Methods for Modeling Early Life Stress in Rodents.

Animal models of early life stress/adversity (ELS) have provided a foundation from which our understanding of the psychoneuroimmunology of childhood trauma has expanded over recent decades. Rodent models are a cornerstone of the ELS literature with many studies utilizing paradigms based on early life separation/deprivation protocols and manipulating the cage environment. However, no animal model is perfect.

Mitochondrial Functioning: Front and Center in Defining Psychosomatic Mechanisms of Allostasis in Health and Disease.

There is increased awareness among basic and clinical scientists that psychological and social stress can have detrimental effects on physical, cognitive, and mental health. Data have been published indicating that social, economic, psychological, and physical environmental stress can influence behavior that has biological and physiological consequences-yet there are major gaps in understanding the physiological and cellular processes that drive increased morbidity and mortality. The potential role of mitochondria has been highlighted in psychosomatic medicine, as their functionality in various biological and physiological processes has earned recognition.

Novel Small Molecules with Anti-Inflammatory and Anti-Angiogenic Activity in a Mouse Model of Oxygen-Induced Retinopathy.

Retinopathy of prematurity (ROP) has a dual-phase disease pathology; in phase 1, hyperoxia-induced vaso-obliteration occurs in the retinal vasculature due to increased oxidative stress (OS) and inflammation, followed by phase 2, where hypoxia increases the overproduction of growth factors, inducing retinal neovascularization. Toll-like receptor 2 and -4 (TLR2 and TLR4) overactivation, hyper-inflammation, macrophages, and neutrophil infiltration contribute to the developing ROP. AVR-121 and AVR-123 are novel classes of small-molecule dual inhibitors of TLR2/4 tested in a human leukemia monocytic cell line (THP-1) and cord-blood-derived mononuclear cells (CBMCs).

Influence of Diet on Reproducible Corticosterone Levels in a Mouse Model of Maternal Separation with Early Weaning.

Maternal separation with early weaning (MSEW) is a popular early life stress (ELS) model in rodents, which emulates childhood neglect through scheduled mother-offspring separation. Although variations of ELS models, including maternal separation and MSEW, have been published for the mouse species, the reported results are inconsistent. Corticosterone is considered the main stress hormone involved in regulating stress responses in rodents-yet generating a robust and reproducible corticosterone response in mouse models of ELS has been elusive.

Short peptides based on the conserved regions of MIEN1 protein exhibit anticancer activity by targeting the MIEN1 signaling pathway.

Migration and invasion enhancer 1 (MIEN1) overexpression characterizes several cancers and facilitates cancer cell migration and invasion. Leveraging conserved immunoreceptor tyrosine-based activation motif and prenylation motifs within MIEN1, we identified potent anticancer peptides. Among them, bioactive peptides LA3IK and RP-7 induced pronounced transcriptomic and protein expression changes at sub-IC50 concentrations.

Surgical Primary Tumor Resection Reduces Accumulation of CD11b Myeloid Cells in the Lungs Augmenting the Efficacy of an Intranasal Cancer Vaccination against Secondary Lung Metastasis.

A hallmark of effective cancer treatment is the prevention of tumor reoccurrence and metastasis to distal organs, which are responsible for most cancer deaths. However, primary tumor resection is expected to be curative as most solid tumors have been shown both experimentally and clinically to accelerate metastasis to distal organs including the lungs. In this study, we evaluated the efficacy of our engineered nasal nano-vaccine (CpG-NP-Tag) in reducing accelerated lung metastasis resulting from primary tumor resection.

Mitochondrial SOS: how mtDNA may act as a stress signal in Alzheimer's disease.

Background: Alterations in mitochondrial DNA (mtDNA) levels have been observed in Alzheimer's disease and are an area of research that shows promise as a useful biomarker. It is well known that not only are the mitochondria a key player in producing energy for the cell, but they also are known to interact in other important intracellular processes as well as extracellular signaling and communication. BODY: This mini review explores how cells use mtDNA as a stress signal, particularly in Alzheimer's disease.

