Integrated genetic and metabolic landscapes predict vulnerabilities of temozolomide resistant glioblastoma cells.

Metabolic reprogramming and its molecular underpinnings are critical to unravel the duality of cancer cell function and chemo-resistance. Here, we use a constraints-based integrated approach to delineate the interplay between metabolism and epigenetics, hardwired in the genome, to shape temozolomide (TMZ) resistance. Differential metabolism was identified in response to TMZ at varying concentrations in both the resistant neurospheroidal (NSP) and the susceptible (U87MG) glioblastoma cell-lines. The genetic basis of this metabolic adaptation was characterized by whole exome sequencing that identified mutations in signaling pathway regulators of growth and energy metabolism. Remarkably, our integrated approach identified rewiring in glycolysis, TCA cycle, malate aspartate shunt, and oxidative phosphorylation pathways. The differential killing of TMZ resistant NSP by Rotenone at low concentrations with an IC50 value of 5 nM, three orders of magnitude lower than for U87MG that exhibited an IC50 value of 1.8 mM was thus identified using our integrated systems-based approach

Experience of the Ural federal university for implementation of international educational program in water conditioning and wastewater treatment

This paper briefly reports on the first international summer school on Traditional and Innovative Technologies of Water and Wastewater Treatment, which was held June 18 – July 29, 2018, Yekaterinburg, Russia as part of the project “UrFU Summer University”

Water Penetration of Veneer Made with Various Clay Bricks

Rainwater penetration through building enclosures is one of the critical factors affecting building performance and durability. Understanding and assessing rainwater penetration within and through the veneer is crucial to controlling and avoiding moisture-related problems such as biological growth and corrosion in interior structural elements. Adding a layer of clay bricks as a cladding to the windward surface of a building envelope is customary in Canadian residential building construction. Cladding made of clay bricks (often known as clay brick veneer) serves multiple purposes, such as providing additional thermal insulation, aiding in weather resistance, and improving the building’s aesthetics. Though clay brick veneer provides adequate weather resistance for the building, it does not offer complete resistance to rainwater penetration. Rainwater tends to seep through masonry walls, especially when rain is combined with heavy wind conditions. The accumulated excess moisture inside the building may degrade building materials, reduce the insulation quality, and facilitate the growth of fungal mold, endangering the health of the occupants of the building. Hence, studying the resistance of commonly used cladding systems to water penetration is of utmost importance. The experimental program involved the through-wall water penetration of nine full-scale test panels as per ASTM E514/E514M - 20 and supplement surface treatment tests. The water permeance of the brick veneer under air pressure was studied in the laboratory. This research project is laid out to evaluate and compare the resilience of four commonly used clay bricks and stucco cladding systems when subjected to wind-driven rain

Not Available

Not AvailableA chromatography-free atmospheric pressure matrix-assisted laser desorption/ionization high-resolution massspectrometry (AP-MALDI HRMS) method is described for the simultaneous and quantitative detection of triazines and triazoles in grapes. The analytes were detected reproducibly with high mass accuracy (mass error within 5 ppm) and further confirmed by collision-induced dissociation fragmentation in tandem MS. The LODs and LOQs forall the analytes were found to be in the nanogram per gram level (15–20 ng/g LOQ). Internal standard–normalized high-resolution accurate mass–extracted (HR-AM) peak intensities of the detected ions were used to generate the concentration response curves. Linearity (with R2 values around 0.99) was obtained for these curves within a concentration range of 20–200 ng/g of the individual analytes. The accuracy and precision of the method were further established using QC samples. Validation and performancecomparison of the AP-MALDI HRMS method with an existing standard method using LC with triple quadrupole MS was carried out (evaluating sensitivity, accuracy, precision, and analysis time) using 20 table-grape field samples after QuEChERS extraction.Not Availabl

Gene expression: protein interaction system network modeling identifies transformation-associated molecules and pathways in ovarian cancer

Multiple, dissimilar genetic defects in cancers of the same origin contribute to heterogeneity in tumor phenotypes and therapeutic responses of patients, yet the associated molecular mechanisms remain elusive. Here, we show at the systems level that serous ovarian carcinoma is marked by the activation of interconnected modules associated with a specific gene set that was derived from three independent tumor-specific gene expression data sets. Network prediction algorithms combined with pre established protein interaction networks and known functionalities affirmed the importance of genes associated with ovarian cancer as predictive biomarkers, besides "discovering" novel ones purely on the basis of interconnectivity, whose precise involvement remains to be investigated. Copy number alterations and aberrant epigenetic regulation were identified and validated as significant influences on gene expression. More importantly, three functional modules centering on c-Myc activation, altered retinoblastoma signaling, and p53/cell cycle/DNA damage repair pathways have been identified for their involvement in transformation-associated events. Further studies will assign significance to and aid the design of a panel of specific markers predictive of individual- and tumor-specific pathways. In the parlance of this emerging field, such networks of gene-hub interactions may define personalized therapeutic decisions

