分类： 地球科学 >> 地球科学史 提交时间： 2020-10-20 合作期刊: 《干旱区科学》
摘要： Short-term climate reconstruction, i.e., the reproduction of short-term (several decades) historical climatic time series based on the relationship between observed data and available longer-term reference data in a certain area, can extend the length of climatic time series and offset the shortage of observations. This can be used to assess regional climate change over a much longer time scale. Based on monthly grid climate data from a Coupled Model Inter-comparison Project phase 5 (CMIP5) dataset for the period of 1850–2000, the Climatic Research Unit (CRU) dataset for the period of 1901–2000 and the observed data from 53 meteorological stations located in the Tianshan Mountains region (TMR) of China during the period of 1961–2011, we calibrated and validated monthly average temperature (MAT) and monthly accumulated precipitation (MAP) in the TMR using the delta, physical scaling (SP) and artificial neural network (ANN) methods. Performance and uncertainty during the calibration (1971–1999) and verification (1961–1970) periods were assessed and compared using traditional performance indices and a revised set pair analysis (RSPA) method. The calibration and verification processes were subjected to various sources of uncertainty due to the influence of different reconstructed variables, different data sources, and/or different methods used. According to traditional performance indices, both the CRU and CMIP5 datasets resulted in satisfactory calibrated and verified MAT time series at 53 meteorological stations and MAP time series at 20 meteorological stations using the delta and SP methods for the period of 1961–1999. However, the results differed from those obtained by the RSPA method. This showed that the CRU dataset produced a low degree of uncertainty (positive connection degree) during the calibration and verification of MAT using the delta and SP methods compared to the CMIP5 dataset. Overall, the calibrated and verified MAP had a high degree of uncertainty (negative connection degree) regardless of the dataset or reconstruction method used. Therefore, the reconstructed time series of MAT for the period of 1850 (or 1901)–1960 based on the CRU and CMIP5 datasets using the delta and SP methods could be used for further study. The results of this study will be useful for short-term (several decades) regional climate reconstruction and longer-term (100 a or more) assessments of regional climate change.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
摘要： The (3R)-hydroxyacyl-ACP dehydratase HadAB, involved in the biosynthetic pathway for mycolic acid (MA) of Mycobacterium tuberculosis, catalyzes the third step in the fatty acid (FA) elongation cycle, which is an ideal and actual target for anti-tubercular agent. Though HadAB is predicted to be a member of the hotdog superfamily, it shares no sequence identity with typical hotdog fold isoenzyme FabZ. To characterize the significance of HadAB from the perspective of structural biology, large amount of pure HadAB complex is required for biochemical characterization and crystallization. Here, we used a unique expression and purification method. HadA and HadB were cloned separately and co-expressed in Escherichia coli. After GST affinity chromatography, two steps of anion exchange chromatography and gel filtration, the purity of the protein as estimated by SDS-PAGE was >95%. Using hanging-drop vapor-diffusion method, crystals were obtained and diffracted X-rays to 1.75 angstrom resolution. The crystal belongs to space group P4(1)2(1)2, with unit-cell parameters a = b = 82.0 angstrom, c = 139.8 angstrom, alpha = beta = gamma = 90.0 degrees. (C) 2015 The Authors. Published by Elsevier Inc.
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： 2016-05-15
摘要： The cyclic nucleotide-binding (CNB)-like protein (CNB-L) from Brucella abortus shares sequence homology with CNB domain-containing proteins. We determined the crystal structure of CNB-L at 2.0 angstrom resolution in the absence of its C-terminal helix and nucleotide. The 3D structure of CNB-L is in a twofold symmetric form. Each protomer shows high structure similarity to that of cGMP-binding domain-containing proteins, and likely mimics their nucleotide-free conformation. A key residue, Glu17, mediates the dimerization and prevents binding of cNMP to the canonical ligand-pocket. The structurally observed dimer of CNB-L is stable in solution, and thus is likely to be biologically relevant. (C) 2015 Elsevier Inc. All rights reserved.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-15
Dong, Jing
Zhang, Yong
Zhang, Yu
Deng, Xuming
Dong, Jing
Chen, Yutao
Wang, Quan
Li, Xuemei
Niu, Xiaodi
Yang, Cheng
摘要： Shiga-like toxins (Stxs), produced by pathogenic Escherichia coli, are a major virulence factor involved in severe diseases in human and animals. These toxins are ribosome-inactivating proteins, and treatment for diseases caused by them is not available. Therefore, there is an urgent need for agents capable of effectively targeting this lethal toxin. In this study, we identified baicalin, a flavonoid compound used in Chinese traditional medicine, as a compound against Shiga-like toxin 2 (Stx2). We found that baicalin significantly improves renal function and reduces Stx2-induced lethality in mice. Further experiments revealed that baicalin induces the formation of oligomers by the toxin by direct binding. We also identified the residues important for such interactions and analyzed their roles in binding baicalin by biophysical and biochemical analyses. Our results establish baicalin as a candidate compound for the development of therapeutics against diseases caused by Stxs.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Liu, Wu
Chen, Yutao
Yang, Yang
Li, Xuemei
Rao, Zihe
Jiang, Xi
Xia, Ming
Tan, Ming
Jiang, Xi
Tan, Ming
摘要： Norovirus (NoV) causes epidemic acute gastroenteritis in humans, whereby histo-blood group antigens (HBGAs) play an important role in host susceptibility. Each of the two major genogroups (GI and GII) of human NoVs recognizes a unique set of HBGAs through a distinct binding interface that is conserved within a genogroup, indicating a distinct evolutionary path for each genogroup. Here, we characterize a Lewis a (Le(a)) antigen binding strain (OIF virus) in the GII. 21 genotype that does not share the conserved GII binding interface, revealing a new evolution lineage with a distinct HBGA binding interface. Sequence alignment showed that the major residues contributing to the new HBGA binding interface are conserved among most members of the GII. 21, as well as a closely related GII. 13 genotype. In addition, we found that glycerol inhibits OIF binding to HBGAs, potentially allowing production of cheap antivirals against human NoVs. Taken together, our results reveal a new evolutionary lineage of NoVs selected by HBGAs, a finding that is important for understanding the diversity and widespread nature of NoVs.
