The PP2A regulator IER5L supports prostate cancer progression.

Prostate cancer exhibits high prevalence and accounts for a high number of cancer-related deaths. The discovery and characterization of molecular determinants of aggressive prostate cancer represents an active area of research. The Immediate Early Response (IER) family of genes, which regulate Protein Phosphatase 2A (PP2A) activity, has emerged among the factors that influence cancer biology.

The Catalan initiative for the Earth BioGenome Project: contributing local data to global biodiversity genomics.

The Catalan Initiative for the Earth BioGenome Project (CBP) is an EBP-affiliated project network aimed at sequencing the genome of the >40 000 eukaryotic species estimated to live in the Catalan-speaking territories (Catalan Linguistic Area, CLA). These territories represent a biodiversity hotspot. While covering less than 1% of Europe, they are home to about one fourth of all known European eukaryotic species.

The Effect of Dietary Nitrate on the Oral Microbiome and Salivary Biomarkers in Individuals with High Blood Pressure.

Background: Green leafy vegetables (GLV) contain inorganic nitrate, an anion with potential prebiotic effects on the oral microbiome. However, it remains unclear whether GLV and pharmacological supplementation [potassium nitrate (PN)] with a nitrate salt induce similar effects on the oral microbiome.

Objectives: This study aimed to compare the effect of GLV with PN supplementation on the oral microbiome composition and salivary biomarkers in individuals with high blood pressure.

Human EWS-FLI protein levels and neomorphic functions show a complex, function-specific dose-response relationship in .

Ewing sarcoma (EwS) is a cancer that arises in the bones and soft tissues, typically driven by the Ewing's sarcoma breakpoint region 1-Friend leukemia virus integration 1 (EWS-FLI) oncogene. Implementation of genetically modified animal models of EwS has proved difficult largely owing to EWS-FLI's high toxicity. The EWS-FLI frameshift variant that circumvents toxicity but is still able to perform key oncogenic functions provided the first study model in .

In vivo photocontrol of orexin receptors with a nanomolar light-regulated analogue of orexin-B.

Orexinergic neurons are critically involved in regulating arousal, wakefulness, and appetite. Their dysfunction has been associated with sleeping disorders, and non-peptide drugs are currently being developed to treat insomnia and narcolepsy. Yet, no light-regulated agents are available to reversibly control their activity.

Implications of noncoding regulatory functions in the development of insulinomas.

Insulinomas are rare neuroendocrine tumors arising from pancreatic β cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions.

FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA).

Assessing Diagnosis of Infections: A Study on Species Prevalence and Antifungal Resistance in Northern Morocco.

The incidence of infections has increased in the last decade, posing a serious threat to public health. Appropriately facing this challenge requires precise epidemiological data on species and antimicrobial resistance incidence, but many countries lack appropriate surveillance programs. This study aims to bridge this gap for Morocco by identifying and phenotyping a year-long collection of clinical isolates (n = 93) from four clinics in Tetouan.

Using interactive Jupyter Notebooks and BioConda for FAIR and reproducible biomolecular simulation workflows.

Interactive Jupyter Notebooks in combination with Conda environments can be used to generate FAIR (Findable, Accessible, Interoperable and Reusable/Reproducible) biomolecular simulation workflows. The interactive programming code accompanied by documentation and the possibility to inspect intermediate results with versatile graphical charts and data visualization is very helpful, especially in iterative processes, where parameters might be adjusted to a particular system of interest. This work presents a collection of FAIR notebooks covering various areas of the biomolecular simulation field, such as molecular dynamics (MD), protein-ligand docking, molecular checking/modeling, molecular interactions, and free energy perturbations.

Proof of Concept Study: Comparability of Microbiome Diversity in Self- and Physician-Collected HPV-Positive and HPV-Negative Cervicovaginal Samples.

Recent studies have revealed the impact of human papillomavirus (HPV) infections on the cervicovaginal microbiome; however, few have explored the utility of self-collected specimens (SCS) for microbiome detection, obtained using standardised methods for HPV testing. Here, we present a proof-of-concept analysis utilising Oxford Nanopore sequencing of the 16S rRNA gene in paired samples collected either by the patient using an Evalyn Brush or collected by a physician using liquid-based cytology (LBC). We found no significant differences in the α-diversity estimates between the SCS and LBC samples.

Stereochemically-aware bioactivity descriptors for uncharacterized chemical compounds.

Stereochemistry plays a fundamental role in pharmacology. Here, we systematically investigate the relationship between stereoisomerism and bioactivity on over 1 M compounds, finding that a very significant fraction (~ 40%) of spatial isomer pairs show, to some extent, distinct bioactivities. We then use the 3D representation of these molecules to train a collection of deep neural networks (Signaturizers3D) to generate bioactivity descriptors associated to small molecules, that capture their effects at increasing levels of biological complexity (i.

