Ion Channels in the Immune Response of Asthma.

Asthma is a common respiratory disorder characterized by chronic inflammation of the lower airways, contributing to significant morbidity, mortality, and a substantial global economic burden. It is now understood as a heterogeneous condition, with ongoing research shedding light on its complex immunological underpinnings. Ion channels, which are specialized transmembrane proteins that facilitate ion movement based on electrochemical gradients, play a crucial role in the pathophysiology of asthma.

Finding the last bits of positional information.

In a developing embryo, information about the position of cells is encoded in the concentrations of morphogen molecules. In the fruit fly, the local concentrations of just a handful of proteins encoded by the gap genes are sufficient to specify position with a precision comparable to the spacing between cells along the anterior-posterior axis. This matches the precision of downstream events such as the striped patterns of expression in the pair-rule genes, but is not quite sufficient to define unique identities for individual cells.

Arginine vasopressin (AVP) treatment increases the expression of inhibitory immune checkpoint molecules in monocyte-derived dendritic cells.

Arginine vasopressin (AVP) has disparate impacts on immune responses by divergent receptors on cells including DCs. This study was conducted with the aim of investigating the impact of AVP on the maturation and expression of the inhibitory immune checkpoint molecules in tolerogenic monocyte-derived DCs. CD14 marker was used to separate monocytes from peripheral blood mononuclear cells (PBMCs) by MACS method.

Chemical waves in reaction-diffusion networks of small organic molecules.

Chemical waves represent one of the fundamental behaviors that emerge in nonlinear, out-of-equilibrium chemical systems. They also play a central role in regulating behaviors and development of biological organisms. Nevertheless, understanding their properties and achieving their rational synthesis remains challenging.

Alternative splicing induces sample-level variation in gene-gene correlations.

Background: The vast majority of genes in the genome are multi-exonic, and are alternatively spliced during transcription, resulting in multiple isoforms for each gene. For some genes, different mRNA isoforms may have differential expression levels or be involved in different pathways. Bulk tissue RNA-seq, as a widely used technology for transcriptome quantification, measures the total expression (TE) levels of each gene across multiple isoforms in multiple cell types for each tissue sample.

Photosynthetic directed endosymbiosis to investigate the role of bioenergetics in chloroplast function and evolution.

Cyanobacterial photosynthesis (to produce ATP and NADPH) might have played a pivotal role in the endosymbiotic evolution to chloroplast. However, rather than meeting the ATP requirements of the host cell, the modern-day land plant chloroplasts are suggested to utilize photosynthesized ATP predominantly for carbon assimilation. This is further highlighted by the fact that the plastidic ADP/ATP carrier translocases from land plants preferentially import ATP.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Structural basis of Cas9 DNA interrogation with a 5' truncated sgRNA.

The efficiency and accuracy of CRISPR-Cas9 targeting varies considerably across genomic targets and remains a persistent issue for using this system in cells. Studies have shown that the use of 5' truncated single guide RNAs (sgRNAs) can reduce the rate of unwanted off-target recognition while still maintaining on-target specificity. However, it is not well-understood how reducing target complementarity enhances specificity or how truncation past 15 nucleotides (nts) prevents full Cas9 activation without compromising on-target binding.

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver.

Predicting survival in patients with SARS-CoV-2 based on cytokines and soluble immune checkpoint regulators.

Background: Coronavirus disease 2019 (COVID-19) has been widespread for over four years and has progressed to an endemic stage. Accordingly, the evaluation of host immunity in infected patients and the development of markers for prognostic prediction in the early stages have been emphasized. Soluble immune checkpoints (sICs), which regulate T cell activity, have been reported as promising biomarkers of viral infections.

frameshift variants impair GABA receptor proteostasis.

The gamma-aminobutyric acid type A receptor (GABAR) is the most common inhibitory neurotransmitter-gated ion channel in the central nervous system. Pathogenic variants in genes encoding GABAR subunits can cause receptor dysfunction and lead to genetic epilepsy. Frameshift variants in these genes can result in a premature termination codon, producing truncated receptor subunit variants.

Monitoring mammary gland development in preweaning dairy heifers using ultrasound imaging.

Existing literature on the long-term effects of nutritional manipulation on milk production is incomplete and inconsistent as animals are typically culled before lactation. In addition, longitudinal studies are rarely conducted due to high costs and constraints related to tissue sampling; therefore, additional research is necessary to better understand the effect of early nutrition and growth on subsequent growth and milk production. Thirty Holstein heifer calves were pair-fed high (H; 27% CP and 20% fat) or low (L; 22% CP and 15%) milk replacers.

