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.

Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect.

Cardiac glycosides, known as inhibitors of Na,K-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA).

Thermal gradient ring for analysis of temperature-dependent behaviors involving TRP channels in mice.

There are a lot of temperature-sensitive proteins including transient receptor potential (TRP) channels. Some TRP channels are temperature receptors having specific activation temperatures in vitro that are within the physiological temperature range. Mice deficient in specific TRP channels show abnormal thermal behaviors, but the role of TRP channels in these behaviors is not fully understood.

Granulomatous Variant of Giant Centrifugal Miliaria Profunda in an 8-Month-Old Boy: Expanding the Dermatologic Phenotype of Cardiofaciocutaneous Syndrome.

Miliarias are a group of eccrine disorders characterized by sweat retention due to the occlusion of eccrine ducts. Miliaria profunda is the rarest form of miliaria and occurs when eccrine ducts are obstructed at the dermal-epidermal junction. A granulomatous variant of centrifugal miliaria profunda classic findings of granulomatous infiltrate on histology and centrifugal expansion of deep nodules or plaques.

Diverse Cre recombinase expression pattern in Albumin-Cre driver rats.

Rats (Rattus norvegicus) have been widely utilized as model animals due to their physiological characteristics, making them suitable for surgical and long-term studies. They have played a crucial role in biomedical research, complementing studies conducted in mice. The advent of genome editing technologies has facilitated the generation of genetically modified rat strains, advancing studies in experimental animals.

An overview of BAP1 biological functions and current therapeutics.

BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that was first identified in 1998. Germline loss of functional variants in BAP1 is associated with a tumor predisposition syndrome with at least four cancers; uveal melanoma (UM), malignant mesothelioma (MMe), renal cell carcinoma (RCC), and cutaneous melanoma (CM). Furthermore, somatic BAP1 mutations are important drivers for several cancers most notably UM, MMe, RCC, intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC).

Data management and sharing.

Guided by the FAIR principles (Findable, Accessible, Interoperable, Reusable), responsible data sharing requires well-organized, high-quality datasets. However, researchers often struggle with implementing Data Management and Sharing Plans (DMSPs) due to lack of knowledge on how to do this, time constraints, legal, technical and financial challenges, particularly concerning data ownership and privacy. While patients support data sharing, researchers and funders may hesitate, fearing the loss of intellectual property or competitive advantage.

The role of the jasmonate signalling transcription factors MYC2/3/4 in circadian clock-mediated regulation of immunity in Arabidopsis.

Plants are exposed to pathogens at specific, yet predictable times of the day-night cycle. In Arabidopsis, the circadian clock influences temporal differences in susceptibility to the necrotrophic pathogen . The jasmonic acid (JA) pathway regulates immune responses against .

BioClocks UK: driving robust cycles of discovery to impact.

Chronobiology is a multidisciplinary field that extends across the tree of life, transcends all scales of biological organization, and has huge translational potential. For the UK to harness the opportunities presented within applied chronobiology, we need to build our network outwards to reach stakeholders that can directly benefit from our discoveries. In this article, we discuss the importance of biological rhythms to our health, society, economy and environment, with a particular focus on circadian rhythms.