Secondary metabolite as therapeutic agent from endophytic fungi Alternaria longipes strain VITN14G of mangrove plant Avicennia officinalis

Endophytic fungi, especially from mangrove plants, are rich source of secondary metabolites, which plays a major role in various pharmacological actions preferably in cancer and bacterial infections. To perceive its role in antidiabetic activity we isolated and tested the metabolites derived from a novel strain Alternaria longipes strain VITN14G obtained from mangrove plant Avicennia officinalis. The crude extract was analyzed for antidiabetic activity and subjected to column chromatography. The isolated fractions were screened in vitro for α-glucosidase and α-amylase inhibitory activities. The cytotoxicity of the isolated fractions was studied on L929 cell lines. Following which, the screened fraction 2 was allowed for structure elucidation using gas chromatography-mass spectrometry, one-dimensional, two-dimensional nuclear magnetic resonance spectroscopy, ultraviolet, and Fourier-transform infrared analysis. The binding energies of the isolated fraction 2 with glycolytic enzymes were calculated by molecular docking studies using AutoDock Vina. The isolated fraction 2 identified as 2,4,6-triphenylaniline, showed no significant difference in α-amylase inhibition rates and a significant difference of 10% in α-glucosidase inhibition rates than that of the standard drug acarbose. Further, the cytotoxicity assay of the isolated fraction 2 resulted in a cell viability of 73.96%. Supportingly, in silico studies showed 2,4,6-triphenylaniline to produce a stronger binding affinity toward the glycolytic enzyme targets. The compound 2,4,6-triphenylaniline isolated from A. longipes strain VITN14G exhibited satisfactory antidiabetic activity for type 2 diabetes in vitro, which will further be confirmed by in vivo studies. Successful outcome of the study will result in a natural substitute for existing synthetic antidiabetic drugs.     

Site-Specific Structural Variations Accompanying Tubular Assembly of the HIV-1 Capsid Protein

The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent ¹⁵N and ¹³C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide ¹H nuclei, and quantitative measurements of site-specific ¹⁵N–¹⁵N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 3₁₀-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant.     

Pore-forming Activity of the Escherichia coli Type III Secretion System Protein EspD

Enterohemorrhagic Escherichia coli is a causative agent of gastrointestinal and diarrheal diseases. Pathogenesis associated with enterohemorrhagic E. coli involves direct delivery of virulence factors from the bacteria into epithelial cell cytosol via a syringe-like organelle known as the type III secretion system. The type III secretion system protein EspD is a critical factor required for formation of a translocation pore on the host cell membrane. Here, we show that recombinant EspD spontaneously integrates into large unilamellar vesicle (LUV) lipid bilayers; however, pore formation required incorporation of anionic phospholipids such as phosphatidylserine and an acidic pH. Leakage assays performed with fluorescent dextrans confirmed that EspD formed a structure with an inner diameter of ∼2.5 nm. Protease mapping indicated that the two transmembrane helical hairpin of EspD penetrated the lipid layer positioning the N- and C-terminal domains on the extralumenal surface of LUVs. Finally, a combination of glutaraldehyde cross-linking and rate zonal centrifugation suggested that EspD in LUV membranes forms an ∼280–320-kDa oligomeric structure consisting of ∼6–7 subunits.     

Purification and partial characterization of a type V like collagen from the muscle of marine prawn,Penaeus indicus

The muscle collagen of marine prawn,Penaeus indicus, was isolated by limited pepsin digestion. Based on selective salt precipitation, amino acid composition and gel electrophoretic pattern, the major collagen was found to be a homotrimer of á 1 chain, similar to type V collagen of vertebrates. Electron microscopy of reconstituted fibrils, made for the first time from a crustacean species, revealed a characteristic 64 nm periodicity. Biochemical studies indicate a less than normal amount of associated carbohydrates and an increased alanine content The major collagen had a denatu ration temperature of 37°C with an intrinsic viscosity of 11.3 dl/g. Spectral characteristics of the major collagen were studied. Results suggest the presence of genetically distinct collagen types and acid resistant cross links in crustacean muscle.     

典型矿区植被覆盖度时空分布特征及影响因素

植被状况可以直接或间接地反映采煤对生态环境的影响。以长河井工煤矿、离柳井工煤矿、平朔露天煤矿3个典型矿区为研究区域。以Landsat数据为数据源，基于地形调节植被指数的像元二分模型提取植被覆盖度；采用趋势分析、线性回归斜率、稳定性分析方法，分析了3个典型矿区2001-2016年植被覆盖度的时空变化特征；运用"以时间换空间"的方法，采用相关分析方法对植被覆盖度变化的自然影响因素进行了分析。结果表明：（1）近16年3个典型矿区植被覆盖度呈增加趋势，长河、离柳、平朔矿区的增长速率分别为0.09%/10 a、0.10%/10 a、0.08%/10 a（P > 0.05）。（2）空间上，长河、离柳、平朔矿区植被覆盖度变化不明显比例分别占到66.63%，59.90%，62.25%，呈增加趋势的比例仅分别占28.14%、32.55%、27.81%，而呈减少趋势的比例分别占到5.23%、7.55%、9.94%。长河矿区明显改善的区域位于自然植被和耕作区的北部和东北部，离柳矿区明显改善的区域位于以低植被覆盖度为主的北部，平朔矿区明显改善的区域位于复垦的中西部。（3）不区分植被类型时，3个矿区的植被覆盖度变化与高程、高程与温度的交互作用表现出显著相关性（P < 0.01），与各自然因素的相关性总体表现为长河 > 离柳 > 平朔矿区；区分植被类型时，草地与坡度的相关性不显著（P > 0.05），与降雨量、高程存在显著正相关（P < 0.05）；灌木林与温度相关性不显著，与高程和降雨量的交互作用存在显著正相关；旱地与高程、高程与温度的交互作用存在显著相关性；疏林地与坡向、降雨量与坡向坡度的交互作用均没有表现出相关性；有林地与高程降雨量的交互作用表现出显著正相关性。探讨不同植被类型对自然因素的响应，可为矿区植被结构的选择，矿区复垦提供参考依据。     

The role of lipid second messengers in aldosterone synthesis and secretion

Second messengers are small rapidly diffusing molecules or ions that relay signals between receptors and effector proteins to produce a physiological effect. Lipid messengers constitute one of the four major classes of second messengers. The hydrolysis of two main classes of lipids, glycerophospholipids and sphingolipids, generate parallel profiles of lipid second messengers: phosphatidic acid (PA), diacylglycerol (DAG), and lysophosphatidic acid versus ceramide, ceramide-1-phosphate, sphingosine, and sphingosine-1-phosphate, respectively. In this review, we examine the mechanisms by which these lipid second messengers modulate aldosterone production at multiple levels. Aldosterone is a mineralocorticoid hormone responsible for maintaining fluid volume, electrolyte balance, and blood pressure homeostasis. Primary aldosteronism is a frequent endocrine cause of secondary hypertension. A thorough understanding of the signaling events regulating aldosterone biosynthesis may lead to the identification of novel therapeutic targets. The cumulative evidence in this literature emphasizes the critical roles of PA, DAG, and sphingolipid metabolites in aldosterone synthesis and secretion. However, it also highlights the gaps in our knowledge, such as the preference for phospholipase D-generated PA or DAG, as well as the need for further investigation to elucidate the precise mechanisms by which these lipid second messengers regulate optimal aldosterone production.