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).

Sphingolipid metabolism orchestrates establishment of the hair follicle stem cell compartment.

Sphingolipids serve as building blocks of membranes to ensure subcellular compartmentalization and facilitate intercellular communication. How cell type-specific lipid compositions are achieved and what is their functional significance in tissue morphogenesis and maintenance has remained unclear. Here, we identify a stem cell-specific role for ceramide synthase 4 (CerS4) in orchestrating fate decisions in skin epidermis.

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.

Low levels of Plasmodium falciparum parasitaemia among patients receiving antiretroviral therapy at the treatment centre of the Regional Hospital Bamenda, Northwest Cameroon.

Background: Malaria and HIV are leading causes of death in Africa, including Cameroon. Antiretroviral therapy (ART) is expected to boost immunity and reduce vulnerability to opportunistic infections. Reports on comorbidities including malaria are common in Cameroon.

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).

Cross-trait GWAS in COVID-19 and systemic sclerosis reveals novel genes implicated in fibrotic and inflammation pathways.

Objectives: COVID-19 and systemic sclerosis (SSc) share multiple similarities in their clinical manifestations, alterations in immune response, and therapeutic options. These resemblances have also been identified in other immune-mediated inflammatory diseases where a common genetic component has been found. Thus, we decided to evaluate for the first time this shared genetic architecture with SSc.

Eco-friendly zinc oxide nanoparticle biosynthesis powered by probiotic bacteria.

The rapid advancement of nanotechnology, particularly in the realm of pharmaceutical sciences, has significantly transformed the potential for treating life-threatening diseases. A pivotal aspect of this evolution is the emergence of "green nanotechnology," which emphasizes the environmentally sustainable synthesis of raw materials through biological processes. This review focuses on the biological synthesis and application of zinc oxide (ZnO) nanoparticles (NPs) from probiotic bacteria, particularly those sourced from wastewater.

Intralesional injection of CpG ODNs complexed with glatiramer acetate mitigates systemic cytokine toxicities and synergistically advances checkpoint blockade efficacy.

PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.

Phyto-mediated fabrication of silver nanoparticles from Scrophularia striata extract (AgNPs-SSE): a potential inducer of apoptosis in breast cancer cells.

Background: Breast carcinoma stands out as the most widespread invasive cancer and the top contributor to cancer-related mortality in women. Nanoparticles have emerged as promising tools in cancer detection, diagnosis, and prevention. In this study, the antitumor and apoptotic capability of silver nanoparticles synthesized through Scrophularia striata extract (AgNPs-SSE) was investigated toward breast cancer cells.

The effects of prenatal administration of tumor necrosis factor-α on osteocalcin and RANK expression in newborn mice.

Tumor necrosis factor-α (TNF-α) induces a multitude of actions and consequences in bone and cartilage resorption and immune response augmentation. In this research, we aimed to investigate the effects of TNF-α on osteogenesis parameters in newborn mice. Experimental research was conducted on 42 pregnant mice, dividing into seven groups as follows: control (no injection), vehicle 1 (PBS injection on 7-9th pregnancy days (PD)), vehicle 2 (PBS injection during pregnancy), experimental 1 (injection of 10 ng/kg of TNF-α on 7-9th PD), experimental 2 (injection of 100 ng/kg of TNF-α on 7-9th PD), experimental 3 (injection of 10 ng/kg of TNF-α during pregnancy) and experimental 4 (injection of 100 ng/kg of TNF-α during pregnancy).

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.

Quantitative Profiling pH Heterogeneity of Acidic Endolysosomal Compartments using Fluorescence Lifetime Imaging Microscopy.

The endo-lysosomal system plays a crucial role in maintaining cellular homeostasis and promoting organism fitness. The pH of its acidic compartments is a crucial parameter for proper function, and it is dynamically influenced by both intracellular and environmental factors. Here, we present a method based on fluorescence lifetime imaging microscopy (FLIM) for quantitatively analyzing the pH profiles of acidic endolysosomal compartments in diverse types of primary mammalian cells and in live organism .

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.

With a little help from my friends: importance of protist-protist interactions in structuring marine protistan communities in the San Pedro Channel.