Integrative blood-based characterization of oxidative mitochondrial DNA damage variants implicates Mexican American's metabolic risk for developing Alzheimer's disease.

Alzheimer's Disease (AD) continues to be a leading cause of death in the US. As the US aging population (ages 65 +) expands, the impact will disproportionately affect vulnerable populations, e.g.

Integrative Blood-Based Characterization of Oxidative Mitochondrial DNA Damage Variants Implicates Mexican Americans' Metabolic Risk for Developing Alzheimer's Disease.

Alzheimer's Disease (AD) continues to be a leading cause of death in the US. As the US aging population (ages 65+) expands, the impact will disproportionately affect vulnerable populations, e.g.

Nasal Tumor Vaccination Protects against Lung Tumor Development by Induction of Resident Effector and Memory Anti-Tumor Immune Responses.

Lung metastasis is a leading cause of cancer-related deaths. Here, we show that intranasal delivery of our engineered CpG-coated tumor antigen (Tag)-encapsulated nanoparticles (NPs)-nasal nano-vaccine-significantly reduced lung colonization by intravenous challenge of an extra-pulmonary tumor. Protection against tumor-cell lung colonization was linked to the induction of localized mucosal-associated effector and resident memory T cells as well as increased bronchiolar alveolar lavage-fluid IgA and serum IgG antibody responses.

Combination of Small Extracellular Vesicle-Derived Annexin A2 Protein and mRNA as a Potential Predictive Biomarker for Chemotherapy Responsiveness in Aggressive Triple-Negative Breast Cancer.

Small extracellular vesicles (sEVs), mainly exosomes, are nanovesicles that shed from the membrane as intraluminal vesicles of the multivesicular bodies, serve as vehicles that carry cargo influential in modulating the tumor microenvironment for the multi-step process of cancer metastasis. Annexin A2 (AnxA2), a calcium(Ca)-dependent phospholipid-binding protein, is among sEV cargoes. sEV-derived AnxA2 (sEV-AnxA2) protein is involved in the process of metastasis in triple-negative breast cancer (TNBC).

Religious service attendance and mortality among older Black men.

Religious institutions have been responsive to the needs of Black men and other marginalized populations. Religious service attendance is a common practice that has been associated with stress management and extended longevity. The objective of this study was to examine the relationship between religious service attendance and all-cause mortality among Black men 50 years of age and older.

The Minority Scientists' Experience: Challenging and Overcoming Barriers to Enhancing Diversity and Career Advancement.

Minority groups face barriers in accessing quality health care, professional advancement, and representation in immunology research efforts as a result of institutional racism that if unaddressed can perpetuate a lack of diversity. In 2021, the AAI Minority Affairs Committee convened a cross section of academic and industry scientists from underrepresented groups at various stages of their professions to discuss how best to address the toll racism takes on study design and scientific careers. Panelists drew directly from their own experiences as scientists to share perspectives and strategies for countering a lack of representation in clinical research, responding to microaggressions, navigating academic advancement, and providing effective mentorship.

Variations of a group coaching intervention to support early-career biomedical researchers in Grant proposal development: a pragmatic, four-arm, group-randomized trial.

Background: Funded grant proposals provide biomedical researchers with the resources needed to build their research programs, support trainees, and advance public health. Studies using National Institutes of Health (NIH) data have found that investigators from underrepresented groups in the biomedical workforce are awarded NIH research grants at disproportionately lower rates. Grant writing training initiatives are available, but there is a dearth of rigorous research to determine the effectiveness of such interventions and to discern their essential features.

The Association Between NRMN STAR Grantsmanship Self-Efficacy and Grant Submission.

Background: Eliminating the NIH funding gap among underrepresented minorities (URMs) remains a high priority for the National Institutes of Health. In 2014, the National Research Mentoring Network Steps Toward Academic Research (NRMN STAR) program recruited postdoctoral, early-stage and junior faculty to participate in a 12-month grant writing and professional development program. The expectation of the program was to increase the number of grant submissions and awards to URM researchers.

