Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes

BACKGROUND: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. METHODS: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. FINDINGS: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammation and MBOAT7 genotype. Hepatic MBOAT7 levels were reduced in murine models of fatty liver, and by hyper-insulinemia. In wild-type mice, Mboat7 was down-regulated by refeeding and insulin, concomitantly with insulin signalling activation. Acute hepatic Mboat7 silencing promoted hepatic steatosis in vivo and enhanced expression of fatty acid transporter Fatp1. MBOAT7 deletion in hepatocytes reduced the incorporation of arachidonic acid into phosphatidylinositol, consistently with decreased enzymatic activity, determining the accumulation of saturated triglycerides, enhanced lipogenesis and FATP1 expression, while FATP1 deletion rescued the phenotype. INTERPRETATION: MBOAT7 down-regulation by hyper-insulinemia contributes to hepatic fat accumulation, impairing phosphatidylinositol remodelling and up-regulating FATP1. FUNDING: LV was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02,364,358, Ricerca corrente Fondazione IRCCS Ca\u27 Granda Ospedale Maggiore Policlinico; LV and AG received funding from the European Union Programme Horizon 2020 (No. 777,377) for the project LITMUS- Liver Investigation: Testing Marker Utility in Steatohepatitis . MM was supported by Fondazione Italiana per lo Studio del Fegato (AISF) \u27Mario Coppo\u27 fellowship

Changes in population structure and body dimensions of two xanthid crabs: A long-term study in a single boulder-shore

Two xanthid crab species were studied during 29 months over a period of 14 years between 1986 and 1999 all in exactly the same boulder shore. One of the crab species studied was the xanthid, Eriphia verrucosa (Forskall, 1775) with 60 specimens, the other species, Xantho poressa (Olivi, 1792), with 155 specimens. A significant change in numbers of both males and females of E. verrucosa was noticeable between 1986 and 1996 with a marked drop in numbers between these years. In 1997 male numbers increased again to almosttheir previous numbers in the population during 1986. The population of X. poressa declined significantly towards the end of the study period. Numbers of both genders peaked in spring and again, in summer. There was generally a decline in numbers of both crab species during autumn and winter. Thus, the average capture during the seasons was highest in spring for males of both E. verrucosa, and X. poressa. The body dimensions: mass, carapace length (CL) and width (CW) were measured in both xanthids. The aim of this long-term study was to determine whether temporal changes in the population structure and allometric changes in the dimensions of these crabs took place. Only such long-term observations could reveal these changes in population

On The Potential of Minimal Flavour Violation

Assuming the Minimal Flavour Violation hypothesis, we derive the general scalar potential for fields whose background values are the Yukawa couplings. We analyze the minimum of the potential and discuss the fine-tuning required to dynamically generate the mass hierarchies and the mixings between different quark generations. Two main cases are considered, corresponding to Yukawa interactions being effective operators of dimension five or six (or, equivalently, resulting from bi-fundamental and fundamental scalar fields, respectively). At the renormalizable and classical level, no mixing is naturally induced from dimension five Yukawa operators. On the contrary, from dimension six Yukawa operators one mixing angle and a strong mass hierarchy among the generations result.Comment: 33 pages, 6 figures; Note added in proof on the stability of the minima of the scalar potential; results unchanged; references adde

Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016

BACKGROUND: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. OBJECTIVE: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. DESIGN: Descriptive, using GeoSentinel records. SETTING: 63 travel and tropical medicine clinics in 30 countries. PATIENTS: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. MEASUREMENTS: Frequencies of demographic, trip, and clinical characteristics and complications. RESULTS: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain–Barre syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). LIMITATION: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. CONCLUSION: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission

A quark model framework for the study of nuclear medium effects

A quark-model framework for studying nuclear medium effects on nucleon resonances is described and applied here to pion photoproduction on the deuteron, which is the simplest composite nucleon system and serves as a first test case. Pion photoproduction on nuclei is discussed within a chiral constituent quark model in which the quark degrees of freedom are explicitly introduced through an effective chiral Lagrangian for the quark-pseudoscalar-meson coupling. The advantage of this model is that a complete set of nucleon resonances can be systematically included with a limited number of parameters. Also, the systematic description of the nucleon and its resonances at quark level allows us to self-consistently relate the nuclear medium's influence on the baryon properties to the intrinsic dynamic aspects of the baryons. As the simplest composite nucleus, the deuteron represents the first application of this effective theory for meson photoproduction on light nuclei. The influence of the medium on the transition operators for a free nucleon is investigated in the Delta resonance region. No evidence is found for a change of the Delta properties in the pion photoproduction reaction on the deuteron since the nuclear medium here involves just one other nucleon and the low binding energy implies low nuclear density. However, we show that the reaction mechanism is in principle sensitive to changes of Delta properties that would be produced by the denser nuclear medium of heavier nuclei through the modification of the quark model parameters.Comment: Revtex, 8 pages, 4 figure

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Decision making in child protection:An international comparative study on maltreatment substantiation, risk assessment and interventions recommendations, and the role of professionals’ child welfare attitudes

Item does not contain fulltextChild welfare professionals regularly make crucial decisions that have a significant impact on children and their families. The present study presents the Judgments and Decision Processes in Context model (JUDPIC) and uses it to examine the relationships between three independent domains: case characteristic (mother's wish with regard to removal), practitioner characteristic (child welfare attitudes), and protective system context (four countries: Israel, the Netherlands, Northern Ireland and Spain); and three dependent factors: substantiation of maltreatment, risk assessment, and intervention recommendation. The sample consisted of 828 practitioners from four countries. Participants were presented with a vignette of a case of alleged child maltreatment and were asked to determine whether maltreatment was substantiated, assess risk and recommend an intervention using structured instruments. Participants’ child welfare attitudes were assessed. The case characteristic of mother's wish with regard to removal had no impact on judgments and decisions. In contrast, practitioners’ child welfare attitudes were associated with substantiation, risk assessments and recommendations. There were significant country differences on most measures. The findings support most of the predictions derived from the JUDPIC model. The significant differences between practitioners from different countries underscore the importance of context in child protection decision making. Training should enhance practitioners’ awareness of the impact that their attitudes and the context in which they are embedded have on their judgments and decisions