Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders

Eating disorders (EDs) are complex psychiatric diseases that include anorexia nervosa and bulimia nervosa, and have higher than 50% heritability. Previous studies have found association of BDNF and NTRK2 to ED, while animal models suggest that other neurotrophin genes might also be involved in eating behavior. We have performed a family-based association study with 151 TagSNPs covering 10 neurotrophin signaling genes: NGFB, BDNF, NTRK1, NGFR/p75, NTF4/5, NTRK2, NTF3, NTRK3, CNTF and CNTFR in 371 ED trios of Spanish, French and German origin. Besides several nominal associations, we found a strong significant association after correcting for multiple testing (P = 1.04 × 10−4) between ED and rs7180942, located in the NTRK3 gene, which followed an overdominant model of inheritance. Interestingly, HapMap unrelated individuals carrying the rs7180942 risk genotypes for ED showed higher levels of expression of NTRK3 in lymphoblastoid cell lines. Furthermore, higher expression of the orthologous murine Ntrk3 gene was also detected in the hypothalamus of the anx/anx mouse model of anorexia. Finally, variants in NGFB gene appear to modify the risk conferred by the NTRK3 rs7180942 risk genotypes (P = 4.0 × 10−5) showing a synergistic epistatic interaction. The reported data, in addition to the previous reported findings for BDNF and NTRK2, point neurotrophin signaling genes as key regulators of eating behavior and their altered cross-regulation as susceptibility factors for EDs.

Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.

Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins

Voltage-gated K+ channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to −10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 −/− mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.

Invisible work, unseen hazards: the health of women immigrant household service workers in Spain

Backgroud: Household service work has been largely absent from occupational health studies. We examine the occupational hazards and health effects identified by immigrant women household service workers. Methods: Exploratory, descriptive study of 46 documented and undocumented immigrant women in household services in Spain, using a phenomenological approach. Data were collected between September 2006 and May 2007 through focus groups and semi-structured individual interviews. Data were separated for analysis by documentation status and sorted using a mixed-generation process. In a second phase of analysis, data on psychosocial hazards were organized using the Copenhagen Psychosocial Questionnaire as a guide. Results: Informants reported a number of environmental, ergonomic and psychosocial hazards and corresponding health effects. Psychosocial hazards were especially strongly present in data. Data on reported hazards were similar by documentation status and varied by several emerging categories: whether participants were primarily cleaners or carers and whether they lived in or outside of the homes of their employers. Documentation status was relevant in terms of empowerment and bargaining, but did not appear to influence work tasks or exposure to hazards directly. Conclusions:Female immigrant household service workers are exposed to a variety of health hazards that could be acted upon by improved legislation, enforcement, and preventive workplace measures, which are discussed.

The quest for a message: budding yeast, a model organism to study the control of pre-mRNA splicing

Removal of introns during pre-mRNA splicing is a critical process in gene expression, and understanding its control at both single-gene and genomic levels is one of the great challenges in Biology. Splicing takes place in a dynamic, large ribonucleoprotein complex known as the spliceosome. Combining Genetics and Biochemistry, Saccharomyces cerevisiae provides insights into its mechanisms, including its regulation by RNA-protein interactions. Recent genome-wide analyses indicate that regulated splicing is broad and biologically relevant even in organisms with a relatively simple intronic structure, such as yeast. Furthermore, the possibility of coordination in splicing regulation at genomic level is becoming clear in this model organism. This should provide a valuable system to approach the complex problem of the role of regulated splicing in genomic expression.

Toward integrated management of cerebral aneurysms

In the last few years, some of the visionary concepts behind the virtual physiological human began to be demonstrated on various clinical domains, showing great promise for improving healthcare management. In the current work, we provide an overview of image- and biomechanics-based techniques that, when put together, provide a patient-specific pipeline for the management of intracranial aneurysms. The derivation and subsequent integration of morphological, morphodynamic, haemodynamic and structural analyses allow us to extract patient-specific models and information from which diagnostic and prognostic descriptors can be obtained. Linking such new indices with relevant clinical events should bring new insights into the processes behind aneurysm genesis, growth and rupture. The development of techniques for modelling endovascular devices such as stents and coils allows the evaluation of alternative treatment scenarios before the intervention takes place and could also contribute to the understanding and improved design of more effective devices. A key element to facilitate the clinical take-up of all these developments is their comprehensive validation. Although a number of previously published results have shown the accuracy and robustness of individual components, further efforts should be directed to demonstrate the diagnostic and prognostic efficacy of these advanced tools through large-scale clinical trials.

