14,224 research outputs found

    Differential Tissue Response to Growth Hormone in Mice

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    Growth hormone (GH) has been shown to act directly on multiple tissues throughout the body. Historically, it was believed that GH acted directly in the liver and only indirectly in other tissues via insulin‐like growth hormone 1 (IGF‐1). Despite extensive work to describe GH action in individual tissues, a comparative analysis of acute GH signaling in key metabolic tissues has not been performed. Herein, we address this knowledge gap. Acute tissue response to human recombinant GH was assessed in mice by measuring signaling via phospho‐STAT5 immunoblotting. STAT5 activation is an easily and reliably detected early marker of GH receptor engagement. We found differential tissue sensitivities; liver and kidney were equally GH‐sensitive and more sensitive than white adipose tissue, heart, and muscle (gastrocnemius). Gastrocnemius had the greatest maximal response compared to heart, liver, white adipose tissue, and whole kidney. Differences in maximum responsiveness were positively correlated with tissue STAT5 abundance, while differences in sensitivity were not explained by differences in GH receptor levels. Thus, GH sensitivity and responsiveness of distinct metabolic tissues differ and may impact physiology and disease

    Electrically tunable multi-terminal SQUID-on-tip

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    We present a new nanoscale superconducting quantum interference device (SQUID) whose interference pattern can be shifted electrically in-situ. The device consists of a nanoscale four-terminal/four-junction SQUID fabricated at the apex of a sharp pipette using a self-aligned three-step deposition of Pb. In contrast to conventional two-terminal/two-junction SQUIDs that display optimal sensitivity when flux biased to about a quarter of the flux quantum, the additional terminals and junctions allow optimal sensitivity at arbitrary applied flux, thus eliminating the magnetic field "blind spots". We demonstrate spin sensitivity of 5 to 8 ÎŒB/Hz1/2\mu_B/\text{Hz}^{1/2} over a continuous field range of 0 to 0.5 T, with promising applications for nanoscale scanning magnetic imaging

    Assessing the SNAP Consumer Environment at Farmers Markets

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    The SNAP at Farmers Market Environmental Assessment was developed as a tool for market managers to examine SNAP participant accessibility for redeeming SNAP benefits at farmers markets. By completing the SNAP at Farmers Market Environmental Assessment, the tool can serve as a guide for providing practical next steps for market improvement. Extension practitioners and researchers, including SNAP-Ed staff, can use the assessment tool to support policy, systems, and environment change efforts that promote access to local, high-quality foods by SNAP consumers, the redemption of SNAP benefits, and potentially increased sales at farmers markets

    Augmented cardiac growth hormone signaling contributes to cardiomyopathy following genetic disruption of the cardiomyocyte circadian clock

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    Circadian clocks regulate numerous biological processes, at whole body, organ, and cellular levels. This includes both hormone secretion and target tissue sensitivity. Although growth hormone (GH) secretion is time-of-day-dependent (increased pulse amplitude during the sleep period), little is known regarding whether circadian clocks modulate GH sensitivity in target tissues. GH acts in part through induction of insulin-like growth factor 1 (IGF1), and excess GH/IGF1 signaling has been linked to pathologies such as insulin resistance, acromegaly, and cardiomyopathy. Interestingly, genetic disruption of the cardiomyocyte circadian clock leads to cardiac adverse remodeling, contractile dysfunction, and reduced lifespan. These observations led to the hypothesis that the cardiomyopathy observed following cardiomyocyte circadian clock disruption may be secondary to chronic activation of cardiac GH/IGF1 signaling. Here, we report that cardiomyocyte-specific BMAL1 knockout (CBK) mice exhibit increased cardiac GH sensitivity, as evidenced by augmented GH-induced STAT5 phosphorylation (relative to littermate controls) in the heart (but not in the liver). Moreover

