Non-antibiotic pharmaceuticals are toxic against Escherichia coli with no evolution of cross-resistance to antibiotics.

Antimicrobial resistance can arise in the natural environment via prolonged exposure to the effluent released by manufacturing facilities. In addition to antibiotics, pharmaceutical plants also produce non-antibiotic pharmaceuticals, both the active ingredients and other components of the formulations. The effect of these on the surrounding microbial communities is less clear.

Multi-locus inherited neoplasia alleles syndromes in cancer: implications for clinical practice.

The popularity of multi-gene testing has identified more families with two or more pathogenic variants (PV) in cancer predisposition genes, also known as 'MINAS' (multilocus inherited neoplasia alleles syndromes). They are at risk of suboptimal treatment and management as little on this topic is known. We conducted a systematic review of published MINAS cases within cancer predisposition genes to understand their association with more severe presentations.

A dataset of Antarctic ecosystems in ice-free lands: classification, descriptions, and maps.

Antarctica, Earth's least understood and most remote continent, is threatened by human disturbances and climate-related changes, underscoring the imperative for biodiversity inventories to inform conservation. Antarctic ecosystems support unique species and genetic diversity, deliver essential ecosystem services and contribute to planetary stability. We present Antarctica's first comprehensive ecosystem classification and map of ice-free lands, which host most of the continent's biodiversity.

Intrinsic p53 activation restricts gammaherpesvirus driven germinal center B cell expansion during latency establishment.

Gammaherpesviruses are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus and murine gammaherpesvirus 68, this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center B cells. Intrinsic host mechanisms that control virus-driven cellular expansion are incompletely defined.

Genomic sequencing: the case for equity of care in the era of personalized medicine.

Over the past two decades, genomic sequencing (exome and genome) has proven to be critical in providing a faster and more accurate diagnosis as well as tailored treatment plans for a variety of populations. Despite its potential, disparities in access to genomic sequencing persist, predominantly among underrepresented and socioeconomically disadvantaged groups and populations. This inequity stems from factors such as: 1) high costs of sequencing, 2) significant gaps in insurance coverage, 3) limited availability of genetic services in many healthcare institutions and geographic areas, and 4) lack of diversity in genetic research and databases.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Multiscale footprints reveal the organization of cis-regulatory elements.

Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

RELMβ sets the threshold for microbiome-dependent oral tolerance.

Tolerance to dietary antigens is critical for avoiding deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens are poorly understood. Here we demonstrate that the goblet-cell-derived resistin-like molecule β (RELMβ) is a critical regulator of oral tolerance.

Small molecules and heat treatments reverse vernalization via epigenetic modification in Arabidopsis.

Monocarpic plants flower only once and then produce seeds. Many monocarpic plants require a cold treatment known as vernalization before they flower. This requirement delays flowering until the plant senses warm temperatures in the spring.

Long-Term Safety of Ixekizumab Treatment in Patients with Psoriasis, Psoriatic Arthritis, or Axial Spondyloarthritis: a Post Hoc Analysis of Cerebro-Cardiovascular Events.

Introduction: Psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) may confer an increased risk for cardiovascular (CV) disease, including major adverse cerebro-cardiovascular events (MACE), deep vein thrombosis (DVT), and pulmonary embolism (PE). Patients with these conditions are often exposed for extended time periods to biologics, such as ixekizumab (IXE). Therefore, understanding the risk of CV events, especially MACE, in patients with PsO, PsA, and axSpA exposed to IXE is important.

Clinical and genetic spectrum of patients with IRF2BPL syndrome.

Interferon regulatory factor 2 binding protein-like (IRF2BPL) is a single-exon gene that is ubiquitously expressed in various tissues, including the brain. IRF2BPL encodes a transcription factor with two zinc-finger domains that potentially downregulate WNT signaling in the nervous system. Pathogenic IRF2BPL variants have been reported to cause developmental delay, seizures, myoclonus epilepsies, autistic spectrum disorder, and other neurodevelopmental disorders.

FABP4 as a therapeutic host target controlling SARS-CoV-2 infection.

Host metabolic fitness is a critical determinant of infectious disease outcomes. Obesity, aging, and other related metabolic disorders are recognized as high-risk disease modifiers for respiratory infections, including coronavirus infections, though the underlying mechanisms remain unknown. Our study highlights fatty acid-binding protein 4 (FABP4), a key regulator of metabolic dysfunction and inflammation, as a modulator of SARS-CoV-2 pathogenesis, correlating strongly with disease severity in COVID-19 patients.

Are associations of adulthood overweight and obesity with all-cause mortality, cardiovascular disease, and obesity-related cancer modified by comparative body weight at age 10 years in the UK Biobank study?

Objective: Adults living with overweight or obesity do not represent a single homogenous group in terms of mortality and disease risks. The aim of our study was to evaluate how the associations of adulthood overweight and obesity with mortality and incident disease are modified by (i.e.

Biosynthetic pathway for leukotrienes is stimulated by lipopolysaccharide and cytokines in pig endometrial stromal cells.

