HIV-1 gp41 and TCRα Trans-Membrane Domains Share a Motif Exploited by the HIV Virus to Modulate T-Cell Proliferation

Viruses have evolved several strategies to modify cellular processes and evade the immune response in order to successfully infect, replicate, and persist in the host. By utilizing in-silico testing of a transmembrane sequence library derived from virus protein sequences, we have pin-pointed a nine amino-acid motif shared by a group of different viruses; this motif resembles the transmembrane domain of the α-subunit of the T-cell receptor (TCRα). The most striking similarity was found within the immunodeficiency virus (SIV and HIV) glycoprotein 41 TMD (gp41 TMD). Previous studies have shown that stable interactions between TCRα and CD3 are localized to this nine amino acid motif within TCRα, and a peptide derived from it (TCRα TMD, GLRILLLKV) interfered and intervened in the TCR function when added exogenously. We now report that the gp41 TMD peptide co-localizes with CD3 within the TCR complex and inhibits T cell proliferation in vitro. However, the inhibitory mechanism of gp41 TMD differs from that of the TCRα TMD and also from the other two known immunosuppressive regions within gp41.     

An Analytically Solvable Model for Rapid Evolution of Modular Structure

Biological systems often display modularity, in the sense that they can be decomposed into nearly independent subsystems. Recent studies have suggested that modular structure can spontaneously emerge if goals (environments) change over time, such that each new goal shares the same set of sub-problems with previous goals. Such modularly varying goals can also dramatically speed up evolution, relative to evolution under a constant goal. These studies were based on simulations of model systems, such as logic circuits and RNA structure, which are generally not easy to treat analytically. We present, here, a simple model for evolution under modularly varying goals that can be solved analytically. This model helps to understand some of the fundamental mechanisms that lead to rapid emergence of modular structure under modularly varying goals. In particular, the model suggests a mechanism for the dramatic speedup in evolution observed under such temporally varying goals.     

Fabrication and characterization of silver nanoparticle and its potential antibacterial activity

In the present research silver nanoparticle was fabricated by chemical reduction of silver salt (Silver nitrate, AgNO₃) solution. Sodium citrate was used as a reducer. The formation of silver nanoparticle was observed visually by color change (greenish yellow). The surface plasmon resonance peak in absorption spectra of silver nanoparticle showed an absorption maximum at 420 nm in UV-VIS spectrometry. The X-ray diffraction pattern showed the presence of sharp reflections at 111, 200, 220, and 311. This would indicate the presence of silver nanoparticle. The scanning electron micrograph revealed that the average size of silver nanoparticle was 21.22 ± 5.17 nm. Silver nanoparticle exhibited better antimicrobial activity against Staphylococcus aureus than the other bacterial pathogens. The correlation coefficient between silver nanoparticles and selected bacterial pathogens revealed that there is a strong negative correlation with Escherichia coli, S. aureus and Klebsiella pneumonia (r = −0.975, −0.993, and −0.998, respectively).     

Inhibition of amyloid fibril formation and cytotoxicity by hydroxyindole derivatives

Gaining insight into the mechanism of amyloid fibril formation, the hallmark of multiple degenerative syndromes of unrelated origin, and exploring novel directions of inhibition are crucial for preventing disease development. Specific interactions between aromatic moieties were suggested to have a key role in the recognition and self-assembly processes leading to the formation of amyloid fibrils by several amyloidogenic polypeptides, including the beta-amyloid polypeptide associated with Alzheimer's disease. Our finding of the high-affinity molecular recognition and intense amyloidogenic potential of tryptophan-containing peptide fragments led to the hypothesis that screening for indole derivatives might lead to the identification of potential inhibitors of amyloid formation. Such inhibitors could mediate specific recognition processes without allowing further growth of the well-ordered amyloid chain. Using fluorescence spectroscopy, atomic force microscopy, and electron microscopy to screen 29 indole derivatives, we identified three potent inhibitors: indole-3-carbinol (I3C), 3-hydroxyindole (3HI), and 4-hydroxyindole (4HI). The latter, a simple low-molecular weight aromatic compound, was the most effective, completely abrogating not only the formation of aggregated structures by Abeta but also the cytotoxic activity of aggregated Abeta toward cultured cells. The results of this study provide further experimental support for the paradigm of amyloid inhibition by heteroaromatic interaction and point to indole derivatives as a simple molecular platform for the development of novel fibrillization inhibitors.     

