Geographic variation of mercury in breeding tidal marsh sparrows of the northeastern United States.

Saltmarsh sparrows (Ammospiza caudacuta) and seaside sparrows (A. maritima) are species of conservation concern primarily due to global sea-level rise and habitat degradation. Environmental mercury (Hg) contamination may present additional threats to their reproductive success and survival. To assess site-specific total mercury (THg) exposure and identify environmental correlates of THg detection, we sampled blood from adult male saltmarsh and seaside sparrows at 27 sites between Maine and Virginia, USA. The mean THg concentration (±1 SD) throughout the entire sampling range was 0.531 ± 0.287 µg/g wet weight (ww) for saltmarsh sparrows and 0.442 ± 0.316 µg/g ww for seaside sparrows. Individual THg concentrations ranged from 0.135-1.420 µg/g ww for saltmarsh sparrows and 0.153-1.530 µg/g ww for seaside sparrows. Model averaging from a suite of linear mixed models showed that saltmarsh sparrows averaged 20.1% higher blood THg concentrations than seaside sparrows, potentially due to differences in diet or foraging behavior. We found no evidence for a relationship between sparrow THg concentrations and land cover surrounding sampled marshes or average precipitation-based Hg deposition. Overall, our results suggest considerable, unexplained variation in tidal marsh sparrow blood THg concentrations over their co-occurring breeding ranges.

Natural underlying mtDNA heteroplasmy as a potential source of intra-person hiPSC variability.

Functional variability among human clones of induced pluripotent stem cells (hiPSCs) remains a limitation in assembling high-quality biorepositories. Beyond inter-person variability, the root cause of intra-person variability remains unknown. Mitochondria guide the required transition from oxidative to glycolytic metabolism in nuclear reprogramming. Moreover, mitochondria have their own genome (mitochondrial DNA [mtDNA]). Herein, we performed mtDNA next-generation sequencing (NGS) on 84 hiPSC clones derived from a cohort of 19 individuals, including mitochondrial and non-mitochondrial patients. The analysis of mtDNA variants showed that low levels of potentially pathogenic mutations in the original fibroblasts are revealed through nuclear reprogramming, generating mutant hiPSCs with a detrimental effect in their differentiated progeny. Specifically, hiPSC-derived cardiomyocytes with expanded mtDNA mutations non-related with any described human disease, showed impaired mitochondrial respiration, being a potential cause of intra-person hiPSC variability. We propose mtDNA NGS as a new selection criterion to ensure hiPSC quality for drug discovery and regenerative medicine.

Period pain presenteeism: investigating associations of working while experiencing dysmenorrhea.

Although menstrual pain (dysmenorrhea) is common and can have detrimental effects on work and social functioning, little is known about how people manage it in their professional life. Existing evidence indicates that people with dysmenorrhea often engage in presenteeism, meaning they work despite experiencing symptoms and report perceptions of social stigma around menstruation. In this study, we investigated individual health-related factors, psychosocial factors, and work factors associated with period pain presenteeism in a cross-sectional survey study including N = 668 employed people with experiences of dysmenorrhea. Our results show that symptom severity, disclosure of menstrual pain to the leader, and remote work are directly associated with period pain presenteeism. We further found that the presence of medical diagnosis moderates the association between symptom severity and presenteeism. Disclosure to the leader was associated with leader gender, leader-member exchange (LMX), and the absence of a medical diagnosis, indicating a potential mediating effect. We did not, however, find the perceptions of public beliefs regarding the concealment of menstruation to be related to presenteeism or disclosure. Our findings have important implications for research on menstrual health and occupational health management practice.

Mission to Psyche: Including Undergraduates and the Public on the Journey to a Metal World.

The NASA Psyche mission's program to engage university undergraduates and the public in the mission is inspired by and built upon the extensive foundation of public engagement, educational outreach activities, and expertise of NASA and mission partner institutions. The program leverages the enthusiasm and contributions of undergraduates nationwide to the benefit of the mission, the students and their institutions and communities, and the broader public. Psyche Student Collaborations consists of four main programs, two (Psyche Capstone and Psyche Inspired) are available solely to undergraduates enrolled at universities or community colleges in the United States and its territories and two (Innovation Toolkit free online courses and Science Outreach Interns and Docents) invite broader participation by engaging the talents and creativity of undergraduate interns to help create content and events to reach the public and lifelong learners. Together, these offerings provide multiple entry points and a spectrum of intensity of experiences, numbers of participants, disciplinary diversity, and mode of delivery. Involving undergraduates in all phases of the program supports the development of the next generation of explorers, contributes to the nation's workforce preparation, and complements NASA's existing undergraduate offerings by providing long-term opportunities for students to participate with the mission through established postsecondary education structures like capstone courses.

