02558nas a2200193   4500008004100000245014400041210006900185260000800254300001200262490000700274520180700281100003802088700002602126700001602152700001902168700003102187700001902218856012702237       2017                        eng d00aCHO Cells Adapted to Inorganic Phosphate Limitation Show Higher Growth and Higher Pyruvate Carboxylase Flux in Phosphate Replete Conditions0 aCHO Cells Adapted to Inorganic Phosphate Limitation Show Higher   cMAY  a749-7580 v333 aInorganic phosphate (P-i) is an essential ion involved in diverse cellular processes including metabolism. Changes in cellular metabolism upon long term adaptation to P-i limitation have been reported in E. coli. Given the essential role of P-i, adaptation to P-i limitation may also result in metabolic changes in animal cells. In this study, we have adapted CHO cells producing recombinant IgG to limiting P-i conditions for 75 days. Not surprisingly, adapted cells showed better survival under P-i limitation. Here, we report the finding that such cells also showed better growth characteristics compared to control in batch culture replete with P-i ( higher peak density and integral viable cell density), accompanied by a lower specific oxygen uptake rate and cytochrome oxidase activity towards the end of exponential phase. Surprisingly, the adapted cells grew to a lower peak density under glucose limitation. This suggests long term P-i limitation may lead to selection for an altered metabolism with higher dependence on glucose availability for biomass assimilation compared to control. Steady state U-C-13 glucose labeling experiments suggest that adapted cells have a higher pyruvate carboxylase flux. Consistent with this observation, supplementation with aspartate abolished the peak density difference whereas supplementation with serine did not abolish the difference. This supports the hypothesis that cell growth in the adapted culture might be higher due to a higher pyruvate carboxylase flux. Decreased fitness under carbon limitation and mutations in the sucABCD operon has been previously reported in E. coli upon long term adaptation to P-i limitation, suggestive of a similarity in cellular response among such diverse species. (C) 2017 American Institute of Chemical Engineers1 aMaralingannavar, Vishwanathgouda;1 aParmar, Dharmeshkumar1 aPant, Tejal1 aGadgil, Chetan1 aPanchagnula, Venkateswarlu1 aGadgil, Mugdha  uhttps://library.ncl.res.in/content/cho-cells-adapted-inorganic-phosphate-limitation-show-higher-growth-and-higher-pyruvate02451nas a2200193   4500008004100000245025800041210006900299260000800368490000700376520146600383653013101849100002501980700002602005700002702031700002502058700003102083700002102114856012202135       2017                        eng d00aScalable metabolite supplementation strategy against antibiotic resistant pathogen Chromobacterium violaceum induced by NAD(+)/NADH(+) imbalanceA scalable metabolite supplementation strategy against antibiotic resistant pathogen Chromobacterium violaceu0 aScalable metabolite supplementation strategy against antibiotic   cAPR0 v113 a<p>BACKGROUND: The 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. RESULTS: Controlled 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. CONCLUSIONS: The 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.</p>10aAntibiotic resistance; Flux balance analysis; Flux variability analysis; Metabolism; Metabolomic; NAD; NADH; Redox homeostasis1 aBanerjee, Deepanwita1 aParmar, Dharmeshkumar1 aBhattacharya, Nivedita1 aGhanate, Avinash, D.1 aPanchagnula, Venkateswarlu1 aRaghunathan, Anu  uhttps://library.ncl.res.in/content/scalable-metabolite-supplementation-strategy-against-antibiotic-resistant-pathogen00752nas a2200157   4500008004100000245010700041210006900148260009700217100003700314700002600351700001600377700001900393700003100412700001900443856013200462       2018                        eng d00aDifferential responses of CHO cells adapted to limitation of inorganic phosphate, glucose or glutamine0 aDifferential responses of CHO cells adapted to limitation of ino  aNew Orleans, LAbAmerican-Chemical-Society, 1155 16TH ST, NW, Washington, DC 20036 USAcMAR 1 aMaralingannavar, Vishwanathgouda1 aParmar, Dharmeshkumar1 aPant, Tejal1 aGadgil, Chetan1 aPanchagnula, Venkateswarlu1 aGadgil, Mugdha  uhttps://library.ncl.res.in/content/differential-responses-cho-cells-adapted-limitation-inorganic-phosphate-glucose-or-glutamine02699nas a2200277   4500008004100000022001400041245019500055210006900250260001200319300001500331490000700346520166900353653002502022653001402047653002502061653002502086653001102111653001102122653004002133653001102173100003702184700002602221700003102247700001902278856012402297       