Cost-effective Whole Exome Sequencing discovers pathogenic variant causing Neurofibromatosis type 1 in a family from Jammu and Kashmir, India.

Neurofibromatosis type 1 (NF1) is a multisystemic hereditary disorder associated with an increased risk of benign and malignant tumor formation predominantly on the skin, bone, and peripheral nervous system. It has been reported that out of all the NF1 cases, more than 95% cases develop the disease due to heterozygous loss-of-function variants in Neurofibromin (NF1) gene. However, identification of NF1 causative variants by presently recommended method of gene-targeted Sanger sequencing is challenging and cost-intensive due to the large size of the NF1gene with 60 exons spanning about 350 kb.

Genetic interaction between F-box motif encoding YDR131C and retrograde signaling-related RTG1 regulates the stress response and apoptosis in Saccharomyces cerevisiae.

The retrograde signaling pathway is well conserved from yeast to humans, which regulates cell adaptation during stress conditions and prevents cell death. One of its components, RTG1 encoded Rtg1p in association with Rtg3p communicates between mitochondria, nucleus, and peroxisome during stress for adaptation, by regulation of transcription. The F-box motif protein encoded by YDR131C  constitutes a part of SCF -E3 ligase complex, with unknown function; however, it is known that retrograde signaling is modulated by the E3 ligase complex.

DNA base excision repair genes variants rs25487 (X-ray repair cross-complementing 1) and rs1052133 (human 8-oxoguanine glycosylase 1) with susceptibility to ovarian cancer in the population of the Jammu region, India.

Background: Ovarian cancer is highly prevalent in the population of Jammu, in India; the ovarian cancer ranks third among other types of cancer prevalent in females. However, association studies on ovarian cancer are lacking in this region. We aimed to investigate the disease susceptible variants rs1052133 (human 8-oxoguanine glycosylase 1 [hOGG1]) and rs25487 (X-ray repair cross-complementing 1 [XRCC1]) with ovarian cancer in population of Jammu, India.

Genetic variants of DNAH11 and LRFN2 genes and their association with ovarian and breast cancer.

Objective: To investigate the association of newly identified genetic variants G>A (rs2285947) of the DNAH11 gene and G>A (rs2494938) of the LRFN2 gene with ovarian and breast cancers in women belonging to Jammu and Kashmir state, where the prevalence of ovarian and breast cancers is remarkably high in the population.

Methods: A candidate gene prospective case-control association study design was adopted, in which 354 cases (219 cases of ovarian cancer and 135 cases of breast cancer) were histopathologically confirmed and 330 healthy controls matched for age and ethnicity were recruited. The details of cases and controls were also recorded in a predesigned pro forma after their written informed consent.

A hydrolase with esterase activity expressed from a fosmid gene bank prepared from DNA of a North West Himalayan glacier frozen soil sample.

Screening of 20,000 clones of a fosmid gene bank, constructed from DNA extracted from North West Himalaya (NWH) glacier soil sample, using functional approach identified 10 esterase/lipase-producing clones. Of these, a clone designated pFG43 with an insert size of 45 kb which produced the highest concentration of enzyme (467.43 U/mg) was sequenced.

Production and purification of an alkaline lipase from sp. for enantioselective resolution of (±)-Ketoprofen butyl ester.

The present study was conducted to purify lipase from indigenous strain Kakrayal_1 (BSK-L) for enantioselective resolution of racemic-ketoprofen. The production of lipase (BSK-L) was optimized using Plackett-Burman and central composite design of response surface methodology (RSM). The optimized media containing olive oil (3.

Molecular dynamics analysis of the effects of GTP, GDP and benzimidazole derivative on structural dynamics of a cell division protein FtsZ from .

The prevailing multi-drug resistance in continues to remain one of the main challenges to combat tuberculosis. Hence, it becomes imperative to focus on novel drug targets. Filamenting temperature-sensitive mutant Z (FtsZ) is an essential cell division protein, a eukaryotic tubulin homologue and a promising drug target.

In silico evaluation of the resistance of the T790M variant of epidermal growth factor receptor kinase to cancer drug Erlotinib.