Unlabelled: Marine protists form complex communities that are shaped by environmental and biological ecosystem properties, as well as ecological interactions between organisms. While all of these factors play a role in shaping protistan communities, the specific ways in which these properties and interactions influence protistan communities remain poorly understood. Fourteen years and 9 months of eukaryotic amplicon (18S-V4 rRNA gene) data collected monthly at the San Pedro Ocean Time-series (SPOT) station were used to evaluate the impacts that environmental and biological factors, and protist-protist interactions had on protistan community composition.

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.

Human-derived microRNA 21 regulates indole and L-tryptophan biosynthesis transcripts in the gut commensal .

Unlabelled: In the gut, microRNAs (miRNAs) produced by intestinal epithelial cells are secreted into the lumen and can shape the composition and function of the gut microbiome. Crosstalk between gut microbes and the host plays a key role in irritable bowel syndrome (IBS) and inflammatory bowel diseases, yet little is known about how the miRNA-gut microbiome axis contributes to the pathogenesis of these conditions. Here, we investigate the ability of miR-21, a miRNA that we found decreased in fecal samples from IBS patients, to associate with and regulate gut microbiome function.

Structural analysis of extracellular ATP-independent chaperones of streptococcal species and protein substrate interactions.

Unlabelled: During infection, bacterial pathogens rely on secreted virulence factors to manipulate the host cell. However, in gram-positive bacteria, the molecular mechanisms underlying the folding and activity of these virulence factors after membrane translocation are not clear. Here, we solved the protein structures of two secreted parvulin and two secreted cyclophilin-like peptidyl-prolyl isomerase (PPIase) ATP-independent chaperones found in gram-positive streptococcal species.

Multi-omics analysis reveals distinct gene regulatory mechanisms between primary and organoid-derived human hepatocytes.

Hepatic organoid cultures are a powerful model to study liver development and diseases in vitro. However, hepatocyte-like cells differentiated from these organoids remain immature compared to primary human hepatocytes (PHHs), which are the benchmark in the field. Here, we applied integrative single-cell transcriptome and chromatin accessibility analysis to reveal gene regulatory mechanisms underlying these differences.

Epigenetic modulation rescues neurodevelopmental deficits in Syngap1 mice.

SYNGAP1 is a Ras GTPase-activating protein that plays a crucial role during brain development and in synaptic plasticity. Sporadic heterozygous mutations in SYNGAP1 affect social and emotional behaviour observed in intellectual disability (ID) and autism spectrum disorder (ASD). Although neurophysiological deficits have been extensively studied, the epigenetic landscape of SYNGAP1 mutation-mediated intellectual disability is unexplored.

MftG is crucial for ethanol metabolism of mycobacteria by linking mycofactocin oxidation to respiration.

Mycofactocin is a redox cofactor essential for the alcohol metabolism of mycobacteria. While the biosynthesis of mycofactocin is well established, the gene , which encodes an oxidoreductase of the glucose-methanol-choline superfamily, remained functionally uncharacterized. Here, we show that MftG enzymes are almost exclusively found in genomes containing mycofactocin biosynthetic genes and are present in 75% of organisms harboring these genes.

Cell-Free Systems to Mimic and Expand Metabolism.

Cell-free synthetic biology incorporates purified components and/or crude cell extracts to carry out metabolic and genetic programs. While protein synthesis has historically been the primary focus, more metabolism researchers are now turning toward cell-free systems either to prototype pathways for cellular implementation or to design new-to-nature reaction networks that incorporate environmentally relevant substrates or new energy sources. The ability to design, build, and test enzyme combinations has accelerated efforts to understand metabolic bottlenecks and engineer high-yielding pathways.

Telomemore enables single-cell analysis of cell cycle and chromatin condensation.

Single-cell RNA-seq methods can be used to delineate cell types and states at unprecedented resolution but do little to explain why certain genes are expressed. Single-cell ATAC-seq and multiome (ATAC + RNA) have emerged to give a complementary view of the cell state. It is however unclear what additional information can be extracted from ATAC-seq data besides transcription factor binding sites.