A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements.

Chromosomal instability (CIN) generates micronuclei-aberrant extranuclear structures that catalyze the acquisition of complex chromosomal rearrangements present in cancer. Micronuclei are characterized by persistent DNA damage and catastrophic nuclear envelope collapse, which exposes DNA to the cytoplasm. We found that the autophagic receptor p62/SQSTM1 modulates micronuclear stability, influencing chromosome fragmentation and rearrangements.

The association between food preferences, eating behavior, and body weight among female university students in the United Arab Emirates.

Introduction: This cross-sectional study investigated the associations between lifestyle, eating habits, food preferences, consumption patterns, and obesity among female university students in the United Arab Emirates (UAE).

Methods: Approximately 4,728 participants, including both Emirati and Non-Emirati students (International Students). Data collection involved face-to-face interviews and anthropometric measurements, showing an interrelated relationship between food preferences and obesity among female university students.

New facets in the chromatin-based regulation of genome maintenance.

The maintenance of genome integrity by DNA damage response machineries is key to protect cells against pathological development. In cell nuclei, these genome maintenance machineries operate in the context of chromatin, where the DNA wraps around histone proteins. Here, we review recent findings illustrating how the chromatin substrate modulates genome maintenance mechanisms, focusing on the regulatory role of histone variants and post-translational modifications.

Inspiration4 data access through the NASA Open Science Data Repository.

The increasing accessibility of commercial and private space travel necessitates a profound understanding of its impact on human health. The NASA Open Science Data Repository (OSDR) provides transparent and FAIR access to biological studies, notably the SpaceX Inspiration4 (I4) mission, which amassed extensive data from civilian astronauts. This dataset encompasses omics and clinical assays, facilitating comprehensive research on space-induced biological responses.

Identification and prediction of association patterns between nutrient intake and anemia using machine learning techniques: results from a cross-sectional study with university female students from Palestine.

Purpose: This study utilized data mining and machine learning (ML) techniques to identify new patterns and classifications of the associations between nutrient intake and anemia among university students.

Methods: We employed K-means clustering analysis algorithm and Decision Tree (DT) technique to identify the association between anemia and vitamin and mineral intakes. We normalized and balanced the data based on anemia weighted clusters for improving ML models' accuracy.

Lysosomal damage sensing and lysophagy initiation by SPG20-ITCH.

Cells respond to lysosomal membrane permeabilization by membrane repair or selective macroautophagy of damaged lysosomes, termed lysophagy, but it is not fully understood how this decision is made. Here, we uncover a pathway in human cells that detects lipid bilayer perturbations in the limiting membrane of compromised lysosomes, which fail to be repaired, and then initiates ubiquitin-triggered lysophagy. We find that SPG20 binds the repair factor IST1 on damaged lysosomes and, importantly, integrates that with the detection of damage-associated lipid-packing defects of the lysosomal membrane.

The histone chaperone SPT2 regulates chromatin structure and function in Metazoa.

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response.

BioE3 identifies specific substrates of ubiquitin E3 ligases.

Hundreds of E3 ligases play a critical role in recognizing specific substrates for modification by ubiquitin (Ub). Separating genuine targets of E3s from E3-interactors remains a challenge. We present BioE3, a powerful approach for matching substrates to Ub E3 ligases of interest.

Mitotic chromatin marking governs asymmetric segregation of DNA damage.

The faithful segregation of intact genetic material and the perpetuation of chromatin states through mitotic cell divisions are pivotal for maintaining cell function and identity across cell generations. However, most exogenous mutagens generate long-lasting DNA lesions that are segregated during mitosis. How this segregation is controlled is unknown.

Machine learning techniques for the identification of risk factors associated with food insecurity among adults in Arab countries during the COVID-19 pandemic.

Background: A direct consequence of global warming, and strongly correlated with poor physical and mental health, food insecurity is a rising global concern associated with low dietary intake. The Coronavirus pandemic has further aggravated food insecurity among vulnerable communities, and thus has sparked the global conversation of equal food access, food distribution, and improvement of food support programs. This research was designed to identify the key features associated with food insecurity during the COVID-19 pandemic using Machine learning techniques.

A planar polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia.

