Ethological and environmental significance of Bergaueria hemispherica from the Late Cretaceous of the Bagh Group,Western India

The probable trace maker of B. hemispherica is the fact that one encounters different age groups of sea anemone burrows extended at variable depths in soft, unconsolidated, non-fluidized mud to get stability. It occurs as densely packed, vertical to subvertical, usually unornamented, occasionally showing faint, thin, ring-like structures, allochemic sandstone-filled cylinders with hemispherical base extending to variable depths in the shale. The diameter-to-height ratio calculated for 44 burrow specimens shows that the diameters of most of the specimen are smaller than their height. The probable trace maker of B. hemispherica is the fact that one encounters different age groups of sea anemones, which extended their column at variable depth in soft, unconsolidated, non-fluidized mud to get stability. The inclined nature of paired burrows towards each other suggests social aggression while unpaired inclined burrows suggest swaying in search of food. The monodominant occurrence of B. hemispherica as pre-storm colonization of r-selected organisms (sea anemones) suggest sstressed environment and simultaneous vacation of the burrower reflects rapid sedimentation due to high-energy storm events. Further, storm and inter-storm events deposited sandy allochemic limestone and shale series, respectively, but did not form an identical condition for the colonization of the sea anemone. The species B. hemispherica of the Bagh Group revealed physicochemical parameters (energy conditions, turbidity, sedimentation rate, bathymetry, suspended organic matter, substrate consistency, oxygen, and salinity) of the Late Cretaceous transgressive sea.     

Discovery and optimization of heteroaryl piperazines as potent and selective PI3Kδ inhibitors

A high-throughput screening (HTS) campaign identified a class of heteroaryl piperazines with excellent baseline affinity and selectivity for phosphoinositide 3-kinase δ (PI3Kδ) over closely related isoforms. Rapid evaluation and optimization of structure-activity relationships (SAR) for this class, leveraging the modular nature of this scaffold, facilitated development of this hit class into a series of potent and selective inhibitors of PI3Kδ. This effort culminated in the identification of 29, which displayed excellent potency in enzyme and cell-based assays, as well as favorable pharmacokinetic and off-target profiles.     

Extraction,purification and characterization of water-soluble polysaccharides from green walnut husk with anti-oxidant and anti-proliferative capacities

This work was designed to study the physicochemical properties, and bioactivity of green walnut husk polysaccharides (GWHP). The crude GWHP was fractionated into three fractions, namely, GWHP-1, GWHP-2 and GWHP-3, using Cellulose DEAE-52 and Sephadex G-150. HPLC analysis showed that the three fractions were heteropolysaccharides consisting primarily of glucose, galactose and arabinose with average molecular weights of 165.06, 179.64 and 255.75 kDa, respectively, and that the monosaccharide composition of GWHP-1 was more complicated than those of GWHP-2 and GWHP-3. The primary structures of the GWHP fractions were similar to each other. GWHP-1, obtained from water elution, showed higher anti-oxidant activities in the tested concentration range of 0.1–1.8 mg/mL than did GWHP-2 and GWHP-3, which were obtained by elution with 0.1 M and 0.2 M NaCl solutions. Additionally, the GWHP-1 fraction showed the most effective anti-proliferative activity among the three fractions, which was associated with the weakened cell proliferation and increased lactate dehydrogenase (LDH) leakage of LoVo cells. However, GWHP-1 displayed a lower growth inhibition effect on colonic NCM640 cells, which was characterized by low LDH leakage. The above results indicated that the polysaccharides, especially GWHP-1, may be a valuable natural anti-oxidant and anti-cancer cell source for applications in the pharmaceutical and food industries.     

产紫色素真菌H-1的鉴定及其色素的理化性质和生物活性

从腐殖土样中分离得到一株产水溶性紫色素真菌,编号为H-1。通过对该真菌β-微管蛋白基因序列分析,并构建系统进化树进行初步鉴定,对色素性质如色素特征性吸收峰、溶解性、稳定性、细胞增殖抑制活性、抗菌活性等进行研究。结果表明,H-1与萨氏曲霉(Aspergillus sydowii)的同源性达到了100%,属于萨氏曲霉。该色素在520 nm处有特征性吸收峰,极易溶于水,低浓度乙醇和甲醇溶液,不溶于其他非极性溶剂。该色素对光的稳定性表现为:紫外光>黑暗>-白光;100℃处理色素4 h,色素残存率为86.8%,热稳定性较好,在碱性条件下稳定,在Na+溶液残存率为99.9%,基本无损失。与正常人肝细胞HL-7702相比,该色素具有抑制人肝癌细胞HepG2增殖作用,其半数抑制浓度(IC50)为1.282 mg/mL;同时该色素具有清除羟自由基与超氧阴离子自由基的作用,也能明显抑制藤黄八叠球菌、金黄色葡萄球菌的生长,其最低抑菌浓度(minimal inhibitory concentration, MIC)均为195.312μg/mL,对大肠杆菌无明显抑菌活性。     

