Evolutionary and Functional Analysis of Monoamine Oxidase F (MAO F): A Novel Member of the MAO Gene Family.

The monoamine oxidase (MAO) gene family encodes for enzymes that perform the oxidative deamination of monoamines, a process required to degrade norepinephrine, serotonin, dopamine, and other amines. While mammalian MAO enzymes, MAO A and MAO B, have been extensively studied, the molecular properties of the other family members are only partly uncovered. This study aims to explore the evolution of monoamine oxidases, emphasizing understanding the MAO gene repertoire among vertebrates.

Genetic and Phenotypic Intra-Clade Variation in Candida auris Isolated from Critically Ill Patients in a New York City Tertiary Care Center.

Background: Candida auris is an emerging multidrug-resistant pathogen. Interpretation of susceptibility testing can be difficult since minimum inhibitory concentration (MIC) breakpoints have not been fully established.

Methods: All C.

Standardization of Genomic Nomenclature across a Diverse Ecosystem of Stakeholders: Evolution and Challenges.

Background: Genetic testing has traditionally been divided into molecular genetics and cytogenetics, originally driven by the use of different assays and their associated limitations. Cytogenetic technologies such as karyotyping, fluorescent in situ hybridization or chromosomal microarrays are used to detect large "megabase level" copy number variants and other structural variants such as inversions or translocations. In contrast, molecular methodologies are heavily biased toward subgenic "small variants" such as single nucleotide variants, insertions/deletions, and targeted detection of intragenic, exon level deletions or duplications.

Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling.

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls.

The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.

Association between genetically predicted leisure and social activities and cardiovascular disease and other health outcomes.

Participation in leisure and social activities (LSA) is associated with better health outcomes and lower mortality. Previous observational studies demonstrated a relationship between engagement in LSA and both mental and physical health. Although several studies examined the association between LSA and health outcomes, including cardiovascular disease, their possible causal relationship has not been studied.

System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans.

We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity.

A stromal inflammasome Ras safeguard against Myc-driven lymphomagenesis.

The inflammasome plays multifaceted roles in cancer, but less is known about its function during premalignancy upon initial cell transformation. We report a homeostatic function of the inflammasome in suppressing malignant transformation through Ras inhibition. We identified increased hematopoietic stem cell (HSC) proliferation within the bone marrow of inflammasome-deficient mice.

A new class of natural anthelmintics targeting lipid metabolism.

Parasitic helminths are a major global health threat, infecting nearly one-fifth of the human population and causing significant losses in livestock and crops. Resistance to the few anthelmintic drugs is increasing. Here, we report a set of avocado fatty alcohols/acetates (AFAs) that exhibit nematocidal activity against four veterinary parasitic nematode species: Brugia pahangi, Teladorsagia circumcincta and Heligmosomoides polygyrus, as well as a multidrug resistant strain (UGA) of Haemonchus contortus.

H3K56 acetylation regulates chromatin maturation following DNA replication.

Following DNA replication, the newly reassembled chromatin is disorganized and must mature to its steady state to maintain both genome and epigenome integrity. However, the regulatory mechanisms governing this critical process remain poorly understood. Here, we show that histone H3K56 acetylation (H3K56ac), a mark on newly-synthesized H3, facilitates the remodeling of disorganized nucleosomes in nascent chromatin, and its removal at the subsequent G2/M phase of the cell cycle marks the completion of chromatin maturation.

A deep multiple instance learning framework improves microsatellite instability detection from tumor next generation sequencing.

Microsatellite instability (MSI) is a critical phenotype of cancer genomes and an FDA-recognized biomarker that can guide treatment with immune checkpoint inhibitors. Previous work has demonstrated that next-generation sequencing data can be used to identify samples with MSI-high phenotype. However, low tumor purity, as frequently observed in routine clinical samples, poses a challenge to the sensitivity of existing algorithms.

STAT1 regulates immune-mediated intestinal stem cell proliferation and epithelial regeneration.

The role of the immune system in regulating tissue stem cells remains poorly understood, as does the relationship between immune-mediated tissue damage and regeneration. Graft vs. host disease (GVHD) occurring after allogeneic bone marrow transplantation (allo-BMT) involves immune-mediated damage to the intestinal epithelium and its stem cell compartment.

Mms22-Rtt107 axis attenuates the DNA damage checkpoint and the stability of the Rad9 checkpoint mediator.

The DNA damage checkpoint is a highly conserved signaling pathway induced by genotoxin exposure or endogenous genome stress. It alters many cellular processes such as arresting the cell cycle progression and increasing DNA repair capacities. However, cells can downregulate the checkpoint after prolonged stress exposure to allow continued growth and alternative repair.

Cardiac MRI Evaluation of Determinants and Prognostic Implications of Right Ventricular Dysfunction in Aortic Regurgitation.

Purpose To investigate the determinants and effect of right ventricular (RV) dysfunction in aortic regurgitation (AR) using cardiac MRI. Materials and Methods This study included patients with moderate or severe AR who were enrolled in the DEBAKEY-CMR registry between January 2009 and June 2020. Patients with previous valve intervention, cardiomyopathy deemed unrelated to AR, severe aortic stenosis, and other confounders were excluded.

Identification of Transdiagnostic Childhood Externalizing Pathology Within an Electronic Medical Records Database and Application to the Analysis of Rare Copy Number Variation.

Externalizing traits and behaviors are broadly defined by impairments in self-regulation and impulse control that typically begin in childhood and adolescence. Externalizing behaviors, traits, and symptoms span a range of traditional psychiatric diagnostic categories. In this study, we sought to generate an algorithm that could reliably identify transdiagnostic childhood-onset externalizing cases and controls within a university hospital electronic health record (EHR) database.

The impact of interethnic lipidomic variation in falciparum malaria.

Background: Shifts in dietary patterns during lifestyle transitions are integral components of the dynamic interactions between humans and their environments. Investigating the link between dietary diversity, the composition of the human lipidome and infection is key to understanding the interplay between diet and susceptibility to pathogens.

Methods: Here we address this question by performing a comparative study of two ethnic groups with divergent dietary patterns: Fulani, who are nomad pastoralists with a dairy-centric diet, and Mossi, who are farmers with a plant-based diet.

Whole Genome Sequencing Reveals Substantial Genetic Structure and Evidence of Local Adaptation in Alaskan Red King Crab.

High-latitude ocean basins are the most productive on earth, supporting high diversity and biomass of economically and socially important species. A long tradition of responsible fisheries management has sustained these species for generations, but modern threats from climate change, habitat loss, and new fishing technologies threaten their ecosystems and the human communities that depend on them. Among these species, Alaska's most charismatic megafaunal invertebrate, the red king crab, faces all three of these threats and has declined substantially in many parts of its distribution.