Energetics and protomer communication in the dynamical structure of S100A13 in free and protein-bound states

S100A13 is S100 family of EF-hand-containing calcium-binding protein involved in the secretion of some growth factors and pro-inflammatory cytokines lacking signal peptides. The involvement of S100A13 in cancer progression and inflammatory diseases has been reported. In this study, structures generated during atomistic molecular dynamics simulation were studied. Dynamical network analysis data revealed that native inter-protomer communication network driven principally by vdW interaction (~550 kj/mol) is altered (Receptor for advanced glycation end products (RAGE) C2- and Fibroblast growth factor (FGF)-1-bound S100A13) or completely abolished (interleukin-1 (IL1)-α- and C2A-p40Syt1-bound S100A13) in protein-bound S100A13 homodimer. Bulk water density (weighted atomic density) around exposed S100A13 homodimer surface explored tends to follow the dynamical network lead as S100A13 homodimer appeared densely solvated in C2A-p40Syt1- and IL1)-α-bound states but not in RAGE C2- and FGF-1-bound biosystems. Furthermore, projection of radius of gyration and root mean square deviation (from native structure) variables of the generated structures along the 3D-free energy surface showed anti-parallel β-sheet proximal to Ca²⁺-binding loops-I/II in most metastable complexes retrieved from energy minima state with strong indications for β-sheet network formation during protein binding. Interaction between S100A13 homodimer and ligand–proteins may be dictated by the strength of vdW and electrostatic interaction with possible involvement of bulk water desolvation in some complexes. All these results strongly suggest that disruption of multiprotein receptor complex can be achieved by designing specific compounds targeting a specific aspect of S100A13/protein interaction; such drugs may have clinical usefulness in blocking angiogenesis, reversing cell proliferation and attenuating inflammatory processes.     

20世纪90年代以来中国生态空间演化的时空格局和梯度效应

改革开放以来中国经济和城市化的快速发展促使生产和生活空间挤占大量生态空间，系统认识和评估我国生态空间演化的宏观格局和过程对于生态文明建设具有重要的理论和现实意义。为揭示全国生态空间变化的时空过程，在对生态空间内涵进行界定的基础上，结合全国尺度时序土地利用数据构建生态空间分类体系，并评估1990-2015年中国生态空间演化特征。结果表明：1990-2015年中国生态用地面积持续减少，主要向半生态用地转变，发生在重要的粮食生产区域及周边；半生态用地面积波动明显，前期主要表现为不断扩张，后期大量转换为弱生态用地，发生在主要城市群地区；弱生态用地持续扩张，与城镇化进程不断加速相关。中国生态空间演变过程表现出一定的区域差异和梯度效应，不同区域生态空间变化发生的拐点时间有所不同，呈现"自东向西、由南到北"的3级梯度特征，区域生态空间状况与经济发展战略及生态空间管控具有较强的相关性。本研究对于国家生态空间管控近远期战略方案制订具有一定启示，建议处于不同梯度的各地区应基于区域生态空间演化所处阶段和不同驱动机制，确定分区域生态空间安全红线目标和生态空间管控方案。     

Prophylactic and curative effects of Bacopa monniera in gastric ulcer models.

Bacopa monniera Wettst. (BM, syn. Herpestis monniera L; Scrophulariaceae), is an Ayurvedic drug used as a rasayana. Its fresh juice was earlier reported to have significant antiulcerogenic activity. In continuation, methanolic extract of BM (BME) standardized to bacoside-A content (percentage-38.0 ± 0.9), when given in the dose of 10–50 mg/kg, twice daily for 5 days, showed dose-dependent anti-ulcerogenic on various gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. BME in the dose of 20 mg/kg, given for 10 days, twice daily showed healing effects against 50% acetic acid-induced gastric ulcers. Further work was done to investigate the possible mechanisms of its action by studying its effect on various mucosal offensive acid-pepsin secretion and defensive factors like mucin secretion, mucosal cell shedding, cell proliferation and antioxidant activity in rats. BME 20 mg/kg showed no effect on acid-pepsin secretion, increased mucin secretion, while it decreased cell shedding with no effect on cell proliferation. BME showed significant antioxidant effect per se and in stressed animals. Thus, the gastric prophylactic and curative effects of BME may be due to its predominant effect on mucosal defensive factors.     

Effect of Different Carbon and Nitrogen Sources on Clostridium argentinense Toxigenicity in Coculture withPseudomonas mendocina

The effect of different carbon and nitrogen sources on the production of toxin by Clostridium argentinense was examined. The toxin production by C. argentinense in coculture with Pseudomonas mendocina increased in all the cases in relation to that produced by monocultures independent of the nature of the source. Using dextrin as carbon source C. argentinense produced the highest levels of toxin both in monocultures (300 LD₅₀/mL) and in cocultures with P. mendocina (5000 LD₅₀/mL). Experiments run in a microfermenter showed that the slow growth of cocultures associated with the assimilation of dextrin and the pH and Eh profiles favoured the production of toxin. Of the nitrogen sources assayed, corn steep liquor sustained the highest levels of toxin in both monocultures and cocultures with 3 and 2.8 fold increases with respect to that obtained using proteose peptone. The toxin production by C. argentinense cultures and C. argentinense–P. mendocina cocultures was highly dependent on the nature of the carbon and nitrogen sources used in the culture media. Growth of C. argentinense on substrates slowly assimilated stimulated the production of toxin.     

