Delving into Vertebrate Serpins for Understanding their Evolution

The superfamily of serine proteinase inhibitors (serpins) is involved in an array of fundamental biological processes such as blood coagulation, cell differentiation, cell migration, complement activation, embryo implantation, fibrinolysis, angiogenesis, and inflammation, and tumor suppression. Vertebrate serpins can be conveniently classified into six sub-groups, based on three independent biological features - genomic organization, diagnostic amino acid sites and rare indels. The present vertebrate serpins are derived from an original serpin most probably by intron insertion and we are trying to reconstruct the phylogeny of vertebrate serpin and looking for the reconstruction of original vertebrate gene(s). We started with fish genomes and characterized fish serpins and assigned orthology with respect to human serpins. Most fish serpins are characterised as stereotype vertebrate serpins with some interesting exceptions which suggest that either there are some fish-specific serpins or some fish serpins do not have human orthologs.

Presented at "BREW 2005":http://cmb.molgen.mpg.de/brew/program.html

Deciphering the phylogenetic history of neuroserpin orthologs across metazoans by analysis of synteny and rare genomic characters

The superfamily of serine proteinase inhibitors (serpins) is involved in wide arrays of fundamental biological processes such as blood coagulation, complement activation, fibrinolysis, angiogenesis, inflammation and tumor suppression. The average protein size of a serpin family member is 350-400 amino acids, but gene structure varies in terms of number and position of exons and introns. All known serpins can be grouped into 16 clades and 10 orphan sequences. Vertebrate serpins can be conveniently classified into six sub-groups, based on three independent biological features - genomic organization, diagnostic amino acid sites and rare indels.
The objective of this study was to elucidate the phylogenetic kinships of serpins involved in surveying the secretory pathway routes against uncontrolled proteolytic activity. Though phylogenetic classification of vertebrate serpins into six groups based on gene organisation is well established, the evolutionary roots beyond the fish/tetrapod split are unresolved. This study illustrates that the analysis of microsynteny and other rare characters can provide insight into the intricate family history of metazoan serpins. Rare genomic characters/changes (RGC) are used to decipher that orthologs of neuroserpin, a prominent representative of vertebrate group 3 serpin genes, exist in early diverging deuterostomes and probably also in cnidarians, indicating that the origin of a mammalian serpin can be traced back far in the history of eumetazoans.
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Structural analysis of outer membrane beta-stranded porins using B-factor

Computational and statistical analysis has formed a large component of the biophysical efforts put forth to understand protein structure and function, due to the diversity and complexity of their structure. Outer membrane proteins form a diverse and complex set of proteins. Of these, porins that allow passage of molecules across the membrane interface have been analyzed here from a biophysical and structural perspective. The objective of this study is to analyze the structural organization of porins using atomic temperature factor as a parameter. Generally atomic temperature factors of molecules from crystal structures indicate the degree of mobility or disorder seen in the crystal structure. As good crystal structures have lesser possibilities of errors so there is lesser chance that errors are playing roles in temperature factors. Structures of six porins (four 16-stranded beta barrel porins and two 8-stranded beta barrel porins) were taken from the PDB for the analysis based on resolution and R-factor. Programs and scripts were written for extracting the temperature factors for the beta strands, loops and turns so that the analysis could be done for different atom-types and residue-types. The residue distribution and mobility distribution was found to be characteristic of each of the porins. The mobility and residue distribution amongst the secondary structural elements were found to follow the level of homology at the sequence and structural level. The loops that had defined functional roles in structural terms were found to have lower temperature factors than the other loops. The turn regions that are thought to face the periplasmic region in the cell, showed higher temperature factors. For both the 16 stranded and the 8-stranded barrels it was found one part of the barrel (the lower wall or 'inner' wall comprising the trimer interface in the case of the 16-stranded barrels) was more rigid and the other half of the barrel (the higher or 'outer' wall) showed more mobility as seen from the temperature factors. This seems to be an intrinsic structural component of the beta barrels

Moving Beyond Sub-Gaussianity in High-Dimensional Statistics: Applications in Covariance Estimation and Linear Regression

Concentration inequalities form an essential toolkit in the study of high dimensional (HD) statistical methods. Most of the relevant statistics literature in this regard is based on sub-Gaussian or sub-exponential tail assumptions. In this paper, we first bring together various probabilistic inequalities for sums of independent random variables under much weaker exponential type (namely sub-Weibull) tail assumptions. These results extract a part sub-Gaussian tail behavior in finite samples, matching the asymptotics governed by the central limit theorem, and are compactly represented in terms of a new Orlicz quasi-norm - the Generalized Bernstein-Orlicz norm - that typifies such tail behaviors. We illustrate the usefulness of these inequalities through the analysis of four fundamental problems in HD statistics. In the first two problems, we study the rate of convergence of the sample covariance matrix in terms of the maximum elementwise norm and the maximum k-sub-matrix operator norm which are key quantities of interest in bootstrap, HD covariance matrix estimation and HD inference. The third example concerns the restricted eigenvalue condition, required in HD linear regression, which we verify for all sub-Weibull random vectors through a unified analysis, and also prove a more general result related to restricted strong convexity in the process. In the final example, we consider the Lasso estimator for linear regression and establish its rate of convergence under much weaker than usual tail assumptions (on the errors as well as the covariates), while also allowing for misspecified models and both fixed and random design. To our knowledge, these are the first such results for Lasso obtained in this generality. The common feature in all our results over all the examples is that the convergence rates under most exponential tails match the usual ones under sub-Gaussian assumptions.Comment: 64 pages; Revised version (discussions added and some results modified in Section 4, minor changes made throughout

X-ray Diffraction Analysis of Cu2+ Doped Zn1-xCuxFe2O4 Spinel Nanoparticles using Williamson-Hall Plot Method

The nanoparticles (NPs) of Zn1-xCuxFe2O4 (ZCFO) spinels with x = 0, 0.2, 0.4, 0.6 and 0.8 were synthesized by a sol-gel combustion method using acetate precursor. The NPs of ZCFO were prepared by following calcination process at 600C for 8hrs. The synthesized NPs of ZCFO were characterized by X-ray diffraction (XRD) analysis using Rietveld refinement. The Rietveld refinement of the XRD patterns revealed that the ZCFO spinels crystallize into single diamond cubic structure with Fd-3m space group. The lattice constant and unit cell volume for ZCFO NPs shrink with enhancing doping concentration of Cu2+ ion. The crystalline growth in the NPs of ZCFO was examined by peak broadening present in the XRD pattern. The Williamson-Hall (W-H) plot method were used to study the individual involvements of crystallite sizes and lattice strain on the peak broadening of the NPs of ZCFO spinels. Whereas, particle size of the ZCFO sample with x = 0.40 was estimated by high-resolution scanning electron microscopy micrograph