The master male sex determinant Gdf6Y of the turquoise killifish arose through allelic neofunctionalization.

Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development.

Gene regulation by convergent promoters.

Convergent transcription, that is, the collision of sense and antisense transcription, is ubiquitous in mammalian genomes and believed to diminish RNA expression. Recently, antisense transcription downstream of promoters was found to be surprisingly prevalent. However, functional characteristics of affected promoters are poorly investigated.

Too old for healthy aging? Exploring age limits of longevity treatments.

It is well documented that aging elicits metabolic failures, while poor metabolism contributes to accelerated aging. Metabolism in general, and energy metabolism in particular are also effective entry points for interventions that extend lifespan and improve organ function during aging. In this review, we discuss common metabolic remedies for healthy aging from the angle of their potential age-specificity.

The oncogenic lncRNA MIR503HG suppresses cellular senescence counteracting supraphysiological androgen treatment in prostate cancer.

Background: The androgen receptor (AR), a ligand-dependent transcription factor, plays a key role in regulating prostate cancer (PCa) growth. The novel bipolar androgen therapy (BAT) uses supraphysiological androgen levels (SAL) that suppresses growth of PCa cells and induces cellular senescence functioning as a tumor suppressive mechanism. The role of long non-coding RNAs (lncRNAs) in the regulation of SAL-mediated senescence remains unclear.

has mammal-like mutation rates facilitating fast adaptation despite its nonaging phenotype.

Growing evidence suggests that somatic mutations may be a major cause of the aging process. However, it remains to be tested whether the predictions of the theory also apply to species with longer life spans than humans. is a genus of freshwater polyps with remarkable regeneration abilities and a potentially unlimited life span under laboratory conditions.

Proteomic profiling reveals CEACAM6 function in driving gallbladder cancer aggressiveness through integrin receptor, PRKCD and AKT/ERK signaling.

Gallbladder cancer (GBC) presents as an aggressive malignancy with poor patient outcome. Like other epithelial cancers, the mechanisms of GBC cancer progression remain vague and efforts in finding targeted therapies fall below expectations. This study combined proteomic analysis of formalin-fixed paraffin-embedded (FFPE) GBC samples, functional and molecular characterization of potential oncogenes and identification of potential therapeutic strategies for GBC.

Cell-Type Resolved Protein Atlas of Brain Lysosomes Identifies SLC45A1-Associated Disease as a Lysosomal Disorder.

Mutations in lysosomal genes cause neurodegeneration and neurological lysosomal storage disorders (LSDs). Despite their essential role in brain homeostasis, the cell-type-specific composition and function of lysosomes remain poorly understood. Here, we report a quantitative protein atlas of the lysosome from mouse neurons, astrocytes, oligodendrocytes, and microglia.

Surface microlayer-mediated virome dissemination in the Central Arctic.

Background: Aquatic viruses act as key players in shaping microbial communities. In polar environments, they face significant challenges such as limited host availability and harsh conditions. However, due to the restricted accessibility of these ecosystems, our understanding of viral diversity, abundance, adaptations, and host interactions remains limited.

Autoantigen-specific CD4 T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases.

Pro-inflammatory autoantigen-specific CD4 T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocyte antigen (HLA)-tetramer-based and activation-based multidimensional ex vivo analyses. In aquaporin4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) patients, auto-Th cells expressed CD154, but proliferative capacity and pro-inflammatory cytokines were strongly reduced.

Exploring the impact of primer length on efficient gene detection via high-throughput sequencing.

Reverse transcription (RT) is a crucial step in most RNA analysis methods. Optimizing protocols for this initial stage is critical for effective target detection, particularly when working with limited input RNA. Several factors, such as the input material quality and reaction conditions, influence RT efficiency.

Determinants of p53 DNA binding, gene regulation, and cell fate decisions.

The extent to which transcription factors read and respond to specific information content within short DNA sequences remains an important question that the tumor suppressor p53 is helping us answer. We discuss recent insights into how local information content at p53 binding sites might control modes of p53 target gene activation and cell fate decisions. Significant prior work has yielded data supporting two potential models of how p53 determines cell fate through its target genes: a selective target gene binding and activation model and a p53 level threshold model.

An artificial intelligence-assisted clinical framework to facilitate diagnostics and translational discovery in hematologic neoplasia.

Background: The increasing volume and intricacy of sequencing data, along with other clinical and diagnostic data, like drug responses and measurable residual disease, creates challenges for efficient clinical comprehension and interpretation. Using paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) as a use case, we present an artificial intelligence (AI)-assisted clinical framework clinALL that integrates genomic and clinical data into a user-friendly interface to support routine diagnostics and reveal translational insights for hematologic neoplasia.

Methods: We performed targeted RNA sequencing in 1365 cases with haematological neoplasms, primarily paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) from the AIEOP-BFM ALL study.

Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia.

Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion (I/R) injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner.

Gene regulation by the tumor suppressor p53 - The omics era.

The transcription factor p53 is activated in response to a variety of cellular stresses and serves as a prominent and potent tumor suppressor. Since its discovery, we have sought to understand how p53 functions as both a transcription factor and a tumor suppressor. Two decades ago, the field of gene regulation entered the omics era and began to study the regulation of entire genomes.

Nonlinear DNA methylation trajectories in aging male mice.

Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow the gap, we investigate the methylation trajectories of male mouse colon at five different time points of aging. Our study indicates the existence of sudden hypermethylation events at specific stages of life.

Bashing irreproducibility with shournal.

Arguably, the most important tool for many computational scientists is the Linux shell. Processing steps carried out there are critical for a large number of analyses. While the manual documentation of the work is time-consuming and error-prone, existing tools do not integrate well into the shell or suffer from a large overhead.

Systematic computational hunting for small RNAs derived from ncRNAs during dengue virus infection in endothelial HMEC-1 cells.

In recent years, a population of small RNA fragments derived from non-coding RNAs (sfd-RNAs) has gained significant interest due to its functional and structural resemblance to miRNAs, adding another level of complexity to our comprehension of small-RNA-mediated gene regulation. Despite this, scientists need more tools to test the differential expression of sfd-RNAs since the current methods to detect miRNAs may not be directly applied to them. The primary reasons are the lack of accurate small RNA and ncRNA annotation, the multi-mapping read (MMR) placement, and the multicopy nature of ncRNAs in the human genome.

Acetylation-induced proteasomal degradation of the activated glucocorticoid receptor limits hormonal signaling.

Glucocorticoid (GC) signaling is essential for mounting a stress response, however, chronic stress or prolonged GC therapy downregulates the GC receptor (GR), leading to GC resistance. Regulatory mechanisms that refine this equilibrium are not well understood. Here, we identify seven lysine acetylation sites in the amino terminal domain of GR, with lysine 154 (Lys) in the AF-1 region being the dominant acetyl-acceptor.

Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain.

Aging and neurodegeneration entail diverse cellular and molecular hallmarks. Here, we studied the effects of aging on the transcriptome, translatome, and multiple layers of the proteome in the brain of a short-lived killifish. We reveal that aging causes widespread reduction of proteins enriched in basic amino acids that is independent of mRNA regulation, and it is not due to impaired proteasome activity.