Enhancing lactic acid tolerance in Fructilactobacillus sanfranciscensis via adaptive evolution for sourdough fermentation applications.

Fructilactobacillus sanfranciscensis is extensively used in the food industry, notably for sourdough fermentation; however, its mass production is hindered by growth inhibition due to lactic acid accumulation in the medium. This study aimed to enhance the acid tolerance of F. sanfranciscensis SPC-SNU 70-4 via adaptive laboratory evolution (ALE) to improve its viability as an industrial sourdough starter.

Allosteric pluripotency: challenges and opportunities.

Allosteric pluripotency arises when the functional response of an allosteric receptor to an allosteric stimulus depends on additional allosteric modulators. Here, we discuss allosteric pluripotency as observed in the prototypical Protein Kinase A (PKA) as well as in other signaling systems, from typical multidomain signaling proteins to bacterial enzymes. We identify key drivers of pluripotent allostery and illustrate how hypothesizing allosteric pluripotency may solve apparent discrepancies currently present in the literature regarding the dual nature of known allosteric modulators.

Divergent allostery reveals critical differences between structurally homologous regulatory domains of Plasmodium falciparum and human protein kinase G.

Malaria is a life-threatening infectious disease primarily caused by the Plasmodium falciparum parasite. The increasing resistance to current antimalarial drugs and their side effects has led to an urgent need for novel malaria drug targets, such as the P. falciparum cGMP-dependent protein kinase (pfPKG).

State-selective frustration as a key driver of allosteric pluripotency.

Allosteric pluripotency arises when an allosteric effector switches from agonist to antagonist depending on the experimental conditions. For example, the Rp-cAMPS ligand of Protein Kinase A (PKA) switches from agonist to antagonist as the MgATP concentration increases and/or the kinase substrate affinity or concentration decreases. Understanding allosteric pluripotency is essential to design effective allosteric therapeutics with minimal side effects.

Backbone resonance assignment of the cAMP-binding domains of the protein kinase A regulatory subunit Iα.

Protein kinase A (PKA) is the main receptor for the universal cAMP second messenger. PKA is a tetramer with two catalytic (C) and two regulatory (R) subunits, each including two tandem cAMP-binding domains, i.e.

Dynamical Basis of Allosteric Activation for the Protein Kinase G.

The cGMP-dependent protein kinase (PKG) is required for the progression of the 's life cycle and is therefore a promising malaria drug target. PKG includes four cGMP-binding domains (CBD-A to CBD-D). CBD-D plays a crucial role in PKG regulation as it is the primary determinant for the inhibition and cGMP-dependent activation of the catalytic domain.

Noncanonical protein kinase A activation by oligomerization of regulatory subunits as revealed by inherited Carney complex mutations.

Familial mutations of the protein kinase A (PKA) R1α regulatory subunit lead to a generalized predisposition for a wide range of tumors, from pituitary adenomas to pancreatic and liver cancers, commonly referred to as Carney complex (CNC). CNC mutations are known to cause overactivation of PKA, but the molecular mechanisms underlying such kinase overactivity are not fully understood in the context of the canonical cAMP-dependent activation of PKA. Here, we show that oligomerization-induced sequestration of R1α from the catalytic subunit of PKA (C) is a viable mechanism of PKA activation that can explain the CNC phenotype.

Allosteric inhibition explained through conformational ensembles sampling distinct "mixed" states.

Allosteric modulation provides an effective avenue for selective and potent enzyme inhibition. Here, we summarize and critically discuss recent advances on the mechanisms of allosteric partial agonists for three representative signalling enzymes activated by cyclic nucleotides: the cAMP-dependent protein kinase (PKA), the cGMP-dependent protein kinase (PKG), and the exchange protein activated by cAMP (EPAC). The comparative analysis of partial agonism in PKA, PKG and EPAC reveals a common emerging theme, the sampling of distinct "mixed" conformational states, either within a single domain or between distinct domains.

Mechanism of allosteric inhibition in the cGMP-dependent protein kinase.

