Correcting a pathogenic mitochondrial DNA mutation by base editing in mice.

Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.

Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection.

At this stage in the COVID-19 pandemic, most infections are "breakthrough" infections that occur in individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and adaptive immunity in breakthrough infections. We performed single-cell transcriptomic, proteomic, and functional profiling of primary and breakthrough infections to compare immune responses from unvaccinated and vaccinated individuals during the SARS-CoV-2 Delta wave.

Ketogenesis supports hepatic polyunsaturated fatty acid homeostasis via fatty acid elongation.

Ketogenesis is a dynamic metabolic conduit supporting hepatic fat oxidation particularly when carbohydrates are in short supply. Ketone bodies may be recycled into anabolic substrates, but a physiological role for this process has not been identified. Here, we use mass spectrometry-based C-isotope tracing and shotgun lipidomics to establish a link between hepatic ketogenesis and lipid anabolism.

chitinase-like protein orchestrates cyst wall glycosylation to facilitate effector export and cyst turnover.

bradyzoites reside in tissue cysts that undergo cycles of expansion, rupture, and release to foster chronic infection. The glycosylated cyst wall acts as a protective barrier, although the processes responsible for formation, remodeling, and turnover are not understood. Herein, we identify a noncanonical chitinase-like enzyme TgCLP1 that localizes to micronemes and is targeted to the cyst wall after secretion.

HIV-1 resistance mutations and genetic diversity among children failing antiretroviral treatment in five healthcare facilities in Benin, West Africa.

Background: Antiretroviral treatment increases the risk of accumulation of resistance mutations that negatively impact the possibilities of future treatment. This study aimed to present the frequency of HIV-1 antiretroviral resistance mutations and the genetic diversity among children with virological failure in five pediatric care facilities in Benin.

Methods: A cross-sectional study was carried out from November 20, 2020, to November 30, 2022, in children under 15 years of age who failed ongoing antiretroviral treatment at five facilities care in Benin (VL > 3log10 on two consecutive realizations three months apart).

Exploring the relationship between established HIV risk factors and depressive symptoms amongst young women without HIV in two sites in South Africa.

Purpose: Adolescent girls are at high risk for depression and human immunodeficiency virus (HIV) acquisition. Poor mental health can increase vulnerability to risky sexual behaviours. Therefore, this study aims to determine the prevalence of depressive symptomology and explore the convergence of HIV risk factors with depressive symptoms amongst cis-gender adolescent girls and young women (AGYW) in rural KwaZulu-Natal (KZN) and peri-urban Western Cape (WC) communities in South Africa.

Unraveling the metabolic landscape of Exophiala spinifera strain FM: Model reconstruction, insights into biodesulfurization and beyond.

Exophiala spinifera strain FM, a black yeast and melanized ascomycete, shows potential for oil biodesulfurization by utilizing dibenzothiophene (DBT) as its sole sulfur source. However, the specific pathway and enzymes involved in this process remain unclear due to limited genome sequencing and metabolic understanding of E. spinifera.

Relationships between multivitamins, blood biochemistry markers, and BMC and BMD based on RF: A cross-sectional and population-based study of NHANES, 2017-2018.

Background: Previous studies have separately suggested a possible association between the vitamin exposure, blood biochemical indicators, and bone density. Our study aimed to investigate the relationship between vitamin exposure serum concentrations, blood biochemical indicator serum concentrations, and BMC and BMD using the NHANES 2017-2018 nutrient survey data. This population-based cross-sectional study aimed to explore these associations.

Hypercapnic warm-up and re-warm-up-A novel experimental approach in swimming sprint.

The purpose of this study was to determine the effective warm-up protocol using an added respiratory dead space (ARDS) 1200 ml volume mask to determine hypercapnic conditions, on the swimming velocity of the 50 m time trial front crawl. Eight male members of the university swimming team, aged 19-25, performed three different warm-up protocols: 1) standardized warm-up in water (WUCON); 2) hypercapnic warm-up in water (WUARDS); 3) hypercapnic a 20-minute transition phase on land, between warm-up in water and swimming test (RE-WUARDS). The three warm-up protocols were implemented in random order every 7th day.

eIF3 engages with 3'-UTR termini of highly translated mRNAs.

Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs).

Antibiotic-derived approaches in cancer therapy: effectiveness of ikarugamycin in hexokinase-2 inhibition, tissue factor modulation, and metabolic regulation in breast cancer.

We aimed to explore the role of ikarugamycin (IKA) in breast cancer, its connection with hexokinase-2 (HK-2) repression, and tissue factor (TF). This study sought to extend the role of HK-2 as a TF activator in a comprehensive analysis of these interactions from the enzyme, gene, and protein levels. The investigation was performed with MDA-MB-231 and MCF-7 breast cancer lines.

Targeted insertion of heterogenous DNA using Cas9-gRNA ribonucleoprotein-mediated gene editing in .

Gene editing is emerging as a powerful tool for introducing novel functionalities in mushrooms. While CRISPR/Cas9-induced double-strand breaks (DSBs) typically rely on non-homologous end joining (NHEJ) for gene disruption, precise insertion of heterologous DNA in mushrooms is less explored. Here, we evaluated the efficacy of inserting donor DNAs (8-1008 bp) with or without homologous arms at Cas9-gRNA RNP-induced DSBs.

Protective effect of dapagliflozin on lipopolysaccharide-induced acute lung injury via the SIRT-1/PGC-1α pathway.

Background: Acute systemic inflammation affects many organs and it occurs in a wide range of conditions such as acute lung injury (ALI). Inflammation-triggered oxidative pathways together with the caspase activation seen in ALI, result in apoptosis. Dapagliflozin (DPG) is an agent that is known to have oxidative stress-reducing and anti-inflammatory effects in many tissues.

