Modeling of ion permeation in calcium and sodium channel selectivity filters

Structure-function studies have shown that it is possible to convert a sodium channel to a calcium-selective channel by a single amino acid substitution in the selectivity filter locus. Ion permeation through the "model selectivity filter" was modeled with a reduced set of functional groups representative of the constituent amino acid side chains. Force-field minimizations were conducted to obtain the energy profile of the cations as they get desolvated and bind to the "model selectivity filter." The calculations suggest that the ion selectivity in the calcium channel is due to preferential binding, whereas in the sodium channel it is due to exclusion. Energetics of displacement of a bound cation from the calcium "model selectivity filter" by another cation suggest that "multi-ion mechanism" reduces the activation barrier for ion permeation. Thus, the simple model captures qualitatively most of the conduction characteristics of sodium and calcium channels. However, the computed barriers for permeation are fairly large, suggesting that ion interaction with additional residues along the transport path may be essential to effect desolvation

Microbial transformation of xenobiotics for environmental bioremediation

The accumulation of recalcitrant xenobiotic compounds is due to continuous efflux from population and industrial inputs that have created a serious impact on the pristine nature of our environment. Apart from this, these compounds are mostly carcinogenic, posing health hazards which persist over a long period of time. Metabolic pathways and specific operon systems have been found in diverse but limited groups of microbes that are responsible for the transformation of xenobiotic compounds.Distinct catabolic genes are either present on mobile genetic elements, such as transposons and plasmids, or the chromosome itself that facilitates horizontal gene transfer and enhances the rapid microbial transformation of toxic xenobiotic compounds. Biotransformation of xenobiotic compounds in natural environment has been studied to understand the microbial ecology, physiology and evolution for their potential in bioremediation. Recent advance in the molecular techniques including DNA fingerprinting, microarrays and metagenomics is being used to augment the transformation of xenobiotic compounds. The present day understandings of aerobic, anaerobic and reductive biotransformation by co-metabolic processes and an overview of latest developments in monitoring the catabolic genes of xenobiotic-degrading bacteria are discussed elaborately in this work. Till date, several reviews have come up, highlighting the problem of xenobiotic pollution, yet a comprehensiveunderstanding of the microbial biodegradation of xenobiotics and its application is in nascent stage. Therefore, this is an attempt to understand the microbial role in biotransformation of xenobiotic compounds in context to the modern day biotechnology

Statistics of leading digits leads to unification of quantum correlations

We show that the frequency distribution of the first significant digits of the numbers in the data sets generated from a large class of measures of quantum correlations, which are either entanglement measures, or belong to the information-theoretic paradigm, exhibit a universal behaviour. In particular, for Haar uniformly simulated arbitrary two-qubit states, we find that the first-digit distribution corresponding to a collection of chosen computable quantum correlation quantifiers tend to follow the first-digit law, known as the Benford's law, when the rank of the states increases. Considering a two-qubit state which is obtained from a system governed by paradigmatic spin Hamiltonians, namely, the XY model in a transverse field, and the XXZ model, we show that entanglement as well as information theoretic measures violate the Benford's law. We quantitatively discuss the violation of the Benford's law by using a violation parameter, and demonstrate that the violation parameter can signal quantum phase transitions occurring in these models. We also comment on the universality of the statistics of first significant digits corresponding to appropriate measures of quantum correlations in the case of multipartite systems as well as systems in higher dimensions.Comment: v1: 11 pages, 5 figures, 2 tables; v2: 11 pages, 6 figures, 2 tables, new results added, extended version of the published pape

Antimicrobial and anti-inflammatory screening of four indian medicinal plants

Inflammatory diseases including different types of rheumatic diseases are very common throughout the world. The greatest disadvantage in the presently available potent synthetic drugs lies in their side effects, toxicity and reappearance of the symptoms after discontinuation. Hence search for new antimicrobial and anti-inflammatory agents are needed. Antimicrobial study was done by agar disc diffusion method against 5 Gram positive, 7 Gram negative and 3 fungal strains and acute anti-inflammatory activity was studied by carrageenan induced paw edema in rats. Plants screened were Aristolochia indica, Argemone mexicana, Alpinia speciosa and Gymnema sylvestre. Methanolic extract of these plants were studied at 200 mg/kg and 400 mg/kg dose level. The results were compared with standard drug indomethacin. All the plant extracts showed better antibacterial activity than antifungal activity. The Gram positive bacteria were more susceptible than Gram negative bacteria. Argemone mexicana gave more antimicrobial and anti-inflammatory activity than the other three plants.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Genome-Wide and Functional Annotation of Human E3 Ubiquitin Ligases Identifies MULAN, a Mitochondrial E3 that Regulates the Organelle's Dynamics and Signaling

Specificity of protein ubiquitylation is conferred by E3 ubiquitin (Ub) ligases. We have annotated ∼617 putative E3s and substrate-recognition subunits of E3 complexes encoded in the human genome. The limited knowledge of the function of members of the large E3 superfamily prompted us to generate genome-wide E3 cDNA and RNAi expression libraries designed for functional screening. An imaging-based screen using these libraries to identify E3s that regulate mitochondrial dynamics uncovered MULAN/FLJ12875, a RING finger protein whose ectopic expression and knockdown both interfered with mitochondrial trafficking and morphology. We found that MULAN is a mitochondrial protein – two transmembrane domains mediate its localization to the organelle's outer membrane. MULAN is oriented such that its E3-active, C-terminal RING finger is exposed to the cytosol, where it has access to other components of the Ub system. Both an intact RING finger and the correct subcellular localization were required for regulation of mitochondrial dynamics, suggesting that MULAN's downstream effectors are proteins that are either integral to, or associated with, mitochondria and that become modified with Ub. Interestingly, MULAN had previously been identified as an activator of NF-κB, thus providing a link between mitochondrial dynamics and mitochondria-to-nucleus signaling. These findings suggest the existence of a new, Ub-mediated mechanism responsible for integration of mitochondria into the cellular environment

A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps