New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Short-term plant-decomposer feedbacks in grassland plants

Plant species differ in their effects on ecosystem productivity and it is recognised that these effects are partly due to plant species-specific influences on soil processes. Until recently, however, not much attention was given to the potential role played by soil biota in these species-specific effects. While soil decomposers are responsible for governing the availability of nutrients for plant production, they simultaneously depend on the amount of carbon provided by plants. Litter and rhizodeposition constitute the two basal resources that plants provide to soil decomposer food webs. While it has been shown that both of these can have effects on soil decomposer communities that differ among plant species, the putative significance of these effects for plant nitrogen (N) acquisition is currently understudied. My PhD work aimed at clarifying whether the species-specific influences of three temperate grassland plants on the soil microfood-web, through rhizodeposition and litter, can feed back to plant N uptake. The methods and approach used (15N labelling of plant litter in microcosm experiments) revealed to be an effective combination of tools in studying these feedbacks. Plant effects on soil organisms were shown to differ significantly between plant species and the effects could be followed across several trophic levels. The labelling of litter further permitted the evaluation of plant acquisition of N derived from soil organic matter. The results show that the structure of the soil microfood-web can have a significant role in plant N acquisition when the structure is experimentally manipulated, such as when comparing systems consisting of microbes to those consisting of microbes and their grazers. However, despite this, the results indicate that differences in N uptake from soil organic matter between different plant species are not related to the effects these species exert on the structure of the soil microfood-web. Rather, these differences in N uptake seem to be determined by other species-specific traits of live plants and their litter. My results thus indicate that different resources provided by different plant species may not induce species-specific decomposer feedbacks on plant N uptake from soil organic matter. This further suggests that the species-specific plant effects on soil decomposer communities may not, at least in the short term, have significant consequences on plant production.

Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans

Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.

A decidable temporal logic with repeating values

Various logical formalisms with the freeze quantifier have been recently considered to model computer systems even though this is a powerful mechanism that often leads to undecidability. In this paper, we study a linear-time temporal logic with past-time operators such that the freeze operator is only used to express that some value from an infinite set is repeated in the future or in the past. Such a restriction has been inspired by a recent work on spatio-temporal logics. We show decidability of finitary and infinitary satisfiability by reduction into the verification of temporal properties in Petri nets. This is a surprising result since the logic is closed under negation, contains future-time and past-time temporal operators and can express the nonce property and its negation. These ingredients are known to lead to undecidability with a more liberal use of the freeze quantifier.

Knowledge Exchange RDM Training & Skills Workshop, 9-10 Feb 2016, London

In today’s changing research environment, RDM is important in all stages of research. The skills and know-how in RDM that researchers and research support staff need, should be nurtured all though their career. At the end of 2015, KE initiated a project to compare approaches in RDM training within the partnership’s five member countries. The project was structured around two strands of activity: In the last months of 2015 a survey was conducted to collect information on current practice around RDM training, in order to provide an overview of the RDM training landscape. In February 2016 a workshop was held to share successful approaches to RDM training and capacity building provided within institutions and by infrastructure. The report describes the outputs of both the analysis of the survey and the outcomes of the workshop. The document provides an evidence base and informed suggestions to help improve RDM training practices in KE partner countries and beyond.

Hans Haacke: afetos e induções para uma arte impregnada de...

A presente dissertação tem como objetivo pautar as possibilidades de leitura da obra do artista alemão Hans Haacke apresentando 6 obras bases de análise. A pesquisa cerca as relações entre arte e sociedade em uma esfera tanto micro quanto macropolítica contando com conceitos sociológicos que pautam a dimensão simbólica da arte frente às relações econômicas e políticas com as quais a obra de Haacke dialoga. A partir da construção de aspectos sociais simbólicos a dissertação visa também explorar o direcionamento afetivo tanto na leitura do trabalho de Haacke quanto no redirecionamento da posição crítica social e artística com que o artista joga enquanto aspecto conceitual de sua própria obra, focando pontos que lidam com a construção coletiva de subjetividades. A dissertação assim aponta para uma investigação de novos lugares de diálogo da própria arte submerssa em uma constante construção e negociação de seu espaço em meio a outras áreas de conhecimento

The s-process nucleosynthesis

Theoretical as well as observational aspects of the s-process nucleosynthesis are reviewed. The classical site-independent s-process model as well as the s-process in massive stars are shortly described. A special attention is paid to the nucleosynthesis taking place in AGB stars and the extra-mixing invoked to explain the production of neutrons in the C-rich layers during the interpulse. We also discuss the nucleosynthesis found in hot AGB stars for which the s-process during the interpulse phase is inhibited, but the one resulting from the large temperatures in the thermal pulse is boosted. We comment on the uncertainties affecting our understanding of the physical mechanisms responsible for a successful s-process. Finally, various types of spectroscopic observations of s-process elements are discussed. © 2005 International Astronomical Union.

Modulational instabilities in passive cavities: theory and experiment

Les Houches workshop, September 28-October 2, 1998.

