complementary, together, only 853 glycoproteins and 1 959 N-glycosylation sites were identified. The overlapping results of identified N-glycosylation sites and N-glycoproteins from the two methods show that lectins enrichment method was better than hydrazide chemistry method.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
摘要： Pneumolysin is one of the major virulence factors elaborated by Streptococcus pneumoniae; this toxin is a member of the cholesterol-dependent cytolysins. Engagement of cholesterol induces the formation of a multi-subunit complex by pneumolysin that lyses host cells by forming pores on the membrane. Because pneumolysin released by bacteria which have been killed by conventional antibiotics is still active, agents capable of directly attacking the toxin are considered advantageous against antimicrobials in the treatment of S. pneumoniae infections. Here we found that the phytosterol, beta-sitosterol, effectively protects against cell lysis caused by pneumolysin. This compound interacts with the toxin at Thr459 and Leu460, two sites important for being recognized by its natural ligand, cholesterol. Similar to cholesterol, beta-sitosterol induces pneumolysin oligomerization. This compound also protects cells from damage by other cholesterol-dependent toxins. Finally, this compound protects mice against S. pneumoniae infection. Thus, beta-sitosterol is a candidate for the development of anti-virulence agents against pathogens that rely on cholesterol-dependent toxins for successful infections.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-12
摘要： NLRP10 is a special member of NOD-like receptors (NLRs) family that lacks the leucine-rich repeats, suggesting that NLRP10 may act as an immunity regulator rather than directly receptor recognizing intracellular pathogen products. Previous studies on NLRP10 show that NLRP10 can interact with several components of NOD1 pathway thereby enhancing NOD1-mediated innate immune responses. In particular models, NLRP10 also negatively affects the activation of NLRP3 inflammasome. It has been proposed that NLRP10 oligomers interact with ASC to form a multi-protein platform for the recruitment of caspase-1 or other signaling components. Here, we show that pyrin-like domain (PYD) degradation induce the formation of NLRP10 oligomers, which present stick-shaped and circular structure. With the NLRP10 mutant G173A made by means of site-directed mutagenesis, we successfully obtain homogeneous full-length NLRP10 preparations. Corresponding gel filtration analysis and electron microscope (EM) data further proved that the PYD domain is important in protecting NLRP10 against aggregation.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-15
摘要： Background: Carcinoembryonic antigen (CEA) is a protein commonly found in human serum, with elevated CEA levels being linked to the progression of a wide range of tumors. It is currently used as a biomarker for malign tumors such as lung cancer and colorectal cancer [Urol Oncol: Semin Orig Invest 352: 644-648, 2013 and Lung Cancer 80: 45-49, 2013]. However, due to its low specificity in clinical applications, CEA can be used for monitoring only, rather than tumor diagnosis. The function of many glycoproteins is critically dependent on their glycosylation pattern, which in turn has the potential to serve in tumor detection. However, little is known about the detailed glycan patterns of CEA. Methods: To determine these patterns, we isolated and purified CEA proteins from human tumor tissues using immunoaffinity chromatography. The glycan patterns of CEA were then analyzed using a Matrix-Assisted Laser Desorption/Ionization-Time of Flight-Mass Spectrometry3 (MALDI-TOF-MS3) approach. Results: We identified 61 glycoforms in tumor tissue, where CEA is upregulated. These glycosylation entities were identified as bi-antennary, tri-antennary and tetra-antennary structures carrying sialic acid and fucose residues, and include a multitude of glycans previously not reported for CEA. Conclusion: Our findings should facilitate a more precise tumor prediction than currently possible, ultimately resulting in improved tumor diagnosis and treatment.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
摘要： Background: Tandem mass spectrometry (MS/MS) acts as a key technique for peptide identification. The MS/MS-based peptide identification approaches can be categorized into two families, namely, de novo and database search. Both of the two types of approaches can benefit from an accurate prediction of theoretical spectrum. A theoretical spectrum consists of m/z and intensity of possibly occurring ions, which are estimated via simulating the spectrum generating process. Extensive researches have been conducted for theoretical spectrum prediction; however, the prediction methods suffer from low prediciton accuracy due to oversimplifications in the spectrum simulation process. Results: In the study, we present an open-source software package, called OpenMS-Simulator, to predict theoretical spectrum for a given peptide sequence. Based on the mobile-proton hypothesis for peptide fragmentation, OpenMS-Simulator trained a closed-form model for the intensity ratio of adjacent y ions, from which the whole theoretical spectrum can be constructed. On a collection of representative spectra datasets with annotated peptide