Tracking Immunity: An Increased Number of COVID-19 Boosters Increases the Longevity of Anti-RBD and Anti-RBD-Neutralizing Antibodies.

Background/objectives: Since the World Health Organization declared COVID-19 a pandemic in March 2020, the virus has caused multiple waves of infection globally. Arizona State University (ASU), the largest four-year university in the United States, offers a uniquely diverse setting for assessing immunity within a large community. This study aimed to test our hypothesis that an increased number of exposures to SARS-CoV-2 RBD through vaccination/boosters/infection will increase SARS-CoV-2 antibody seroprevalence by increasing the longevity of anti-RBD and anti-RBD-neutralizing antibodies.

The omicron variant of SARS-CoV-2 drove broadly increased seroprevalence in a public university setting.

Omicron is the comparatively most transmissible and contagious variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). We conducted a seroprevalence study from March 1-3, 2022, to investigate the seroprevalence of SARS-CoV-2 antibodies among individuals aged 18 years and older after the Omicron outbreak. The seroprevalence of anti-receptor binding domain (RBD) antibodies was found to be 96.

Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft Partitioning.

Development of an understanding of membrane nanodomains colloquially known as "lipid rafts" has been hindered by a lack of pharmacological tools to manipulate rafts and protein affinity for rafts. We screened 24,000 small molecules for modulators of the affinity of peripheral myelin protein 22 (PMP22) for rafts in giant plasma membrane vesicles (GPMVs). Hits were counter-screened against another raft protein, MAL, and tested for impact on raft , leading to two classes of compounds.

Leukemia-mutated proteins PHF6 and PHIP form a chromatin complex that represses acute myeloid leukemia stemness.

Myeloid leukemias are heterogeneous cancers with diverse mutations, sometimes in genes with unclear roles and unknown functional partners. PHF6 and PHIP are two poorly-understood chromatin-binding proteins recurrently mutated in acute myeloid leukemia (AML). mutations are associated with poorer outcomes, while was recently identified as the most common selective mutation in Black patients in AML.

Testing Oncolytic Myxoma Virus in Immunocompetent Mouse Model for Cancer Therapy.

Oncolytic viruses (OVs) have emerged as a class of novel cancer immunotherapeutic. Members of both DNA and RNA viruses developed as OVs for treating diverse types of human cancers. Preclinical research assessing immunotherapeutic efficacy is an essential step toward further development of these OVs.

Adipose-Derived Stem Cells as Carrier of Pro-Apoptotic Oncolytic Myxoma Virus: To Cross the Blood-Brain Barrier and Treat Murine Glioma.

Treatment of glioblastoma is ineffective. Myx-M011L-KO/EGFP, a myxoma virus actively inducing apoptosis in BTICs linked to recurrence, offers innovative treatment. We loaded this construct into adipose-derived stem cells (ADSCs) to mitigate antiviral host responses and enable systemic delivery.

Integrated epigenomic exposure signature discovery.

The epigenome influences gene regulation and phenotypes in response to exposures. Epigenome assessment can determine exposure history aiding in diagnosis. Here we developed and implemented a machine learning algorithm, the exposure signature discovery algorithm (ESDA), to identify the most important features present in multiple epigenomic and transcriptomic datasets to produce an integrated exposure signature (ES).

Microbial Ecology and Metabolism of Emerging Adulthood: Gut Microbiome Insights from a College Freshman Cohort.

The human gut microbiome (GM) undergoes dynamic changes throughout life, transitioning from infancy to adulthood. Despite improved understanding over the past years about how genetics, lifestyle, and the external environment impact the GM, limited research has explored the GM's evolution during late-stage adolescence, especially among college students. This study addresses this gap by investigating the longitudinal dynamics of fecal microbial, functional, and metabolomic signatures in a diverse group of first-year, dormitory-housed college students.

Transcriptional regulation of the postnatal cardiac conduction system heterogeneity.

The cardiac conduction system (CCS) is a network of specialized cardiomyocytes that coordinates electrical impulse generation and propagation for synchronized heart contractions. Although the components of the CCS, including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers, were anatomically discovered more than 100 years ago, their molecular constituents and regulatory mechanisms remain incompletely understood. Here, we demonstrate the transcriptomic landscape of the postnatal mouse CCS at a single-cell resolution with spatial information.

Artificial Intelligence in Metabolomics: A Current Review.