2019                        eng d  a8756-793800aSuperfluous glutamine synthetase activity in Chinese Hamster Ovary cells selected under glutamine limitation is growth limiting in glutamine-replete conditions and can be inhibited by serine0 aSuperfluous glutamine synthetase activity in Chinese Hamster Ova  cSEP-OCT  aUNSP e28560 v353 a<p>Passaging and expansion of animal cells in lean maintenance medium could result in periods of limitation of some nutrients. Over time, such stresses could possibly result in selection of cells with metabolic changes and contribute to heterogeneity. Here, we investigate whether selection of Chinese Hamster Ovary (CHO) cells under glutamine limitation results in changes in growth under glutamine-replete conditions. In glutamine-limiting medium, compared to control cells passaged in glutamine-rich medium, the selected cells showed higher glutamine synthetase (GS) activity and attained a higher peak viable cell density (PVCD). Surprisingly, in glutamine-replete conditions, selected cells still showed a higher GS activity but a lower PVCD. We show that in glutamine-replete medium, PVCD of selected cells was restored on (a) inhibition of GS activity with methionine sulfoximine, (b) supplementation of aspartate-without affecting GS activity, and (c) supplementation of serine, which is reported to inhibit GS in vitro. Consistent with the reported effect of serine, inhibition of GS activity was observed upon serine supplementation along with reduced growth of cells under glutamine-limiting conditions. The latter observation is important for the design of glutamine-free culture medium and feed used for GS-CHO and GS-NS0. In summary, we show that CHO cells selected under glutamine limitation have superfluous GS activity in glutamine-replete medium, which negatively affects their PVCD. This may be due to its effect on availability of aspartate which was the limiting nutrient for the growth of selected cells in glutamine-replete conditions.</p>
10aC-13 tracer analysis10aCHO cells10aglutamine limitation10aGlutamine synthetase10aGS-CHO10aGS-NS010aselection under nutrient limitation10aserine1 aMaralingannavar, Vishwanathgouda1 aParmar, Dharmeshkumar1 aPanchagnula, Venkateswarlu1 aGadgil, Mugdha  uhttps://library.ncl.res.in/content/superfluous-glutamine-synthetase-activity-chinese-hamster-ovary-cells-selected-under02464nas a2200301   4500008004100000022001400041245009900055210006900154260000800223300000900231490000700240520142600247100002601673700002701699700002201726700002301748700002601771700002101797700002701818700002301845700004101868700002201909700002301931700002301954700002701977700003102004856012702035       2020                        eng d  a2045-232200aPlausible diagnostic value of urinary isomeric dimethylarginine ratio for diabetic nephropathy0 aPlausible diagnostic value of urinary isomeric dimethylarginine   cFEB  a29700 v103 a<p>Altered circulatory asymmetric and symmetric dimethylarginines have been independently reported in patients with end-stage renal failure suggesting their potential role as mediators and early biomarkers of nephropathy. These alterations can also be reflected in urine. Herein, we aimed to evaluate urinary asymmetric to symmetric dimethylarginine ratio (ASR) for early prediction of diabetic nephropathy (DN). In this cross-sectional study, individuals with impaired glucose tolerance (IGT), newly diagnosed diabetes (NDD), diabetic microalbuminuria (MIC), macroalbuminuria (MAC), and normal glucose tolerance (NGT) were recruited from Dr. Mohans' Diabetes Specialties centre, India. Urinary ASR was measured using a validated high-throughput MALDI-MS/MS method. Significantly lower ASR was observed in MIC (0.909) and MAC (0.741) in comparison to the NGT and NDD groups. On regression models, ASR was associated with MIC [OR: 0.256; 95% CI: 0.158-0.491] and MAC [OR 0.146; 95% CI: 0.071-0.292] controlled for all the available confounding factors. ROC analysis revealed ASR cut-point of 0.95 had C-statistic of 0.691 (95% CI: 0.627-0.755) to discriminate MIC from NDD with 72% sensitivity. Whereas, an ASR cut-point of 0.82 had C-statistic of 0.846 (95% CI: 0.800 - 0.893) had 91% sensitivity for identifying MAC. Our results suggest ASR as a potential early diagnostic biomarker for DN among the Asian Indians.</p>