Tissue fluidification and collective motility are pivotal in regulating embryonic morphogenesis, wound healing, and tumor metastasis. These processes frequently require that each cell constituent of a tissue coordinates its migration activity and directed motion through the oriented extension of lamellipodium cell protrusions, promoted by RAC1 activity. While the upstream RAC1 regulators in individual migratory cells or leader cells during invasion or wound healing are well characterized, how RAC1 is controlled in follower cells remains unknown.

Assessing a cut-off point for the diagnosis of abnormal uterine bleeding using the Menstrual Bleeding Questionnaire (MBQ): a validation and cultural translation study with Brazilian women.

Background: Abnormal uterine bleeding (AUB) is a common condition, and the Menstrual Bleeding Questionnaire (MBQ) is used for its assessment.

Objectives: To translate, assess the cut-off point for diagnosis, and explore psychometric properties of the MBQ for use in Brazilian Portuguese.

Design And Setting: Prospective cohort study including 200 women (100 with and 100 without AUB) at a tertiary referral center.

The DNA damage response in the chromatin context: A coordinated process.

In the cell nucleus, DNA damage signaling and repair machineries operate on a chromatin substrate, the integrity of which is critical for cell function and viability. Here, we review recent advances in deciphering the tight coordination between chromatin maintenance and the DNA damage response (DDR). We discuss how the DDR impacts chromatin marks, organization and mobility, and, in turn, how chromatin alterations actively contribute to the DDR, providing additional levels of regulation.

A planar-polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia.

Unlabelled: Tissue fluidification and collective motility are pivotal in regulating embryonic morphogenesis, wound healing and tumor metastasis. These processes frequently require that each cell constituent of a tissue coordinates its migration activity and directed motion through the oriented extension of lamellipodia cell protrusions, promoted by RAC1 activity. While the upstream RAC1 regulators in individual migratory cells or leader cells during invasion or wound healing are well characterized, how RAC1 is controlled in follower cells remains unknown.

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.

Monitoring HECT Ubiquitination Activity In Vitro.

In vitro ubiquitination tools have been employed to mechanistically study the ubiquitin enzymatic cascade. Here, we describe an assay capable to monitor ubiquitin conjugation in real time using the Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) system. The assay requires purified E1 and E2 enzymes, the HECT E3 ligase of choice and two fluorophore-labeled ubiquitins.

Imaging the Response to DNA Damage in Heterochromatin Domains.

The eukaryotic genome is assembled in a nucleoprotein complex called chromatin, whose organization markedly influences the repair of DNA lesions. For instance, compact chromatin states, broadly categorized as heterochromatin, present a challenging environment for DNA damage repair. Through transcriptional silencing, heterochromatin also plays a vital role in the maintenance of genomic integrity and cellular homeostasis.

The NEDD4 ubiquitin E3 ligase: a snapshot view of its functional activity and regulation.

Due to its fundamental role in all eukaryotic cells, a deeper understanding of the molecular mechanisms underlying ubiquitination is of central importance. Being responsible for chain specificity and substrate recognition, E3 ligases are the selective elements of the ubiquitination process. In this review, we discuss different cellular pathways regulated by one of the first identified E3 ligase, NEDD4, focusing on its pathophysiological role, its known targets and modulators.

Recurrent Spliceosome Mutations in Cancer: Mechanisms and Consequences of Aberrant Splice Site Selection.

Splicing alterations have been widely documented in tumors where the proliferation and dissemination of cancer cells is supported by the expression of aberrant isoform variants. Splicing is catalyzed by the spliceosome, a ribonucleoprotein complex that orchestrates the complex process of intron removal and exon ligation. In recent years, recurrent hotspot mutations in the spliceosome components U1 snRNA, SF3B1, and U2AF1 have been identified across different tumor types.

Myosin VI regulates ciliogenesis by promoting the turnover of the centrosomal/satellite protein OFD1.

The actin motor protein myosin VI is a multivalent protein with diverse functions. Here, we identified and characterised a myosin VI ubiquitous interactor, the oral-facial-digital syndrome 1 (OFD1) protein, whose mutations cause malformations of the face, oral cavity, digits and polycystic kidney disease. We found that myosin VI regulates the localisation of OFD1 at the centrioles and, as a consequence, the recruitment of the distal appendage protein Cep164.