PPARγ Modulates Long Chain Fatty Acid Processing in the Intestinal Epithelium.

Nuclear receptor PPARγ affects lipid metabolism in several tissues, but its role in intestinal lipid metabolism has not been explored. As alterations have been observed in the plasma lipid profile of ad libitum fed intestinal epithelium-specific PPARγ knockout mice (iePPARγKO), we submitted these mice to lipid gavage challenges. Within hours after gavage with long chain unsaturated fatty acid (FA)-rich canola oil, the iePPARγKO mice had higher plasma free FA levels and lower gastric inhibitory polypeptide levels than their wild-type (WT) littermates, and altered expression of incretin genes and lipid metabolism-associated genes in the intestinal epithelium. Gavage with the medium chain saturated FA-rich coconut oil did not result in differences between the two genotypes. Furthermore, the iePPARγKO mice did not exhibit defective lipid uptake and stomach emptying; however, their intestinal transit was more rapid than in WT mice. When fed a canola oil-rich diet for 4.5 months, iePPARγKO mice had higher body lean mass than the WT mice. We conclude that intestinal epithelium PPARγ is activated preferentially by long chain unsaturated FAs compared to medium chain saturated FAs. Furthermore, we hypothesize that the iePPARγKO phenotype originates from altered lipid metabolism and release in epithelial cells, as well as changes in intestinal motility

The work of registered nurses and care assistants with older people in nursing homes : can the outcomes be distinguished?

The need for Registered Nurses (RNs) in the long-term care of older people is being questioned, particularly in the context of nursing shortages, while suggestions for 'professionalising' Care Assistant (CA) roles are emerging. Despite ongoing debates about the importance of their work, research has so far been unable to provide an evidence-base for the outcomes of the work of either RNs or CAs in UK care homes. Using a multi-method interpretive approach, adopting a structure-process-outcome framework and grounded in the philosophical hermeneutics of Hans-Georg Gadamer, this qualitative research sought to illuminate the distinct contributions made by RNs and CAs to outcomes for older people in care homes. RNs and CAs from around the UK contributed 'significant' examples of their work for Phase 1 of the study and Phase 2 comprised researcher fieldwork (observation, interviews and documentary analysis) in three care homes around England. Participants included RNs, CAs, older residents, relatives, home managers and professionals working in the homes. The findings offer a rich and detailed analysis of the realities of the work, much of which takes place 'behind closed doors' and has been described to a limited extent in the literature. They suggest that the CAs' daily support helps residents to function and to feel valued, and that close, reciprocal, family-type relationships develop. The health knowledge and clinical expertise of good RNs is critical in determining residents' health outcomes, particularly in the long-term, and RNs' 24-hour 'perceptual presence' can make life or death differences in acute or emergency situations. RNs also influence the environment, atmosphere and quality of care in the home. In the context of the literature, the findings offer new insights into the role and contribution of RNs and CAs, the outcomes of their work and the priorities of residents. The study produced new models of RN and CA roles in care homes, encompassing dimensions not previously acknowledged in the literature or their job descriptions, and a new framework within which the outcomes of care for older people could be evaluated. The research offers a positive image of work with older people in independent sector care homes.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Flight of the dragonflies and damselflies

This work is a synthesis of our current understanding of the mechanics, aerodynamics and visually mediated control of dragonfly and damselfly flight, with the addition of new experimental and computational data in several key areas. These are: the diversity of dragonfly wing morphologies, the aerodynamics of gliding flight, force generation in flapping flight, aerodynamic efficiency, comparative flight performance and pursuit strategies during predatory and territorial flights. New data are set in context by brief reviews covering anatomy at several scales, insect aerodynamics, neuromechanics and behaviour. We achieve a new perspective by means of a diverse range of techniques, including laser-line mapping of wing topographies, computational fluid dynamics simulations of finely detailed wing geometries, quantitative imaging using particle image velocimetry of on-wing and wake flow patterns, classical aerodynamic theory, photography in the field, infrared motion capture and multi-camera optical tracking of free flight trajectories in laboratory environments. Our comprehensive approach enables a novel synthesis of datasets and subfields that integrates many aspects of flight from the neurobiology of the compound eye, through the aeromechanical interface with the surrounding fluid, to flight performance under cruising and higher-energy behavioural modes