sequences, experimental results suggest that OpenMS-Simulator can predict theoretical spectra with considerable accuracy. The study also presents an application of OpenMS-Simulator: the similarity between theoretical spectra and query spectra can be used to re-rank the peptide sequence reported by SEQUEST/X!Tandem. Conclusions: OpenMS-Simulator implements a novel model to predict theoretical spectrum for a given peptide sequence. Compared with existing theoretical spectrum prediction tools, say MassAnalyzer and MSSimulator, our method not only simplifies the computation process, but also improves the prediction accuracy. Currently, OpenMS-Simulator supports the prediction of CID and HCD spectrum for peptides with double charges. The extension to cover more fragmentation models and support multiple-charged peptides remains as one of the future works.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Wang, Chun-Yan
Zhou, Xue-Ping
Hong, Jian
Zhang, Chuan-Xi
Zhang, Qin-Fen
Gao, Yuan-Zhu
Ji, Gang
Huang, Xiao-Jun
摘要： Maize chlorotic mottle virus (MCMV) is the only member of the Machlomovirus genus in the family Tombusviridae. Here, we obtained the Cryo-EM structure of MCMV by single particle analysis with most local resolution at approximately 4 angstrom. The C alpha backbone was built based on residues with bulky side chains. The resolved C-terminus of the capsid protein subunit and obvious openings at the 2-fold axis demonstrated the compactness of the asymmetric unit, which indicates an important role in the stability of MCMV. The Asp116 residue from each subunit around the 5-fold and 3-fold axes contributed to the negative charges in the centers of the pentamers and hexamers, which might serve as a solid barrier against the leakage of genomic RNA. Finally, the loops most exposed on the surface were analyzed and are proposed to be potential functional sites related to MCMV transmission. (C) 2015 Elsevier Inc. All rights reserved.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-11
He, Tao
Gao, Jianmin
Roberts, Mary F.
Gershenson, Anne
Eyles, Stephen J.
Lee, Yan-Jiun
Liu, Wenshe R.
Wang, Jiangyun
摘要： Cation-pi interactions, where protein aromatic residues supply pi systems while a positive-charged portion of phospholipid head groups are the cations, have been suggested as important binding modes for peripheral membrane proteins. However, aromatic amino acids can also insert into membranes and hydrophobically interact with lipid tails. Heretofore there has been no facile way to differentiate these two types of interactions. We show that specific incorporation of fluorinated amino acids into proteins can experimentally distinguish cation-pi interactions from membrane insertion of the aromatic side chains. Fluorinated aromatic amino acids destabilize the cation-pi interactions by altering electrostatics of the aromatic ring, whereas their increased hydrophobicity enhances membrane insertion. Incorporation of pentafluorophenylalanine or difluorotyrosine into a Staphylococcus aureus phosphatidylinositol-specific phospholipase C variant engineered to contain a specific PC-binding site demonstrates the effectiveness of this methodology. Applying this methodology to the plethora of tyrosine residues in Bacillus thuringiensis phosphatidylinositol-specific phospholipase C definitively identifies those involved in cation-pi interactions with phosphatidylcholine. This powerful method can easily be used to determine the roles of aromatic residues in other peripheral membrane proteins and in integral membrane proteins.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-12
摘要： With the rapid development of high-throughput sequencing technologies, the emerging of methylated RNA immunoprecipitation sequencing (MeRIP-seq) technology makes it possible to detect RNA epigenetic modifications in a large scale, which allows transcriptome-wide profiling of RNA methylation. Mining the patterns of global mRNA methylation from these MeRIP-seq data can help reveal the potential functional roles of these mRNA methylations in regulating gene expression, splicing, RNA editing and RNA stability, effectively guiding the therapeutic intervention of cancer. Here, the principle of MeRIP-seq sequencing was first introduced. Then, the recent progress of the processing and analysis of MeRIP-seq data were comprehensively discussed. In the end, the computational problems and challenges faced in the process of MeRIP-seq data processing were also summarized.
分类： 生物学 >> 生物物理学 >> 肿瘤学 提交时间： 2016-05-11
Wang, Anxin
Chen, Lisha
Li, Chunlin
Zhu, Yimin
Wang, Anxin
Chen, Lisha
Li, Chunlin
Wang, Anxin
Chen, Lisha
Li, Chunlin
摘要： Accumulating evidence suggests that cancer stem cells (CSCs) are heterogeneous populations and their phenotypes are unstable. A number of intrinsic and extrinsic mechanisms contribute to CSC phenotypic variation. The existence of various CSC subpopulations which would lead to a rapid relapse after primary treatments might pose a problem for CSC targeted therapeutics. In order to develop more effective approaches to cancer therapeutics, more CSC-related surface markers or targeting molecules, as well as some novel targeting strategies should be explored. This review summarized the origin and performance of heterogeneity in CSCs and discussed their therapeutic implications. (c) 2014 Elsevier Ireland Ltd. All rights reserved.