1 aParmar, Dharmeshkumar1 aBhattacharya, Nivedita1 aKannan, Shanthini1 aVadivel, Sangeetha1 aPandey, Gautam, Kumar1 aGhanate, Avinash1 aRagi, Nagarjuna, Chary1 aPrabu, Paramasivam1 aPramodkumar, Thyparambil, Aravindaks1 aManickam, Nagaraj1 aMohan, Viswanathan1 aSripadi, Prabhakar1 aKuppan, Gokulakrishnan1 aPanchagnula, Venkateswarlu  uhttps://library.ncl.res.in/content/plausible-diagnostic-value-urinary-isomeric-dimethylarginine-ratio-diabetic-nephropathy01253nas a2200361   4500008004100000022001400041245014600055210006900201260000800270300001400278490000700292653002300299653001800322653001400340653001500354653003000369100001800399700004000417700002000457700001700477700002600494700002300520700002200543700002100565700002400586700002600610700003200636700002300668700001900691700003100710700002700741856012300768       2024                        eng d  a0939-475300aCirculatory levels of lysophosphatidylcholine species in obese adolescents: Findings from cross-sectional and prospective lipidomics analyses0 aCirculatory levels of lysophosphatidylcholine species in obese a  cJUL  a1807-18160 v3410aAdolescent obesity10aAsian Indians10abiomarker10aLipidomics10aLysophosphatidyl- choline1 aSharma, Sapna1 aSubrahmanyam, Yalamanchili, Venkata1 aRanjani, Harish1 aSidra, Sidra1 aParmar, Dharmeshkumar1 aVadivel, Sangeetha1 aKannan, Shanthini1 aGrallert, Harald1 aUsharani, Dandamudi1 aAnjana, Ranjit, Mohan1 aBalasubramanyam, Muthuswamy1 aMohan, Viswanathan1 aJerzy, Adamski1 aPanchagnula, Venkateswarlu1 aGokulakrishnan, Kuppan  uhttps://library.ncl.res.in/content/circulatory-levels-lysophosphatidylcholine-species-obese-adolescents-findings-cross03451nas a2200433   4500008004100000245014700041210006900188260000900257300000800266490000700274520201300281653002002294653003402314653001702348653002202365653001702387653001502404100001802419700004002437700001702477700002302494700001702517700001702534700002402551700001302575700002002588700002602608700002602634700002102660700003202681700002302713700002302736700001902759700002502778700003102803700002402834700002702858856013202885       2025                        eng d00aPrecision integrated identification of predictive first-trimester metabolomics signatures for early detection of gestational diabetes mellitus0 aPrecision integrated identification of predictive firsttrimester  cNOV   a4340 v243 a<p>
	Background and aimGestational diabetes mellitus (GDM), a common pregnancy-related metabolic disorder, often goes undiagnosed until the second trimester, limiting early intervention opportunities. Given the higher prevalence of GDM in India, there is a critical need to investigate metabolomic biomarkers among Asian Indians, who exhibit greater insulin resistance and are predisposed to developing type 2 diabetes at an earlier age. This study aimed to identify early pregnancy metabolomic signatures predictive of GDM. MethodsAmong 2115 pregnant women from the STratification of Risk of Diabetes in Early pregnancy (STRiDE) study, we performed untargeted metabolomic profiling using UPLC-MS/MS at early pregnancy (&lt; 16 weeks) plasma samples from 100 women-comprising 50 with GDM and 50 normal (without GDM) based on oral glucose tolerance test (OGTT) at 24-28 weeks. Statistical and machine learning approaches, including logistic regression and random forest (RF), were applied to identify GDM-associated metabolites and construct predictive models. Pathway enrichment analysis was conducted using KEGG database annotations. ResultsA total of 49 metabolites were significantly associated with GDM, primarily involving lipid classes such as phosphatidylcholines, sphingomyelins, and triacylglycerols. RF analysis identified a panel of eight metabolites that achieved best predictive performance (AUC 0.880; 95% CI: 0.809-0.951) for GDM. When combined with conventional clinical risk factors, the integrated model showed comparable prediction of GDM with AUC 0.88;: 95% CI: 0.810-0.952). Enrichment analysis highlighted dysregulated pathways including glycerophospholipid and sphingolipid metabolism, autophagy, and insulin resistance. ConclusionThis study demonstrates the utility of early-pregnancy metabolomic profiling for predicting GDM in Indian women. The eight-metabolite panel offers a promising tool for early risk stratification of GDM, warranting validation in diverse populations.</p>
10aFirst trimester10aGestational diabetes mellitus10aIndian women10aMass spectrometry10aMetabolomics10aPrediction1 aSharma, Sapna1 aSubrahmanyam, Yalamanchili, Venkata1 aGupta, Payal1 aVadivel, Sangeetha1 aDeepa, Mohan1 aTandon, Ansh1 aSreedevi, Sreekumar1 aRam, Uma1 aNarad, Priyanka1 aParmar, Dharmeshkumar1 aAnjana, Ranjit, Mohan1 aRaghunathan, Anu1 aBalasubramanyam, Muthuswamy1 aMohan, Viswanathan1 aSengupta, Abhishek1 aAdamski, Jerzy1 aSaravanan, Ponnusamy1 aPanchagnula, Venkateswarlu1 aUsharani, Dandamudi1 aGokulakrishnan, Kuppan  uhttps://library.ncl.res.in/content/precision-integrated-identification-predictive-first-trimester-metabolomics-signatures-early