Genetic and biochemical characterization of a radical SAM enzyme required for post-translational glutamine methylation of methyl-coenzyme M reductase.

Methyl-coenzyme M reductase (MCR), the key catalyst in the anoxic production and consumption of methane, contains an unusual 2-methylglutamine residue within its active site. data show that a B12-dependent radical SAM (rSAM) enzyme, designated MgmA, is responsible for this post-translational modification (PTM). Here, we show that two different MgmA homologs are able to methylate MCR when expressed in , an organism that does not normally possess this PTM.

Mechanistic modelling of allergen-induced airways disease in early life.

Asthma affects approximately 300 million individuals worldwide and the onset predominantly arises in childhood. Children are exposed to multiple environmental irritants, such as viruses and allergens, that are common triggers for asthma onset, whilst their immune systems are developing in early life. Understanding the impact of allergen exposures on the developing immune system and resulting alterations in lung function in early life will help prevent the onset and progression of allergic asthma in children.

Rationalizing mAb Candidate Screening Using a Single Holistic Developability Parameter.

A framework for the rational selection of a minimal suite of nondegenerate developability assays (DAs) that maximize insight into candidate developability or storage stability is lacking. To address this, we subjected nine formulation:mAbs to 12 mechanistically distinct DAs together with measurement of their accelerated and long-term storage stability. We show that it is possible to identify a reduced set of key variables from this suite of DAs by using orthogonal statistical methods.

Basophils: Regulators of lung inflammation over space and time.

In this issue of JEM, Schuijs et al. (https://doi.org/10.

Airway macrophage glycolysis controls lung homeostasis and responses to aeroallergen.

The lungs represent a dynamic microenvironment where airway macrophages (AMs) are the major lung-resident macrophages. AMs dictate the balance between tissue homeostasis and immune activation and thus have contradictory functions by maintaining tolerance and tissue homeostasis, as well as initiating strong inflammatory responses. Emerging evidence has highlighted the connection between macrophage function and cellular metabolism.

Macro- and microplastics leachates: Characterization and impact on seed germination.

Although plastic mulch enhances crop yield, its removal and disposal present significant challenges, contributing to macro- and microplastic pollution in agricultural soils. The adverse effects of this pollution on soil and plant health are not fully understood but may stem from the plastic particles or the toxicity of leached chemical additives. This study assessed the impact of macro- and microplastics from nondegradable LDPE-based (LDPEb) and biodegradable PBAT-based (PBATb) mulch films, along with their leachates, on the germination of three plant species.

Interpretation of river water quality data is strongly controlled by measurement time and frequency.

Water quality monitoring at high temporal frequency provides a detailed picture of environmental stressors and ecosystem response, which is essential to protect and restore lake and river health. An effective monitoring network requires knowledge on optimal monitoring frequency and data variability. Here, high-frequency hydrochemical datasets (dissolved oxygen, pH, electrical conductivity, turbidity, water temperature, total reactive phosphorus, total phosphorus and nitrate) from six UK catchments were analysed to 1) understand the lowest measurement frequency needed to fully capture the variation in the datasets; and 2) investigate bias caused by sampling at different times of the day.

MEDI1814 selectively reduces free Aβ42 in cerebrospinal fluid of non-clinical species and Alzheimer's disease patients.

Introduction: Small molecules and antibodies are being developed to lower amyloid beta (Aβ) peptides.

Methods: We describe MEDI1814, a fully human high-affinity monoclonal antibody selective for Aβ, the pathogenic self-aggregating species of Aβ.

Results: MEDI1814 reduces free Aβ without impacting Aβ in the cerebrospinal fluid of rats and cynomolgus monkeys after systemic administration.

Anticipatory and Consummatory Responses Across Reward Domains in Adolescents With Anorexia Nervosa.

Objective: Anorexia nervosa (AN) is characterized by a tendency to limit intake of food, with specific restriction of foods that are generally considered highly palatable. This observation raises questions about whether reward processing is disturbed in AN. This study examined whether adolescents with AN differ from healthy control peers (HC) in anticipatory and consummatory reward processing.

Deep multiomic profiling reveals molecular signatures that underpin preschool wheeze and asthma.

Background: Wheezing in childhood is prevalent, with over one-half of all children experiencing at least 1 episode by age 6. The pathophysiology of wheeze, especially why some children develop asthma while others do not, remains unclear.

Objectives: This study addresses the knowledge gap by investigating the transition from preschool wheeze to asthma using multiomic profiling.

Diagnosis and mitigation of the systemic impact of genome reduction in DGF-298.

Unlabelled: Microorganisms with simplified genomes represent interesting cell chassis for systems and synthetic biology. However, genome reduction can lead to undesired traits, such as decreased growth rate and metabolic imbalances. To investigate the impact of genome reduction on strain DGF-298, a strain in which ~ 36% of the genome has been removed, we reconstructed a strain-specific metabolic model (AC1061), investigated the regulation of gene expression using iModulon-based transcriptome analysis, and performed adaptive laboratory evolution to let the strain correct potential imbalances that arose during its simplification.