分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-12
Chen, L.
Zhang, G. X.
Zhou, Y.
Zhang, C. X.
Xie, Y. Y.
Xiang, C.
He, X. Y.
Zhang, Q.
Liu, G.
Chen, L.
Zhang, Q.
摘要： p53 is an important tumor suppressor and stress response mediator. Proper control of p53 level and activity is tightly associated with its function. Posttranslational modifications and the interactions with Mdm2 and Mdm4 are major mechanisms controlling p53 activity and stability. As p53 protein is short-lived and hardly detectable in unstressed situations, less is known on its basal level expression and the corresponding controlling mechanisms in vivo. In addition, it also remains obscure how p53 expression might contribute to its functional regulation. In this study, we established bacterial artificial chromosome transgenic E.coli beta-galactosidase Z gene reporter mice to monitor p53 expression in mouse tissues and identify important regulatory elements critical for the expression in vivo. We revealed preferentially high level of p53 reporter expressions in the proliferating, but not the differentiated compartments of the majority of tissues during development and tissue homeostasis. In addition, tumors as well as regenerating tissues in the p53 reporter mice also expressed high level of beta-gal. Furthermore, both the enhancer box sequence (CANNTG) in the p53 promoter and the 3' terminal untranslated region element were critical in mediating the high-level expression of the reporter. We also provided evidence that cellular myelocytomatosis oncogene was a critical player regulating p53 mRNA expression in proliferating cells and tissues. Finally, we found robust p53 activation preferentially in the proliferating compartment of mouse tissues upon DNA damage and the proliferating cells exhibited an enhanced p53 response as compared with cells in a quiescent state. Together, these results suggested a highly regulated expression pattern of p53 in the proliferating compartment controlled by both transcriptional and posttranscriptional mechanisms, and such regulated p53 expression may impose functional significance upon stress by setting up a precautionary mode in defense of cellular transformation and tumorigenesis.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Li, Yan
Shah, Punit
De Marzo, Angelo M.
Chan, Daniel W.
Zhang, Hui
Van Eyk, Jennifer E.
Li, Yan
Lo, Qianqian
Van Eyk, Jennifer E.
摘要： Glycosylation is one of the most common protein modifications. Each glycoprotein can be glycosylated at multiple glycosites, and each glycosites can be modified by different glycans. Due to this heterogeneity of glycosylation, it has proven difficult to study the structure-function relationship of specific glycans and their affected glycoproteins. Here, we report a novel method for rapid and quantitative identification of glycoproteins containing specific glycans. Lectin affinity isolations are followed by chemical immobilization of the captured glycopeptides, allowing the identification of glycoproteins containing specific glycans by subsequent mass spectrometry. The application of the method should be useful to facilitate our understanding of how changes in glycan associate with diseases, and to discover novel glycoproteins with certain glycans that could serve as biomarkers or therapeutic targets.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-11
Wang, Zai
You, Jia
Xu, Shiqing
Zhang, Wenjian
Deng, Tingting
Fang, Qing
Liu, Honglin
Peng, Liang
Lou, Jinning
Hua, Zhan
Fang, Ni
Wang, Peigang
摘要： A significant portion of human and rat insulinomas coexpress multiple hormones. This character termed as multihormonality is also observed in some early pancreatic endocrine cells which coexpress insulin and glucagon, suggesting an incomplete differentiation status of both cells. Here we demonstrate that insulinoma cells INS-1 and INS-1-derived single cell clone INS-1-15 coexpressed insulin and glucagon in a portion of cells. These two hormones highly colocalized in the intracellular vesicles within a cell. Due to the existence of both PC1/3 and PC2 in INS-1-derived cells, proglucagon could be processed into glucagon, GLP-1 and GLP-2. These glucagon-family peptides and insulin were secreted simultaneously corresponding to the elevating glucose concentrations. The coexpression and partial colocalization of insulin and glucagon was also observed in rat fetal pancreatic endocrine cells, but the colocalization rate was generally lower and more diverse, suggesting that in the developing pancreatic endocrine cells, insulin and glucagon may be stored in nonidentical pools of secreting vesicles and might be secreted discordantly upon stimulus. (C) 2015 Elsevier Inc. All rights reserved.
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