Dissecting metabolic landscape of alveolar macrophage.

The highly plastic nature of Alveolar Macrophage (AM) plays a crucial role in the defense against inhaled particulates and pathogens in the lungs. Depending on the signal, AM acquires either the classically activated M1 phenotype or the alternatively activated M2 phenotype. In this study, we investigate the metabolic shift in the activated phases of AM (M1 and M2 phases) by reconstructing context specific Genome-Scale Metabolic (GSM) models.

Exploring putative enteric methanogenesis inhibitors using molecular simulations and a graph neural network.

Atmospheric methane (CH) acts as a key contributor to global warming. As CH is a short-lived climate forcer (12 years atmospheric lifespan), its mitigation represents the most promising means to address climate change in the short term. Enteric CH (the biosynthesized CH from the rumen of ruminants) represents 5.

Inhibiting the cGAS-STING Pathway in Ulcerative Colitis with Programmable Micelles.

Ulcerative colitis is a chronic condition in which a dysregulated immune response contributes to the acute intestinal inflammation of the colon. Current clinical therapies often exhibit limited efficacy and undesirable side effects. Here, programmable nanomicelles were designed for colitis treatment and loaded with RU.

A multi-organ maize metabolic model connects temperature stress with energy production and reducing power generation.

Climate change has adversely affected maize productivity. Thereby, a holistic understanding of metabolic crosstalk among its organs is important to address this issue. Thus, we reconstructed the first multi-organ maize metabolic model, ZMA6517, and contextualized it with heat and cold stress transcriptomics data using expression distributed reaction flux measurement (EXTREAM) algorithm.

Relation between glycosidic linkage, structure and dynamics of α- and β-glucans in water.

In a molecular dynamics simulation study of several oligosaccharides comprising of the very basic building block of carbohydrate, the α- or β-d glucopyranose units, linked by any one of the 1-3/1-4 or 1-6 glycosidic linkages, we compare and contrast their structural and dynamical properties. Results indicate that the litheness of the oligosaccharide chain is noticeably controlled by the composition, anomeric nature and glycosidic linkage type of the units. In mixed β 1-4/1-3 d-glucopyranosides, as those found in oats and barley, the ratio of the β 1-4 and β 1-3 linked residues is crucial in determining the structural and dynamical attributes.

Principal Component Analysis of a Conotoxin Delineates the Link among Peptide Sequence, Dynamics, and Disulfide Bond Isoforms.

Replica exchange molecular dynamics (REMD) and subsequent principal component analysis (PCA) of the dynamical modes of α-conotoxins, GI and its two mutants, in water and an aqueous biocompatible ionic liquid, 1-ethyl-3-methyl-imidazolium acetate (50%, v/v), provide perceptions into how the mutations affect the global correlated motions in the peptide backbone, eventually ending up influencing the combination of disulfide links in such multiple cysteine-containing venom toxins. Region-wise breakup of the contribution of the three peptides to the first two principal components (PCs) reveals disparate dynamical patterns in water and a water-ionic liquid mixture. Additionally, K-means clustering within the conformation space spanned by PC1 and PC2 compares and contrasts the different peptide-solvent systems, sorting further the disulfide bond isoforms into specific clusters.

Peptide Sequence and Solvent as Levers to Control Disulfide Connectivity in Multiple Cysteine Containing Venom Toxins.

Judicious choice of solvent, temperature, and strategic mutations along a peptide backbone can minimize formation of non-native disulfide bond isoforms in chemical synthesis of multiple cysteine containing venom toxins. By exploiting these controls, one can drive the population distribution in favor of a particular isoform. Some chosen ionic liquids (ILs), like 1-ethyl-3-methyl-imidazolium acetate, [Im][OAc], have proven efficient in favoring the native globular isoform in some conotoxins.

Aqueous ionic liquids influence the disulfide bond isoform equilibrium in conotoxin AuIB: a consequence of the Hofmeister effect?

The appearance of several disulfide bond isoforms in multiple cysteine containing venom peptides poses a significant challenge in their synthesis and purification under laboratory conditions. Recent experiments suggest that careful tuning of solvent and temperature conditions can propel the disulfide bond isoform equilibrium in favor of the most potent, native form. Certain aqueous ionic liquids (ILs) have proven significantly useful as solvents for this purpose, while exceptions have also been noted.

Temperature-dependent molecular dynamics study reveals an ionic liquid induced 3 - to α-helical switch in a neurotoxin.

Thermal melting and recooling of AuIB, a neurotoxic conopeptide and a highly potent nonaddictive pain reliever is investigated thoroughly in water and an ionic liquid (IL) 1-butyl-3-methylimidazolium Chloride, [Im ][Cl] by classical molecular dynamics simulations. Structural evolution of AuIB in water and the IL is observed at different temperatures between 305 and 400 K, to explore how highly viscous ionic solvents affect the peptide structure as compared to conventional solvent water. At 305 K, unlike water, the coercive effect of IL frustrates AuIB secondary structural motifs significantly.