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-pyruvate00752nas 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-glutamine01845nas a2200193   4500008004100000022001400041245013700055210006900192260000900261300001200270490000700282520115600289100000501445700001901450700002001469700001801489700002301507856012101530       2019                        eng d  a2213-671100aClathrin-mediated endocytosis regulates a balance between opposing signals to maintain the pluripotent state of embryonic stem cells0 aClathrinmediated endocytosis regulates a balance between opposin  cJAN   a152-1640 v123 a<p>Endocytosis is implicated in the maintenance of embryonic stem cell (ESC) pluripotency, although its exact role and the identity of molecular players remain poorly understood. Here, we show that the clathrin heavy chain (CLTC), involved in clathrin-mediated endocytosis (CME), is vital for maintaining mouse ESC (mESC) pluripotency. Knockdown of Cltc resulted in a loss of pluripotency accompanied by reduced E-cadherin (E-CAD) levels and increased levels of transforming growth factor beta (TGF-beta) and extracellular signal-regulated kinase (ERK) signaling. We demonstrate that both E-CAD and TGF-beta receptor type 1 (TGF-beta R1) are internalized through CME in mESCs. While E-CAD is recycled, TGF-beta R1 is targeted for lysosomal degradation thus maintaining inverse levels of these molecules. Finally, we show that E-CAD interacts with ERK, and that the decreased pluripotency upon CME loss can be rescued by inhibiting TGF-beta R, MEK, and GSK3 beta, or overexpressing E-CAD. Our results demonstrate that CME is critical for balancing signaling outputs to regulate ESC pluripotency, and possibly cell fate choices in early development.</p>1 a1 aGadgil, Chetan1 aMote, Ridim, D.1 aRajan, Raghav1 aSubramanyam, Deepa  uhttps://library.ncl.res.in/content/clathrin-mediated-endocytosis-regulates-balance-between-opposing-signals-maintain01854nas a2200265   4500008004100000022001400041245010800055210006900163260000900232300000800241490000700249520099900256653001901255653002501274653001501299653001301314653002501327653001601352653001801368653001501386100002301401700001901424700002401443856012101467       2019                        eng d  a1664-302X00aWeb-gLV: a web based platform for lotka-volterra based modeling and simulation of microbial populations0 aWebgLV a web based platform for lotkavolterra based modeling and  cFEB   a2880 v103 a<p>The affordability of high throughput DNA sequencing has allowed us to explore the dynamics of microbial populations in various ecosystems. Mathematical modeling and simulation of such microbiome time series data can help in getting better understanding of bacterial communities. In this paper; we present Web-gLV- a GUI based interactive platform for generalized Lotka-Volterra (gLV) based modeling and simulation of microbial populations. The tool can be used to generate the mathematical models with automatic estimation of parameters and use them to predict future trajectories using numerical simulations. We also demonstrate the utility of our tool on few publicly available datasets. The case studies demonstrate the ease with which the current tool can be used by biologists to model bacterial populations and simulate their dynamics to get biological insights. We expect Web-gLV to be a valuable contribution in the field of ecological modeling and metagenomic systems biology.</p>
10alotka-volterra10amicrobial population10aMicrobiome10aModeling10anumerical-simulation10atime-series10avisualization10aweb-server1 aKuntal, Bhusan, K.1 aGadgil, Chetan1 aMande, Sharmila, S.  uhttps://library.ncl.res.in/content/web-glv-web-based-platform-lotka-volterra-based-modeling-and-simulation-microbial02024nas a2200193   4500008004100000022001400041245003600055210003600091260000800127300001100135490000700146520151300153653001801666653001801684653002401702100001801726700001901744856006701763       2021                        eng d  a1478-396700aBoolean model for melanogenesis0 aBoolean model for melanogenesis  cMAR  a0260040 v183 a<p>Melanogenesis is a highly regulated process through which the pigment melanin is produced in skin cells. Irregularities in the molecular events that govern the process of skin pigmentation can cause disorders like vitiligo. In order to understand the biology of disease progression, it is important to have an in depth understanding of intracellular events. Mathematical models provide an integrated view of intracellular signalling. There are very few models to date that incorporate intracellular processes relevant to melanogenesis and only one to our knowledge that simulates the dynamics of response to varying levels of input. Here, we report the formulation of the largest Boolean model (265 nodes) for melanogenesis to date. The model was built on the basis of a detailed interaction network graph published by Raghunath et al. Through additional manual curation of the reported interactions, we converted the graph into a set of Boolean rules, following the procedure of the first Boolean model (62 nodes) for melanogenesis published by Lee et al. Simulations show that the predicted response to varying UV levels for most of the nodes is similar to the predictions of the existing model. The greater complexity allows investigation of the sensitivity of melanin to additional nodes. We carried out perturbation analysis of the network through node deletion and constitutive activation to identify sensitivity of outcomes, and compared the nodes identified as sensitive to previous reports.</p>
