02697nas a2200241 4500008004100000022001400041245015300055210006900208260008600277300001400363490000700377520171200384653002402096653002902120653003702149653002202186653002602208100002202234700002402256700001902280700002802299856012802327 2015 eng d a0739-110200aDistinct molecular features facilitating ice-binding mechanisms in hyperactive antifreeze proteins closely related to an Antarctic sea ice bacterium0 aDistinct molecular features facilitating icebinding mechanisms i a530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USAbTAYLOR & FRANCIS INCcJUL a1424-14410 v333 a

Antifreeze proteins or ice-binding proteins (IBPs) facilitate the survival of certain cellular organisms in freezing environment by inhibiting the growth of ice crystals in solution. Present study identifies orthologs of the IBP of Colwellia sp. SLW05, which were obtained from a wide range of taxa. Phylogenetic analysis on the basis of conserved regions (predicted as the `ice-binding domain' [IBD]) present in all the orthologs, separates the bacterial and archaeal orthologs from that of the eukaryotes'. Correspondence analysis pointed out that the bacterial and archaeal IBDs have relatively higher average hydrophobicity than the eukaryotic members. IBDs belonging to bacterial as well as archaeal AFPs contain comparatively more strands, and therefore are revealed to be under higher evolutionary selection pressure. Molecular docking studies prove that the ice crystals form more stable complex with the bacterial as well as archaeal proteins than the eukaryotic orthologs. Analysis of the docked structures have traced out the ice-binding sites (IBSs) in all the orthologs which continue to facilitate ice-binding activity even after getting mutated with respect to the well-studied IBSs of Typhula ishikariensis and notably, all these mutations performing ice-binding using `anchored clathrate mechanism' have been found to prefer polar and hydrophilic amino acids. Horizontal gene transfer studies point toward a strong selection pressure favoring independent evolution of the IBPs in some polar organisms including prokaryotes as well as eukaryotes because these proteins facilitate the polar organisms to acclimatize to the adversities in their niche, thus safeguarding their existence.

10aantifreeze proteins10ahorizontal gene transfer10aice-recrystallization inhibition10aMolecular docking10aPhylogenetic analysis1 aBanerjee, Rachana1 aChakraborti, Pratim1 aBhowmick, Rupa1 aMukhopadhyay, Subhasish uhttps://library.ncl.res.in/content/distinct-molecular-features-facilitating-ice-binding-mechanisms-hyperactive-antifreeze-100593nas a2200145 4500008004100000245011600041210006900157260000800226300001200234490000600246100001900252700002600271700002100297856012900318 2015 eng d00aExploring the differences in metabolic behavior of astrocyte and glioblastoma: a flux balance analysis approach0 aExploring the differences in metabolic behavior of astrocyte and cDEC a159-1770 v91 aBhowmick, Rupa1 aSubramanian, Abhishek1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/exploring-differences-metabolic-behavior-astrocyte-and-glioblastoma-flux-balance-analysis02365nas a2200241 4500008004100000022001400041245012400055210006900179260010200248300001200350490000700362520138400369653001801753653003401771653004401805653003001849653003801879100002001917700002201937700001901959700002101978856012401999 2015 eng d a0250-599100aTemporal protein expression pattern in intracellular signalling cascade during T-cell activation: a computational study0 aTemporal protein expression pattern in intracellular signalling  aC V RAMAN AVENUE, SADASHIVANAGAR, P B \#8005, BANGALORE 560 080, INDIAbINDIAN ACAD SCIENCEScOCT a769-7890 v403 a

Various T-cell co-receptor molecules and calcium channel CRAC play a pivotal role in the maintenance of cell's functional responses by regulating the production of effector molecules (mostly cytokines) that aids in immune clearance and also maintaining the cell in a functionally active state. Any defect in these co-receptor signalling pathways may lead to an altered expression pattern of the effector molecules. To study the propagation of such defects with time and their effect on the intracellular protein expression patterns, a comprehensive and largest pathway map of T-cell activation network is reconstructed manually. The entire pathway reactions are then translated using logical equations and simulated using the published time series microarray expression data as inputs. After validating the model, the effect of in silico knock down of co-receptor molecules on the expression patterns of their downstream proteins is studied and simultaneously the changes in the phenotypic behaviours of the T-cell population are predicted, which shows significant variations among the proteins expression and the signalling routes through which the response is propagated in the cytoplasm. This integrative computational approach serves as a valuable technique to study the changes in protein expression patterns and helps to predict variations in the cellular behaviour.