Working With Type 1 Diabetes: Investigating the Associations Between Diabetes-Related Distress, Burnout, and Job Satisfaction.

The present study investigates the association between diabetes-related distress (DD) and work outcomes (burnout and job satisfaction) among employed people with type 1 diabetes. Employed adults with type 1 diabetes (N = 297) completed an online survey. Measures assessed emotional, social, food- and treatment-related DD, burnout, and job satisfaction, as well as the type of insulin treatment. We conducted multiple regression analyses to test our hypotheses. Emotional DD was significantly and positively associated with burnout. Social DD was significantly and negatively associated with job satisfaction. The type of treatment (insulin pen versus insulin pump) had no significant effect on the outcomes. This study sets the stage for research on the interactions between working conditions, work outcomes and illness symptoms, and problems of people with type 1 diabetes, and, generally, employees with chronic illnesses. The findings have implications for individual health and illness management, burnout prevention, and occupational health measures.

Paradoxical resistance to myocardial ischemia and age-related cardiomyopathy in NHE1 transgenic mice: a role for ER stress?

Sarcolemmal Na(+)/H(+) exchanger (NHE) activity, which is provided by the NHE isoform 1 (NHE1), has been implicated in ischemia/reperfusion-induced myocardial injury in animal models and humans, on the basis of studies with pharmacological NHE1 inhibitors. We generated a transgenic (TG) mouse model with cardiac-specific over-expression of NHE1 to determine whether this would be sufficient to increase myocardial susceptibility to ischemia/reperfusion-induced injury. TG mouse hearts exhibited increased sarcolemmal NHE activity and normal morphology and function. Surprisingly, they also showed reduced susceptibility to ischemia/reperfusion-induced injury, as reflected by improved functional recovery and smaller infarcts. Such protection was sustained in the presence of NHE1 inhibition with zoniporide, indicating a mechanism that is independent of sarcolemmal NHE activity. Immunoblot analysis revealed accumulation of immature NHE1 protein as well as marked upregulation of both cytoprotective (78/94 kDa glucose-regulated proteins, calreticulin, protein disulfide isomerase) and pro-apoptotic (C/EBP homologous protein) components of the endoplasmic reticulum (ER) stress response in TG myocardium. With increasing age, NHE1 TG mice exhibited increased myocyte apoptosis, developed left ventricular contractile dysfunction, underwent cardiac remodelling and died prematurely. Our findings indicate that: (1) Cardiac-specific NHE1 over-expression induces the ER stress response in mouse myocardium, which may afford protection against ischemia/reperfusion-induced injury despite increased NHE activity; (2) Ageing NHE1 TG mice exhibit myocyte apoptosis, cardiac remodelling and failure, likely as a result of sustained ER stress; (3) The pluripotent effects of the ER stress response may confound studies that are based on the chronic over-expression of complex proteins in myocardium.

Targeting Na+/H+ exchanger regulation for cardiac protection: a RSKy approach?

Extensive pre-clinical work indicates that inhibition of the Na(+)/H(+) exchanger (NHE) affords significant protection to myocardium subjected to ischaemia and reperfusion. By contrast, clinical studies with the NHE inhibitors cariporide, eniporide and zoniporide, in patients with evolving myocardial infarction and those at risk of myocardial infarction, have provided largely disappointing data. Nevertheless, some of these studies have confirmed that, in certain settings, NHE inhibition does indeed protect human myocardium. Furthermore, pre-clinical work suggests that NHE inhibition may provide therapeutic benefit in heart failure also. As an alternative to direct and global NHE inhibition, which may trigger non-cardiac adverse effects, the molecular mechanisms that stimulate cardiac NHE activity in disease may be targeted to attenuate such activity selectively in jeopardized tissue. Many factors associated with cardiac pathology activate RSK, an established NHE kinase, and several selective RSK inhibitors have been described recently. The role of RSK as a potential therapeutic target for indirectly suppressing cardiac NHE activity warrants further investigation.