10aBoolean model10amelanogenesis10aSignal transduction1 aDnyane, Pooja1 aGadgil, Chetan  uhttps://library.ncl.res.in/content/boolean-model-melanogenesis00868nas a2200253   4500008004100000022001400041245012800055210006900183260000900252300001100261490000700272653001900279653002500298653001500323653001300338653002500351653001600376653001800392653001500410100002300425700001900448700002400467856012300491       2021                        eng d  a1664-302X00aWeb-gLV: a web based platform for lotka-volterra based modeling and simulation of microbial populations (vol 10, 288, 2019)0 aWebgLV a web based platform for lotkavolterra based modeling and  cJAN   a6053080 v1110alotka-volterra10amicrobial population10aMicrobiome10aModeling10anumerical-simulation10atime-series10avisualization10aweb-server1 aKuntal, Bhusan, K.1 aGadgil, Chetan1 aMande, Sharmila, S.  uhttps://library.ncl.res.in/content/web-glv-web-based-platform-lotka-volterra-based-modeling-and-simulation-microbial-000651nas a2200181   4500008004100000022001400041245009200055210006900147260000800216300000800224490000800232100001900240700001700259700002300276700001900299700003000318856012100348       2022                        eng d  a0006-349500aKinetic model of GPCR-G protein interactions reveals allokairic modulation of signaling0 aKinetic model of GPCRG protein interactions reveals allokairic m  cFEB  a1220 v1211 aCulhane, Kelly1 aGupte, Tejas1 aMadhugiri, Indrani1 aGadgil, Chetan1 aSivaramakrishnan, Sivaraj  uhttps://library.ncl.res.in/content/kinetic-model-gpcr-g-protein-interactions-reveals-allokairic-modulation-signaling02449nas a2200325   4500008004100000022001400041245010200055210006900157260000800226300001300234490000700247520140400254100001901658700001801677700001801695700002001713700002301733700002001756700001801776700001801794700001801812700002601830700001901856700001901875700002701894700002201921700002501943700002401968856013101992       2022                        eng d  a1544-917300aTemporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator0 aTemporal analysis of melanogenesis identifies fatty acid metabol  cMAY  ae30016340 v203 a<p>
	Therapeutic methods to modulate skin pigmentation has important implications for skin cancer prevention and for treating cutaneous hyperpigmentary conditions. Towards defining new potential targets, we followed temporal dynamics of melanogenesis using a cell-autonomous pigmentation model. Our study elucidates 3 dominant phases of synchronized metabolic and transcriptional reprogramming. The melanogenic trigger is associated with high MITF levels along with rapid uptake of glucose. The transition to pigmented state is accompanied by increased glucose channelisation to anabolic pathways that support melanosome biogenesis. SREBF1-mediated up-regulation of fatty acid synthesis results in a transient accumulation of lipid droplets and enhancement of fatty acids oxidation through mitochondrial respiration. While this heightened bioenergetic activity is important to sustain melanogenesis, it impairs mitochondria lately, shifting the metabolism towards glycolysis. This recovery phase is accompanied by activation of the NRF2 detoxication pathway. Finally, we show that inhibitors of lipid metabolism can resolve hyperpigmentary conditions in a guinea pig UV-tanning model. Our study reveals rewiring of the metabolic circuit during melanogenesis, and fatty acid metabolism as a potential therapeutic target in a variety of cutaneous diseases manifesting hyperpigmentary phenotype.</p>
1 aSultan, Farina1 aBasu, Reelina1 aMurthy, Divya1 aKochar, Manisha1 aAttri, Kuldeep, S.1 aAggarwal, Ayush1 aKumari, Pooja1 aDnyane, Pooja1 aTanwar, Jyoti1 aMotiani, Rajender, K.1 aSingh, Archana1 aGadgil, Chetan1 aBhavesh, Neel, Sarovar1 aSingh, Pankaj, K.1 aNatarajan, Vivek, T.1 aGokhale, Rajesh, S.  uhttps://library.ncl.res.in/content/temporal-analysis-melanogenesis-identifies-fatty-acid-metabolism-key-skin-pigment-regulator02081nas a2200205   4500008004100000245009500041210006900136260000800205300000900213490000700222520140100229100001701630700001601647700002001663700001501683700001801698700001901716700001801735856012201753       2024                        eng d00aFeedback driven autonomous cycles of assembly and disassembly from minimal building blocks0 aFeedback driven autonomous cycles of assembly and disassembly fr  cNOV  a99800 v153 a<p>
	The construction of complex systems by simple chemicals that can display emergent network dynamics might contribute to our understanding of complex behavior from simple organic reactions. Here we design single amino acid/dipeptide-based systems that exhibit multiple periodic changes of (dis)assembly under non-equilibrium conditions in closed system, importantly in the absence of evolved biocatalysts. The two-component based building block exploits pH driven non-covalent assembly and time-delayed accelerated catalysis from self-assembled state to install orthogonal feedback loops with a single batch of reactants. Mathematical modelling of the reaction network establishes that the oscillations are transient for this network structure and helps to predict the relative contribution of the feedback loop to the ability of the system to exhibit such transient oscillation. Such autonomous systems with purely synthetic molecules are the starting point that can enable the design of active materials with emergent properties. The study of the network dynamics of complex systems formed by simple chemicals can contribute to our understanding of complex behavior from simple organic reactions. Here, built on the minimal building blocks, the authors describe a system with periodic (dis)assembly utilizing feedback loops controlled by time-delayed catalysis and pH-driven assembly.</p>
1 aReja, Antara1 aJha, Sangam1 aSreejan, Ashley1 aPal, Sumit1 aBal, Subhajit1 aGadgil, Chetan1 aDas, Dibyendu  uhttps://library.ncl.res.in/content/feedback-driven-autonomous-cycles-assembly-and-disassembly-minimal-building-blocks00752nas a2200205   4500008004100000022001400041245013700055210006900192260000800261490000700269653001500276653001700291653001600308653001400324100001900338700002300357700001900380700001900399856012800418       2024                        eng d  a8756-793800aLeveraging machine learning to dissect role of combinations of amino acids in modulating the effect of zinc on mammalian cell growth0 aLeveraging machine learning to dissect role of combinations of a  cMAY0 v4010aAbsorption10aCytotoxicity10aENTEROCYTES10aHISTIDINE1 aPandey, Ujjiti1 aMadhugiri, Indrani1 aGadgil, Chetan1 aGadgil, Mugdha  uhttps://library.ncl.res.in/content/leveraging-machine-learning-dissect-role-combinations-amino-acids-modulating-effect-zinc