Modifying Pharmacy Enrollments by Employment Realities.

: The objective of this commentary is to consider the fluctuations in pharmacy school enrollments and to review some of the strategies employed in other health care professions, as well as to consider policies that might lead to a closer balance between admissions to PharmD programs and employment opportunities. This balance provides job stability, decreased underemployment, and greater attractiveness to study pharmacy. : Pharmacy school entry requirements have been relaxed to enroll as many students as possible due to current declining applicant numbers.

Airway extracellular LTAH concentrations are governed by release from liver hepatocytes and changes in lung vascular permeability.

Leukotriene A hydrolase (LTAH) is a bifunctional enzyme, with dual activities critical in defining the scale of tissue inflammation and pathology. LTAH classically operates intracellularly, primarily within myeloid cells, to generate pro-inflammatory leukotriene B. However, LTAH also operates extracellularly to degrade the bioactive collagen fragment proline-glycine-proline to limit neutrophilic inflammation and pathological tissue remodeling.

"Uncovering the unspoken": a narrative analysis of patients' experiences with testicular cancer.

Background: The aim of this study was to understand the experiences of young men with a diagnosis of testicular cancer (TC) using a narrative approach, with the intention of informing models of care and support in clinical services.

Methods: TC patients were recruited to participate in one of four focus groups examining their lived experiences from diagnosis. Focus groups were recorded and transcribed and analyzed using a narrative approach.

Rapid, Selective, and Ultra-Sensitive Field Effect Transistor-Based Detection of .

() was among the first organisms to have its complete genome published (Genome Sequence of 1997 Science). It is used as a model system in microbiology research. can cause life-threatening illnesses, particularly in children and the elderly.

Anti-Cytokine Active Immunotherapy Based on Supramolecular Peptides for Alleviating IL-1β-Mediated Inflammation.

IL-1β is a principal proinflammatory cytokine underlying multiple local and systemic chronic inflammatory conditions including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and type 2 diabetes. Passive immunotherapies and biologic drugs targeting IL-1β, while offering significant clinical benefit, nevertheless have limitations such as significant non-response rates, induction of anti-drug antibodies, and high costs. Here, an active immunotherapy raising antibody responses against IL-1β employing self-assembling peptide nanofibers is described.

Grief intensity following adolescent miscarriage or abortion: A descriptive study of recollections of adult women.

Objective: The purpose of this study was to examine women's recollected lifespan perceptions of the effect of grief intensity following adolescent perinatal death.

Participants: Nineteen adult women who had experienced either a miscarriage or an abortion during adolescence. The study involved the recollection of events surrounding the experience which had occurred between three and 28 years previously.

A decade's summary of transcatheter tricuspid valve repair.

Tricuspid regurgitation (TR) is the most common pathology for the tricuspid valve. Moderate to severe TR is associated with morbidity and adverse outcomes. The concept that TR resolves on its own if the underlying disease is successfully treated has proven to be false.

Inpp5d haplodeficiency alleviates tau pathology in the PS19 mouse model of Tauopathy.

Introduction: A noncoding variant (rs35349669) within INPP5D, a lipid and protein phosphatase restricted to microglia in the brain, is linked to increased susceptibility to Alzheimer's disease (AD). While Inpp5d is well-studied in amyloid pathology, its role in tau pathology remains unclear.

Methods: PS19 Tauopathy mice were crossed with Inpp5d-haplodeficient (Inpp5d+/-) mice to examine the impact of Inpp5d in tau pathology.

Neighborhood Racialized Economic Polarization, Home Visiting Coverage, and Adverse Birth Outcomes in a Medicaid-eligible Population.

Background: Residential polarization shaped by racial segregation and concentrations of wealth (hereafter neighborhood racialized economic polarization) results in both highly deprived and highly privileged neighborhoods. Numerous studies have found a negative relationship between neighborhood racialized economic polarization and birth outcomes. We investigated whether community-informed home visiting programs achieve high rates of service coverage in highly deprived neighborhoods and can attenuate the deleterious effect of neighborhood polarization on birth outcomes.

Conventional versus minimally invasive extra-corporeal circulation in patients undergoing cardiac surgery: A randomized controlled trial (COMICS).

Introduction: The trial hypothesized that minimally invasive extra-corporeal circulation (MiECC) reduces the risk of serious adverse events (SAEs) after cardiac surgery operations requiring extra-corporeal circulation without circulatory arrest.

Methods: This is a multicentre, international randomized controlled trial across fourteen cardiac surgery centres including patients aged ≥18 and <85 years undergoing elective or urgent isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR) surgery, or CABG + AVR surgery. Participants were randomized to MiECC or conventional extra-corporeal circulation (CECC), stratified by centre and operation.