Role of the Senescence-Associated Factor Dipeptidyl Peptidase 4 in the Pathogenesis of SARS-CoV-2 Infection.

During cellular senescence, persistent growth arrest and changes in protein expression programs are accompanied by a senescence-associated secretory phenotype (SASP). In this study, we detected the upregulation of the SASP-related protein dipeptidyl peptidase 4 (DDP4) in human primary lung cells rendered senescent by exposure to ionizing radiation. DPP4 is an exopeptidase that plays a crucial role in the cleavage of various proteins, resulting in the loss of N-terminal dipeptides and proinflammatory effects.

Paternal obesity induces epigenetic aberrations and gene expression changes in placenta and fetus.

Paternal epigenome regulates placental and fetal growth. However, the effect of paternal obesity on placenta and its subsequent effect on the fetus via sperm remains unknown. We previously discovered abnormal methylation of imprinted genes involved in placental and fetal development in the spermatozoa of obese rats.

Risk Factors for Hospital-Acquired Pressure Injury in Adult Critical Care Patients.

Background: Accurately measuring the risk of pressure injury remains the most important step for effective prevention and intervention. Relative contributions of risk factors for the incidence of pressure injury in adult critical care patients are not well understood.

Objective: To develop and validate a model to identify risk factors associated with hospital-acquired pressure injuries among adult critical care patients.

Diet-induced- and genetic-obesity differentially alters male germline histones.

Obesity, an established risk factor for male subfertility or infertility, is primarily due to genetic and environmental causes. Our earlier studies have shown differential effects of high-fat diet-induced- (DIO) and genetically inherited- (GIO) obesity on DNA methylation in male germline and its subsequent effect on fertility. Here, we hypothesized that the effects of DIO and GIO on histone modifications in male germline could also contribute to fertility defects.

High fat diet-induced- and genetically inherited- obesity differential alters DNA demethylation pathways in the germline of adult male rats.

Obesity is a multifactorial condition with predominantly genetic and environmental causes and is an emerging risk factor for male infertility/subfertility. Epigenetic mechanisms are vulnerable to genetic and environmental changes. Our earlier studies have shown differential effects of genetically inherited (GIO) - and diet-induced- obesity (DIO) on DNA methylation in male germline.

The Transmission of SARS-CoV-2 Infection on the Ocular Surface and Prevention Strategies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health problem. Although the respiratory system is the main impaired organ, conjunctivitis is one of its common findings. However, it is not yet understood if SARS-CoV-2 can infect the eye and if the ocular surface can be a potential route of SARS-CoV-2 transmissions.

Sex hormones regulate lipid metabolism in adult Sertoli cells: A genome-wide study of estrogen and androgen receptor binding sites.

Optimal functioning of Sertoli cells is crucial for spermatogenesis which is under tight regulation of sex hormones, estrogen and androgen. Adult rat Sertoli cells expresses estrogen receptor beta (ERβ) and androgen receptor (AR), both of which regulate gene transcription by binding to the DNA. The present study is aimed to acquire a genome-wide map of estrogen- and androgen-regulated genes in adult Sertoli cells.

Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis.

Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation, and many age-related pathologies. By contrast, lipid components of the SASP are understudied.

Young at Gut-Turning Back the Clock with the Gut Microbiome.

Over the past century, we have witnessed an increase in life-expectancy due to public health measures; however, we have also seen an increase in susceptibility to chronic disease and frailty. Microbiome dysfunction may be linked to many of the conditions that increase in prevalence with age, including type 2 diabetes, cardiovascular disease, Alzheimer's disease, and cancer, suggesting the need for further research on these connections. Moreover, because both non-modifiable (e.

Effect of an Adenovirus-Vectored Universal Influenza Virus Vaccine on Pulmonary Pathophysiology in a Mouse Model.

Current influenza vaccines, live attenuated or inactivated, do not protect against antigenically novel influenza A viruses (IAVs) of pandemic potential, which has driven interest in the development of universal influenza vaccines. Universal influenza vaccine candidates targeting highly conserved antigens of IAV nucleoprotein (NP) are promising as vaccines that induce T cell immunity, but concerns have been raised about the safety of inducing robust CD8 T cell responses in the lungs. Using a mouse model, we systematically evaluated effects of recombinant adenovirus vectors (rAd) expressing IAV NP (A/NP-rAd) or influenza B virus (IBV) NP (B/NP-rAd) on pulmonary inflammation and function after vaccination and following live IAV challenge.

DNA methylation defects in spermatozoa of male partners from couples experiencing recurrent pregnancy loss.

Study Question: What is the sperm DNA methylation status of imprinted genes in male partners from couples experiencing recurrent pregnancy loss (RPL)?

Summary Answer: Aberrations in sperm DNA methylation status of several imprinted genes, such as insulin like growth factor-2-H19 differentially methylated region (IGF2-H19 DMR), intergenic differentially methylated region (IG-DMR), mesoderm specific transcript (MEST), zinc finger protein which regulates apoptosis and cell cycle arrest (ZAC), DMR in intron 10 of KCNQ1 gene (KvDMR), paternally expressed gene 3 (PEG3) and paternally expressed gene 10 (PEG10), as well as decreased sperm global 5-methylcytosine (5mC) levels, are associated with RPL.

What Is Known Already: RPL is defined as loss of two or more pregnancies, affecting 1-2% of couples of reproductive age. Although there are several maternal and paternal aetiological factors contributing to RPL, nearly 50% of the cases remain idiopathic.

Female-biased effects of aging on a chimeric hemagglutinin stalk-based universal influenza virus vaccine in mice.

