Tandem duplication of serpin genes yields functional variation and snake venom inhibitors.

Tandem duplication of genes can play a critical role in the evolution of functional novelty, but our understanding is limited concerning gene duplication's role in coevolution between species. Much is known about the evolution and function of tandemly duplicated snake venom genes, however the potential of gene duplication to fuel venom resistance within prey species is poorly understood. In this study, we characterize patterns of gene duplication of the SERPINA subfamily of genes across in vertebrates and experimentally characterize functional variation in the SERPINA3-like paralogs of a wild rodent.

Willingness to Use Oral and Long-Acting Injectable PrEP in Substance-Using Men who have Sex with Men (SU-MSM) in High HIV Incidence Southern U.S. Cities: A NIDA Clinical Trials Network Study.

In Southern U.S. states with high HIV incidence and low HIV Pre-Exposure Prophylaxis (PrEP) uptake, enhanced efforts to increase interest in and willingness to use PrEP are needed.

Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.

Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV).

High-throughput amino acid-level characterization of the interactions of plasminogen activator inhibitor-1 with variably divergent proteases.

While members of large paralogous protein families share structural features, their functional niches often diverge significantly. Serine protease inhibitors (SERPINs), whose members typically function as covalent inhibitors of serine proteases, are one such family. Plasminogen activator inhibitor-1 (PAI-1) is a prototypic SERPIN, which canonically inhibits tissue-and urokinase-type plasminogen activators (tPA and uPA) to regulate fibrinolysis.

Peer Intervention to Link Overdose Survivors to Treatment (PILOT): Protocol for a Multisite, Randomized Controlled Trial Conducted Within the National Institute on Drug Abuse Clinical Trials Network.

Background: The increase in opioid-related overdoses has caused a decrease in average life expectancy, highlighting the need for effective interventions to reduce overdose risk and prevent subsequent overdoses. Peer support specialists (PSSs) offer an appealing strategy to engage overdose survivors and reduce overdose risk, but randomized controlled trials are needed to formalize peer-led interventions and evaluate their effectiveness.

Objective: This National Institute on Drug Abuse Clinical Trials Network (CTN) study is a multisite, prospective, pilot randomized (1:1) controlled trial (CTN protocol 0107) that aims to evaluate the effectiveness of an emergency department (ED)-initiated, peer-delivered intervention tailored for opioid overdose survivors (Peer Intervention to Link Overdose survivors to Treatment [PILOT]), compared with treatment as usual (TAU).

Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function.

A key challenge in aging research is extending lifespan in tandem with slowing down functional decline so that life with good health (healthspan) can be extended. Here, we show that monthly clearance, starting from 20 months, of a small number of cells that highly express p21 (p21) improves cardiac and metabolic function and extends both median and maximum lifespans in mice. Importantly, by assessing the health and physical function of these mice monthly until death, we show that clearance of p21 cells improves physical function at all remaining stages of life, suggesting healthspan extension.

UBXN3B is crucial for B lymphopoiesis.

Background: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity.

Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.

Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV).

Cellular senescence is a double-edged sword in regulating aged immune responses to influenza.

Clearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection.

Lipid Droplets: Formation, Degradation, and Their Role in Cellular Responses to Flavivirus Infections.

Lipid droplets (LDs) are cellular organelles derived from the endoplasmic reticulum (ER), serving as lipid storage sites crucial for maintaining cellular lipid homeostasis. Recent attention has been drawn to their roles in viral replication and their interactions with viruses. However, the precise biological functions of LDs in viral replication and pathogenesis remain incompletely understood.

Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis.

Little is known about the prevalence of cellular senescence among immune cells (i.e., immune cells expressing senescence markers, iSCs) nor is there a gold-standard to efficiently measure iSCs.

Characterization of peer support services for substance use disorders in 11 US emergency departments in 2020: findings from a NIDA clinical trials network site selection process.

Introduction: Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs.

"What Matters to You?": A Participant-Centered Approach to Needs Identification and Referral to Community Resources.

Objective: Referral to social and health services is a core process of the Special Supplemental Nutrition Program for Women, Infants and Children (WIC). We evaluate the feasibility and acceptability of a referral innovation implemented at two New York City WIC sites. This program aimed to improve retention by increasing WIC's perceived value by addressing unmet needs of WIC families.

Investigating the phylogenetic history of toxin tolerance in mushroom-feeding .

