Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index.

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.

Clinical pharmacology of atrial natriuretic (3-28) eicosahexapeptide.

The clinical pharmacology of a synthetic rat atrial natriuretic peptide (rANP) was evaluated in normal volunteers. During a dose-ranging study at 1-40 micrograms/min we observed a dose-dependent decrease in mean intra-arterial blood pressure, an acceleration of the heart rate and a transient increase in blood flow to the skin. During a 4-h constant-dose infusion at 0.5 and 5.0 micrograms/min, inulin clearance remained unchanged but there was a dose-related fall in paraaminohippurate (PAH) clearance and an increase in the filtration fraction. Urinary excretion of sodium, chloride and calcium increased in a dose-related fashion, but with the high dose the excretion curve had a bell-shape. No change in plasma renin activity, angiotensin II and aldosterone was observed during the rANP infusion despite the excretion of large amounts of sodium and a blood pressure reduction with the high dose. Indocyanine green clearance, a measure of hepatic blood flow, was significantly decreased by a 2-h rANP infusion at 1.0 microgram/min. In normal volunteers, therefore, rANP induced vasodilation and blood pressure reduction, a decrease in renal and hepatic blood flow and a natriuretic and transient diuretic effect without activation of the renin-angiotensin-aldosterone system.

New Genetic and Linguistic Analyses Show Ancient Human Influence on Baobab Evolution and Distribution in Australia

This study investigates the role of human agency in the gene flow and geographical distribution of the Australian baobab, Adansonia gregorii. The genus Adansonia is a charismatic tree endemic to Africa, Madagascar, and northwest Australia that has long been valued by humans for its multiple uses. The distribution of genetic variation in baobabs in Africa has been partially attributed to human-mediated dispersal over millennia, but this relationship has never been investigated for the Australian species. We combined genetic and linguistic data to analyse geographic patterns of gene flow and movement of word-forms for A. gregorii in the Aboriginal languages of northwest Australia. Comprehensive assessment of genetic diversity showed weak geographic structure and high gene flow. Of potential dispersal vectors, humans were identified as most likely to have enabled gene flow across biogeographic barriers in northwest Australia. Genetic-linguistic analysis demonstrated congruence of gene flow patterns and directional movement of Aboriginal loanwords for A. gregorii. These findings, along with previous archaeobotanical evidence from the Late Pleistocene and Holocene, suggest that ancient humans significantly influenced the geographic distribution of Adansonia in northwest Australia.

Assessment of debris-flow susceptibility at medium-scale in the Barcelonnette Basin, France

Debris flows are among the most dangerous processes in mountainous areas due to their rapid rate of movement and long runout zone. Sudden and rather unexpected impacts produce not only damages to buildings and infrastructure but also threaten human lives. Medium- to regional-scale susceptibility analyses allow the identification of the most endangered areas and suggest where further detailed studies have to be carried out. Since data availability for larger regions is mostly the key limiting factor, empirical models with low data requirements are suitable for first overviews. In this study a susceptibility analysis was carried out for the Barcelonnette Basin, situated in the southern French Alps. By means of a methodology based on empirical rules for source identification and the empirical angle of reach concept for the 2-D runout computation, a worst-case scenario was first modelled. In a second step, scenarios for high, medium and low frequency events were developed. A comparison with the footprints of a few mapped events indicates reasonable results but suggests a high dependency on the quality of the digital elevation model. This fact emphasises the need for a careful interpretation of the results while remaining conscious of the inherent assumptions of the model used and quality of the input data.

Consumption of macrophytes by invertebrates in Tancada lagoon (NE Spain)

Gammarus aequicauda and Sphaeroma hookeri are the most abundant macroinvertebrates on Ruppia cirrhosa (1275 and 1290 individuals.m-2) and Potamogeton pectinatus (140 and 680 individuals. m-2) in Tancada lagoon, a Mediterranean coastal lagoon in the Ebro Delta (NE Spain). Consumption and assimilation efficiencies were calculated from bell jar experiments. Gammarus grazing effects are higher than Sphaeroma on both Ruppia cirrhosa and Potamogeton pectinatus. Green Ruppia leaves lost 0.3 mg per mg Gammarus per day, while Potamogeton leaves lost 0.2 mg per mg Gammarus per day. Decomposing Ruppia leaves lost 0.35-0.54 mg per mg Gammarus per day. Losses of weight by both Ruppia and Potamogeton due to Sphaeroma feeding were less than half those by Gammarus. Assimilation efficiencies are higher for Gammarus (44-78% feeding on Ruppia 2% feeding on Potamogeton) than for Sphaeroma (26-48%) feeding on Ruppia). These assimilation efficiencies were higher than those reported by other authors working at higher latitudes perhaps because of the higher temperature under which the experiments were carried out.

An integrated encyclopedia of DNA elements in the human genome.

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

Senex, el vell savi : Estudi del reconeixement del papa el 750

Breu assaig de caràcter hermenèutic on l'autor es proposa una lectura d'un esdeveniment històric particular. L'autor pren com a excusa per a la seva interpretació dels esdeveniments els fets que tingueren lloc el 750 al bell mig del regne franc quan els merovingis reconeixen explícitament la figura d'autoritat del papa en la comunitat cristiana occidental i com el papa l'assumeix pròpiament.