Formation of left-handed helices by C2'-fluorinated nucleic acids under physiological salt conditions.

Recent findings in cell biology have rekindled interest in Z-DNA, the left-handed helical form of DNA. We report here that two minimally modified nucleosides, 2'F-araC and 2'F-riboG, induce the formation of the Z-form under low ionic strength. We show that oligomers entirely made of these two nucleosides exclusively produce left-handed duplexes that bind to the Zα domain of ADAR1.

K29-linked free polyubiquitin chains affect ribosome biogenesis and direct ribosomal proteins to the intranuclear quality control compartment.

Ribosome assembly requires precise coordination between the production and assembly of ribosomal components. Mutations in ribosomal proteins that inhibit the assembly process or ribosome function are often associated with ribosomopathies, some of which are linked to defects in proteostasis. In this study, we examine the interplay between several yeast proteostasis enzymes, including deubiquitylases (DUBs) Ubp2 and Ubp14, and E3 ligases Ufd4 and Hul5, and we explore their roles in the regulation of the cellular levels of K29-linked unanchored polyubiquitin (polyUb) chains.

and mutations in a patient with a neurodevelopmental disorder and immunodeficiency.

The Tousled-like kinases 1 and 2 (TLK1/TLK2) regulate DNA replication, repair and chromatin maintenance. TLK2 variants underlie the neurodevelopmental disorder (NDD) 'Intellectual Disability, Autosomal Dominant 57' (MRD57), characterized by intellectual disability and microcephaly. Several TLK1 variants have been reported in NDDs but their functional significance is unknown.

Strand-resolved mutagenicity of DNA damage and repair.

DNA base damage is a major source of oncogenic mutations. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair.

Patient-derived organoid biobank identifies epigenetic dysregulation of intestinal epithelial MHC-I as a novel mechanism in severe Crohn's Disease.

Objective: Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and pathways affected as well as their potential impact on disease phenotype and outcome remain unknown. We set out to investigate the role of intestinal epithelial DNAm in CD pathogenesis.

Several secondary metabolite gene clusters in the genomes of ten Penicillium spp. raise the risk of multiple mycotoxin occurrence in chestnuts.

Penicillium spp. produce a great variety of secondary metabolites, including several mycotoxins, on food substrates. Chestnuts represent a favorable substrate for Penicillium spp.

CGeNArate: a sequence-dependent coarse-grained model of DNA for accurate atomistic MD simulations of kb-long duplexes.

We present CGeNArate, a new model for molecular dynamics simulations of very long segments of B-DNA in the context of biotechnological or chromatin studies. The developed method uses a coarse-grained Hamiltonian with trajectories that are back-mapped to the atomistic resolution level with extreme accuracy by means of Machine Learning Approaches. The method is sequence-dependent and reproduces very well not only local, but also global physical properties of DNA.

Mechanisms of metastatic colorectal cancer.

Despite extensive research and improvements in understanding colorectal cancer (CRC), its metastatic form continues to pose a substantial challenge, primarily owing to limited therapeutic options and a poor prognosis. This Review addresses the emerging focus on metastatic CRC (mCRC), which has historically been under-studied compared with primary CRC despite its lethality. We delve into two crucial aspects: the molecular and cellular determinants facilitating CRC metastasis and the principles guiding the evolution of metastatic disease.

Cholesterol Modulation Attenuates the AD-like Phenotype Induced by Herpes Simplex Virus Type 1 Infection.

Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer's disease (AD). Previous research from our group has demonstrated that herpes simplex virus type I (HSV-1) induces an AD-like phenotype in several cell models of infection.

Metabolic homeostasis of tissue macrophages across the lifespan.

Macrophages are present in almost all organs. Apart from being immune sentinels, tissue-resident macrophages (TRMs) have organ-specific functions that require a specialized cellular metabolism to maintain homeostasis. In addition, organ-dependent metabolic adaptations of TRMs appear to be fundamentally distinct in homeostasis and in response to a challenge, such as infection or injury.

Nucleic acids in modern molecular therapies: A realm of opportunities for strategic drug design.

RNA vaccines have made evident to society what was already known by the scientific community: nucleic acids will be the "drugs of the future." By modifying the genome, interfering in transcription or translation, and by introducing new catalysts into the cell or by mimicking antibody effects, nucleic acids can generate therapeutic activities that are not accessible by any other therapeutic agents. There are, however, challenges that need to be solved in the next few years to make nucleic acids usable in a wide range of therapeutic scenarios.