Inorganic nitrate (NO) has been proposed to be of therapeutic use as a dietary supplement in obesity and related conditions including the Metabolic Syndrome (MetS), type-II diabetes and metabolic dysfunction associated steatotic liver disease (MASLD). Administration of NO to endothelial nitric oxide synthase-deficient mice reversed aspects of MetS, however the impact of NO supplementation in diet-induced obesity is not well understood. Here we investigated the whole-body metabolic phenotype and cardiac and hepatic metabolism in mice fed a high-fat high-sucrose (HFHS) diet for up to 12-months of age, supplemented with 1 mM NaNO (or NaCl) in their drinking water.
View Article and Find Full Text PDFBackground: Stakeholder engagement is widely considered democratic, transparent, and essential in the shared decision-making process for improving health services. However, the integrated evidence of stakeholders' engagement activities in maternal and newborn health (MNH) services in the context of low- and middle-income countries (LMICs) is lacking. Therefore, this review aims to generate synthesised evidence of different practices for stakeholder engagements, characteristics of stakeholder engagements and outcomes of stakeholder engagements in improving the MNH services uptake and delivery.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
In , proteins that are posttranslationally modified with a prokaryotic ubiquitin-like protein (Pup) can be degraded by bacterial proteasomes. A single Pup-ligase and depupylase shape the pupylome, but the mechanisms regulating their substrate specificity are incompletely understood. Here, we identified a depupylation regulator, a protein called CoaX, through its copurification with the depupylase Dop.
View Article and Find Full Text PDFInfected macrophages transition into aerobic glycolysis, a metabolic program crucial for control of bacterial infection. However, antimicrobial mechanisms supported by aerobic glycolysis are unclear. Methylglyoxal is a highly toxic aldehyde that modifies proteins and DNA and is produced as a side-product of glycolysis.
View Article and Find Full Text PDFEating less meat is associated with a healthier body and planet. Yet, we remain reluctant to switch to a plant-based diet, largely due to the sensory experience of plant-based meat. Food scientists characterize meat using a double compression test, which only probes one-dimensional behavior.
View Article and Find Full Text PDFThe surface of epithelial tissues is covered by an apical extracellular matrix (aECM). The aECMs of different tissues have distinct compositions to serve distinct functions, yet how a particular cell type assembles the proper aECM is not well understood. We used the cell type-specific matrix of the C.
View Article and Find Full Text PDFUnlabelled: In , alginate biosynthesis gene expression is inhibited by the transmembrane anti-sigma factor MucA, which sequesters the AlgU sigma factor. Cell envelope stress initiates cleavage of the MucA periplasmic domain by site-1 protease AlgW, followed by further MucA degradation to release AlgU. However, after colonizing the lungs of people with cystic fibrosis, converts to a mucoid form that produces alginate constitutively.
View Article and Find Full Text PDFThe surface of epithelial tissues is covered by an apical extracellular matrix (aECM). The aECMs of different tissues have distinct compositions to serve distinct functions, yet how a particular cell type assembles the proper aECM is not well understood. We used the cell-type specific matrix of the vulva to investigate the connection between cell identity and matrix assembly.
View Article and Find Full Text PDFBackground: Many common diseases exhibit uncontrolled mTOR signaling, prompting considerable interest in the therapeutic potential of mTOR inhibitors, such as rapamycin, to treat a range of conditions, including cancer, aging-related pathologies, and neurological disorders. Despite encouraging preclinical results, the success of mTOR interventions in the clinic has been limited by off-target side effects and dose-limiting toxicities. Improving clinical efficacy and mitigating side effects require a better understanding of the influence of key clinical factors, such as sex, tissue, and genomic background, on the outcomes of mTOR-targeting therapies.
View Article and Find Full Text PDFObjective: Endoscopic retrograde cholangiopancreatography (ERCP) may be unsuccessful in patients with duodenal stenosis or malignant ampullary infiltration. Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been proposed as an alternative. We aimed to assess the efficacy and safety of EUS-BD for malignant distal bile duct obstruction using the newly introduced smaller caliber 6 or 8 mm cautery-enhanced lumen-apposing metal stent.