Distinguishing Drift and Selection Empirically: “The Great Snail Debate” of the 1950s

Biologists and philosophers have been extremely pessimistic about the possibility of demonstrating random drift in nature, particularly when it comes to distinguishing random drift from natural selection. However, examination of a historical case – Maxime Lamotte’s study of natural populations of the land snail, Cepaea nemoralis in the 1950s – shows that while some pessimism is warranted, it has been overstated. Indeed, by describing a unique signature for drift and showing that this signature obtained in the populations under study, Lamotte was able to make a good case for a significant role for␣drift. It may be difficult to disentangle the causes of drift and selection acting in a population, but it is not (always) impossible.     

Butterfly Response to Microclimatic Conditions Following Ponderosa Pine Restoration

Efforts to restore ponderosa pine ecosystems to open, park‐like conditions that predominated prior to European‐American settlement result in altered stand structure and increased landscape heterogeneity, potentially altering habitat suitability for invertebrates and other forest organisms. We examined the responses of two butterfly species, Colias eurytheme and Neophasia menapia, to microclimatic changes at structural edges created by experimental restoration treatments in northern Arizona. We monitored microclimate, including air temperature, light intensity, and vapor pressure deficit (VPD), on several mornings during butterfly releases. We placed adult butterflies at east‐ and west‐facing edges approximately one half‐hour before dawn to determine their behavioral response to microclimatic differences between east‐ and west‐facing edges. After sunrise, all three microclimatic variables were higher at east‐facing edges, and the difference in microclimate between the two edge orientations increased through early morning. For both species, butterflies placed at east‐facing edges flew earlier than butterflies at west‐facing edges. Colias eurytheme, an open‐habitat species, tended to move toward the treated forest during initial flight, while movements of Neophasia menapia, a forest‐dwelling species, did not differ from random flight. Our results indicate that butterflies respond to microclimatic factors associated with restoration treatments, while responses to structural changes in habitat vary among species, based on habitat and food plant preferences. These changes in forest structure and microclimate may affect the distribution of many mobile invertebrates in forested landscapes undergoing restoration treatments.     

追溯山茱萸科植物的性状进化和生物地理学历史——方法选择的影响?

This study compares results on reconstructing the ancestral state of characters and ancestral areas of distribution in Cornaceae to gain insights into the impact of using different analytical methods. Ancestral character state reconstructions were compared among three methods (parsimony, maximum likelihood, and stochastic character mapping) using MESQUITE and a full Bayesian method in BAYESTRAITS and inferences of ancestral area distribution were compared between the parsimony-based dispersal-vicariance analysis (DIVA) and a newly developed maximum likelihood (ML) method. Results indicated that among the six inflorescence and fruit characters examined, "perfect" binary characters (no homoplasy, no polymorphism within terminals, and no missing data) are little affected by choice of method, while homoplasious characters and missing data are sensitive to methods used. Ancestral areas at deep nodes of the phylogeny are substantially different between DIVA and ML and strikingly different between analyses including and excluding fossils at three deepest nodes. These results, while raising caution in making conclusions on trait evolution and historical biogeography using conventional methods, demonstrate a limitation in our current understanding of character evolution and biogeography. The biogeographic history favored by the ML analyses including fossils suggested the origin and early radiation of Cornus likely occurred in the late Cretaceous and earliest Tertiary in Europe and intercontinental disjunctions in three lineages involved movements across the North Atlantic Land Bridge (BLB) in the early and mid Tertiary. This result is congruent with the role of NALB for post-Eocene migration and in connecting tropical floras in North America and Africa, and in eastern Asia and South America. However, alternative hypotheses with an origin in eastern Asia and early Trans-Beringia migrations of the genus cannot be ruled out.     

The Oxidative Inactivation of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) by Hypochlorous Acid (HOCl) is Suppressed by Anti-Rheumatic Drugs

Tissue inhibitors of metalloproteinases (TIMPs) prevent uncontrolled connective tissue destruction by limiting the activity of matrix metalloproteinases (MMPs). That TIMPs should be susceptible to oxidative inactivation is suggested by their complex tertiary structure which is dependent upon 6 disulphide bonds. We examined the oxidative inactivation of human recombinant TIMP-1 (hr TIMP-1) by HOCl and the inhibition of this process by anti-rheumatic agents.

TIMP-1 was exposed to HOCl in the presence of a variety of disease modifying anti-rheumatic drugs. TIMP-1 activity was measured by its ability to inhibit BC1 collagenase activity as measured by a fluorimetric assay using the synthetic pEptide substrate (DNP-Pro-Leu-Ala-Leu-Trp-Ala-Arg), best cleaved by MMP-1.

The neutrophil derived oxidant HOCl, but not the derived oxidant N-chlorotaurine, can inactivate TIMP-1 at concentrations achieved at sites of inflammation. Anti-rheumatic drugs have the ability to protect hrTIMP-1 from inactivation by HOCl. For D-penicil-lamine, this effect occurs at plasma levels achieved with patients taking the drug but for other anti-rheumatic drugs tested this occurs at relatively high concentrations that are unlikely to be achieved in vivo, except possibly in a microenvironment. These results are in keeping with the concept that biologically derived oxidants can potentiate tissue damage by inactivating key but susceptible protein inhibitors such as TIMP-1 which form the major local defence against MMP induced tissue breakdown.