Biochemistry

Renal failure or kidney failure is a situation in which the kidneys fail to function adequately. Angiotensin
converting enzyme plays a pivotal role in blood pressure regulation and electrolyte balance by hydrolyzing
angiotensin I to angiotensin II. The Angiotensin Converting Enzyme (ACE) gene contains a polymorphism
which is believed to be associated with the interpersonal variability of ACE levels in circulating blood. Elevated
angiotensin II level makes deleterious effects on renal hemodynamics and induces the expression of other growth
factors, leading to glomerulosclerosis. This paper attempts to find the association of ACE polymorphism with
renal failure using Random Amplification of Polymorphic DNA technique arriving to the major conclusion that
ACE polymorphism is an innate property in End Stage Renal Failure (ESRF) and ACE screening would be a
valuable diagnostic tool in screening clinical ESRF.

The rapid development of shotgun proteomics is paving the way for extensive proteome profiling, while
providing extensive information on various post translational modifications (PTMs) that occur to a proteome
of interest. For example, the current phosphoproteomic methods can yield more than 10,000 phosphopeptides
identified from a proteome sample. Despite these developments, it remains a challenging issue to pinpoint the
true phosphorylation sites, especially when multiple sites are possible for phosphorylation in the peptides. We
developed the Phospho-UMC filter, which is a simple method of localizing the site of phosphorylation using
unique mass classes (UMCs) information to differentiate phosphopeptides with different phosphorylation sites
and increase the confidence in phosphorylation site localization. The method was applied to large scale
phosphopeptide profiling data and was demonstrated to be effective in the reducing ambiguity associated with
the tandem mass spectrometric data analysis of phosphopeptides.

Air pollution is one of the serious problems faced by the people globally, especially in urban areas of developing countries like India. All these in turn lead to an increase in the air pollution levels and have adverse effects on the health of people and plants. In any well planned urban set up, industrial pollution takes a back seat and vehicular emissions take precedence as the major cause of urban air pollution. The unplanned growth of cities in India has led to the problems of increasing slums, vehicular traffic and air pollution. Automobile exhaust, which also consists of all major air pollutants is a significant source of air pollution in the urban context. The present paper deals with the study on concentration of major air pollutants from vehicles and their influence on local biota like plants and human beings in Tiruchirappalli city besides this the impact on plant species and human health has been undertaken.

Mass spectrometry (MS)-based proteomics, which uses high-resolution hybrid mass spectrometers such as the quadrupole-orbitrap mass spectrometer, can yield tens of thousands of tandem mass (MS/MS) spectra of high resolution during a routine bottom-up experiment. Despite being a fundamental and key step in MS-based proteomics, the accurate determination and assignment of precursor monoisotopic masses to the MS/MS spectra remains difficult. The difficulties stem from imperfect isotopic envelopes of precursor ions, inaccurate charge states for precursor ions, and cofragmentation. We describe a composite method of utilizing MS data to assign accurate monoisotopic masses to MS/MS spectra, including those subject to cofragmentation. The method, " multiplexed post-experiment monoisotopic mass refinement " (mPE-MMR), consists of the following: multiplexing of precursor masses to assign multiple monoisotopic masses of cofragmented peptides to the corresponding multiplexed MS/MS spectra, multiplexing of charge states to assign correct charges to the precursor ions of MS/ MS spectra with no charge information, and mass correction for inaccurate monoisotopic peak picking. When combined with MS-GF+, a database search algorithm based on fragment mass difference, mPE-MMR effectively increases both sensitivity and accuracy in peptide identification from complex high-throughput proteomics data compared to conventional methods.

Proteogenomics provide opportunities for proteomic validation of gene structures, genomic alterations and functional relevance of novel findings obtained from genomic data analysis. However, for effective proteogenomic data integration, an extensive proteome profiling, approaching the gene coverage of genomics data, is critical. Here we developed a multi-stage database search method for comprehensive proteomics data analysis to complement whole transcriptome sequencing data. The method utilizes two complementary database search engines, MS-GF+ and MODa/MODi, in tandem. The MS/MS data were first subjected to MS-GF+ database search (1st stage search) and the unidentified MS/MS data from the 1st stage search were subsequently analyzed with the combined use of MODa and MODi (2nd stage search), tools for blind and unrestrictive modification search, respectively. When combined with mPE-MMR, a tool for accurate and extensive precursor masses assignments to MS/MS data, the multi-stage method exhibited a significant increase in identified peptides, modified peptides, mutated peptides, identified proteins and coding genes, compared to a conventional single-stage method. With the increased coverage of proteome profile, the genomics and proteomics data obtained from the same gastric tumor tissue were effectively integrated as evidenced by proBAMsuite analysis results, which showed abundant examples of peptides uniquely mapped to genomic locations as well as increased coverages of exon-exon junctions and coding regions with the multi-stage search method.

BACKGROUND: The cluster of differentiation (CD) 74 is known for its immunological functions and its elevated level was reported in various cancer cells. AIM: The aim of the present study was to investigate the expression and potential roles of CD74 in the proliferative and apoptotic activity of breast cancer. METHODS: Expression of CD74, macrophage migration inhibitory factor (MIF) and CD44 was assayed in CAMA-1 and MDA-MB-231 cell lines using flow cytometry. CD74 was knocked down using CD74 siRNA-transfection in CAMA-1, and MDA-MB-231 cells and proliferation and apoptosis were determined in the transfected breast cancer cells. RESULTS: The data showed that CD74, MIF and CD44 were expressed in breast cancer cell lines and were associated with cell proliferation and apoptosis. Correlation analysis revealed that CD74 was positively correlated and colocalised with MIF on the cell-surface of CAMA-1 and MDA-MB-231. The knockdown of CD74 significantly reduced CAMA-1 and MDA-MB-231 cell pr...

