A cross talk on the role of contemporary biomarkers in depression.

Introduction: Biomarkers can be used to identify determinants of response to various treatments of mental disorders. Evidence to date demonstrates that markers of inflammatory, neurotransmitter, neurotrophic, neuroendocrine, and metabolic function can predict the psychological and physical consequences of depression in individuals, allowing for the development of new therapeutic targets with fewer side effects. Extensive research has included hundreds of potential biomarkers of depression, but their roles in depression, abnormal patients, and how bioinformatics can be used to improve diagnosis, treatment, and prognosis have not been determined or defined. To determine which biomarkers can and cannot be used to predict treatment response, classify patients for specific treatments, and develop targets for new interventions, proprietary strategies, and current research projects need to be tailored.Material and Methods: This review article focuses on - biomarker systems that would help in the further development and expansion of newer targets - which holds great promise for reducing the burden of depression.Results and Discussion: Further, this review point to the inflammatory response, metabolic marker, and microribonucleic acids, long non-coding RNAs, HPA axis which are - related to depression and can serve as future targets.

Effects of Single-Session Meditation on Aortic Pulsatility and Anxiety in Mildly to Moderately Anxious Adults.

Context: Anxiety is a common mental health concern in the USA that is associated with an increased risk of hypertension, arterial stiffness, and cardiovascular disease. Therapists have used eight-week programs for mindfulness meditation to treat anxiety; however little is known about the psychophysiological effects of a single meditation session. Objective: The study intended to assess the effects of a one-hour, mindfulness-meditation session on anxiety symptomology and cardiovascular function, including aortic pulsatility. Design: The research team performed a prospective, single-group study. Setting: The study took place at Michigan Technological University. Participants: Participants were 14 young adults with an initial Beck Anxiety Inventory (BAI) score of 8 to 26, showing mild to moderate anxiety. Intervention: Participants took part in a single, one-hour, guided, mindfulness-meditation session. Outcome Measures: The research team: (1) administered the BAI during an orientation session and at 60-minutes post intervention, and (2) measured the cardiovascular variables of qualified participants at the orientation, at baseline prior to the intervention, immediately post intervention, and at 60 minutes post intervention, including systolic arterial blood pressure (SAP), diastolic arterial blood pressure (DAP), heart rate (HR), aortic pulse pressure (aPP), aortic pulsatility, aortic augmentation index (AIx) at 75 bpm, carotid-radial pulse wave velocity (crPWV), carotid-femoral pulse wave velocity (cfPWV), and respiratory rate. Results: Participants had a significant decrease in the BAI scores between baseline and 60-minutes post intervention (P = .01) and a significant reduction in aortic pulsatility-aPP x HR-between baseline and immediately post intervention and between baseline and 60-minutes post intervention (both P < .01). Conclusions: Preliminary results suggest that one hour of introductory mindfulness meditation can have both psychological and cardiovascular benefits for anxious individuals.

Fission Yeast Schizosaccharomyces pombe: A Unicellular "Micromammal" Model Organism.

The fission yeast Schizosaccharomyces pombe is a rod-shaped unicellular eukaryote, well known for its contributions as a model organism for our understanding of regulation and conservation of the eukaryotic cell cycle. As a yeast divergent from the budding yeast Saccharomyces cerevisiae, S. pombe shares more common features with humans including gene structures, chromatin dynamics, and the prevalence of introns, as well as the control of gene expression through pre-mRNA splicing, epigenetic gene silencing, and RNAi pathways. With the advent of new methodologies for research, S. pombe has become an increasingly used model to investigate various molecular and cellular processes over the last 50 years. Also, S. pombe serves as an excellent system for undergraduate students to obtain hands-on research experience. Versatile experimental approaches are amenable using the fission yeast system due to its relative ease of maintenance, its inherent cellular properties, its power in classic and molecular genetics, and its feasibility in genomics and proteomics analyses. This article provides an overview of S. pombe's rise as a valuable model organism and presents examples to highlight the significance of S. pombe as a unicellular "micromammal" in investigating biological questions. We especially focus on the advantages of and the advancements in using fission yeast for studying biological processes that are characteristic of metazoans to decipher the underlining molecular mechanisms fundamental to all eukaryotes. © 2021 Wiley Periodicals LLC.

Phosphoproteomics Reveals Novel Targets and Phosphoprotein Networks in Cell Cycle Mediated by Dsk1 Kinase.

