Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2

Deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in humans leads to the syndrome of apparent mineralocorticoid excess (SAME), in which cortisol illicitly occupies mineralocorticoid receptors, causing sodium retention, hypokalemia, and hypertension. However, the disorder is usually incompletely corrected by suppression of cortisol, suggesting additional and irreversible changes, perhaps in the kidney. To examine this further, we produced mice with targeted disruption of the 11β-HSD2 gene. Homozygous mutant mice (11β-HSD2(–/–)) appear normal at birth, but ∼50% show motor weakness and die within 48 hours. Both male and female survivors are fertile but exhibit hypokalemia, hypotonic polyuria, and apparent mineralocorticoid activity of corticosterone. Young adult 11β-HSD2(–/–) mice are markedly hypertensive, with a mean arterial blood pressure of 146 ± 2 mmHg, compared with 121 ± 2 mmHg in wild-type controls and 114 ± 4 mmHg in heterozygotes. The epithelium of the distal tubule of the nephron shows striking hypertrophy and hyperplasia. These histological changes do not readily reverse with mineralocorticoid receptor antagonism in adulthood. Thus, 11β-HSD2(–/–) mice demonstrate the major features of SAME, providing a unique rodent model to study the molecular mechanisms of kidney resetting leading to hypertension. J. Clin. Invest. 103:683–689 (1999

Alloparental behaviour and long-term costs of mothers tolerating other members of the group in a plurally breeding mammal

Cooperative-breeding studies tend to focus on a few alloparental behaviours in highly cooperative species exhibiting high reproductive skew and the associated short-term, but less frequently long-term, fitness costs. We analysed a suite of alloparental behaviours (assessed via filming) in a kin-structured, high-density population of plurally breeding European badgers, Meles meles, which are not highly cooperative. Group members, other than mothers, performed alloparental behaviour; however, this was not correlated with their relatedness to within-group young. Furthermore, mothers babysat, allogroomed cubs without reciprocation, and allomarked cubs more than other members of the group (controlling for observation time). For welfare reasons, we could not individually mark cubs; however, the number observed pre-independence never exceeded that trapped. All 24 trapped cubs, in three filmed groups, were assigned both parents using 22 microsatellites. Mothers may breed cooperatively, as the time they babysat their assigned, or a larger, litter size did not differ. Furthermore, two mothers probably allonursed, as they suckled more cubs than their assigned litter size. An 18-year genetic pedigree, however, detected no short-term (litter size; maternal survival to the following year) or long-term (offspring breeding probability; offspring lifetime breeding success) fitness benefits with more within-group mothers or other members of the group. Rather, the number of other members of the group (excluding mothers) correlated negatively with long-term fitness. Mothers may tolerate other members of the group, as nonbreeders undertook more digging. Our study highlights that alloparental care varies on a continuum from that seen in this high-density badger population, where alloparenting behaviour is minimal, through to species where alloparental care is common and provides fitness benefits. (C) 2010 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved

Bedrock erosion surfaces record former East Antarctic Ice Sheet extent

East Antarctica hosts large subglacial basins into which the East Antarctic Ice Sheet (EAIS) likely retreated during past warmer climates. However, the extent of retreat remains poorly constrained, making quantifying past and predicted future contributions to global sea level rise from these marine basins challenging. Geomorphological analysis and flexural modeling within the Wilkes Subglacial Basin is used to reconstruct the ice margin during warm intervals of the Oligocene–Miocene. Flat‐lying bedrock plateaus are indicative of an ice sheet margin positioned >400–500 km inland of the modern grounding zone for extended periods of the Oligocene–Miocene, equivalent to a 2 meter rise in global sea level. Our findings imply that if major EAIS retreat occurs in the future, isostatic rebound will enable the plateau surfaces to act as seeding points for extensive ice rises, thus limiting extensive ice margin retreat of the scale seen during the early EAIS

The effect of curricular and extracurricular activities on university students? entrepreneurial intention and competences

This study examines how the alliance-building process affects the intention to enter into international alliances in the case of small and medium-sized enterprises (SMEs). From a psychological perspective (Perceived Behavioural Control), the authors analyse the alliance-building process as an inhibitor of the international collaboration intention, considering to what extent the experience affects the intention of the partners involved. The study explores these hypotheses based on a sample of 220 Spanish SMEs. The results provide empirical evidence showing that the intention to develop international alliances is negatively affected by the search and the selection process as well as by the negotiation of the agreement, which reduces the intention to establish an international agreement. In addition, the intention is moderated by the experience of the SME manager. Moreover, there is a negative relationship between the extent of the SME manager's international experience and the intention to develop an international alliance

A Greater Means to the Greater Good: Ethical Guidelines to Meet Social Movement Organization Advocacy Challenges

Existing public relations ethics literature often proves inadequate when applied to social movement campaigns, considering the special communication challenges activists face as marginalized moral visionaries in a commercial public sphere. The communications of counter-hegemonic movements is distinct enough from corporate, nonprofit, and governmental organizations to warrant its own ethical guidelines. The unique communication guidelines most relevant to social movement organizations include promoting asymmetrical advocacy to a greater extent than is required for more powerful organizations and building flexibility into the TARES principles to privilege social responsibility over respect for audience values in activist campaigns serving as ideological critique

Measurement of νˉμ\bar{\nu}_{\mu} and νμ\nu_{\mu} charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$in units of cm$^{2}$/nucleon and$R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.Comment: 18 pages, 8 figure

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space