Epidermal growth factor receptor kinase is implicated in cancer development due to either overexpression or activation variants in its functional intracellular kinase domain. Threonine to methionine (Thr 790 Met) is one such variant observed commonly in patients showing resistance to kinase inhibitor drug Erlotinib. Two mechanisms for resistance have been proposed (1) steric hindrance and (2) enhanced binding to ATP.

In Silico Evaluation of Variable pH on the Binding of Epidermal Growth Factor Receptor Ectodomain to its Ligand Through Molecular Dynamics Simulation in Tumors.

Many aggressive and metastatic cancer cell types show Warburg Effect; therefore, it is a possible adaptation helping cancer cells to rapidly divide and utilize the glycolytic intermediates for biosynthesis of ribose sugars (for nucleotide biosynthesis), fatty acid synthesis (lipids for membrane synthesis), NADPH (cellular currency for reductive biosynthesis) and lactate. This in due course results in decrease of extracellular pH, leading to acidic tumor micro-environment. EGFR is a crucial cell surface signaling receptor implicated in cancer cell survival and progression.

A variation in PANK2 gene is causing Pantothenate kinase-associated Neurodegeneration in a family from Jammu and Kashmir - India.

Pantothenate kinase-associated neurodegeneration is a rare hereditary neurodegenerative disorder associated with nucleotide variation(s) in mitochondrial human Pantothenate kinase 2 (hPanK2) protein encoding PANK2 gene, and is characterized by symptoms of extra-pyramidal dysfunction and accumulation of non-heme iron predominantly in the basal ganglia of the brain. In this study, we describe a familial case of PKAN from the State of Jammu and Kashmir (J&K), India based on the clinical findings and genetic screening of two affected siblings born to consanguineous normal parents. The patients present with early-onset, progressive extrapyramidal dysfunction, and brain Magnetic Resonance imaging (MRI) suggestive of symmetrical iron deposition in the globus pallidi.

Biotransformation of methyl-β-D-glucopyranoside to higher chain alkyl glucosides by cell bound β-glucosidase of Pichia etchellsii.

In the present study, we have investigated the use of Pichia etchellsii whole cells for synthesis of long-chain alkyl glucosides. Methyl-β-d-glucopyranoside (MG) was used in reaction with fatty alcohols, n-hexanol, n-octanol, n-decanol and n-dodecanol to synthesize the respective alkyl glucosides. The initial reaction conditions were first optimized at 2.

Comparative analysis of mesothelial invasion by single- and multi-wall carbon nanotubes using computational approach.

This study explored the interactions of carbon nanotubes (CNTs) with mesothelial cells. We carried out molecular dynamic simulation studies on the mesothelial cell invasion by single and multi walled carbon nanotubes. In our simulation experiments SWCNTs showed greater binding affinity with membrane in comparison to MWCNTs with similar aspect ratio.

In silico identification of novel protective VSG antigens expressed by Trypanosoma brucei and an effort for designing a highly immunogenic DNA vaccine using IL-12 as adjuvant.

African trypanosomiasis continues to be a major health problem, with more adults dying from this disease world-wide. As the sequence diversity of Trypanosoma brucei is extreme, with VSGs having 15-25% identity with most other VSGs, hence it displays a huge diversity of adaptations and host specificities. Therefore the need for an improved vaccine has become an international priority.

In silico proteomic characterization of human epidermal growth factor receptor 2 (HER-2) for the mapping of high affinity antigenic determinants against breast cancer.

Multiple different approaches are being used to activate the immune system against breast cancer. Vaccine therapy in general follows the principle that injections of various substances ultimately result in the presentation of tumor peptides to the patient's immune system. We proposed a potential in silico DNA vaccine against breast cancer by integrating high affinity T cell (MHC-I and MHC-II) and B cell (continuous and discontinuous) epitopes.

In silico designing and optimization of anti-breast cancer antibody mimetic oligopeptide targeting HER-2 in women.