Metabolomics and artificial intelligence (AI) form a synergistic partnership. Metabolomics generates large datasets comprising hundreds to thousands of metabolites with complex relationships. AI, aiming to mimic human intelligence through computational modeling, possesses extraordinary capabilities for big data analysis.

Wastewater and clinical surveillance of respiratory viral pathogens on a university campus.

Areas of dense population congregation are prone to experience respiratory virus outbreaks. We monitored wastewater and clinic patients for the presence of respiratory viruses on a large, public university campus. Campus sewer systems were monitored in 16 locations for the presence of viruses using next generation sequencing over 22 weeks in 2023.

Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator.

The urokinase-type plasminogen activator receptor (uPAR) is a unique protease binding receptor, now recognized as a key regulator of inflammation. Initially, uPA/uPAR was considered thrombolytic (clot-dissolving); however, recent studies have demonstrated its predominant immunomodulatory functions in inflammation and cancer. The uPA/uPAR complex has a multifaceted central role in both normal physiological and also pathological responses.

Late-Season Influenza Vaccine Effectiveness Against Medically Attended Outpatient Illness, United States, December 2022-April 2023.

Background: The 2022-23 US influenza season peaked early in fall 2022.

Methods: Late-season influenza vaccine effectiveness (VE) against outpatient, laboratory-confirmed influenza was calculated among participants of the US Influenza VE Network using a test-negative design.

Results: Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory-confirmed influenza cases primarily had A(H1N1)pdm09 (6B.

Evidence that the cold- and menthol-sensing functions of the human TRPM8 channel evolved separately.

Transient receptor potential melastatin 8 (TRPM8) is a temperature- and menthol-sensitive ion channel that contributes to diverse physiological roles, including cold sensing and pain perception. Clinical trials targeting TRPM8 have faced repeated setbacks predominantly due to the knowledge gap in unraveling the molecular underpinnings governing polymodal activation. A better understanding of the molecular foundations between the TRPM8 activation modes may aid the development of mode-specific, thermal-neutral therapies.

CountASAP: A Lightweight, Easy to Use Python Package for Processing ASAPseq Data.

Declining sequencing costs coupled with the increasing availability of easy-to-use kits for the isolation of DNA and RNA transcripts from single cells have driven a rapid proliferation of studies centered around genomic and transcriptomic data. Simultaneously, a wealth of new techniques have been developed that utilize single cell technologies to interrogate a broad range of cell-biological processes. One recently developed technique, transposase-accessible chromatin with sequencing (ATAC) with select antigen profiling by sequencing (ASAPseq), provides a combination of chromatin accessibility assessments with measurements of cell-surface marker expression levels.

Influenza Virus Genomic Surveillance, Arizona, USA, 2023-2024.

Influenza viruses are constantly evolving and are therefore monitored worldwide in the hope to reduce the burden of disease by annual updates to vaccine recommendations. We conducted genomic sequencing of 110 influenza A and 30 influenza B viruses from specimens collected between October 2023 and February 2024 in Arizona, USA. We identified mutations in the hemagglutinin (HA) antigenic sites as well as the neuraminidase (NA) gene in our samples.

Incremental increases in physiological fluid shear progressively alter pathogenic phenotypes and gene expression in multidrug resistant .

The ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant .

Shape restricted additive hazards models: Monotone, unimodal, and U-shape hazard functions.

We consider estimation of the semiparametric additive hazards model with an unspecified baseline hazard function where the effect of a continuous covariate has a specific shape but otherwise unspecified. Such estimation is particularly useful for a unimodal hazard function, where the hazard is monotone increasing and monotone decreasing with an unknown mode. A popular approach of the proportional hazards model is limited in such setting due to the complicated structure of the partial likelihood.

Surgically repaired tetralogy of Fallot in the 7th decade: a late presentation of severe pulmonic regurgitation.

Background: Surgically repaired tetralogy of Fallot (TOF) is a congenital heart disease with a cumulative survival rate of 72% in the 4th decade of life in longitudinal single-cohort studies. Debate surrounds conservative versus surgical management in adults with TOF once pulmonary regurgitation occurs.

Case Presentation: A 73-year-old male with surgically corrected TOF presented with heart failure symptoms.

SIRT1 Coordinates Transcriptional Regulation of Neural Activity and Modulates Depression-Like Behaviors in the Nucleus Accumbens.

Background: Major depression and anxiety disorders are significant causes of disability and socioeconomic burden. Despite the prevalence and considerable impact of these affective disorders, their pathophysiology remains elusive. Thus, there is an urgent need to develop novel therapeutics for these conditions.