Reversal of cardiac vagal effects of physostigmine by adjunctive muscarinic blockade.

Pre-treatment with reversible acetylcholinesterase (AChE) inhibitors is an effective strategy for reducing lethality following organophosphate nerve agent exposure. AChE inhibition may have unwanted cardiac side effects, which could be negated by adjunctive anti-cholinergic therapy. The aims of the present study were to examine the concentration-dependent effects of physostigmine on cardiac responses to vagus nerve stimulation (VNS), to test whether adjunctive treatment with hyoscine can reverse these effects and to assess the functional interaction and electrophysiological consequences of a combined pre-treatment. Studies were performed in an isolated innervated rabbit heart preparation. The reduction in heart rate with VNS was augmented by physostigmine (1-1000nmol/L), in a concentration-dependent manner - with an EC50 of 19nmol/L. Hyoscine was shown to be effective at blocking the cardiac responses to VNS with an IC50 of 11nmol/L. With concomitant perfusion of physostigmine, the concentration-response curve for hyoscine was shifted downward and to the right, increasing the concentration of hyoscine required to normalise (to control values) the effects of physostigmine on heart rate. At the lowest concentration of hyoscine examined (1nmol/L) a modest potentiation of heart rate response to VNS (+15±3%) was observed. We found no evidence of cardiac dysfunction or severe electrophysiological abnormalities with either physostigmine or hyoscine alone, or as a combined drug-therapy. The main finding of this study is that hyoscine, at concentrations greater than 10-8M, is effective at reversing the functional effects of physostigmine on the heart. However, low-concentrations of hyoscine may augment cardiac parasympathetic control.

Nucleolar localization of an isoform of the IGF-I precursor.

BACKGROUND Alternative exons encode different isoforms of the human insulin-like growth factor-I (IGF-I) precursor without altering mature IGF-I. We hypothesized that the various IGF-I precursors may traffic IGF-I differently. Chimeric IGF-I precursors were made with green fluorescent protein (GFP) cloned between the signal and mature IGF-I domains. RESULTS Chimeras containing exons 1 or 2 were located in the cytoplasm, consistent with a secretory pathway, and suggesting that both exons encoded functional signal peptides. Exon 5-containing chimeras localized to the nucleus and strongly to the nucleolus, while chimeras containing exon 6 or the upstream portion of exon 5 did not. Nuclear and nucleolar localization also occurred when the mature IGF-I domain was deleted from the chimeras, or when signal peptides were deleted. CONCLUSIONS We have identified a nucleolar localization for an isoform of the human IGF-I precursor. The findings are consistent with the presence of a nuclear and nucleolar localization signal situated in the C-terminal part of the exon 5-encoded domain with similarities to signals in several other growth factors.

Hydrogen bond-mediated recognition of the chemical warfare agent soman (GD).

NMR titration studies in acetonitrile-d(3)/DMSO-d(6) mixtures demonstrate that diindolylurea-based receptors can form complexes with the organophosphorus nerve agent soman in organic solution.

Longitudinal trends in trauma mortality and survival in Stoke-on-Trent 1992-1998.

OBJECTIVES: To identify factors related to mortality and to test the null hypothesis of no longitudinal trend in mortality in patients admitted to the North Staffordshire Hospital (NSH) with an Injury Severity Score (ISS) greater than 15, between April 1992 and March 1998. DESIGN: Longitudinal prospective study of 18 factors, including age, sex, mechanism of injury, anatomical injury scores and year of admission. Outcome, based on mortality at discharge, was analysed in two ways: alive or dead at discharge (mortality) and time to death or discharge (survival). RESULTS: A decreasing trend (P < 0.01 ) in mortality with year of admission was detected on the log-odds scale. The trend could not be explained by a case-mix analysis, which allowed for the 17 other factors. Using multiple logistic regression analysis (mortality) and Cox proportional hazards analysis (survival), eight factors were identified as determinants of outcome: age, head AIS score, chest AIS score, abdominal AIS score, calendar year of admission, external injury AIS score, mechanism of the injury and primary receiving hospital. CONCLUSIONS: The observed improvement in survival in severely injured patients must result from the interplay of factors not controlled in this analysis or improvements in patient care or both.