EXPLORATION OF POTENT ACTINOBACTERIUM NOCARDIOPSIS HALOTOLERANS VJPR-2 ISOLATED FROM MANGROVE HABITATS

ABSTRACTObjectives: This study was aimed at isolation and identification of potent bioactive metabolite producing actinobacterial strain VJPR-2 isolated fromthe mangrove ecosystem of Nizampatnam, Andhra Pradesh, India.Methods: Soil sediments collected were subjected to pre-treatment with CaCO, and actinobacterial strains were isolated using selective media. Thescreening of the isolated strains was carried out and the potent bioactive metabolite producing strain was designated as VJPR-2. An identification ofthe strain was carried out by employing polyphasic approach including morphological, cultural, physiological, biochemical, and phylogenetic analysisof 16S rRNA gene sequence. Antimicrobial potency of the isolate was tested against bacterial and fungal pathogens.3Results: The strain VJPR-2 was identified as Nocardiopsis halotolerans by morphological, cultural, physiological, and biochemical studies along with16S rRNA gene sequence analysis. The rRNA sequence was deposited in the NCBI GenBank with the accession number KP313613. The strain exhibitedantimicrobial activities against Gram-positive as well as Gram-negative bacteria and fungi.Conclusion: Actinobacterium strain N. halotolerans VJPR-2 having good antimicrobial potential was identified from the 16 strains isolated from thesediment samples of Nizampatnam mangrove ecosystem using CaCObased approach. The present study reveals the isolation, identification andbiological evaluation of the bioactive metabolites produced by strain VJPR-2.3 Keywords: Mangrove ecosystem, Nocardiopsis halotolerans VJPR-2, Polyphasic approach, Bioactive metabolites

Patchy layered structure of tropical troposphere as seen by Indian MST radar

The MST radar observations at Gadanki (13.47° N, 79.18° E) show, almost every day throughout the year, stratified layers of intense reflectivity near the tropopause level (17 km) and also at a couple of levels between 4 km and 10 km. Highest individual reflectivity values occur near 17 km, but they occur for a short while. The region between 11 km and 15 km shows the lowest values of reflectivity alongwith vertical downward motion almost on all days of the year. High values of reflectivity are attributed to the existence of visible or sub-visible clouds; the layered structure of clouds is attributed to inertio-gravity waves with vertical wavelength of 2-3 km. It is suggested that each high reflectivity layer consists mainly of thin sheets and patches of visible and sub-visible cloud material. Hydrometeors inside the cloud material go up and down due to gravity, precipitation-loading, Brunt-Vaisala oscillations, and Kelvin-Helmholtz waves. In these small-scale motions, thin air sheets and patches get formed with sharp temperature and humidity discontinuities through contact cooling, melting, evaporation, condensation and freezing. Also, melting and freezing at low temperatures generate electrical charges in these thin sheets and patches. These thin sheets and patches have vertical dimensions ranging from a few centimetres to several metres and horizontal dimensions of the order of 1km. These thin sheets and patches have corresponding vertical and horizontal discontinuities and sharp gradients in refractive index for the MST radar beam. These show up as regions of high values of reflectivity

Principles of meiotic chromosome assembly revealed in S. cerevisiae

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

The Goldbeter-Koshland switch in the first-order region and its response to dynamic disorder

In their classical work (Proc. Natl. Acad. Sci. USA, 1981, 78:6840-6844), Goldbeter and Koshland mathematically analyzed a reversible covalent modification system which is highly sensitive to the concentration of effectors. Its signal-response curve appears sigmoidal, constituting a biochemical switch. However, the switch behavior only emerges in the "zero-order region", i.e. when the signal molecule concentration is much lower than that of the substrate it modifies. In this work we showed that the switching behavior can also occur under comparable concentrations of signals and substrates, provided that the signal molecules catalyze the modification reaction in cooperation. We also studied the effect of dynamic disorders on the proposed biochemical switch, in which the enzymatic reaction rates, instead of constant, appear as stochastic functions of time. We showed that the system is robust to dynamic disorder at bulk concentration. But if the dynamic disorder is quasi-static, large fluctuations of the switch response behavior may be observed at low concentrations. Such fluctuation is relevant to many biological functions. It can be reduced by either increasing the conformation interconversion rate of the protein, or correlating the enzymatic reaction rates in the network.Comment: 23 pages, 4 figures, accepted by PLOS ON

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease

The interplay of intrinsic and extrinsic bounded noises in genetic networks

After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a genetic network. The influence of intrinsic and extrinsic noises on genetic networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: $(i)$ the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, $(ii)$ a model of enzymatic futile cycle and $(iii)$ a genetic toggle switch. In $(ii)$ and $(iii)$ we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possibile functional role of bounded noises