Nuclear ingredients for cross section calculation of exotic nuclei

The increasing need for cross sections far from the valley of stability, especially for applications such as nuclear astrophysics, poses a challenge for nuclear reaction models. So far, predictions of cross sections have relied on more or less phenomenological approaches, depending on parameters adjusted to available experimental data or deduced from systematic relations. While such predictions are expected to be reliable for nuclei not too far from the experimentally known regions, it is clearly preferable to use more fundamental approaches, based on sound physical bases, when dealing with very exotic nuclei. Thanks to the high computer power available today, all major ingredients required to model a nuclear reaction can now be (and have been) microscopically (or semi-microscopically) determined starting from the information provided by an effective nucleon-nucleon interaction. All these microscopic ingredients have been included in the latest version of the TALYS nuclear reaction code (http://www.talys.eu/).

Latest development of the combinatorial model of nuclear level densities

The combinatorial model of nuclear level densities has now reached a level of accuracy comparable to that of the best global analytical expressions without suffering from the limits imposed by the statistical hypothesis on which the latter expressions rely. In particular, it provides, naturally, non-Gaussian spin distribution as well as non-equipartition of parities which are known to have an impact on cross section predictions at low energies [1, 2, 3]. Our previous global models developed in Refs. [1, 2] suffered from deficiencies, in particular in the way the collective effects - both vibrational and rotational - were treated. We have recently improved this treatment using simultaneously the single-particle levels and collective properties predicted by a newly derived Gogny interaction [4], therefore enabling a microscopic description of energy-dependent shell, pairing and deformation effects. In addition for deformed nuclei, the transition to sphericity is coherently taken into account on the basis of a temperature-dependent Hartree-Fock calculation which provides at each temperature the structure properties needed to build the level densities. This new method is described and shown to give promising results with respect to available experimental data.

CS 30322--023: An Ultra Metal-Poor TP-AGB Star?

info:eu-repo/semantics/published

Differential T and B cell responses against Mycobacterium tuberculosis heparin-binding hemagglutinin adhesin in infected healthy individuals and patients with tuberculosis.

Because only 10% of individuals infected with Mycobacterium tuberculosis will eventually develop disease, antigens that are recognized differently by the immune systems of infected healthy and diseased subjects may constitute potential vaccine candidates. Here, the heparin-binding hemagglutinin adhesin (HBHA) is identified as such an antigen. Lymphocytes from 60% of healthy infected individuals (n=25) produced interferon (IFN)-gamma after stimulation with HBHA, compared with only 4% of patients with active tuberculosis (n=24). In the responders, both CD4(+) and CD8(+) cells secreted HBHA-specific IFN-gamma, and the antigen was presented by both major histocompatibility complex class I and II molecules. In contrast to the reduced ability of patients with tuberculosis to produce HBHA-specific IFN-gamma, most of them (82%) produced anti-HBHA antibodies, compared with 36% of the infected healthy subjects. These observations indicate that HBHA is recognized differently by the immune systems of patients with tuberculosis and infected healthy individuals and might provide a marker for protection against tuberculosis.

Bordetella pertussis infection in 2-month-old infants promotes type 1 T cell responses.

Neonatal immaturity of the immune system is currently believed to generally limit the induction of immune responses to vaccine Ags and to skew them toward type 2 responses. We demonstrated here that Bordetella pertussis infection in very young infants (median, 2 mo old) as well as the first administration of whole-cell pertussis vaccine induces B. pertussis Ag-specific IFN-gamma secretion by the PBMC of these infants. IFN-gamma was secreted by both CD4(+) and CD8(+) T lymphocytes, and the levels of Ag-induced IFN-gamma secretion did not correlate with the age of the infants. Appearance of the specific Th-1 cell-mediated immunity was accompanied by a general shift of the cytokine secretion profile of these infants toward a stronger Th1 profile, as evidenced by the response to a polyclonal stimulation. We conclude that the immune system of 2-mo-old infants is developmentally mature enough to develop Th1 responses in vivo upon infection by B. pertussis or vaccination with whole-cell pertussis vaccines.

Optimal kinetics for quantification of antigen-induced cytokines in human peripheral blood mononuclear cells by real-time PCR and by ELISA.

Real-time polymerase chain reaction (PCR) has recently been described as a new tool to measure and accurately quantify mRNA levels. In this study, we have applied this technique to evaluate cytokine mRNA synthesis induced by antigenic stimulation with purified protein derivative (PPD) or heparin-binding haemagglutinin (HBHA) in human peripheral blood mononuclear cells (PBMC) from Mycobacterium tuberculosis-infected individuals. Whereas PPD and HBHA optimally induced IL-2 mRNA after respectively 8 and 16 to 24 h of in vitro stimulation, longer in vitro stimulation times were necessary for optimal induction of interferon-gamma (IFN-gamma) mRNA, respectively 16 to 24 h for PPD and 24 to 96 h for HBHA. IL-13 mRNA was optimally induced by in vitro stimulation after 16-48 h for PPD and after 48 to 96 h for HBHA. Comparison of antigen-induced Th1 and Th2 cytokines appears, therefore, valuable only if both cytokine types are analysed at their optimal time point of production, which, for a given cytokine, may differ for each antigen tested. Results obtained by real-time PCR for IFN-gamma and IL-13 mRNA correlated well with those obtained by measuring the cytokine concentrations in cell culture supernatants, provided they were high enough to be detected. We conclude that real-time PCR can be successfully applied to the quantification of antigen-induced cytokine mRNA and to the evaluation of the Th1/Th2 balance, only if the kinetics of cytokine mRNA appearance are taken into account and evaluated for each cytokine measured and each antigen analysed.