Allosteric regulation of pyruvate kinase enables efficient and robust gluconeogenesis by preventing metabolic conflicts and carbon overflow.

Gluconeogenesis, the reciprocal pathway of glycolysis, is an energy-consuming process that generates glycolytic intermediates from non-carbohydrate sources. In this study, we demonstrate that robust and efficient gluconeogenesis in bacteria relies on the allosteric inactivation of pyruvate kinase, the enzyme responsible for the irreversible final step of glycolysis. Using the model bacterium as an example, we discovered that pyruvate kinase activity is inhibited during gluconeogenesis via its extra C-terminal domain (ECTD), which is essential for autoinhibition and metabolic regulation.

Investigation of Bile Salt Hydrolase Activity in Human Gut Bacteria Reveals Production of Conjugated Secondary Bile Acids.

Through biochemical transformation of host-derived bile acids (BAs), gut bacteria mediate host-microbe crosstalk and sit at the interface of nutrition, the microbiome, and disease. BAs play a crucial role in human health by facilitating the absorption of dietary lipophilic nutrients, interacting with hormone receptors to regulate host physiology, and shaping gut microbiota composition through antimicrobial activity. Bile acid deconjugation by bacterial bile salt hydrolase (BSH) has long been recognized as the first necessary BA modification required before further transformations can occur.

Extensive Admixture Among Karst-Obligate Salamanders Reveals Evidence of Recent Divergence and Gene Exchange Through Aquifers.

Karst ecosystems often contain extraordinary biodiversity, but the complex underground aquifers of karst regions present challenges for assessing and conserving stygobiont diversity and investigating their evolutionary history. We examined the karst-obligate salamanders of the species complex in the Edwards Plateau region of central Texas using population genomics data to address questions about population connectivity and the potential for gene exchange within the underlying aquifer system. The species complex has historically been divided into three nominal species, but their status, and spatial extent of species ranges, have remained uncertain.

Angiotensin-(1-7) and Central Control of Cardiometabolic Outcomes: Implications for Obesity Hypertension.

Hypertension is a leading independent risk factor for the development of cardiovascular disease, the leading cause of death globally. Importantly, the prevalence of hypertension is positively correlated with obesity, with obesity-related hypertension being difficult to treat due to a lack of current guidelines in this population as well as limited efficacy and adverse off-target effects of currently available antihypertensive therapeutics. This highlights the need to better understand the mechanisms linking hypertension with obesity to develop optimal therapeutic approaches.

Discovery of Carbonic Anhydrase 9 as a Novel CLEC2 Ligand in a Cellular Interactome Screen.

Membrane proteins, especially extracellular domains, are key therapeutic targets due to their role in cell communication and associations. Yet, their functions and interactions often remain unclear. This study presents a general method to discover interactions of membrane proteins with immune cells and subsequently to deorphanize their respective receptors.