    Zinc-enriched fertilisers as a potential public health intervention in Africa

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    Background In this review, we examine the potential of Zn-enriched fertilisers to alleviate human dietary Zn deficiency. The focus is on ten African countries where dietary Zn supply is low and where fertiliser subsidies are routinely deployed on cereal crops. Scope Dietary Zn supply and deficiency prevalence were quantified from food supply and composition data. Typical effects of soil (granular) and foliar Zn applications on Zn concentrations in maize (Zea mays L.), rice (Oryza sativa L.) and wheat (Triticum aestivum L.) grains were based on a systematic literature review. Reductions in disease burdens attributable to Zn deficiency and cost-effectiveness were estimated using a disability-adjusted life years (DALYs) approach. Conclusions Baseline Zn supply in 2009 ranged from 7.1 (Zambia) to 11.9 (Mali) mg capita−1 day−1; prevalence of Zn deficiency ranged from 24 (Nigeria) to 66 % (Zambia). In reviewed studies, soil Zn application led to an increase in median Zn concentration in maize, rice and wheat grains of 23, 7 and 19 %; foliar application led to increases of 30, 25 and 63 %. Enriching granular fertilisers within current subsidy schemes would be most effective in Malawi, reducing DALYs lost due to Zn deficiency by 10 %. The cost per DALY saved ranged from US624to5893viagranularfertilisersandfromUS 624 to 5893 via granular fertilisers and from US 46 to 347 via foliar fertilisers. Foliar applications are likely to be more cost effective than soil applications due to fixation of Zn in the soil but may be more difficult to deploy. Zinc fertilisation is likely to be less cost-effective than breeding in the longer term although other micronutrients such as selenium could be incorporated

    Deletion of LBR N-terminal domains recapitulates Pelger-Huet anomaly phenotypes in mouse without disrupting X chromosome inactivation

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    Mutations in the gene encoding Lamin B receptor (LBR), a nuclear-membrane protein with sterol reductase activity, have been linked to rare human disorders. Phenotypes range from a benign blood disorder, such as Pelger-Huet anomaly (PHA), affecting the morphology and chromatin organization of white blood cells, to embryonic lethality as for Greenberg dysplasia (GRBGD). Existing PHA mouse models do not fully recapitulate the human phenotypes, hindering efforts to understand the molecular etiology of this disorder. Here we show, using CRISPR/Cas-9 gene editing technology, that a 236bp N-terminal deletion in the mouse Lbr gene, generating a protein missing the N-terminal domains of LBR, presents a superior model of human PHA. Further, we address recent reports of a link between Lbr and defects in X chromosome inactivation (XCI) and show that our mouse mutant displays minor X chromosome inactivation defects that do not lead to any overt phenotypes in vivo. We suggest that our N-terminal deletion model provides a valuable pre-clinical tool to the research community and will aid in further understanding the etiology of PHA and the diverse functions of LBR

    Anatomical correlates of cursoriality are compromised by body size and propensity to burrow in a group of small mammals (Lagomorpha)

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    Highly cursorial animals are specialised for fast, sustained running via specific morphological adaptations, notably including changes in limb segment length and mechanical advantage. Members of the order Lagomorpha (hares, rabbits and pikas) vary in cursorial ability; hares are generally highly cursorial, rabbits more frequently saltate, and pikas predominantly trot. Previous investigations of lagomorphs have identified anatomical trends correlated with this ‘cursoriality gradient’, however, the phylogenetic sampling of such investigations has been limited to three American species, namely the American pika (Ochotona princeps), brush rabbit (Sylvilagus bachmani), and black-tailed jackrabbit (Lepus californicus). Here, we expand the phylogenetic sample and body size range by including novel data from Australian samples of the European rabbit (Oryctolagus cuniculus) and European hare (L. europaeus), alongside unpublished data on the Eastern cottontail (S. floridanus). X-ray Computed Tomography and digital landmarking were used to capture proportions within the appendicular skeleton of ~ 40 specimens of each European species. In doubling the number of species studied, we find the previously-identified morphological gradients associated with cursorial behaviour are complicated when evaluated in the larger sample. The relative length and joint velocity of limbs was found to be lower than predicted in European rabbits and hares. Furthermore, we present a novel assessment of morphological integration in the lagomorph appendicular skeleton, finding between-limb covariation patterns that are generally similar to those of other mammals. Broadly, these results suggest cursoriality is only one of many selective forces driving lagomorph skeletal evolution, with variations in body size and fossoriality potentially having measurable impacts.Ellen M. Martin, Jesse W. Young, Connie D. Fellmann, Brian Kraatz, Emma Sherrat

    Nab: Measurement Principles, Apparatus and Uncertainties

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    The Nab collaboration will perform a precise measurement of 'a', the electron-neutrino correlation parameter, and 'b', the Fierz interference term in neutron beta decay, in the Fundamental Neutron Physics Beamline at the SNS, using a novel electric/magnetic field spectrometer and detector design. The experiment is aiming at the 10^{-3} accuracy level in (Delta a)/a, and will provide an independent measurement of lambda = G_A/G_V, the ratio of axial-vector to vector coupling constants of the nucleon. Nab also plans to perform the first ever measurement of 'b' in neutron decay, which will provide an independent limit on the tensor weak coupling.Comment: 12 pages, 6 figures, 1 table, talk presented at the International Workshop on Particle Physics with Slow Neutrons, Grenoble, 29-31 May 2008; to appear in Nucl. Instrum. Meth. in Physics Research
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