This study was undertaken to evaluate the association of polymorphism of angiotensin I converting enzyme (ACE) gene with casual and ambulatory blood pressure in the Chinese population. Genomic DNA was amplified by polymerase chain reaction (PCR) using primers flanking the ...

This study was undertaken to evaluate the association of polymorphism of angiotensin I converting enzyme (ACE) gene with causal and ambulatory blood pressure in the Chinese population. Genomic DNA was amplified by polymerase chain reaction (PCR) using primers flanking the polymorphic region in intron 16 of the ACE gene. Alleles were detected on agarose gels stained with ethidium bromide. Causal blood pressure was measured in the 133 normotensive and 122 essential hypertensive subjects; of the essential hypertensive subjects, 65 patients underwent non-invasive ambulatory blood pressure. There was no significant difference of ACE genotype and allele frequencies between the hypertensive and normotensive subjects. Non-significant differences were demonstrated in gender, age, causal blood pressure according to the ACE gene genotypes in the 65 patients who underwent non-invasive ambulatory blood pressure; however, effects of the ACE gene genotypes were observed on the derivatives of ambulatory blood pressure, including sleeping blood pressure levels and circadian blood pressure rhythm (p < 0.05). We suggest that insertion/deletion polymorphism of the ACE gene should be associated with blood pressure and ambulatory blood pressure might be superior to causal blood pressure at the molecular level.

Numerical simulations have been performed to study the stability of heated, incompressible Taylor-Couette flow for a radius ratio of 0.7 and a Prandtl number of 0.7. As Gr is increased, the Taylor cell that has the same direction of circulation as the natural convection current increases in size and the counterrotating cell becomes smaller. The flow remains axisymmetric and the average heat transfer decreases with the increase in Gr. When the cylinder is impulsively heated, the counterrotating cell vanishes and n = 1 spiral is formed for Gr = 1000. This transition marks an increase in the heat transfer due to an increase in the radial velocity component of the fluid. By slowly varying the Grashof number, the simulations demonstrate the existence of a hysteresis loop. Two different stable states with same heat transfer are found to exist at the same Grashof number. A time-delay analysis of the radial velocity and the local heat transfer coefficient time is performed to determine the ...

Alzheimer’s disease (AD) is most common form of dementia affecting elderly people, and sixth leading cause of death worldwide. The two abnormal structures formed in AD patient’s brain are beta-amyloid plaques and neurofibrillary. The beta-amyloid plaque formation is accelerated due to acetylcholinestarases. Treatment of AD has majorly dependent on inhibition of acetylcholinestarase. In the present study, acetylcholinesterase receptor is docked with solanine and its derivatives and with a commercially available drug. The lead 3 compounds, are selected based on minimum binding energy and interaction with the active site of the receptor, are much better compared to commercially available drug. Molecular interactions of the receptor complexes with lead solanine compounds are also found to be higher in number. By this it can be hypothesize that solanine derivatives can inhibit acetylcholinesterase more effectively, which controls rapid breaking of acetylcholine, a neurotransmitter to ace...

Cell cycle progression through mitosis and meiosis involves regulation by serine/threonine kinases from the aurora family. Aurora kinase b (Aurkb) is mainly involved in the proper segregation of chromosomes during mitosis as well as meiosis. However, over expression of Aurkb leads to the unequal distribution of genetic information creating aneuploid cells, a hallmark of cancer. Thus, Aurkb can be used as an effective molecular target for computer-aided drug discovery against cancer. Existing Aurkb inhibitors are less efficient, hence an in silico work was carried out to identify novel potent inhibitors. Three published inhibitors azd1152, zm447439 and N-(4-{[6-methoxy-7-(3-morpholin-4-ylpropoxy) quinazolin- 4-yl] amino} phenyl) benzamide were subjected to high throughput virtual screening of over 1 million entries from a ligand info meta database, to generate a 1161 compound library. The crystal structure was optimized and energy was minimized applying an OPLS force field in Maestro...

Alzheimer’s disease (AD) is most common form of dementia affecting elderly people, and sixth leading cause of death worldwide. The two abnormal structures formed in AD patient’s brain are beta-amyloid plaques and neurofibrillary. The beta-amyloid plaque formation is accelerated due to acetylcholinestarases. Treatment of AD has majorly dependent on inhibition of acetylcholinestarase. In the present study, acetylcholinesterase receptor is docked with solanine and its derivatives and with a commercially available drug. The lead 3 compounds, are selected based on minimum binding energy and interaction with the active site of the receptor, are much better compared to commercially available drug. Molecular interactions of the receptor complexes with lead solanine compounds are also found to be higher in number. By this it can be hypothesize that solanine derivatives can inhibit acetylcholinesterase more effectively, which controls rapid breaking of acetylcholine, a neurotransmitter to ace...

ABSTRACT Objective: To evaluate the variation of neuraminidase (NA) protein from various H1N1 strain for drug designing. Methods: In this study we have used 12 sequences of NA protein from various countries, retrieved from Uniprot KB database. We have performed structural analysis, antigenic and glycosylation site prediction between NA proteins of influenza A strains. Results: Antigenic variants in sequence of NA H1N1 strain from Italy were found to be unique and were not present in any other NA H1N1. Strains from Italy and Thailand were found to be distantly related while others are closely related. We observed the maximum similarity from position 84 to 448 using disorder prediction analysis of different strains. Sequences from 1 to 83 and 449 to 469 showed the maximum dissimilarity among the NA Proteins. Conclusion: This study focuses on the regions of sequence similarity and dissimilarity of NA in H1N1 strains from different countries. The results in this paper are based on curre...