View Article and Find Full Text PDFBioTechnologia (Pozn)
June 2024
Lactic acid (LA) production from microbial fermentation using low-cost renewable sources has emerged as an attractive alternative to the use of petroleum-based products. This approach not only offers sustainable solutions for waste management but also enables the production of value-added products in an eco-friendly manner. However, to make this approach economically viable, optimizing the production process for high yield, productivity, and purity while minimizing costs is crucial.
View Article and Find Full Text PDFUnlabelled: In alginate biosynthesis gene expression is inhibited by the transmembrane anti-sigma factor MucA, which sequesters the AlgU sigma factor. Cell envelope stress initiates cleavage of the MucA periplasmic domain by site-1 protease AlgW, followed by further MucA degradation to release AlgU. However, after colonizing the lungs of people with cystic fibrosis, converts to a mucoid form that produces alginate constitutively.
View Article and Find Full Text PDFIn Caenorhabditis elegans, expanded families of divergent Hedgehog-related and patched-related proteins promote numerous processes ranging from epithelial and sense organ development to pathogen responses to cuticle shedding during the molt cycle. The molecular functions of these proteins have been mysterious since nematodes lack a canonical Hedgehog signaling pathway. Here we show that Hedgehog-related proteins are components of the cuticle and precuticle apical extracellular matrices that coat, shape, and protect external epithelia.
View Article and Find Full Text PDFEndoscopic retrograde cholangiopancreatography (ERCP) poses the risk of radiation exposure (RE) to patients and staff and increases the risk of adverse biological effects such as cataracts, sterility, and cancer. Newer fluoroscopy equipment (C-Arm) provides options to limit radiation in the form of lower radiation dose and frame rate or time-limited "pulsed" settings. However, the impact of lower settings on image quality has not been assessed, and no standard protocol exists for fluoroscopy settings used during ERCP.
View Article and Find Full Text PDFBackground: As modern medicine continues to make strides in effective surgical treatments, we must also consider the critical impact of anesthesia on neuropsychological outcomes. Recent evidence suggests that anesthesia exposure may be a risk factor for postoperative cognitive decline and the eventual development of dementia.
Objectives: To explore the vulnerability of the aging brain in the context of anesthesia exposure in surgery, studies will be reviewed, and pertinent findings will be highlighted and explored to better understand risks and possible factors that need to be considered when contemplating surgery.
Unlabelled: In proteins that are post-translationally modified with Pup, a prokaryotic ubiquitin-like protein, can be degraded by proteasomes. While pupylation is reversible, mechanisms regulating substrate specificity have not been identified. Here, we identify the first depupylation regulators: CoaX, a pseudokinase, and pantothenate, an essential, central metabolite.
View Article and Find Full Text PDFUnlabelled: Cytokinins are adenine-based hormones that have been well-characterized in plants but are also made by bacteria, including the human-exclusive pathogen . In , cytokinins activate transcription of an operon that affects the bacterial cell envelope. In plants, cytokinins are broken down by dedicated enzymes called cytokinin oxidases into adenine and various aldehydes.
View Article and Find Full Text PDFSuperoxide, an anionic dioxygen molecule, plays a crucial role in redox regulation within the body but is implicated in various pathological conditions when produced excessively. Efforts to develop superoxide detection strategies have led to the exploration of organic-based contrast agents for magnetic resonance imaging (MRI). This study compares the effectiveness of two such agents, nTMV-TEMPO and kTMV-TEMPO, for detecting superoxide in a mouse liver model with lipopolysaccharide (LPS)-induced inflammation.
View Article and Find Full Text PDFDuring bacterial cell growth, hydrolases cleave peptide cross-links between strands of the peptidoglycan sacculus to allow new strand insertion. The Pseudomonas aeruginosa carboxyl-terminal processing protease (CTP) CtpA regulates some of these hydrolases by degrading them. CtpA assembles as an inactive hexamer composed of a trimer-of-dimers, but its lipoprotein binding partner LbcA activates CtpA by an unknown mechanism.
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