The Many Faces of Innate Immunity in SARS-CoV-2 Infection.

The innate immune system is important for initial antiviral response. SARS-CoV-2 can result in overactivity or suppression of the innate immune system. A dysregulated immune response is associated with poor outcomes; with patients having significant Neutrophil-to-Lymphocyte ratios (NLR) due to neutrophilia alongside lymphopenia.

The National Institute of Neurological Disorders and Stroke's efforts on diversifying the neuroscience research workforce.

Research innovation that leads to discovery in the battle against neurological disease and disorders requires diverse ideas. The National Institute of Neurological Disorders and Stroke, one of the National Institutes of Health's 27 institutes and centers, strives to reduce the burden of neurological disease and disorders. The National Institutes of Neurologic Disorders and Stroke is very interested in increasing the diversity of researchers by addressing the existing barriers responsible for the low numbers of underrepresented populations from traditionally minority-serving institutions (MSIs) and non-minority serving institutions (non-MSIs).

The Association Between Depressive Symptoms and Accumulation of Stress Among Black Men in the Health and Retirement Study.

Background And Objectives: Among the multiple factors posited to drive the health inequities that black men experience, the fundamental role of stress in the production of poor health is a key component. Allostatic load (AL) is considered to be a byproduct of stressors related to cumulative disadvantage. Exposure to chronic stress is associated with poorer mental health including depressive symptoms.

Grant application outcomes for biomedical researchers who participated in the National Research Mentoring Network's Grant Writing Coaching Programs.

Background: A diverse research workforce is essential for catalyzing biomedical advancements, but this workforce goal is hindered by persistent sex and racial/ethnic disparities among investigators receiving research grants from the National Institutes of Health (NIH). In response, the NIH-funded National Research Mentoring Network implemented a Grant Writing Coaching Program (GCP) to provide diverse cohorts of early-career investigators across the United States with intensive coaching throughout the proposal development process. We evaluated the GCP's national reach and short-term impact on participants' proposal submissions and funding outcomes.

Understanding the Interplay Between Health Disparities and Epigenomics.

Social epigenomics has emerged as an integrative field of research focused on identification of socio-environmental factors, their influence on human biology through epigenomic modifications, and how they contribute to current health disparities. Several health disparities studies have been published using genetic-based approaches; however, increasing accessibility and affordability of molecular technologies have allowed for an in-depth investigation of the influence of external factors on epigenetic modifications (e.g.

The Perfect Storm: COVID-19 Health Disparities in US Blacks.

Coronavirus disease 2019 (COVID-19) accounts for over 180,000 deaths in the USA. Although COVID-19 affects all racial ethnicities, non-Hispanic Blacks have the highest mortality rates. Evidence continues to emerge, linking the disproportion of contagion and mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a result of adverse social determinants of health.

The Impact of Grantsmanship Self-Efficacy on Early Stage Investigators of The National Research Mentoring Network Steps Toward Academic Research (NRMN STAR).

The NRMN STAR program was created to address the persistent underrepresentation in grant submissions and receipt of National Institutes of Health (NIH) awards by racial/ethnic minority groups. In our current study, we assessed program impact on trainees' self-efficacy related to grant writing. The program was conducted with two cohorts: one in June 2014 and one in June 2015.

Preparing the Next Generation of Diverse Biomedical Researchers: The University of North Texas Health Science Center's Initiative for Maximizing Student Development (IMSD) Predoctoral Program.

The National Science Foundation (NSF) reports that underrepresented minority students are just as interested as their White counterparts in majoring in science upon entering college.1 However, the numbers of those receiving bachelors' degrees, attending graduate school, and earning doctorates remain lower than their White peers. To close this gap, the National Institutes of General Medical Science's (NIGMS) Initiative for Maximizing Student Development (IMSD) at University of Texas Health Science Center (UNTHSC) supports the timely completion of PhD degrees by underrepresented students and their transition into successful biomedical research careers.