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
Dong, Jing
Zhang, Yong
Zhang, Yu
Li, Rui
Deng, Xuming
Dong, Jing
Chen, Yutao
Wang, Quan
Li, Xuemei
Niu, Xiaodi
Yang, Cheng
摘要： Toxic ribosome-inactivating proteins abolish cell viability by inhibiting protein synthesis. Ricin, a member of these lethal proteins, is a potential bioterrorism agent. Despite the grave challenge posed by these toxins to public health, post-exposure treatment for intoxication caused by these agents currently is unavailable. In this study, we report the identification of baicalin extracted from Chinese herbal medicine as a compound capable of inhibiting the activity of ricin. More importantly, post-exposure treatment with baicalin significantly increased the survival of mice poisoned by ricin. We determined the mechanism of action of baicalin by solving the crystal structure of its complex with the A chain of ricin (RTA) at 2.2 angstrom resolution, which revealed that baicalin interacts with two RTA molecules at a novel binding site by hydrogen bond networks and electrostatic force interactions, suggesting its role as molecular glue of the RTA. Further biochemical and biophysical analyses validated the amino acids directly involved in binding the inhibitor, which is consistent with the hypothesis that baicalin exerts its inhibitory effects by inducing RTA to form oligomers in solution, a mechanism that is distinctly different from previously reported inhibitors. This work offers promising leads for the development of therapeutics against ricin and probably other ribosome-inactivating proteins.
分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-11
Hao, Ning
Chen, Yutao
Liu, Wu
Guan, Xiaotao
Li, Xuemei
Rao, Zihe
Hao, Ning
Xia, Ming
Tan, Ming
Jiang, Xi
Xia, Ming
Jiang, Xi
摘要： Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as attachment factors, in which genogroup (G) I and GII huNoVs use distinct binding interfaces. The genetic and evolutionary relationships of GII huNoVs under selection by the host HBGAs have been well elucidated via a number of structural studies; however, such relationships among GI NoVs remain less clear due to the fact that the structures of HBGA-binding interfaces of only three GI NoVs with similar binding profiles are known. In this study the crystal structures of the P dimers of a Lewis-binding strain, the GI.8 Boxer virus (BV) that does not bind the A and H antigens, in complex with the Lewis b (Le(b)) and Le(y) antigens, respectively, were determined and compared with those of the three previously known GI huNoVs, i.e. GI.1 Norwalk virus (NV), GI.2 FUV258 (FUV) and GI.7 TCH060 (TCH) that bind the A/H/Le antigens. The HBGA binding interface of BV is composed of a conserved central binding pocket (CBP) that interacts with the beta-galactose of the precursor, and a well-developed Le epitope-binding site formed by five amino acids, including three consecutive residues from the long P-loop and one from the S-loop of the P1 subdomain, a feature that was not seen in the other GI NoVs. On the other hand, the H epitope/acetamido binding site observed in the other GI NoVs is greatly degenerated in BV. These data explain the evolutionary path of GI NoVs selected by the polymorphic human HBGAs. While the CBP is conserved, the regions surrounding the CBP are flexible, providing freedom for changes. The loss or degeneration of the H epitope/acetamido binding site and the reinforcement of the Le binding site of the GI.8 BV is a typical example of such change selected by the host Lewis epitope.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Wang, Xiangxi
Gao, Qiang
Sun, Yao
Li, Xuemei
Rao, Zihe
Ren, Jingshan
Stuart, David I.
Fry, Elizabeth E.
Gao, Qiang
Yin, Weidong
Hu, Zhongyu
Wang, Junzhi
Rowlands, David J.
Rowlands, David J.
Stuart, David I.
Rao, Zihe
Rao, Zihe
摘要： Hepatitis A virus(HAV) remains enigmatic, despite 1.4 million cases worldwide annually(1). It differs radically from other picornaviruses, existing in an enveloped form(2) and being unusually stable, both genetically and physically(3), but has proved difficult to study. Here we report high-resolution X-ray structures for the mature virus and the empty particle. The structures of the two particles are indistinguishable, apart from some disorder on the inside of the empty particle. The full virus contains the small viral protein VP4, whereas the empty particle harbours only the uncleaved precursor, VP0. The smooth particle surface is devoid of depressions that might correspond to receptor-binding sites. Peptide scanning data extend the previously reported VP3 antigenic site4, while structure-based predictions(5) suggest further epitopes. HAV contains no pocket factor and can withstand remarkably high temperature and low pH, and empty particles are even more robust than full particles. The virus probably uncoats via a novel mechanism, being assembled differently to other picornaviruses. It utilizes a VP2 'domain swap' characteristic of insect picorna-like viruses(6,7), and structure-based phylogenetic analysis places HAV between typical picornaviruses and the insect viruses. The enigmatic properties of HAV may reflect its position as a link between 'modern' picornaviruses and the more 'primitive' precursor insect viruses; for instance, HAV retains the ability to move from cell-to-cell by transcytosis(8,9).
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