Rationally designed turn promoting mutation in the amyloid-β peptide sequence stabilizes oligomers in solution

Enhanced production of a 42-residue beta amyloid peptide (Aβ(42)) in affected parts of the brain has been suggested to be the main causative factor for the development of Alzheimer's Disease (AD). The severity of the disease depends not only on the amount of the peptide but also its conformational transition leading to the formation of oligomeric amyloid-derived diffusible ligands (ADDLs) in the brain of AD patients. Despite being significant to the understanding of AD mechanism, no atomic-resolution structures are available for these species due to the evanescent nature of ADDLs that hinders most structural biophysical investigations. Based on our molecular modeling and computational studies, we have designed Met35Nle and G37p mutations in the Aβ(42) peptide (Aβ(42)Nle35p37) that appear to organize Aβ(42) into stable oligomers. 2D NMR on the Aβ(42)Nle35p37 peptide revealed the occurrence of two β-turns in the V24-N27 and V36-V39 stretches that could be the possible cause for the oligomer stability. We did not observe corresponding NOEs for the V24-N27 turn in the Aβ(21-43)Nle35p37 fragment suggesting the need for the longer length amyloid peptide to form the stable oligomer promoting conformation. Because of the presence of two turns in the mutant peptide which were absent in solid state NMR structures for the fibrils, we propose, fibril formation might be hindered. The biophysical information obtained in this work could aid in the development of structural models for toxic oligomer formation that could facilitate the development of therapeutic approaches to AD.     

Environmental factors determining ammonia-oxidizing organism distribution and diversity in marine environments

Ammonia-oxidizing bacteria (AOB) and archaea (AOA) play a vital role in bridging the input of fixed nitrogen, through N-fixation and remineralization, to its loss by denitrification and anammox. Yet the major environmental factors determining AOB and AOA population dynamics are little understood, despite both groups having a wide environmental distribution. This study examined the relative abundance of both groups of ammonia-oxidizing organisms (AOO) and the diversity of AOA across large-scale gradients in temperature, salinity and substrate concentration and dissolved oxygen. The relative abundance of AOB and AOA varied across environments, with AOB dominating in the freshwater region of the Chesapeake Bay and AOA more abundant in the water column of the coastal and open ocean. The highest abundance of the AOA amoA gene was recorded in the oxygen minimum zones (OMZs) of the Eastern Tropical South Pacific (ETSP) and the Arabian Sea (AS). The ratio of AOA : AOB varied from 0.7 in the Chesapeake Bay to 1600 in the Sargasso Sea. Relative abundance of both groups strongly correlated with ammonium concentrations. AOA diversity, as determined by phylogenetic analysis of clone library sequences and archetype analysis from a functional gene DNA microarray, detected broad phylogenetic differences across the study sites. However, phylogenetic diversity within physicochemically congruent stations was more similar than would be expected by chance. This suggests that the prevailing geochemistry, rather than localized dispersal, is the major driving factor determining OTU distribution.     

Effect of Phenolic Compounds Against A<Emphasis Type="Italic">β</Emphasis> Aggregation and A<Emphasis Type="Italic">β</Emphasis>-Induced Toxicity in Transgenic <Emphasis Type="Italic">C. elegans</Emphasis>

Substantial evidence suggests that the aggregation of amyloid-β (Aβ) peptide into fibrillar structures that is rich in β-sheets is implicated as the cause of Alzheimer’s disease. Therefore, an attractive therapeutic strategy is to prevent or alter Aβ aggregation. Phenolic compounds are natural substances that are composed of one or more aromatic phenolic rings and present in wine, tea, fruits, vegetables and a wide variety of plants. In this work, we investigated the effects of ferulic acid, morin, quercetin and gossypol against Aβ aggregation. From the ThT and turbidity assays, it is observed that in addition to the fibril aggregate, another type of aggregate is formed in the presence of morin, quercetin, and gossypol. On the other hand, ferulic acid did not prevent fibril formation, but it did appear to reduce the average length of fibrils compared to Aβ alone. To study the protective effects of phenolic compounds on Aβ-induced toxicity, we utilized the nematode Caenorhabditis elegans (C. elegans) as an in vivo model organism, human Aβ is expressed intracellularly in the body wall muscle. We found that exposure of Caenorhabditis elegans to ferulic acid give more protection against Aβ toxicity than morin, quercetin and gossypol.     

Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats

Antioxidants are one of the key players in tumorigenesis, several natural and synthetic antioxidants were shown to have anticancer effects. The aim of the present study is to divulge the chemopreventive nature of carvacrol during diethylnitrosamine (DEN)-induced liver cancer in male wistar albino rats. Administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transpeptidase (γGT). The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR). Carvacrol supplementation (15 mg/kg body weight) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer. Histological observations and transmission electron microscopy studies were also carried out, which added supports to the chemopreventive action of the carvacrol against DEN-induction during liver cancer progression. These findings suggest that carvacrol prevents lipid peroxidation, hepatic cell damage, and protects the antioxidant system in DEN-induced hepatocellular carcinogenesis.     

Biocompatible alginate/nano bioactive glass ceramic composite scaffolds for periodontal tissue regeneration

Periodontal regeneration is of utmost importance in the field of dentistry which essentially reconstitutes and replaces the lost tooth supporting structures. For this purpose, nano bioactive glass ceramic particle (nBGC) incorporated alginate composite scaffold was fabricated and characterized using SEM, EDAX, AFM, FTIR, XRD and other methods. The swelling ability, in vitro degradation, biomineralization and cytocompatibility of the scaffold were also evaluated. The results indicated reduced swelling and degradation and enhanced biomineralization and protein adsorption. In addition, the human periodontal ligament fibroblast (hPDLF) and osteosarcoma (MG-63) cells were viable, adhered and proliferated well on the alginate/bioglass composite scaffolds in comparison to the control alginate scaffolds. The presence of nBGC enhanced the alkaline phosphatase (ALP) activity of the hPDLF cells cultured on the composite scaffolds. Thus results suggest that these biocompatible composite scaffolds can be useful for periodontal tissue regeneration.     

Critical Analysis of Forest Degradation in the Southern Eastern Ghats of India: Comparison of Satellite Imagery and Soil Quality Index

India has one of the largest assemblages of tropical biodiversity, with its unique floristic composition of endemic species. However, current forest cover assessment is performed via satellite-based forest surveys, which have many limitations. The present study, which was performed in the Eastern Ghats, analysed the satellite-based inventory provided by forest surveys and inferred from the results that this process no longer provides adequate information for quantifying forest degradation in an empirical manner. The study analysed 21 soil properties and generated a forest soil quality index of the Eastern Ghats, using principal component analysis. Using matrix modules and geospatial technology, we compared the forest degradation status calculated from satellite-based forest surveys with the degradation status calculated from the forest soil quality index. The Forest Survey of India classified about 1.8% of the Eastern Ghats’ total area as degraded forests and the remainder (98.2%) as open, dense, and very dense forests, whereas the soil quality index results found that about 42.4% of the total area is degraded, with the remainder (57.6%) being non-degraded. Our ground truth verification analyses indicate that the forest soil quality index along with the forest cover density data from the Forest Survey of India are ideal tools for evaluating forest degradation.     

Synthesis and antibacterial activity of some novel imidazole-based dicationic quinolinophanes

Synthesis of novel quinoline based dicationic benzimidazolophanes and imidazolophanes incorporating various spacer units is described. Some of the quinolinophanes 1b, 3a, 3b and 4a exhibit good antibacterial activity against most of the human pathogenic bacteria in the tested concentrations as compared to the other cyclophanes as well as the test control, streptomycin.