Maria-Mercè Marçal en el mirall : sobre l'imaginari femení i el llenguatge poètic

Per Maria-Mercè Marçal, la poeta no es pot trobar, no es pot veure, en el «mirall del bell», que sempre han fomentat els discursos dominants. El seu és una altra mena de mirall trencat que reflecteix un ésser complex, híbrid i contaminat que lluita «entre un jo que es vol fer i els múltiples personatges que, des del mirall, li retornen una imatge múltiple». En aquest article, per explorar el tema de l’imaginari femení i el llenguatge poètic, hem escollit dialogar amb Maria- Mercè Marçal i examinar tres dels múltiples bocins que conformen la seva imatge en el mirall. Conversem amb dues mares i un pare simbòlics de l’altre cantó del seu espill, tots tres proveïdors de material ideològic i eixos vertebradors dels assaigs marçalians. Es tracta d’intel·lectuals ben diversos: l’escriptora anglesa Virginia Woolf, el filòsof francès Jacques Derrida i la poeta catalana Maria-Antònia Salvà. En definitiva, dividim la investigació en tres apartats, que volen coincidir amb el diàleg que Marçal suposem que hi mantingué. De primer, amb Virginia Woolf, explorem la necessitat de la poeta de descobrir el sentiment de «fúria» que porta a dins per tal d’assumir la irracionalitat del seu llenguatge. Després, ens endinsem en les teories derridianes sobre la dona i l’escriptura, en un intent de demostrar que ambdues són espècies híbrides que viuen en el llindar, en un espai d’entremig. A l’últim, amb Maria-Antònia Salvà, revisem la imatge de la dona-monstre amb la certesa que «el salvatge» i «l’incert » són el motor del llenguatge poètic femení.

Glucocorticoid-induced MIF expression by human CEM T cells.

Macrophage migration inhibitory factor (MIF) is an upstream activator of the immune response that counter-regulates the immunosuppressive effects of glucocorticoids. While MIF is released by cells in response to diverse microbial and invasive stimuli, evidence that glucocorticoids in low concentrations also induce MIF secretion suggests an additional regulatory relationship between these mediators. We investigated the expression of MIF from the human CEM T cell line, which exists in two well-characterized, glucocorticoid-sensitive (CEM-C7) and glucocorticoid-resistant (CEM-C1) variant clones. Dexamethasone in low concentrations induced MIF secretion from CEM-C7 but not CEM-C1 T cells by a bell-shaped dose response that was similar to that reported previously for the release of MIF by monocytes/macrophages. Glucocorticoid stimulation of CEM-C7 T cells was accompanied by an MIF transcriptional response, which by promoter analysis was found to involve the GRE and ATF/CRE transcription factor binding sites. These data support a glucocorticoid-mediated MIF secretion response by T cells that may contribute to the regulation of the adaptive immune response.

Long term retention of retigabine in a cohort of people with drug resistant epilepsy.

PURPOSE: To assess the utility of retigabine (RTG) for epilepsy in clinical practice at a single UK tertiary centre. METHODS: We identified all individuals who were offered RTG from April 2011 to May 2013. We collected demographics, seizure types, previous and current antiepileptic drugs (AEDs), starting and maximum attained daily dose of RTG, clinical benefits, side effects, and reason to discontinue RTG from in- and outpatient encounters until February 28, 2014. RESULTS: 145 people who had failed a median of 11 AEDs took at least one dose of RTG. One year retention was 32% and decreased following the safety alert by the US Federal Drug Administration (FDA) in April 2013. None became seizure free. 34 people (24%) reported a benefit that was ongoing at last assessment in five (3%). The most relevant benefit was the significant reduction or cessation of drop attacks or seizure-related falls in four women, this persisted at last assessment in two. The presence of simple partial seizures was associated with longer retention, as was a higher attained dose of RTG. Adverse effects were seen in 74% and largely CNS-related or nonspecific and affected the genitourinary system in 13%. CONCLUSION: Retention of RTG was less favourable compared to data from open label extension studies of the regulatory trials. In comparison with historical data on similar retention audits retention of RTG at one year appears to be less than lamotrigine, topiramate, levetiracetam, pregabalin, zonisamide, and lacosamide, and slightly higher than gabapentin.

Anàlisi experimental de la capacitat d'emmagatzematge d'energia tèrmica de dos tancs connectats en cascada amb diferent pcm

En aquest treball es pretén estudiar el potencial d'emmagatzematge d'energia tèrmica, per aplicacions de refrigeració solar d'un sistema format per dos tancs intercanviadors acumuladors connectats en cascada. Cada tanc conté un PCM diferent amb diferent temperatura de canvi de fase. Concretament es tracta d'hidroquinona i d-mannitol. Els quals posseixen temperatures de canvi de fase entre 140 i 200 Cº requerides per aplicacions de fred solar. També es pretén comparar el sistema en cascada amb el mateix sistema connectat en paral·lel.