10aBoolean model10aco-receptors and CRAC channel10asynchronous and asynchronous simulation10aT-cell signalling pathway10atemporal gene expression patterns1 aGanguli, Piyali1 aChowdhury, Saikat1 aBhowmick, Rupa1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/temporal-protein-expression-pattern-intracellular-signalling-cascade-during-t-cell-001835nas a2200157 4500008004100000022001400041245015800055210006900213260000800282300001300290490000700303520119500310100001901505700002101524856013201545 2020 eng d a1932-620300aDifferential suitability of reactive oxygen species and the role of glutathione in regulating paradoxical behavior in gliomas: a mathematical perspective0 aDifferential suitability of reactive oxygen species and the role cJUN ae02352040 v153 a

Manipulative strategies of ROS in cancer are often exhibited as changes in the redox and thiol ratio of the cells. Cellular responses to oxidative insults are generated in response to these changes which are triggered due to the rerouting of the metabolic framework to maintain survival under stress. However, mechanisms of these metabolic re-routing are not clearly understood and remained debatable. In the present work, we have designed a context-based dynamic metabolic model to establish that the coordinated functioning of glutathione peroxidase (GTHP), glutathione oxidoreductase (GTHO) and NADPH oxidase (NOX) is crucial in determining cancerous transformation, specifically in gliomas. Further, we propose that the puzzling duality of ROS (represented by changes inh(2)o(2)in the present model) in exhibiting varying cellular fates can be determined by considering simultaneous changes innadph/nadp(+)andgsh/gssgthat occur during the reprogramming of metabolic reactions. This will be helpful in determining the pro-apoptotic or anti-apoptotic fate of gliomas and can be useful in designing effective pro-oxidant and/or anti-oxidant therapeutic approaches against gliomas.

1 aBhowmick, Rupa1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/differential-suitability-reactive-oxygen-species-and-role-glutathione-regulating-paradoxical02794nas a2200265 4500008004100000022001400041245009800055210006900153260000800222300000700230490000700237520190500244653001502149653002302164653003202187653002102219653003502240653002102275653002002296100002102316700001902337700002302356700002102379856012802400 2022 eng d a0250-599100aEmerging landscape of molecular interaction networks: opportunities, challenges and prospects0 aEmerging landscape of molecular interaction networks opportuniti cAPR a240 v473 a

Network biology finds application in interpreting molecular interaction networks and providing insightful inferences using graph theoretical analysis of biological systems. The integration of computational bio-modelling approaches with different hybrid network-based techniques provides additional information about the behaviour of complex systems. With increasing advances in high-throughput technologies in biological research, attempts have been made to incorporate this information into network structures, which has led to a continuous update of network biology approaches over time. The newly minted centrality measures accommodate the details of omics data and regulatory network structure information. The unification of graph network properties with classical mathematical and computational modelling approaches and technologically advanced approaches like machine-learning- and artificial intelligence-based algorithms leverages the potential application of these techniques. These computational advances prove beneficial and serve various applications such as essential gene prediction, identification of drug-disease interaction and gene prioritization. Hence, in this review, we have provided a comprehensive overview of the emerging landscape of molecular interaction networks using graph theoretical approaches. With the aim to provide information on the wide range of applications of network biology approaches in understanding the interaction and regulation of genes, proteins, enzymes and metabolites at different molecular levels, we have reviewed the methods that utilize network topological properties, emerging hybrid network-based approaches and applications that integrate machine learning techniques to analyse molecular interaction networks. Further, we have discussed the applications of these approaches in biomedical research with a note on future prospects.