As the ortholog of human SR protein kinase 1 in fission yeast Schizosaccharomyces pombe, Dsk1 specifically phosphorylates SR proteins (serine/arginine-rich proteins) and promotes splicing of nonconsensus introns. The SRPK (SR protein-specific kinase) family performs highly conserved functions in eukaryotic cells including cell proliferation, differentiation, development, and apoptosis. Although Dsk1 was originally identified as a mitotic regulator, its specific targets involved in cell cycle have yet been unexplored. In this study, using a phosphoproteomics approach, we examined differential protein phosphorylation between wild-type cells and dsk1-deletion mutants. We found reduced phosphorylation of 149 peptides corresponding to 133 proteins in the dsk1-null cells. These proteins are involved in various cellular processes, including cytoskeleton organization and signal transduction, and specifically enriched in multiple steps of cell cycle control. Further, targeted MS analyses and in vitro biochemical assays established Cdr2 protein kinase and kinesin motor Klp9 as novel substrates of Dsk1, which function in cell size control for mitotic entry and in chromosome segregation for mitotic exit, respectively. The phosphoprotein networks mediated by Dsk1 reveal, for the first time, the molecular links connecting Dsk1 to mitotic phase transition, sister-chromatid segregation, and cytokinesis, providing further evidence of Dsk1's diverse influence on cell cycle progression and regulation.

Anhydrous Ammonia Chemical Release - Lake County, Illinois, April 2019.

On April 25, 2019, a farm tractor towing two 2-ton ammonia tanks on a county road in Lake County, Illinois, experienced a mechanical failure that resulted in the release of anhydrous ammonia, a colorless, pungent, irritating gas that can cause severe respiratory and ocular damage (1). Approximately 80% of anhydrous ammonia produced in the United States is used as a fertilizer in agriculture (1). Eighty-three persons, including first responders, motorists, and neighborhood residents, were evaluated at area hospitals because of exposure to the gas. Two weeks after the release, the Agency for Toxic Substances and Disease Registry (ATSDR) and CDC's National Center for Environmental Health (NCEH) collaborated with the Lake County Health Department and the Illinois Department of Public Health on an investigation using ATSDR's Assessment of Chemical Exposures program to describe the release, review the emergency response, and determine health effects associated with the exposure. First responders, community residents, and hospital personnel reported communication challenges related to the nature of the gas release and effective protective measures. Among the 83 persons evaluated at six area hospitals for effects of the chemical release, 14 (17%) were hospitalized, including eight (10%) who were admitted to the intensive care unit (ICU), seven (8%) of whom required endotracheal intubation and mechanical ventilation; no deaths occurred. In addition, ICU health care providers experienced symptoms of secondary exposure. The National Institute for Occupational Safety and Health's Emergency Responder Health Monitoring and Surveillance Program has specific recommendations and tools to protect responders during all phases of a response (2). Hospitals also need to review institutional policies and procedures for chemical mass casualty events, including decontamination (3). Prompt and correct identification of hazardous material (hazmat) events, and clear communication among responding entities, including on-scene and hospital responders, is important to ensure effective response after a chemical release.

NADP+ is an endogenous PARP inhibitor in DNA damage response and tumor suppression.

ADP-ribosylation is a unique posttranslational modification catalyzed by poly(ADP-ribose) polymerases (PARPs) using NAD+ as ADP-ribose donor. PARPs play an indispensable role in DNA damage repair and small molecule PARP inhibitors have emerged as potent anticancer drugs. However, to date, PARP inhibitor treatment has been restricted to patients with BRCA1/2 mutation-associated breast and ovarian cancer. One of the major challenges to extend the therapeutic potential of PARP inhibitors to other cancer types is the absence of predictive biomarkers. Here, we show that ovarian cancer cells with higher level of NADP+, an NAD+ derivative, are more sensitive to PARP inhibitors. We demonstrate that NADP+ acts as a negative regulator and suppresses ADP-ribosylation both in vitro and in vivo. NADP+ impairs ADP-ribosylation-dependent DNA damage repair and sensitizes tumor cell to chemically synthesized PARP inhibitors. Taken together, our study identifies NADP+ as an endogenous PARP inhibitor that may have implications in cancer treatment.

The role of poly ADP-ribosylation in the first wave of DNA damage response.

Poly ADP-ribose polymerases (PARPs) catalyze massive protein poly ADP-ribosylation (PARylation) within seconds after the induction of DNA single- or double-strand breaks. PARylation occurs at or near the sites of DNA damage and promotes the recruitment of DNA repair factors via their poly ADP-ribose (PAR) binding domains. Several novel PAR-binding domains have been recently identified. Here, we summarize these and other recent findings suggesting that PARylation may be the critical event that mediates the first wave of the DNA damage response. We also discuss the potential for functional crosstalk with other DNA damage-induced post-translational modifications.

Gender differences in orthostatic hypotension.

Orthostatic hypotension is a decrease in systolic blood pressure of more than 20 mm Hg or a decrease in diastolic blood pressure of at least 10 mm Hg, within 3 minutes of changing from a supine to an upright position. The typical clinical presentation of orthostatic hypotension includes dizziness, syncope, blurry vision and loss of balance. Symptoms may be more frequent in women, but the complicating roles played by comorbid factors and the estrogen mechanisms are not well understood. Women have a more active parasympathetic system, higher estrogen levels and a lower center of gravity. Thus, women less effectively compensate for the drop of blood pressure in response to positional change. An understanding of these mechanisms contributing to orthostatic hypotension may improve diagnosis and treatment of the problem.