The rate of glucose metabolism sets the cell morphology across yeast strains and species.

Yeasts are a diverse group of unicellular fungi that have developed a wide array of phenotypes and traits over 400 million years of evolution. However, we still lack an understanding of the biological principles governing the range of cell morphologies, metabolic modes, and reproductive strategies yeasts display. In this study, we explored the relationship between cell morphology and metabolism in sixteen yeast strains across eleven species.

Generation of a human induced pluripotent stem cell line (BIHi292-A) from PBMCs of a female patient diagnosed with Nasu-Hakola disease (NHD)/polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) carrying a novel heterozygous mutation in the TREM2 gene.

NHD/PLOSL is an orphan disease characterized by progressive presenile dementia associated with recurrent fractures due to polycystic bone lesions. In this study, we generated the human induced pluripotent stem cell (hiPSC) line BIHi292-A from a 30-year-old women diagnosed with NHD/PLOSL, carrying two compound heterozygous frameshift mutations [c.313del (p.

Artificial intelligence for diagnosis and predictive biomarkers in Non-Small cell lung cancer Patients: New promises but also new hurdles for the pathologist.

The rapid development of artificial intelligence (AI) based tools in pathology laboratories has brought forward unlimited opportunities for pathologists. Promising AI applications used for accomplishing diagnostic, prognostic and predictive tasks are being developed at a high pace. This is notably true in thoracic oncology, given the significant and rapid therapeutic progress made recently for lung cancer patients.

Chromosome length genome assembly of the stone marten (Martes foina, Mustelidae): a new view on one of the cornerstones in carnivore cytogenetics.

The stone marten (Martes foina) is an important species for cytogenetic studies in the order Carnivora. ZooFISH probes created from its chromosomes provided a strong and clean signal in chromosome painting experiments and were valuable for studying the evolution of carnivoran genome architecture. The research revealed that the stone marten chromosome set is similar to the presumed ancestral karyotype of the Carnivora, which added an additional value for the species.

Protocol for visualizing the chromatin assembly properties of epigenetic protein complexes via an HTM module-mediated artificial tethering system.

The detailed chromatin assembly processes for many epigenetic regulatory complexes are largely unknown. Here, we present a protocol utilizing heterochromatin-targeting module (HTM) module-mediated chromatin tethering followed by microscopy-based visualization to detect the recruitment priority between two components in Polycomb repressive complex 1 (PRC1). Moreover, we detail procedures for detecting the resultant histone-modifying activities of PRC1 using immunofluorescence (IF) analyses.

Serine phosphorylation facilitates protein degradation by the human mitochondrial ClpXP protease.

ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of the caseinolytic protease P (ClpP) for proteolysis. ClpXP degrades damaged respiratory chain proteins and is necessary for cancer cell survival.

Hsp90, DnaK, and ClpB collaborate in protein reactivation.

Hsp70, Hsp90, and ClpB/Hsp100 are molecular chaperones that help regulate proteostasis. Bacterial and yeast Hsp70s and their cochaperones function synergistically with Hsp90s to reactivate inactive and aggregated proteins by a mechanism that requires a direct interaction between Hsp90 and Hsp70 both in vitro and in vivo. and yeast Hsp70s also collaborate in bichaperone systems with ClpB and Hsp104, respectively, to disaggregate and reactivate aggregated proteins and amyloids such as prions.

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.

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).

Proximity Ligation Assay to Study Oncogene-Derived Transcription-Replication Conflicts.

Both DNA replication and RNA transcription utilize genomic DNA as their template, necessitating spatial and temporal separation of these processes. Conflicts between the replication and transcription machinery, termed transcription-replication conflicts (TRCs), pose a considerable risk to genome stability, a critical factor in cancer development. While several factors regulating these collisions have been identified, pinpointing primary causes remains difficult due to limited tools for direct visualization and clear interpretation.

Evaluating Therapeutic and Chemical Toxicity Using Organ-Cultured Porcine Corneas and Epithelial Wound Healing.

Due to its anatomical and physiological similarities to the human eye, the porcine eye serves as a robust model for biomedical research and ocular toxicity assessment. An air/liquid corneal culture system using porcine eyes was developed, and ex vivo epithelial wound healing was utilized as a critical parameter for these studies. Fresh pig corneas were processed for organ culture, with or without epithelial wounding.

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.

The key role of the NUDT3 gene in lung adenocarcinoma progression and its association with the manganese ion metabolism family.

Background: Lung adenocarcinoma is one of the most common malignant tumors worldwide. Its complex molecular mechanisms and high tumor heterogeneity pose significant challenges for clinical treatment. The manganese ion metabolism family plays a crucial role in various biological processes, and the abnormal expression of the NUDT3 gene in multiple cancers has drawn considerable attention.

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 .

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.

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.

Programmable Stapling Peptide Based on Sulfonium as Universal Vaccine Adjuvants for Multiple Types of Vaccines.

Adjuvants are non-specific immune enhancers commonly used to improve the responsiveness and persistence of the immune system toward antigens. However, due to the undefined chemical structure, toxicity, non-biodegradability, and lack of design technology in many existing adjuvants, it remains difficult to achieve substantive breakthroughs in the adjuvant research field. Here, a novel adjuvant development strategy based on stapling peptides is reported to overcome this challenge.

Nuclear blebs are associated with destabilized chromatin packing domains.

Disrupted nuclear shape is associated with multiple pathological processes including premature aging disorders, cancer-relevant chromosomal rearrangements, and DNA damage. Nuclear blebs (i.e.

Clearing the path for whole-mount labeling and quantification of neuron- and vessel-density in adipose tissue.

White adipose tissue (WAT) comprises a plethora of cell types beyond adipocytes forming a regulatory network that ensures systemic energy homeostasis. Intertissue communication is facilitated by metabolites and signaling molecules that are spread by vasculature and nerves. Previous works indicated that WAT responds to environmental cues by adapting the abundance of these "communication routes", however, high intra-tissue heterogeneity questions the informative value of bulk or single cell analyses and underscores the necessity of whole-mount imaging.

A chromosome-level, haplotype-resolved genome assembly and annotation for the Eurasian minnow (Leuciscidae: Phoxinus phoxinus) provide evidence of haplotype diversity.

Background: In this study, we present an in-depth analysis of the Eurasian minnow (Phoxinus phoxinus) genome, highlighting its genetic diversity, structural variations, and evolutionary adaptations. We generated an annotated haplotype-phased, chromosome-level genome assembly (2n = 50) by integrating high-fidelity (HiFi) long reads and chromosome conformation capture data (Hi-C).

Results: We achieved a haploid size of 940 megabase pairs (Mbp) for haplome 1 and 929 Mbp for haplome 2 with high scaffold N50 values of 36.