Overexpression of HER-2 is of frequent (20-30%) occurrence in breast cancer. Therapeutic targeting of HER-2 with humanized antibody derived oligopeptide may be a promising approach to the treatment of breast cancer. HER-2 gene is part of a family of genes that play critical roles in regulating transmembrane growth of breast cancer cells.

Functional cloning and predictive structural modeling of a novel esterase from Bacillus subtilis strain, RRL 1789.

We have recently reported the purification and characterization of a novel esterase from the Bacillus subtilis strain. In the present study we report the genomic DNA cloning and predictive structural modeling of this novel esterase. Tributyrin- and Rhodamine B-based functional screen of a Bacillus subtilis genomic library led to the identification of a potential lipolytic gene.

Application of a multiplex PCR assay for the detection of Shigella, Escherichia coli and Shiga toxin-producing Esch. coli in milk.

A multiplex PCR (mPCR) assay using previously known genetic markers of Shigella, Escherichia coli and Shiga-toxic Esch. coli was standardized. uidA gene was targeted for the common detection of Esch.

Evaluation of three different molecular markers for the detection of Staphylococcus aureus by polymerase chain reaction.

The aim of this study was to target three genes of Staphylococcus aureus-fmhA (coding for a factor of unknown function), catalase and femA (coding for a factor essential for methicillin resistance) to establish and validate a PCR assay for the detection of this pathogen. Two pairs of primers were designed for fmhA and one pair each for catalase and femA genes. The PCR assays were standardized and found to give specific amplicons under similar reaction parameters.

Development of simple sequence repeat markers in cymbopogon species.

The genus Cymbopogon comprises about 140 species, which produce characteristic aromatic essential oils. However, the phenotypic identification of species of Cymbopogon has been difficult as a result of widespread occurrence of natural variants, which differ in ploidy levels and chemotaxonomic complexities. Therefore, we have developed a set of simple sequence repeat markers from a genomic library of Cymbopogon jwarancusa to help in the precise identification of the species (including accessions) of Cymbopogon.

Phytochemical and genetic analysis in selected chemotypes of Withania somnifera.

The main active components and genetic profile of 15 selected accessions of Withania somnifera Dunal. were analysed. Ethanolic extract of the dried roots/leaves of the plant was concentrated under pressure at 50+/-5 degrees C and was analysed for main compounds (withanolides and withaferin A) by HPLC.

Molecular cloning of carboxylesterase gene and biochemical characterization of encoded protein from Bacillus subtilis (RRL BB1).

An isolated strain of Bacillus subtilis identified by 16S rDNA sequence analysis produces an enantioselective ester hydrolase. Whole cells of B. subtilis (RRL BB1) and enzyme derived from it was capable of enantioselective hydrolysis of several racemates including drug intermediates with moderate to high enantioselectivity as already reported by us.

Piperine, a phytochemical potentiator of ciprofloxacin against Staphylococcus aureus.

Piperine, a trans-trans isomer of 1-piperoyl-piperidine, in combination with ciprofloxacin markedly reduced the MICs and mutation prevention concentration of ciprofloxacin for Staphylococcus aureus, including methicillin-resistant S. aureus. The enhanced accumulation and decreased efflux of ethidium bromide in the wild-type and mutant (CIPr-1) strains in the presence of piperine suggest its involvement in the inhibition of bacterial efflux pumps.

An endophytic fungus from Nothapodytes foetida that produces camptothecin.

A fungal endophytic isolate, camptothecin, has been isolated from the inner bark of the plant Nothapodytes foetidafrom the Western coast of India. The fungus, which belongs to the family Phycomycetes, produced the anticancer drug lead compound camptothecin (1) when grown in a synthetic liquid medium (Sabouraud broth) under shake flask and bench scale fermentation conditions. Compound 1 was identified by means of chromatographic and spectroscopic methods.

The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans.

The aryl tetralin lignans are synthesized by Podophyllum sps. and are in great demand worldwide due to their use in synthesis of topoisomerase inhibitors. However, the sustained production of these aryl tetralin lignans requires large-scale harvesting from the natural environments, which has resulted in the plant-endangered status.