Engineering Proteins for Thermostability with iRDP Web Server

<div><p>Engineering protein molecules with desired structure and biological functions has been an elusive goal. Development of industrially viable proteins with improved properties such as stability, catalytic activity and altered specificity by modifying the structure of an existing protein has widely been targeted through rational protein engineering. Although a range of factors contributing to thermal stability have been identified and widely researched, the <i>in silico</i> implementation of these as strategies directed towards enhancement of protein stability has not yet been explored extensively. A wide range of structural analysis tools is currently available for <i>in silico</i> protein engineering. However these tools concentrate on only a limited number of factors or individual protein structures, resulting in cumbersome and time-consuming analysis. The iRDP web server presented here provides a unified platform comprising of iCAPS, iStability and iMutants modules. Each module addresses different facets of effective rational engineering of proteins aiming towards enhanced stability. While iCAPS aids in selection of target protein based on factors contributing to structural stability, iStability uniquely offers <i>in silico</i> implementation of known thermostabilization strategies in proteins for identification and stability prediction of potential stabilizing mutation sites. iMutants aims to assess mutants based on changes in local interaction network and degree of residue conservation at the mutation sites. Each module was validated using an extensively diverse dataset. The server is freely accessible at <a href="http://irdp.ncl.res.in/" target="_blank">http://irdp.ncl.res.in</a> and has no login requirements.</p></div

A scalable metabolite supplementation strategy against antibiotic resistant pathogen Chromobacterium violaceum induced by NAD+/NADH+ imbalance.

BackgroundThe leading edge of the global problem of antibiotic resistance necessitates novel therapeutic strategies. This study develops a novel systems biology driven approach for killing antibiotic resistant pathogens using benign metabolites.ResultsControlled laboratory evolutions established chloramphenicol and streptomycin resistant pathogens of Chromobacterium. These resistant pathogens showed higher growth rates and required higher lethal doses of antibiotic. Growth and viability testing identified malate, maleate, succinate, pyruvate and oxoadipate as resensitising agents for antibiotic therapy. Resistant genes were catalogued through whole genome sequencing. Intracellular metabolomic profiling identified violacein as a potential biomarker for resistance. The temporal variance of metabolites captured the linearized dynamics around the steady state and correlated to growth rate. A constraints-based flux balance model of the core metabolism was used to predict the metabolic basis of antibiotic susceptibility and resistance.ConclusionsThe model predicts electron imbalance and skewed NAD/NADH ratios as a result of antibiotics - chloramphenicol and streptomycin. The resistant pathogen rewired its metabolic networks to compensate for disruption of redox homeostasis. We foresee the utility of such scalable workflows in identifying metabolites for clinical isolates as inevitable solutions to mitigate antibiotic resistance

Luminescent sensory material for organic-halogen compounds, and methods and apparatus utilizing such

US6998271; US6998271 B2; US6998271B2; US6,998,271; US 6,998,271 B2; 6998271; Appl. No. 10/158,858US2005-2006 > Other Outputs > Patents grantedVersion of Recor

Comparative analysis of various thermostability factors among 16 thermophilic-mesophilic pairs of protein.

<p>* The PDB IDs of Thermophilic (TS), Mesophilic (MS) pair, starting from Column 2, belong to family Citrate Synthase, Malate dehydrogenase, Rubredoxin, Cyclodextrin, Glutamate dehydrogenase, L-Lactate dehydrogenase, Thermolysin, 3-Phosphoglycerate kinase, Chey protein, Methionine aminopeptidase, Endo–1,4-Beta-Xylanase, Adenylate kinase, Ferredoxin, Pyrophosphate phosphohydrolase, Manganese superoxide dismutase and Phosphofructokinase. The parameters listed in Column 1 correspond to aromatic (Aro: residues FWY), uncharged polar (UP: residues NQST), proline (Pro), hydrophobic or aliphatic (ALI: residues VILM), charged (CHG: residues DERKH) residue contents, Arg to Lys ratio (R/K), total percentage of ion-pairs (IP), aromatic-aromatic (AAI), aromatic-sulphur (ASI), cation-pi (CPI), hydrogen bonding (HB), hydrophobic (HP) interactions, proline residue percentages occurring at 2^nd position of beta turns (Bt2P) and Ncap helix positions (NCap), percentage of dipole stabilized helices (Hdip), thermolabile bonds (TL) and conformationally strained residues (CS), ratio of nonpolar to polar accessible surface areas (NP/P) and percentage of loop region (Loop).</p><p>**The value shown in # represents the case in which both MS and TS proteins show absence of the corresponding parameters while the values shown in ~ represents the case in which only the MS protein shows absence of the corresponding features.</p><p>*** Total number of positive values calculated for each parameter; indicates number of families in which thermophilic proteins have higher preference for the parameter than their mesophilic counterparts. Numbers of ~ values are also considered while counting total number of positive values. Detailed results can be found at <a href="http://irdp.ncl.res.in/cgi-bin/result_fetch.php?ID=iCAPScase" target="_blank">http://irdp.ncl.res.in/cgi-bin/result_fetch.php?ID=iCAPScase</a>.</p><p>Comparative analysis of various thermostability factors among 16 thermophilic-mesophilic pairs of protein.</p