To determine if biological sex and age intersect to affect universal influenza vaccine-induced immunity, adult and aged male and female C57BL/6 mice were sequentially immunized with a chimeric-hemagglutinin (cHA) stalk-based H1 vaccine. Adult mice developed greater quantity and quality of H1-stalk antibodies, that were more cross-reactive with other group 1, but not group 2, influenza viruses, than aged mice. The vaccine did not induce neutralizing or hemagglutination inhibition antibodies, but rather antibody-dependent cellular cytotoxicity, which was greater in adult than aged mice.

High-fat diet-induced and genetically inherited obesity differentially alters DNA methylation profile in the germline of adult male rats.

Background: Paternal obesity has been associated with reduced live birth rates. It could lead to inheritance of metabolic disturbances to the offspring through epigenetic mechanisms. However, obesity is a multifactorial disorder with genetic or environmental causes.

Biological sex impacts COVID-19 outcomes.

The current novel coronavirus disease 2019 (COVID-19) pandemic is revealing profound differences between men and women in disease outcomes worldwide. In the United States, there has been inconsistent reporting and analyses of male-female differences in COVID-19 cases, hospitalizations, and deaths. We seek to raise awareness about the male-biased severe outcomes from COVID-19, highlighting the mechanistic differences including in the expression and activity of angiotensin-converting enzyme 2 (ACE2) as well as in antiviral immunity.

Erratum: Author Correction: Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females.

[This corrects the article DOI: 10.1038/s41541-019-0124-6.].

Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females.

Vaccine-induced immunity declines with age, which may differ between males and females. Using human sera collected before and 21 days after receipt of the monovalent A/Cal/09 H1N1 vaccine, we evaluated cytokine and antibody responses in adult (18-45 years) and aged (65+ years) individuals. After vaccination, adult females developed greater IL-6 and antibody responses than either adult males or aged females, with female antibody responses being positively associated with concentrations of estradiol.

Altered endocrine, cytokine signaling and oxidative stress: A plausible reason for differential changes in testicular cells in diet-induced and genetically-inherited - obesity in adult rats.

Obesity is emerging as a potential risk factor for male infertility. It is a multifactorial disorder with primarily genetic and/or environmental factors. Our earlier studies have shown differential effects of genetically inherited-and high fat diet induced-obesity on hormones, fertility and spermatogenesis in adult male rats.

Unveiling the Role of Prolactin and its Receptor in Male Reproduction.

Prolactin is a peptide hormone known to have multiple functions. However, the role of prolactin has been extensively studied only in female physiology and its function in male reproduction still remains majorly unexplored. Studies in rodents and humans have demonstrated the presence of prolactin and its receptor in testes, thereby suggesting a possible role during spermatogenesis.

Genetically Inherited Obesity and High-Fat Diet-Induced Obesity Differentially Alter Spermatogenesis in Adult Male Rats.

Obesity is a multifactorial disorder with predominantly genetic and/or environmental causes. Our aim was to delineate effects of genetically inherited and high-fat diet-induced obesity on fertility and spermatogenesis using two Wistar rat models: genetically inherited obese (GIO) WNIN/Ob rats and diet-induced obese (DIO) rats, which received a high-fat diet. The terminal body weights were similar in both groups, but there was a significant difference in metabolic and hormone profiles between the groups.

Systemic hormonal modulation induces sperm nucleosomal imbalance in rat spermatozoa.

Sperm chromatin packaging is a very complex and highly regulated phenomenon. While most of the sperm chromatin is replaced by protamines, some are retained in nucleosomes. It is recently being recognised that these nucleosomes are intentionally retained and could be contributing to the expression of genes in the very early stages of embryogenesis.

Delineating the regulation of estrogen and androgen receptor expression by sex steroids during rat spermatogenesis.

Estrogen receptors (ERα and β) and androgen receptor (AR) regulate various critical processes during spermatogenesis. Since spermatogenesis is very sensitive to hormonal stimuli and perturbations, it is important to understand the regulation of expression of these receptors by sex steroid hormones. Although many studies have reported deregulation of steroid receptors on endocrine disruption, there is no consensus on the regulation of their expression by steroid hormones during spermatogenesis, and a lack of clear understanding of the mechanism of regulation.

Placental Defects: An Epigenetic Perspective.

Placenta, the first organ to be formed during gestation, plays a crucial role in intrauterine regulation of fetal growth and is involved in several functions during fetal development such as exchange of nutrients, wastes, and gases; protection against maternal immune rejection; and various metabolic and endocrine functions. Several studies have shown the regulation of epigenetic factors and the phenomenon of genomic imprinting in placentation and embryogenesis. Any gain or loss of imprint marks in the placenta has been shown to associate with severe placental defects which in turn affect both the mother and the growing fetus and can have long-term effects during adulthood.

Estrogen, through estrogen receptor 1, regulates histone modifications and chromatin remodeling during spermatogenesis in adult rats.

Estrogen receptors (ESR1 and ESR2) play crucial roles in various processes during spermatogenesis. To elucidate individual roles of ESRs in male fertility, we developed in vivo selective ESR agonist administration models. Adult male rats treated with ESR1 and ESR2 agonist for 60 days show spermatogenic defects leading to reduced sperm counts and fertility.

Estrogen signaling, through estrogen receptor β, regulates DNA methylation and its machinery in male germ line in adult rats.

Estrogen, through its receptors, regulates various aspects of spermatogenesis and male fertility. To understand the roles of estrogen receptors (ERα and ERβ) in male fertility, we have developed in vivo selective ER agonist administration models. Treatment of adult male rats with ERα or ERβ agonist for 60 d decreases fertility and litter size mainly due to increased pre- and post-implantation embryo loss.