Evolution of Thyroid Enhancement of Embryogenesis and Early Survival

Iodine imparts protective antioxidant actions that improve the fitness of invertebrate organisms, and peptides carrying iodine initially appear to have served in a defensive capacity. Tyrosine carries multiple iodines in some echinoderms, and these peptides transferred to progeny serve both protective and signaling purposes. This parental relationship appears to be the most likely evolutionary basis for emergence of the vertebrate thyroid endocrine system, and its critically important development-promoting actions in larval and (later) fetal ontogeny. Thyroxine (T4) and Triiodothyronine (T3) induce settlement and stimulate transitions to alternative feeding modes in some echinoderms. This transgenerational relationship has been conserved and elaborated in vertebrates, including humans, which share common ancestry with echinoderms. Thyroid insufficiency is damaging or can be lethal to larval fishes; egg yolk that is insufficiently primed with maternal thyroid hormones (TH) results in compromised development and high mortality rates at the time of first-feeding. Maternally-derived TH supplied to offspring supports the onset of independent feeding in fishes (eye, mouth, lateral line, swim bladder and intestinal maturation) and survival by comparable developmental mechanisms in placental mammals. Fishes evolved precise control of TH secretion and peripheral processing; early metamorphic and feeding mode actions were joined by controlled thermogenesis in homeotherms

Behavioral and neuroendocrine correlates of displaced aggression in trout

In humans and other primates, violent actions performed by victims of aggression are often directed toward an individual or object that is not the original source of provocation. This psychological phenomenon is often referred to as displaced aggression. We demonstrate that displaced aggression is either rooted in evolutionarily conserved behavioral and neuroendocrine mechanisms, or represent a convergent pattern that has arisen independently in fish and mammals. Rainbow trout that briefly encountered large, aggressive fish reacted with increased aggression towards smaller individuals. There was a strong negative correlation between received aggression and behavioral change: Individuals subjected to intense aggression were subdued, while moderate assaults induced strong agitation. Patterns of forebrain serotonin turnover and plasma cortisol suggest that the presence of socially subordinate fish had an inhibitory effect on neuroendocrine stress responses. Thus, subordinate individuals may serve as stress reducing means of aggressive outlet, and displaced aggression towards such individuals appears to be a behavioral stress coping strategy in fishes

Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes

<p>Abstract</p> <p>Background</p> <p>The melanocortin (MC) receptors have a key role in regulating body weight and pigmentation. They belong to the rhodopsin family of G protein-coupled receptors (GPCRs). The purpose of this study was to identify ancestral MC receptors in agnathan, river lamprey.</p> <p>Results</p> <p>We report cloning of two MC receptors from river lamprey. The lamprey receptors, designated MCa and MCb, showed orthology to the MC1 and MC4 receptor subtypes, respectively. The molecular clock analysis suggested that lamprey MC receptor genes were not duplicated recently and diverged from each other more than 400 MYR ago. Expression and pharmacological characterization showed that the lamprey MCa receptor was able to bind and be activated by both lamprey and human MSH peptides. The lamprey MCa receptor had relatively high affinity for ACTH derived peptides similarly to the fish MC receptors. We found that both of the lamprey MC receptors were expressed in skin, while the MCb receptor was also found in liver, heart and skeletal muscle.</p> <p>Conclusion</p> <p>This study shows presence of MC receptors in agnathans indicating early signs of specific functions of melanocortin receptor subtypes.</p

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Cloning, tissue distribution, pharmacology and three-dimensional modelling of melanocortin receptors 4 and 5 in rainbow trout suggest close evolutionary relationship of these subtypes.

The rainbow trout (Oncorhynchus mykiss) is one of the most widely used fish species in aquaculture and physiological research. In the present paper, we report the first cloning, 3D (three-dimensional) modelling, pharmacological characterization and tissue distribution of two melanocortin (MC) receptors in rainbow trout. Phylogenetic analysis indicates that these receptors are orthologues of the human MC4 and MC5 receptors. We created 3D molecular models of these rainbow trout receptors and their human counterparts. These models suggest greater divergence between the two human receptors than between their rainbow trout counterparts. The pharmacological analyses demonstrated that ACTH (adrenocorticotropic hormone) had surprisingly high affinity for the rainbow trout MC4 and MC5 receptors, whereas alpha-, beta- and gamma-MSH (melanocyte-stimulating hormone) had lower affinity. In second-messenger studies, the cyclic MSH analogues MTII and SHU9119 acted as potent agonist and antagonist respectively at the rainbow trout MC4 receptor, indicating that these ligands are suitable for physiological studies in rainbow trout. Interestingly, we found that the rainbow trout MC4 receptor has a natural high-affinity binding site for zinc ions (0.5 microM) indicating that zinc may play an evolutionary conserved role at this receptor. Reverse transcription PCR indicates that the rainbow trout receptors are expressed both in peripheral tissues and in the central nervous system, including the telencephalon, optic tectum and hypothalamus. Overall, this analysis indicates that the rainbow trout MC4 and MC5 receptors have more in common than their mammalian counterparts, which may suggest that these two receptors have a closer evolutionary relationship than the other MC receptor subtypes

A systematic review of hand hygiene improvement strategies: a behavioural approach

Contains fulltext : 108114.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Many strategies have been designed and evaluated to address the problem of low hand hygiene (HH) compliance. Which of these strategies are most effective and how they work is still unclear. Here we describe frequently used improvement strategies and related determinants of behaviour change that prompt good HH behaviour to provide a better overview of the choice and content of such strategies. METHODS: Systematic searches of experimental and quasi-experimental research on HH improvement strategies were conducted in Medline, Embase, CINAHL, and Cochrane databases from January 2000 to November 2009. First, we extracted the study characteristics using the EPOC Data Collection Checklist, including study objectives, setting, study design, target population, outcome measures, description of the intervention, analysis, and results. Second, we used the Taxonomy of Behavioural Change Techniques to identify targeted determinants. RESULTS: We reviewed 41 studies. The most frequently addressed determinants were knowledge, awareness, action control, and facilitation of behaviour. Fewer studies addressed social influence, attitude, self-efficacy, and intention. Thirteen studies used a controlled design to measure the effects of HH improvement strategies on HH behaviour. The effectiveness of the strategies varied substantially, but most controlled studies showed positive results. The median effect size of these strategies increased from 17.6 (relative difference) addressing one determinant to 49.5 for the studies that addressed five determinants. CONCLUSIONS: By focussing on determinants of behaviour change, we found hidden and valuable components in HH improvement strategies. Addressing only determinants such as knowledge, awareness, action control, and facilitation is not enough to change HH behaviour. Addressing combinations of different determinants showed better results. This indicates that we should be more creative in the application of alternative improvement activities addressing determinants such as social influence, attitude, self-efficacy, or intention