A combination of gold nanoparticles and laser photobiomodulation to boost antioxidant defenses in the recovery of muscle injuries caused by Bothrops jararaca venom.

Unlabelled: This study aimed to evaluate gold nanoparticles (GNPs) and photobiomodulation (PBM), associated with antibothropic serum (AS), to treat a muscle lesion induced by Bothrops jararaca venom.

Methods: 108 Swiss male mice were used, divided into nine groups (n = 12) with different combinations of treatments. Animals were inoculated with 250 µg of B.

Effects of Tasimelteon Treatment on Traumatic Brain Injury Through NRF-2/HO-1 and RIPK1/RIPK3/MLKL Pathways in Rats.

Secondary brain damageafter traumatic brain injury (TBI) involves oxidative stress, neuroinflammation, apoptosis, and necroptosis and can be reversed by understanding these molecular pathways. The objective of this study was to examine the impact of tasimelteon (Tasi) administration on brain injury through the nuclear factor erythroid 2-related factor 2 (NRF-2)/heme oxygenase-1 (HO-1) and receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like (MLKL) pathways in rats with TBI. Thirty-two male Wistar albino rats weighing 300-350 g were randomly divided into four groups: the control group, trauma group, Tasi-1 group (trauma + 1 mg/kg Tasi intraperitoneally), and Tasi-10 group (trauma + 10 mg/kg Tasi intraperitoneally).

Assessing the diagnostic potential of SATB2 and β-catenin as biomarkers and therapeutic targets in pancreatic ductal adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. The roles of the transcription factor special AT-rich binding protein-2 (SATB2) and β-catenin in PDAC have been a subject of controversy. We aimed to assess the diagnostic and prognostic impact of SATB2 and β-catenin in PDAC.

The protective efficacy of omega-3 polyunsaturated fatty acids on oxidative stress, inflammation, neurotransmitter perturbations, and apoptosis induced by monosodium glutamate in the brain of male rats.

Exaggerated neuronal excitation by glutamate is a well-known cause of excitotoxicity, a key factor in numerous neurodegenerative disorders. This study examined the neurotoxic effect of monosodium glutamate (MSG) in the brain cortex of rats and focused on assessing the potential neuroprotective effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). Four groups of adult male rats (n = 10) were assigned as follows; normal control, ω-3 PUFAs (400 mg/kg) alone, MSG (4 mg/g) alone, and MSG plus ω-3 PUFAs (4 mg/g MSG plus 400 mg/kg ω-3 PUFAs).

Long-Term Outcome of Chronic Hepatitis B-Histological Score and Viral Genotype Are Important Predictors of Hepatocellular Carcinoma.

Current guidelines to prevent hepatocellular carcinoma (HCC) by chronic hepatitis B virus (HBV) infection are based on risk assessments that include age, sex, and virological and biochemical parameters. The study aim was to investigate the impact of predictive markers on long-term outcomes. The clinical outcomes of 100 patients with chronic hepatitis B were investigated 30 years after a baseline assessment that included liver biopsy.

Epstein-Barr virus-associated smooth muscle tumor with multiple lesions in a patient with AIDS.

Epstein-Barr virus-associated smooth muscle tumors (EBV-SMTs) represent a rare category of soft tissue tumors that are predominantly seen in individuals with compromised immune systems. Pathologically, EBV-SMT has malignant potential because of its unpredictable nature. These tumors can manifest at various anatomical sites or even multiple lesions in different locations.

Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration.

Rare inherited diseases caused by mutations in the copper transporters (CTR1) or induce copper deficiency in the brain, causing seizures and neurodegeneration in infancy through poorly understood mechanisms. Here, we used multiple model systems to characterize the molecular mechanisms by which neuronal cells respond to copper deficiency. Targeted deletion of CTR1 in neuroblastoma cells produced copper deficiency that produced a metabolic shift favoring glycolysis over oxidative phosphorylation.

Tetraspanins 10 and 15 support Venezuelan equine encephalitis virus replication in astrocytoma cells.

Tetraspanins (Tspans) are transmembrane proteins that coordinate life cycle steps of viruses from distinct families. Here, we identify the human Tspan10 and Tspan15, both members of the TspanC8 subfamily, as replication factors for alphavirus Venezuelan equine encephalitis virus (VEEV) in astrocytoma cells. Pharmacological inhibition and siRNA-mediated silencing of TspanC8 interactor a disintegrin and metalloproteinase 10 (ADAM10) reduced VEEV infection.

The dark side of fluorescent protein tagging - the impact of protein tags on biomolecular condensation.

Biomolecular condensation has emerged as an important mechanism to control various cellular processes through the formation of membraneless organelles. Fluorescent protein tags have been extensively used to study the formation and the properties of condensates and , but there is evidence that tags may perturb the condensation properties of proteins. In this study, we carefully assess the effects of protein tags on the yeast DEAD-box ATPase Dhh1, a central regulator of processing bodies (P-bodies), which are biomolecular condensates involved in mRNA metabolism.

Perturbation of peptidoglycan recycling by anti-folates and design of a dual-action inhibitor.

Unlabelled: Peptidoglycan (PG) is an important bacterial macromolecule that confers cell shape and structural integrity, and is a key antibiotic target. Its synthesis and turnover are carefully coordinated with other cellular processes and pathways. Despite established connections between the biosynthesis of PG and the outer membrane, or PG and DNA replication, links between PG and folate metabolism remain comparatively unexplored.

Zebrafish optic nerve regeneration involves resident and retinal oligodendrocytes.

The visual system of teleost fish grows continuously, which is a useful model for studying regeneration of the central nervous system. Glial cells are key for this process, but their contribution is still not well defined. We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6, 24, and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.