Prevalence of Cardiovascular-Kidney-Metabolic Stages in US Adolescents and Relationship to Social Determinants of Health.

Importance: Given that many risk factors for atherosclerotic cardiovascular disease (ASCVD) begin in childhood, knowledge of the prevalence of cardio-kidney metabolic syndrome (CKM) in adolescents and its risk factors is critical to understanding the etiology of ASCVD risk burden.

Objective: To calculate the proportion of US adolescents with CKM stages 0, 1, and 2 and to assess the social factors and behaviors most strongly associated with advanced CKM stage.

Design: Cross-sectional analysis of 2017-2020 US National Health and Nutrition Examination Survey (NHANES) sample data.

Real-world outdoor air exposure effects in a model of the human airway epithelium - A comparison of healthy and asthmatic individuals using a mobile laboratory setting.

We developed a mobile laboratory allowing field exposure of lung tissue models to ambient air at localities with various pollution sources (Background, Industrial, Traffic, Urban) in different seasons (summer/fall/winter). In samples originating from healthy and asthmatic individuals, we assessed the parameters of toxicity, lipid peroxidation and immune response; we further performed comprehensive monitoring of air pollutants at sampling sites. We measured lactate dehydrogenase (LDH) and adenylate kinase (AK) production and transepithelial electrical resistance (TEER), analyzed 15-F-isopostane (IsoP) and a panel of 20 cytokines/chemokines/growth factors.

Characterization of an IL-8 cleavage inhibition assay to determine the functionality of anti-SpyCEP antibodies in human sera.

Exposure to Group A Streptococcus leads to a broad spectrum of disease and sequelae, as the bacterium employs a wide range of virulence factors to facilitate colonization of the host, propagation and onward transmission, disrupting both innate and adaptive immune responses. The protease SpyCEP has a crucial role in contributing to bacterial immune evasion by impairing neutrophil recruitment and killing of bacteria through the cleavage of interleukin-8 (IL-8). Given this critical function, SpyCEP represents a key vaccine antigen and quantifying functional anti-SpyCEP antibodies represents not only an important marker of vaccine efficacy, but also a tool to dissect the natural immune response.

Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis.

Histone lysine lactylation is a physiologically and pathologically relevant epigenetic pathway that can be stimulated by the Warburg effect-associated L-lactate. Nevertheless, the mechanism by which cells use L-lactate to generate lactyl-coenzyme A (CoA) and how this process is regulated remains unknown. Here, we report the identification of guanosine triphosphate (GTP)-specific SCS (GTPSCS) as a lactyl-CoA synthetase in the nucleus.

Outcome of Surgery for Hypothalamic Hamartoma-Related Epilepsy: A Systematic Review and Individual Participant Data Meta-Analysis.

Background And Objectives: There is a paucity of data directly comparing the outcome of surgical techniques available for the treatment of hypothalamic hamartomas (HHs). This study aims to evaluate the safety and efficacy of commonly used surgical approaches in the treatment of HH-related epilepsy.

Methods: A systematic review and individual participant data (IPD) meta-analysis was conducted.

Characterizing the genetic architecture of drug response using gene-context interaction methods.

Identifying factors that affect treatment response is a central objective of clinical research, yet the role of common genetic variation remains largely unknown. Here, we develop a framework to study the genetic architecture of response to commonly prescribed drugs in large biobanks. We quantify treatment response heritability for statins, metformin, warfarin, and methotrexate in the UK Biobank.

EGR1 regulates oral epithelial cell responses to via the EGFR- ERK1/2 pathway.

is a fungal pathobiont colonizing mucosal surfaces of the human body, including the oral cavity. Under certain predisposing conditions, invades mucosal tissues activating EGFR-MAPK signalling pathways in epithelial cells via the action of its peptide toxin candidalysin. However, our knowledge of the epithelial mechanisms involved during colonization is rudimentary.

Mendelian randomization reveals predictive, preventive, and personalized insights into inflammatory bowel disease: the role of gut microbiome and circulating inflammatory proteins.

Background: A chronic illness with increasing global frequency, inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), profoundly affects patients' quality of life and healthcare systems. IBD pathogenesis consists of changes in gut microbiota, immune system dysregulation, and genetic predisposition. Although emerging data suggests that gut microbiota and circulating inflammatory proteins play critical roles in IBD, their utility as biomarkers for predictive, preventive, and personalized medicine (PPPM) remains incompletely understood.