10aCentrality10adisease mechanisms10ahybrid network-based models10amachine learning10amolecular interaction networks10anetwork topology10asystems biology1 aPanditrao, Gauri1 aBhowmick, Rupa1 aMeena, Chandrakala1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/emerging-landscape-molecular-interaction-networks-opportunities-challenges-and-prospects02587nas a2200241 4500008004100000022001400041245011400055210006900169260000800238300001200246490000800258520175700266653002402023653002402047653002802071653001302099653002402112653002102136653001802157100001902175700002102194856013002215 2023 eng d a1617-461500aIdentification of potential microRNAs regulating metabolic plasticity and cellular phenotypes in glioblastoma0 aIdentification of potential microRNAs regulating metabolic plast cJAN a161-1810 v2983 a

MicroRNAs (miRNAs) play important role in regulating cellular metabolism, and are currently being explored in cancer. As metabolic reprogramming in cancer is a major mediator of phenotypic plasticity, understanding miRNA-regulated metabolism will provide opportunities to identify miRNA targets that can regulate oncogenic phenotypes by taking control of cellular metabolism. In the present work, we studied the effect of differentially expressed miRNAs on metabolism, and associated oncogenic phenotypes in glioblastoma (GBM) using patient-derived data. Networks of differentially expressed miRNAs and metabolic genes were created and analyzed to identify important miRNAs that regulate major metabolism in GBM. Graph network-based approaches like network diffusion, backbone extraction, and different centrality measures were used to analyze these networks for identification of potential miRNA targets. Important metabolic processes and cellular phenotypes were annotated to trace the functional responses associated with these miRNA-regulated metabolic genes and associated phenotype networks. miRNA-regulated metabolic gene subnetworks of cellular phenotypes were extracted, and important miRNAs regulating these phenotypes were identified. The most important outcome of the study is the target miRNA combinations predicted for five different oncogenic phenotypes that can be tested experimentally for miRNA-based therapeutic design in GBM. Strategies implemented in the study can be used to generate testable hypotheses in other cancer types as well, and design context-specific miRNA-based therapy for individual patient. Their usability can be further extended to other gene regulatory networks in cancer and other genetic diseases.

10aCellular phenotypes10aFunctional analysis10aGlioblastoma metabolism10amicroRNA10amiRNA-based therapy10aNetwork analysis10aTranscriptome1 aBhowmick, Rupa1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/identification-potential-micrornas-regulating-metabolic-plasticity-and-cellular-phenotypes02364nas a2200217 4500008004100000022001400041245011200055210006900167260000900236490000700245520157000252653002801822653003701850653002101887653003001908100001901938700001901957700002001976700002101996856012902017 2024 eng d a2054-570300aMetabolic reprogramming and signalling cross-talks in tumour-immune interaction: a system-level exploration0 aMetabolic reprogramming and signalling crosstalks in tumourimmun cMAR 0 v113 a

Tumour-immune microenvironment (TIME) is pivotal in tumour progression and immunoediting. Within TIME, immune cells undergo metabolic adjustments impacting nutrient supply and the anti-tumour immune response. Metabolic reprogramming emerges as a promising approach to revert the immune response towards a pro-inflammatory state and conquer tumour dominance. This study proposes immunomodulatory mechanisms based on metabolic reprogramming and employs the regulatory flux balance analysis modelling approach, which integrates signalling, metabolism and regulatory processes. For the first time, a comprehensive system-level model is constructed to capture signalling and metabolic cross-talks during tumour-immune interaction and regulatory constraints are incorporated by considering the time lag between them. The model analysis identifies novel features to enhance the immune response while suppressing tumour activity. Particularly, altering the exchange of succinate and oxaloacetate between glioma and macrophage enhances the pro-inflammatory response of immune cells. Inhibition of glutamate uptake in T-cells disrupts the antioxidant mechanism of glioma and reprograms metabolism. Metabolic reprogramming through adenosine monophosphate (AMP)-activated protein kinase (AMPK), coupled with glutamate uptake inhibition, was identified as the most impactful combination to restore T-cell function. A comprehensive understanding of metabolism and gene regulation represents a favourable approach to promote immune cell recovery from tumour dominance.

10ametabolic reprogramming10asignalling-metabolic cross-talks10asystem modelling10atumour-immune interaction1 aShukla, Mudita1 aBhowmick, Rupa1 aGanguli, Piyali1 aSarkar, Ram, Rup uhttps://library.ncl.res.in/content/metabolic-reprogramming-and-signalling-cross-talks-tumour-immune-interaction-system-level