Most malaria deaths are caused by the protozoan parasite Its life cycle is regulated by a cGMP-dependent protein kinase (PKG), whose inhibition is a promising antimalaria strategy. Allosteric kinase inhibitors, such as cGMP analogs, offer enhanced selectivity relative to competitive kinase inhibitors. However, the mechanisms underlying allosteric PKG inhibition are incompletely understood.

NMR methods to dissect the molecular mechanisms of disease-related mutations (DRMs): Understanding how DRMs remodel functional free energy landscapes.

Elucidating the molecular mechanism of disease-related mutations (DRMs) is a critical first step towards understanding the etiology of genetic disorders. DRMs often modulate biological function by altering the free-energy landscape (FEL) of the protein associated with the mutated gene. FELs typically include ground, as well as excited, yet accessible and functionally relevant, states and DRMs may perturb both the thermodynamics and kinetics of the ground vs.

The immunomodulatory effects of 3-monochloro-1,2-propanediol on murine splenocyte and peritoneal macrophage function in vitro.

3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. MCPD has been reported genotoxic in vitro, and reproductive toxicity and carcinogenicity in rats. To evaluate the immunomodulatory effect of MCPD on murine splenocyte and macrophage in vitro, we investigated splenocyte blastogenesis by concanavalin A (Con A), anti-CD3, and lipopolyssacharide (LPS), the production of cytokines from splenocyte, and the activity of mouse peritoneal macrophages.

Evaluation of the potential immunotoxicity of 3-monochloro-1,2-propanediol in Balb/c mice II. Effect on thymic subset, delayed-type hypersensitivity, mixed-lymphocyte reaction, and peritoneal macrophage activity.

3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. To evaluate the immunotoxicity of MCPD, we investigated its effect on the thymic subset, delayed-type hypersensitivity, mixed-lymphocyte reaction and peritoneal macrophage activity. MCPD was administered by gavage for 14 days at 0, 25, 50, and 100 mg/kg/day to female Balb/c mice.

Immunotoxic effect of beta-chlorolactic acid on murine splenocyte and peritoneal macrophage function in vitro.

Beta-chlorolactic acid is a major intermediate of 3-monochloro-1,2-propanediol (MCPD) in mammalian species, which a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. beta-Chlorolactic acid has not been studied on immunotoxicity. To evaluate the immunomodulatory effect of beta-chlorolactic acid on murine splenocyte and macrophage in vitro, we investigated splenocyte blastogenesis by concanavalin A (Con A), anti-CD3 and lipopolysaccharide (LPS), the production of cytokines from splenocyte, and the activity of mouse peritoneal macrophages.

Bisphenol A-induced downregulation of murine macrophage activities in vitro and ex vivo.

Bisphenol A (BPA) is known to have detrimental effects on the reproductive system, but the toxicity of BPA on immune responses has not been systematically investigated. We investigated the effects of BPA exposure on the activities of murine peritoneal macrophages through evaluation of BPA-induced alteration of nitric oxide (NO) production, tumor necrosis factor-α (TNF-α) synthesis, and expression of co-stimulatory molecules B7. Macrophages were examined ex vivo from mice orally treated with various doses of BPA for 5 consecutive days per week for 4 weeks followed by culture for 2 or 4 days in the presence of lipopolysaccharides (LPS).

Evaluation of the potential immunotoxicity of 3-monochloro-1,2-propanediol in Balb/c mice. I. Effect on antibody forming cell, mitogen-stimulated lymphocyte proliferation, splenic subset, and natural killer cell activity.

3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. MCPD has been reported genotoxic in vitro, and reproductive toxicity and carcinogenicity in rats. However, no previous studies have investigated MCPD-induced alterations in the immune system.

Evaluation of lymphocyte subpopulations in draining lymph node cells following allergen and irritant.

The murine local lymph node assay (LLNA) has been developed as an alternative to guinea pig models for the assessment of the contact sensitization potential. However, there is a need to develop a non-radioisotopic endpoint for the LLNA, because of the radioisotopic method's requiring the use of special facilities. In this study, we investigated to evaluate the lymphocyte subpopulations in the lymph node cells following allergen and irritant treatment.