Discovery and evaluation of novel nitrodihydroimidazooxazoles as promising anti-tuberculosis agents

New analogues of antitubercular drug Delamanid were prepared, seeking drug candidates with enhanced aqueous solubility and high efficacy. The strategy involved replacement of phenoxy linker proximal to the 2-nitroimidazooxazole of Delamanid by piperidine fused 5 or 6-membered ring heterocycles (ring A). The new compounds were all more hydrophilic than Delamanid, and several class of analogues showed remarkable activities against M. bovis. And among these series, the tetrahydro-naphthyridine-linked nitroimidazoles displayed excellent antimycobacterial activity against both replicating (MABA) and nonreplicating (LORA) M. tb H37Rv and low cytotoxicity. Compared to Delamanid, these new compounds (6, 7, 45) demonstrated dramatically improved physicochemical properties and are suitable for further in vitro and in vivo evaluation.     

Effect of acetylation and succinylation on physicochemical properties and structural characteristics of oat protein isolate

The effects of acetylation and succinylation on physicochemical properties and structural characteristics of oat protein isolate (OPI) were investigated. The degree of N-acylation rapidly increased prior to O-acylation, due to higher reactivity of ε-amino groups than hydroxyl groups. The acylation was able to decrease zeta potential of OPI at neutral pH, and succinylated OPI had lower zeta potential than acetylated OPI. The surface hydrophobicity (H₀) of OPI was changed significantly by acylation treatment, which varied with the type and level of applied anhydrides. The succinylation led to a remarkable increase in the molecular weight of OPI determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The secondary structure and tertiary conformation of proteins in the OPI was analyzed by Fourier transform infrared (FTIR) and intrinsic fluorescence spectroscopy. The acylation could result in the transformation of β-sheet to α-helix and random coil, and less compact tertiary conformation, especially succinylation.     

Effect of physicochemical properties of peptides from soy protein on their antimicrobial activity

Antimicrobial peptides (AMPs) kill microbial cells through insertion and damage/permeabilization of the cytoplasmic cell membranes and has applications in food safety and antibiotic replacement. Soy protein is an attractive, abundant natural source for commercial production of AMPs. In this research, explicit solvent molecular dynamics (MD) simulation was employed to investigate the effects of (i) number of total and net charges, (ii) hydrophobicity (iii) hydrophobic moment and (iv) helicity of peptides from soy protein on their ability to bind to lipid bilayer and their transmembrane aggregates to form pores. Interaction of possible AMP segments from soy protein with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPC/POPG) bilayers, a mimic of bacterial cell membrane, was investigated. Pore formation was insensitive to helicity and occurred for hydrophobicity threshold in the range of −0.3–0 kcal/mol, hydrophobic moment threshold of 0.3 kcal/mol, net charge threshold of 2. Though low hydrophobicity and high number of charges help in the formation of water channel for transmembrane aggregates, insertion of peptides with these properties requires overcome of energy barrier, as shown by potential of mean force calculations, thereby resulting in low antimicrobial activity. Experimental evaluation of antimicrobial activity of these peptides against Gram positive L. monocytogenes and Gram negative E. coli as obtained by spot-on-lawn assay was consistent with simulation results. These results should help in the development of guidelines for selection of peptides with antimicrobial activity based on their physicochemical properties.     

Biological and Physiochemical Methods of Biofilm Adhesion Resistance Control of Medical-Context Surface

The formation of biofilms on medical-context surfaces gives the EPS embedded bacterial community protection and additional advantages that planktonic cells would not have such as increased antibiotic resistance and horizontal gene transfer. Bacterial cells tend to attach to a conditioning layer after overcoming possible electrical barriers and go through two phases of attachments: reversible and irreversible. In the first, bacterial attachment to the surface is reversible and occurs quickly whilst the latter is permanent and takes place over a longer period of time. Upon reaching a certain density in the bacterial community, quorum sensing causes phenotypical changes leading to a loss in motility and the production of EPS. This position paper seeks to address the problem of bacterial adhesion and biofilm formation for the medical surfaces by comparing inhabiting physicochemical interactions and biological mechanisms. Several physiochemical methodologies (e.g. ultrasonication, alternating magnetic field and chemical surface coating) and utilizing biological mechanisms (e.g. quorum quenching and EPS degrading enzymes) were suggested. The possible strategical applications of each category were suggested and evaluated to a balanced position to possibly eliminate the adhesion and formation of biofilms on medical-context surfaces.