Understanding how and when key novel adaptations evolved is a central goal of evolutionary biology. Within the radiation of , many mushroom-feeding species are tolerant of host toxins, such as cyclopeptides, that are lethal to nearly all other eukaryotes. In this study, we used phylogenetic and functional approaches to investigate the evolution of cyclopeptide tolerance in the radiation of .

Toward a Cenozoic history of atmospheric CO.

The geological record encodes the relationship between climate and atmospheric carbon dioxide (CO) over long and short timescales, as well as potential drivers of evolutionary transitions. However, reconstructing CO beyond direct measurements requires the use of paleoproxies and herein lies the challenge, as proxies differ in their assumptions, degree of understanding, and even reconstructed values. In this study, we critically evaluated, categorized, and integrated available proxies to create a high-fidelity and transparently constructed atmospheric CO record spanning the past 66 million years.

Improving Asthma Action Plan Completion Rates across Five Divisions in an Academic Children's Hospital.

Introduction: Asthma is the most common chronic disease among children. Asthma Action Plans (AAPs) enable asthma self-management tailored to each patient and should be updated annually. At our institution, providers face challenges in creating reliable processes to consistently complete AAPs for patients with asthma.

Impact of senolytic treatment on immunity, aging, and disease.

Cellular senescence has been implicated in the pathophysiology of many age-related diseases. However, it also plays an important protective role in the context of tumor suppression and wound healing. Reducing senescence burden through treatment with senolytic drugs or the use of genetically targeted models of senescent cell elimination in animals has shown positive results in the context of mitigating disease and age-associated inflammation.

Trends in Self-Reported Fentanyl and Other Illicit Substance Use in South Carolina Emergency Department Patients, 2020-2022.

Background: Opioid-involved deaths are continuing to increase across the United States, exceeding 100,000 for the first time in 2021. Contamination with, and intentional use of, synthetic opioids such as fentanyl are a major driver of this increase. Utilizing self-report substance use data of patients being treated in the emergency department (ED) can be useful to determine which substances patients are intentionally seeking.

A study protocol for Project I-Test: a cluster randomized controlled trial of a practice coaching intervention to increase HIV testing in substance use treatment programs.

Background: People with substance use disorders are vulnerable to acquiring HIV. Testing is fundamental to diagnosis, treatment, and prevention; however, in the past decade, there has been a decline in the number of substance use disorder (SUD) treatment programs offering on-site HIV testing. Fewer than half of SUDs in the USA offer on-site HIV testing.

Investigating the phylogenetic history of toxin tolerance in mushroom-feeding .

Understanding how and when key novel adaptations evolved is a central goal of evolutionary biology. Within the radiation of , many mushroom-feeding species are tolerant of host toxins, such as cyclopeptides, that are lethal to nearly all other eukaryotes. In this study, we used phylogenetic and functional approaches to investigate the evolution of cyclopeptide tolerance in the radiation of .

A study protocol for Project I-Test: a cluster randomized controlled trial of a practice coaching intervention to increase HIV testing in substance use treatment programs.

People with substance use disorders are vulnerable to acquiring HIV. Testing is fundamental to diagnosis, treatment, and prevention; however, in the past decade, there has been a decline in the number of substance use disorder (SUD) treatment programs offering on-site HIV testing. Fewer than half of SUDs in the United States offer on-site HIV testing.

Helical TomoTherapy Total Lymphoid Irradiation and Hematopoietic Cell Transplantation for Kidney Transplant Tolerance in Rhesus Macaques.

Development of a post-transplant kidney transplant tolerance induction protocol involving a novel total lymphoid irradiation (TLI) conditioning method in a rhesus macaque model is described. We examined the feasibility of acheiving tolerance to MHC 1-haplotype matched kidney transplants by establishing a mixed chimeric state with infusion of donor hematopoietic cells (HC) using TomoTherapy TLI. The chimeric state was hypothesized to permit the elimination of all immunosuppressive (IS) medications while preserving allograft function long-term without development of graft-versus-host-disease (GVHD) or rejection.

Senolytic treatment with dasatinib and quercetin does not improve overall influenza responses in aged mice.

Age is the greatest risk factor for adverse outcomes following influenza (flu) infection. The increased burden of senescent cells with age has been identified as a root cause in many diseases of aging and targeting these cells with drugs termed senolytics has shown promise in alleviating many age-related declines across organ systems. However, there is little known whether targeting these cells will improve age-related deficits in the immune system.