Hypothyroidism in utero\textit{in utero} stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation

Development of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long-term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration $\textit{in utero}$. Organ growth and pancreatic islet cell proliferation and mass were examined in sheep fetuses following removal of the thyroid gland in utero. The effects of triiodothyronine (T$_{3}$), insulin and leptin on beta cell proliferation rates were determined in isolated fetal ovine pancreatic islets $\textit{in vitro}$. Hypothyroidism in the sheep fetus resulted in an asymmetric pattern of organ growth, pancreatic beta cell hyperplasia, and elevated plasma insulin and leptin concentrations. In pancreatic islets isolated from intact fetal sheep, beta cell proliferation $\textit{in vitro}$ was reduced by T$_{3}$ in a dose-dependent manner and increased by insulin at high concentrations only. Leptin induced a bimodal response whereby beta cell proliferation was suppressed at the lowest, and increased at the highest, concentrations. Therefore, proliferation of beta cells isolated from the ovine fetal pancreas is sensitive to physiological concentrations of T$_{3}$, insulin and leptin. Alterations in these hormones may be responsible for the increased beta cell proliferation and mass observed in the hypothyroid sheep fetus and may have consequences for pancreatic function in later life.The project was funded in part by the Biotechnology and Biological Sciences Research Council (BB/HO1697X/1). S.E.H. was supported by a Nigel Groome PhD Studentship at Oxford Brookes University. S.E.H. was awarded a practical skills grant from the Society for Endocrinology and a travel grant from the Physiological Society to fund work at the University of Arizona

Impact of associated injuries in the Floating knee: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Floating knee injuries are usually associated with other significant injuries. Do these injuries have implications on the management of the floating knee and the final outcome of patients? Our study aims to assess the implications of associated injuries in the management and final outcome of floating knee.</p> <p>Methods</p> <p>29 patients with floating knees were assessed in our institution. A retrospective analysis of medical records and radiographs were done and all associated injuries were identified. The impact of associated injuries on delay in initial surgical management, delay in rehabilitation & final outcome of the floating knee were assessed.</p> <p>Results</p> <p>38 associated injuries were noted. 7 were associated with ipsilateral knee injuries. Lower limb injuries were most commonly associated with the floating knee. Patients with some associated injuries had a delay in surgical management and others a delay in post-operative rehabilitation. Knee ligament and vascular injuries were associated with poor outcome.</p> <p>Conclusion</p> <p>The associated injuries were quite frequent with the floating knee. Some of the associated injuries caused a delay in surgical management and post-operative rehabilitation. In assessment of the final outcome, patients with associated knee and vascular injuries had a poor prognosis. Majority of the patients with associated injuries had a good or excellent outcome.</p

Cortisol in hair measured in young adults - a biomarker of major life stressors?

<p>Abstract</p> <p>Background</p> <p>Stress as a cause of illness has been firmly established. In public health and stress research a retrospective biomarker of extended stress would be an indispensible aid. The objective of this pilot study was to investigate whether concentrations of cortisol in hair correlate with perceived stress, experiences of serious life events, and perceived health in young adults.</p> <p>Methods</p> <p>Hair samples were cut from the posterior vertex area of (n = 99) university students who also answered a questionnaire covering experiences of serious life events, perceived Stress Scale and perceived health during the last three months. Cortisol was measured using a competitive radioimmunoassay in methanol extracts of hair samples frozen in liquid nitrogen and mechanically pulverised.</p> <p>Results</p> <p>Mean cortisol levels were significantly related to serious life events (p = 0.045), weakly negatively correlated to perceived stress (p = 0.025, r = -0.061) but nor affected by sex, coloured/permed hair, intake of pharmaceuticals or self-reported health. In a multiple regression model, only the indicator of serious life events had an independent (p = 0.041) explanation of increased levels of cortisol in hair. Out of four outliers with extremely high cortisol levels two could be contacted, both reported serious psychological problems.</p> <p>Conclusions</p> <p>These findings suggest that measurement of cortisol in hair could serve as a retrospective biomarker of increased cortisol production reflecting exposure to major life stressors and possibly extended psychological illness with important implications for research, clinical practice and public health. Experience of serious life events seems to be more important in raising cortisol levels in hair than perceived stress.</p

Worm Grunting, Fiddling, and Charming—Humans Unknowingly Mimic a Predator to Harvest Bait

Background: For generations many families in and around Florida’s Apalachicola National Forest have supported themselves by collecting the large endemic earthworms (Diplocardia mississippiensis). This is accomplished by vibrating a wooden stake driven into the soil, a practice called ‘‘worm grunting’’. In response to the vibrations, worms emerge to the surface where thousands can be gathered in a few hours. Why do these earthworms suddenly exit their burrows in response to vibrations, exposing themselves to predation? Principal Findings: Here it is shown that a population of eastern American moles (Scalopus aquaticus) inhabits the area where worms are collected and that earthworms have a pronounced escape response from moles consisting of rapidly exiting their burrows to flee across the soil surface. Recordings of vibrations generated by bait collectors and moles suggest that ‘‘worm grunters’ ’ unknowingly mimic digging moles. An alternative possibility, that worms interpret vibrations as rain and surface to avoid drowning is not supported. Conclusions: Previous investigations have revealed that both wood turtles and herring gulls vibrate the ground to elicit earthworm escapes, indicating that a range of predators may exploit the predator-prey relationship between earthworms and moles. In addition to revealing a novel escape response that may be widespread among soil fauna, the results sho

Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV

The results from the STAR Collaboration on directed flow (v_1), elliptic flow (v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a Blast Wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v_2, scaling with the number of constituent quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures modified, but data the same. However, in Fig. 35 the hydro calculations are corrected in this version. The data tables are available at http://www.star.bnl.gov/central/publications/ by searching for "flow" and then this pape

Recombinant HIV Envelope Proteins Fail to Engage Germline Versions of Anti-CD4bs bNAbs

Vaccine candidates for HIV-1 so far have not been able to elicit broadly neutralizing antibodies (bNAbs) although they express the epitopes recognized by bNAbs to the HIV envelope glycoprotein (Env). To understand whether and how Env immunogens interact with the predicted germline versions of known bNAbs, we screened a large panel (N:56) of recombinant Envs (from clades A, B and C) for binding to the germline predecessors of the broadly neutralizing anti-CD4 binding site antibodies b12, NIH45-46 and 3BNC60. Although the mature antibodies reacted with diverse Envs, the corresponding germline antibodies did not display Env-reactivity. Experiments conducted with engineered chimeric antibodies combining the mature and germline heavy and light chains, respectively and vice-versa, revealed that both antibody chains are important for the known cross-reactivity of these antibodies. Our results also indicate that in order for b12 to display its broad cross-reactivity, multiple somatic mutations within its VH region are required. A consequence of the failure of the germline b12 to bind recombinant soluble Env is that Env-induced B-cell activation through the germline b12 BCR does not take place. Our study provides a new explanation for the difficulties in eliciting bNAbs with recombinant soluble Env immunogens. Our study also highlights the need for intense efforts to identify rare naturally occurring or engineered Envs that may engage the germline BCR versions of bNAbs

Web-Based, Participant-Driven Studies Yield Novel Genetic Associations for Common Traits

Despite the recent rapid growth in genome-wide data, much of human variation remains entirely unexplained. A significant challenge in the pursuit of the genetic basis for variation in common human traits is the efficient, coordinated collection of genotype and phenotype data. We have developed a novel research framework that facilitates the parallel study of a wide assortment of traits within a single cohort. The approach takes advantage of the interactivity of the Web both to gather data and to present genetic information to research participants, while taking care to correct for the population structure inherent to this study design. Here we report initial results from a participant-driven study of 22 traits. Replications of associations (in the genes OCA2, HERC2, SLC45A2, SLC24A4, IRF4, TYR, TYRP1, ASIP, and MC1R) for hair color, eye color, and freckling validate the Web-based, self-reporting paradigm. The identification of novel associations for hair morphology (rs17646946, near TCHH; rs7349332, near WNT10A; and rs1556547, near OFCC1), freckling (rs2153271, in BNC2), the ability to smell the methanethiol produced after eating asparagus (rs4481887, near OR2M7), and photic sneeze reflex (rs10427255, near ZEB2, and rs11856995, near NR2F2) illustrates the power of the approach

Heme and innate immunity: new insights for an old molecule

Hemolytic episodes such as sickle cell disease, malaria and ischemia-reperfusion occurrence are often associated to the statement of an inflammatory response which may develop or not to a chronic inflammatory status. Although these pathological states are triggered by distinct etiological agents, all of them are associated to high levels of free heme in circulation. In this review, we aim to focus the very recent achievements that have led to the statement of free heme as a proinflammatory molecule, which may play a central role during the onset and/or persistance of inflammation during these pathologies

Science-Driven Optimization of the LSST Observing Strategy

The Large Synoptic Survey Telescope is designed to provide an unprecedented optical imaging dataset that will support investigations of our Solar System, Galaxy and Universe, across half the sky and over ten years of repeated observation. However, exactly how the LSST observations will be taken (the observing strategy or "cadence") is not yet finalized. In this dynamically-evolving community white paper, we explore how the detailed performance of the anticipated science investigations is expected to depend on small changes to the LSST observing strategy. Using realistic simulations of the LSST schedule and observation properties, we design and compute diagnostic metrics and Figures of Merit that provide quantitative evaluations of different observing strategies, analyzing their impact on a wide range of proposed science projects. This is work in progress: we are using this white paper to communicate to each other the relative merits of the observing strategy choices that could be made, in an effort to maximize the scientific value of the survey. The investigation of some science cases leads to suggestions for new strategies that could be simulated and potentially adopted. Notably, we find motivation for exploring departures from a spatially uniform annual tiling of the sky: focusing instead on different parts of the survey area in different years in a "rolling cadence" is likely to have significant benefits for a number of time domain and moving object astronomy projects. The communal assembly of a suite of quantified and homogeneously coded metrics is the vital first step towards an automated, systematic, science-based assessment of any given cadence simulation, that will enable the scheduling of the LSST to be as well-informed as possible