The BLM-TOP3A-RMI1-RMI2 proximity map reveals that RAD54L2 suppresses sister chromatid exchanges.

Homologous recombination is a largely error-free DNA repair mechanism conserved across all domains of life and is essential for the maintenance of genome integrity. Not only are the mutations in homologous recombination repair genes probable cancer drivers, some also cause genetic disorders. In particular, mutations in the Bloom (BLM) helicase cause Bloom Syndrome, a rare autosomal recessive disorder characterized by increased sister chromatid exchanges and predisposition to a variety of cancers.

Exposomics: a review of methodologies, applications, and future directions in molecular medicine.

The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications, metabolic pathways, and immune responses.

RNA-sequencing unveils FLT4 splice site variants in variable congenital heart disease.

The etiology of congenital heart disease (CHD) is complex, comprising both genetic and environmental factors. Despite documented familial occurrences, the genetic etiology remains largely elusive. Trio exome sequencing identified a heterozygous FLT4 splice site variant in two families with respectively tetralogy of Fallot (TOF), and variable CHD comprising both the TOF spectrum and aortic coarctation.

A bioinformatic approach to characterize the vitellogenin receptor and the low density lipoprotein receptor superfamily in the newt Cynops orientalis.

The Low Density Lipoprotein receptors (LDLRs) gene family includes 15 receptors: very low-density lipoprotein receptor (VLDLR), LDLR, Sorting-related receptor with A-type repeats (SORLA), and 12 LDL receptor-related proteins (LRPs): LRP1, LRP1B, LRP2, LRP3, LRP4, LRP5, LRP6, LRP8, LRP10, LRP11, LRP12, LRP13. Most of these are involved in the transduction of key signals during embryonic development and in the regulation of cholesterol homeostasis. In oviparous animals, the VLDL receptor is also known as VTGR since it facilitates the uptake of vitellogenin in ovary.

Multiplexed spatial mapping of chromatin features, transcriptome and proteins in tissues.

The phenotypic and functional states of cells are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome and metabolome. Spatial omics approaches have enabled the study of these layers in tissue context but are often limited to one or two modalities, offering an incomplete view of cellular identity. Here we present spatial-Mux-seq, a multimodal spatial technology that allows simultaneous profiling of five different modalities: two histone modifications, chromatin accessibility, whole transcriptome and a panel of proteins at tissue scale and cellular level in a spatially resolved manner.

ASIC1a mediated nucleus pulposus cells pyroptosis and glycolytic crosstalk as a molecular basis for intervertebral disc degeneration.

Background: One of the etiologic components of degenerative spinal illnesses is intervertebral disc degeneration (IVDD), and the accompanying lower back pain is progressively turning into a significant public health problem. Important pathologic characteristics of IVDD include inflammation and acidic microenvironment, albeit it is unclear how these factors contribute to the disease.

Purpose: To clarify the functions of inflammation and the acidic environment in IVDD, identify the critical connections facilitating glycolytic crosstalk and nucleus pulposus cells (NPCs) pyroptosis, and offer novel approaches to IVDD prevention and therapy.

The southern house mosquito Culex quinquefasciatus in Abu Dhabi, UAE, is developing resistance to deltamethrin insecticide.

Culex quinquefasciatus is a widely spread mosquito species that poses a significant public health threat in many countries. This insect vector is present in the United Arab Emirates (UAE), yet no studies have been conducted on its resistance to any insecticide group. Research shows that controlling mosquitoes is crucial to eliminating mosquito-borne diseases, but when these vectors develop insecticide resistance, the situation can escalate dangerously out of control.

Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance.

RAF protein kinases are major RAS effectors that function by phosphorylating MEK. Although all three RAF isoforms share a conserved RAS binding domain and bind to GTP-loaded RAS, only ARAF uniquely enhances RAS activity. Here we uncovered the molecular basis of ARAF in regulating RAS activation.

Cytoplasmic mRNA decay and quality control machineries in eukaryotes.

mRNA degradation pathways have key regulatory roles in gene expression. The intrinsic stability of mRNAs in the cytoplasm of eukaryotic cells varies widely in a gene- and isoform-dependent manner and can be regulated by cellular cues, such as kinase signalling, to control mRNA levels and spatiotemporal dynamics of gene expression. Moreover, specialized quality control pathways exist to rid cells of non-functional mRNAs produced by errors in mRNA processing or mRNA damage that negatively impact translation.

Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates.

The tumor suppressor LKB1/STK11 plays important roles in regulating cellular metabolism and stress responses and its mutations are associated with various cancers. We recently identified a novel exon 1b within intron 1 of human LKB1/STK11, which generates an alternatively spliced, mitochondria-targeting LKB1 isoform important for regulating mitochondrial oxidative stress. Here we examined the formation of this novel exon 1b and uncovered its relatively late emergence during evolution.

Piezoelectric biosensor with dissipation monitoring enables the analysis of bacterial lytic agent activity.

Antibiotic-resistant strains of Staphylococcus aureus pose a significant threat in healthcare, demanding urgent therapeutic solutions. Combining bacteriophages with conventional antibiotics, an innovative approach termed phage-antibiotic synergy, presents a promising treatment avenue. However, to enable new treatment strategies, there is a pressing need for methods to assess their efficacy reliably and rapidly.

Exogenous LEA proteins expression enhances cold tolerance in mammalian cells by reducing oxidative stress.

Understanding the molecular mechanisms that confer cold resistance in mammalian cells might be relevant for advancing medical applications. This study aimed to exploit the protective function of Late Embryogenesis Abundant (LEA) proteins, known to provide resistance to low temperatures in extremophiles and plants, by their exogenous expression in mammalian cells, and compare their effects with the well characterized antioxidant, vitamin E.Remarkably, the expression of LEA proteins in mammalian cells exerted cold-protective effect similar to Vitamin E.

Next generation sequencing of multiple SARS-CoV-2 infections in the Omicron Era.

Since the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the need for an effective vaccine has appeared crucial for stimulating immune system responses to produce humoral/cellular immunity and activate immunological memory. It has been demonstrated that SARS-CoV-2 variants escape neutralizing immunity elicited by previous infection and/or vaccination, leading to new infection waves and cases of reinfection. The study aims to gain into cases of reinfections, particularly infections and/or vaccination-induced protection.

Exploration of alcohol dehydrogenase EutG from Bacillus tropicus as an eco-friendly approach for the degradation of polycyclic aromatic compounds.

Polycyclic aromatic compounds (PACs) are pervasive environmental contaminants derived from diverse sources including pyrogenic (e.g., combustion processes), petrogenic (e.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases).

A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.

While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.

Impact of pollution on microbiological dynamics in the pistil stigmas of Orobanche lutea flowers (Orobanchaceae).

Our understanding of the basic relationships of microbiota associated with flowers is still quite limited, especially regarding parasitic plant species. The transient nature of flower parts such as pistil stigmas provides a unique opportunity for temporal investigations. This is the first report of the analysis of bacterial and fungal communities associated with the pistil stigmas of the lucerne parasite, Orobanche lutea.

GPX modulation promotes regenerative axonal fusion and functional recovery after injury through PSR-1 condensation.

Axonal fusion represents an efficient way to recover function after nerve injury. However, how axonal fusion is induced and regulated remains largely unknown. We discover that ferroptosis signaling can promote axonal fusion and functional recovery in C.

Short-term evolutionary implications of an introgressed size-determining supergene in a vulnerable population.

The Thorny Skate (Amblyraja radiata) is a vulnerable species displaying a discrete size-polymorphism in the northwest Atlantic Ocean (NWA). We conducted whole genome sequencing of samples collected across its range. Genetic diversity was similar at all sampled sites, but we discovered a ~ 31 megabase bi-allelic supergene associated with the size polymorphism, with the larger size allele having introgressed in the last ~160,000 years B.

Utilizing TP53 hotspot mutations as effective predictors of gemcitabine treatment outcome in non-small-cell lung cancer.

TP53 mutations are recognized to correlate with a worse prognosis in individuals with non-small cell lung cancer (NSCLC). There exists an immediate necessity to pinpoint selective treatment for patients carrying TP53 mutations. Potential drugs were identified by comparing drug sensitivity differences, represented by the half-maximal inhibitory concentration (IC50), between TP53 mutant and wild-type NSCLC cell lines using database analysis.

msiFlow: automated workflows for reproducible and scalable multimodal mass spectrometry imaging and microscopy data analysis.

Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and microscopy holds potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing software solutions for MALDI MSI data analysis are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries. Here, we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data.