An inflammatory response is related to different inflammatory mediators generated by immune and endometrial cells. The links between lipopolysaccharide (LPS), cytokines, and leukotrienes (LTs) in endometrial stromal cells remain unclear. This study aimed to examine the influence of LPS, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4 and IL-10 on 5-lipooxygenase (5-LO), LTA4 hydrolase (LTAH) and LTC4 synthase (LTCS) mRNA and protein abundances, and LTB4 and cysteinyl (cys)-LTs release including LTC4, by the cultured pig endometrial stromal cells, as well as on cell viability.

A genome-wide association study identifies genetic variants associated with hip pain in the UK Biobank cohort (N = 221,127).

Hip pain is a common musculoskeletal complaint that leads many people to seek medical attention. We conducted a primary genome-wide association study (GWAS) on the hip pain phenotype within the UK Biobank cohort. Sex-stratified GWAS analysis approach was also performed to explore sex specific variants associated with hip pain.

Mechanistic insights into pachymic acid's action on triple-negative breast Cancer through TOP2A targeting.

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, and lack of human epidermal growth factor receptor 2 (HER2) expression. Traditional Chinese medicine (TCM) has demonstrated promising efficacy in treating TNBC. This study explored the mechanisms of pachymic acid (PA) on TNBC by merging network pharmacology with experimental validation.

Structure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide.

Streptococcus mutans, the causative agent of human dental caries, expresses a cell wall attached Serotype c-specific Carbohydrate (SCC) that is critical for cell viability. SCC consists of a polyrhamnose backbone of →3)α-Rha(1 → 2)α-Rha(1→ repeats with glucose (Glc) side-chains and glycerol phosphate (GroP) decorations. This study reveals that SCC has one predominant and two more minor Glc modifications.

Multiplex-PCR technique to predict polymorphic antigens - M, N, S and s - and associations between their alleles and Mi-associated hybrid glycophorins.

Serological typing of MNS polymorphic antigens - M, N, S and s - remains a fundamental technique in transfusion medicine and prenatal care, providing essential information for matching blood donors and recipients and managing haemolytic disease. Although this method is well proven and routinely used, it is not a comprehensive solution, as it has several weaknesses. Alternatively, multiplex polymerase chain reaction (PCR) is a commonly used genotyping tool due to its potency and ability to amplify several DNA targets simultaneously in a single reaction.

Tp53 determines the spatial dynamics of M1/M2 tumor-associated macrophages and M1-driven tumoricidal effects.

The spatial role of M1 and M2 tumor-associated macrophages (M1/M2 TAMs) in precision medicine remains unclear. EGFR and TP53 are among the most frequently mutated genes in lung adenocarcinoma. We characterized the mutation status and density of M1/M2 TAMs within tumor islets and stroma in 117 lung adenocarcinomas using next-generation sequencing and immunohistochemistry, respectively.

Cohort profile: the BangladEsh Longitudinal Investigation of Emerging Vascular and nonvascular Events (BELIEVE) cohort study.

Purpose: Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases (NCDs) in recent decades. There is, however, limited evidence about multidimensional determinants of NCDs in this population. The BangladEsh Longitudinal Investigation of Emerging Vascular and nonvascular Events (BELIEVE) study is a household-based prospective cohort study established to investigate biological, behavioural, environmental and broader determinants of NCDs.

Frequency of anti-IgLON5 disease in patients with a typical clinical presentation of progressive supranuclear palsy/corticobasal syndrome.

Serum anti-IgLON5 antibodies, which were tested in 223 patients meeting the diagnostic criteria for progressive supranuclear palsy/corticobasal syndrome (PSP/CBS), were negative in all patients. Our study suggests that the frequency of anti-IgLON5 disease is extremely rare in patients with typical presentation of PSP/CBS.

Genetic Testing for Monogenic Forms of Male Infertility Contributes to the Clinical Diagnosis of Men with Severe Idiopathic Male Infertility.

Purpose: In recent years, many genes have been associated with male infertility; however, testing of monogenic forms has not yet been clinically implemented in the diagnosis of severe forms of idiopathic male infertility, as the diagnostic utility has not been established yet. The aim of this study was therefore to answer if the implementation of genetic testing for monogenic forms of male infertility could contribute to the clinical diagnosis of men with severe forms of idiopathic male infertility.

Materials And Methods: Based on the ClinGene curation protocol, we defined a panel of genes with sufficient evidence for the involvement with severe male infertility.

Pushing the envelope - How the genome interacts with the nuclear envelope in health and disease.

The nuclear envelope has for long been considered more than just the physical border between the nucleoplasm and the cytoplasm, emerging as a crucial player in genome organisation and regulation within the 3D nucleus. Consequently, its study has become a valuable topic in the research of cancer, ageing and several other diseases where chromatin organisation is compromised. In this chapter, we will delve into its several sub-elements, such as the nuclear lamina, nuclear pore complexes and nuclear envelope proteins, and their diverse roles in nuclear function and maintenance.