02195nas a2200229 4500008004100000022001400041245010600055210006900161260000800230300001000238490000800248520141500256653002501671653001301696653001401709653002301723653002601746100002001772700001901792700002301811856013101834 2022 eng d a0168-165600aMathematical model of the multi-amino acid multi-transporter system predicts uptake flux in CHO cells0 aMathematical model of the multiamino acid multitransporter syste cJAN a40-490 v3443 aSupply and uptake of amino acids is of great importance to mammalian cell culture processes. Mammalian cells such as Chinese hamster ovary (CHO) cells express several amino acid (AA) transporters including uniporters and exchangers. Each transporter transports multiple AAs, making prediction of the effect of changed medium composition or transporter levels on individual AA transport rate challenging. A general kinetic model for such combinatorial amino acid transport, and a simplified analytical expression for the uptake rate as a function of amino acid concentrations and transporter levels is presented. From this general model, a CHO cell-specific AA transport model, to our knowledge the first such network model for any cell type, is constructed. The model is validated by its prediction of reported uptake flux and dependencies from experiments that were not used in model construction or parameter estimation. The model defines theoretical conditions for synergistic/repressive effect on the uptake rates of other AAs upon external addition of one AA. The ability of the CHO-specific model to predict amino acid interdependencies experimentally observed in other mammalian cell types suggests its robustness. This model will help formulate testable hypotheses of the effect of process changes on AA initial uptake, and serve as the AA transport component of kinetic models for cellular metabolism.10aAmino acid transport10aCHO cell10aExchanger10amathematical model10aMultiple transporters1 aSreejan, Ashley1 aGadgil, Mugdha1 aGadgil, Chetan, J. uhttps://library.ncl.res.in/content/mathematical-model-multi-amino-acid-multi-transporter-system-predicts-uptake-flux-cho-cells02217nas a2200229 4500008004100000022001400041245006300055210006100118260000900179490000800188520152000196653001501716653002301731653002001754653000901774653001801783100002101801700002001822700002301842700002801865856009401893 2022 eng d a0016-673100aSUMOylation of dorsal attenuates Toll/NF-kappa B signaling0 aSUMOylation of dorsal attenuates TollNFkappa B signaling cJUL 0 v2213 a

In Drosophila, Toll/NF-kappa B signaling plays key roles in both animal development and in host defense. The activation, intensity, and kinetics of Toll signaling are regulated by posttranslational modifications such as phosphorylation, SUMOylation, or ubiquitination that target multiple proteins in the Toll/NF-kappa B cascade. Here, we have generated a CRISPR-Cas9 edited Dorsal (DL) variant that is SUMO conjugation resistant. Intriguingly, embryos laid by dl(SCR) mothers overcome dl haploinsufficiency and complete the developmental program. This ability appears to be a result of higher transcriptional activation by DLSCR. In contrast, SUMOylation dampens DL transcriptional activation, ultimately conferring robustness to the dorso-ventral program. In the larval immune response, dl(SCR) animals show an increase in crystal cell numbers, stronger activation of humoral defense genes, and high cactus levels. A mathematical model that evaluates the contribution of the small fraction of SUMOylated DL (1-5%) suggests that it acts to block transcriptional activation, which is driven primarily by DL that is not SUMO conjugated. Our findings define SUMO conjugation as an important regulator of the Toll signaling cascade, in both development and host defense. Our results broadly suggest that SUMO attenuates DL at the level of transcriptional activation. Furthermore, we hypothesize that SUMO conjugation of DL may be part of a Ubc9-dependent mechanism that restrains Toll/NF-kappa B signaling.

10aDrosophila10ahaploinsufficiency10ainnate immunity10aSUMO10atranscription1 aHegde, Sushmitha1 aSreejan, Ashley1 aGadgil, Chetan, J.1 aRatnaparkhi, Girish, S. uhttps://library.ncl.res.in/content/sumoylation-dorsal-attenuates-tollnf-kappa-b-signaling02081nas 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

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.

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-blocks02094nas a2200169 4500008004100000022001400041245008200055210006900137260000800206300001200214490000700226520151500233100002001748700002101768700002301789856011201812 2024 eng d a1072-050200aNetwork motifs exhibiting a differential response to spaced and massed inputs0 aNetwork motifs exhibiting a differential response to spaced and  cJUL aa0540120 v313 a

One characteristic of long-term memory is the existence of an inverted U-shaped response to increasing intervals between training sessions, and consequently, an optimal spacing that maximizes memory formation. Current models of this spacing effect focus on specific molecular components and their interactions. Here, we computationally study the underlying network architecture, in particular, the potential of motif dynamics in qualitatively capturing the spacing effect in a manner that is independent of the animal model, biomolecular components, and the timescales involved. We define a common training and test protocol, and computationally identify network topologies that can qualitatively replicate the experimentally observed characteristics of the spacing effect. For 41 motifs derived from fundamental network architectures such as autoregulation, feedback, and feedforward motifs, we tested their capacity to manifest the spacing effect in terms of an inverted U-shaped response curve, using different combinations of stimulation protocols, response metrics, and kinetic parameters. Our findings indicate that positive feedback motifs where the stimulus enhances conversion reaction in the loop replicate the spacing effect across all response metrics, while feedforward motifs exhibit a metric-specific spacing effect. For some parameter combinations, linear cascades of activation and conversion reactions were found sufficient to qualitatively exhibit spacing effect characteristics.

1 aSreejan, Ashley1 aSaxena, Priyanka1 aGadgil, Chetan, J. uhttps://library.ncl.res.in/content/network-motifs-exhibiting-differential-response-spaced-and-massed-inputs