Enhanced Retinal Insulin Receptor-activated Neuroprotective Survival Signal in Mice Lacking the Protein-tyrosine Phosphatase-1B Gene

Protein-tyrosine phosphatase 1B (PTP1B) has been implicated in the negative regulation of insulin signaling. We previously demonstrated that light-induced tyrosine phosphorylation of the retinal insulin receptor (IR) results in the activation of phosphoinositide 3-kinase/Akt survival pathway in rod photoreceptor cells. The molecular mechanism behind light-induced activation of IR is not known. We investigated the in vivo mechanism of IR activation and found that PTP1B activity in dark-adapted retinas was significantly higher than in light-adapted retinas. We made a novel finding in this study that the light-dependent regulation of PTP1B activity is signaled through photobleaching of rhodopsin. Conditional deletion of PTP1B in rod photoreceptors by the Cre-loxP system resulted in enhanced IR signaling. Further PTP1B activity negatively regulated the neuroprotective survival signaling in the retina. One of the challenging questions in the retina research is how mutations in human rhodopsin gene slowly disable and eventually disrupt photoreceptor functions. Our studies suggest that a defect in the photobleaching of rhodopsin and mutation in rhodopsin gene enhances the activity of PTP1B, and this activated activity could down-regulate the IR survival signaling. Our studies suggest that PTP1B antagonists could be potential therapeutic agents to treat stress-induced photoreceptor degenerations and provide further evidence that rhodopsin photoexcitation may trigger signaling events alternative to the classic phototransduction.     

Cumulative antioxidant defense against oxidative challenge in galactose-induced cataractogenesis in Wistar rats

Natural dietary ingredients are known for their antioxidant activity. Of such, curcumin, the active principle of turmeric, at 0.01% in the diet proved as pro-oxidative in galactose-induced cataract in vivo. The purpose of this study was to investigate the effect of vitamin E (VE), a well-known antioxidant, in combination with curcumin on the onset and maturation of galactose induced cataract. Periodic slit-lamp microscope examination indicated that in combination with vitamin-E, 0.01% curcumin (G-IV) delayed the onset and maturation of galactose-induced cataract. Biochemical analyses revealed that combined treatment of 0.01% curcumin and vitamin-E diet exhibited an efficient antioxidant effect, as it inhibited lipid peroxidation and contributed to a distinct rise in reduced glutathione content. The results indicate that natural dietary ingredients are effective in combination rather than the individual administration as they are complementing each other in reducing the risk of galactose induced cataract.     

A comparative analysis of the amino acid and cDNA sequences of bovine elastin a and chick elastin

A comparative analysis of the amino acid and cDNA sequences of bovine elastin a and chick elastin shows that there are considerable differences between these proteins. There is evidence that duplication of segments of DNA and gene rearrangement have occurred in the gene for chick elastin as compared with the gene for bovine elastin. The length of the polypeptide chain of elastin in both species is similar. Therefore, the duplications are compensated for by deletions in the gene for chick elastin.     

Algae and Testacea of the Cho Oyu (Himalayas) expedition-II; Gyanophyta,Chlorophyta, Euglenophyta,Chrysophyta and Testacea

The present paper deals with the taxonomic account of Testacea and Algae other than Bacillariophyta of high altitudes of Himalayas collected during the Cho Oyu expedition. In all 80 taxa are described, out of which 19 members belong to Cyanophyta, 43 to Chlorophyta and 3 each to the groups Euglenophyta and Chrysophyta. The rest of the 12 taxa are members of Testacea. Five taxa, two varieties and three formae are new to Science.     

Pollination Biology of Anisomeles indica and A. malabarica (Lamiaceae)

Abstract The flowers of Anisomeles indica and A. malabarica are zygomorphic, bilabiate, gulletshaped and nectariferous, and are visited by insects as well as birds for nectar and/or pollen. The bees Xylocopa latipes, X. Pubescens, Amegilla sp., Apis florea and Megachile sp., and the sunbirds of the genus Nectarinia are the principal pollinators of A. indica , while the former three and the last and the wasp Rhynchium metallicum are for A. malabarica. Pollination by Xylocopa and Nectarinia is nototribic and that by Apis, Megachile, Amegilla is noto- and/or sternotribic. The small bodied Trigona, Pseudapis and Ceratina collected pollen sternotribically. It is concluded that adaptation of both species to insect and bird pollination and to a flexible breeding system involving both selfing and crossing, safeguards their survival under changing environments.