Quantitative analysis of particles, genomes and infectious particles in supernatants of haemorrhagic fever virus cell cultures

Information on the replication of viral haemorrhagic fever viruses is not readily available and has never been analysed in a comparative approach. Here, we compared the cell culture growth characteristics of haemorrhagic fever viruses (HFV), of the Arenaviridae, Filoviridae, Bunyaviridae, and Flavivridae virus families by performing quantitative analysis of cell culture supernatants by (i) electron microscopy for the quantification of virus particles, (ii) quantitative real time PCR for the quantification of genomes, and (iii) determination of focus forming units by coating fluorescent antibodies to infected cell monolayers for the quantification of virus infectivity

Two Planets, One Species: Does a Mission to Mars Alter the Balance in Favour of Human Enhancement?

In this chapter we examine the implications of a crewed mission to Mars, possible colonisation of the planet, and the wider implications this may have on genetic enhancement in both a terrestrial and space context. We consider the usage of both somatic and germ-line genetic engineering, and its potential impact on the evolution of Homo sapiens. We acknowledge that a mission to Mars may require the usage of such technologies if it is to be successful. Our investigation suggests that the use of such technologies might ultimately be linked with the transformation of our own species. We also consider projected timescales for the development of these genetic enhancements and the ethical questions raised by the possibility of speciation. Cooperation among spacefaring nations in this context and the development of norms for the use of such technologies is desirable

Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass

Aims/hypothesis Pancreatic beta cells secrete insulin to maintain glucose homeostasis, and beta cell failure is a hallmark of type 2 diabetes. Glucose triggers insulin secretion in beta cells via oxidative mitochondrial pathways. However, it also feeds mitochondrial anaplerotic pathways, driving citrate export and cytosolic malonyl-CoA production by the acetyl-CoA carboxylase 1 (ACC1) enzyme. This pathway has been proposed as an alternative glucose-sensing mechanism, supported mainly by in vitro data. Here, we sought to address the role of the beta cell ACC1-coupled pathway in insulin secretion and glucose homeostasis in vivo. Methods Acaca, encoding ACC1 (the principal ACC isoform in islets), was deleted in beta cells of mice using the Cre/loxP system. Acaca floxed mice were crossed with Ins2cre mice (βACC1KO; life-long beta cell gene deletion) or Pdx1creER mice (tmx-βACC1KO; inducible gene deletion in adult beta cells). Beta cell function was assessed using in vivo metabolic physiology and ex vivo islet experiments. Beta cell mass was analysed using histological techniques. Results βACC1KO and tmx-βACC1KO mice were glucose intolerant and had defective insulin secretion in vivo. Isolated islet studies identified impaired insulin secretion from beta cells, independent of changes in the abundance of neutral lipids previously implicated as amplification signals. Pancreatic morphometry unexpectedly revealed reduced beta cell size in βACC1KO mice but not in tmx-βACC1KO mice, with decreased levels of proteins involved in the mechanistic target of rapamycin kinase (mTOR)-dependent protein translation pathway underpinning this effect. Conclusions/interpretation Our study demonstrates that the beta cell ACC1-coupled pathway is critical for insulin secretion in vivo and ex vivo and that it is indispensable for glucose homeostasis. We further reveal a role for ACC1 in controlling beta cell growth prior to adulthood

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Nuclear structure and reaction studies at SPIRAL

The SPIRAL facility at GANIL, operational since 2001, is described briefly. The diverse physics program using the re-accelerated (1.2 to 25 MeV/u) beams ranging from He to Kr and the instrumentation specially developed for their exploitation are presented. Results of these studies, using both direct and compound processes, addressing various questions related to the existence of exotic states of nuclear matter, evolution of new "magic numbers", tunnelling of exotic nuclei, neutron correlations, exotic pathways in astrophysical sites and characterization of the continuum are discussed. The future prospects for the facility and the path towards SPIRAL2, a next generation ISOL facility, are also briefly presented.Comment: 48 pages, 27 figures. Accepted for publication in Journal of Physics