Contrasting the form and use of reformulation markers

This paper deals with the form and use of reformulation markers in research papers written in English, Spanish and Catalan. Considering the form and frequency of themarkers, English papers tends to prefer simple fixed markers and includes less reformulators than Spanish and Catalan. On the contrary, formal Catalan and Spanish papers include more markers, some of which are complex and allow for some structural variability. As for use, reformulation markers establish dynamic relationships between portions of discourse which can be identified in our corpus with expansion, reduction, and permutation. The analysis of the corpus shows that English authors usually reformulate to add more information to the concept (expansion), whereas Catalan and Spanish authors reduce the contents or the implicatures of the previous formulation more frequently than English.

Reconciling context and contact with immigrants effects: an examination of the Catalan case

Contact theory and threat group theory offer contradictory hypotheses regarding the effect of contact with immigrants. Despite recent efforts to test the validity of both approaches, we still lack a definitive conclusion. This article integrates both approaches and tests the effect of contact towards immigrants and how this changes when different contexts are considered. Mainly, we investigate the effect of the economic environment and the immigrant group size on modifying attitudes toward immigration. The hypotheses, which are tested in Catalonia, show that contact with immigrants reduce negative attitudes towards immigration, especially friendship and family contact. However, mixed results are reported regarding the effect of economic environment and immigrant group size. Whereas the former modifies positively the effect of workplace contact, the latter has no effect. Findings have implications for the impact of context when dealing with the impact of contact on attitudes towards immigration.

Amelioration of Duchenne muscular dystrophy in mdx mice by elimination of matrix-associated fibrin-driven inflammation coupled to the αMβ2 leukocyte integrin receptor

In Duchenne muscular dystrophy (DMD), a persistently altered and reorganizing extracellular matrix (ECM) within inflamed muscle promotes damage and dysfunction. However, the molecular determinants of the ECM that mediate inflammatory changes and faulty tissue reorganization remain poorly defined. Here, we show that fibrin deposition is a conspicuous consequence of muscle-vascular damage in dystrophic muscles of DMD patients and mdx mice and that elimination of fibrin(ogen) attenuated dystrophy progression in mdx mice. These benefits appear to be tied to: (i) a decrease in leukocyte integrin α(M)β(2)-mediated proinflammatory programs, thereby attenuating counterproductive inflammation and muscle degeneration; and (ii) a release of satellite cells from persistent inhibitory signals, thereby promoting regeneration. Remarkably, Fib-gamma(390-396A) (Fibγ(390-396A)) mice expressing a mutant form of fibrinogen with normal clotting function, but lacking the α(M)β(2) binding motif, ameliorated dystrophic pathology. Delivery of a fibrinogen/α(M)β(2) blocking peptide was similarly beneficial. Conversely, intramuscular fibrinogen delivery sufficed to induce inflammation and degeneration in fibrinogen-null mice. Thus, local fibrin(ogen) deposition drives dystrophic muscle inflammation and dysfunction, and disruption of fibrin(ogen)-α(M)β(2) interactions may provide a novel strategy for DMD treatment.

La situación de las mujeres en el mercado laboral en Cataluña y Bélgica

Actualment el paper que desenvolupen dones i homes en el mercat laboral i les seves oportunitats son diferenciades per ambdós, motiu pel qual en las últimes dècades s’ha posat un gran accent en l’elaboració i l’anàlisi d’estadístiques per sexes. Aquest treball es una guia que ens mostra la situació de les dones en el mercat laboral a Catalunya i Bèlgica. D’aquesta forma, cerquem conèixer en quin mercat laboral seria més fàcil trobar un adequat treball per una dona, en aspectes com la taxa d’atur, la jornada laboral, el sector i el salari. Per realitzar aquest treball ens plantegem analitzar la següent hipòtesi: “La situació de la dona en el mercat laboral a Bèlgica, en referència a la taxa d’atur, la jornada laboral, l’elecció del sector y del salari, es millor que en el mercat laboral a Catalunya. Per resoldre aquesta hipòtesis, estudiarem la taxa d’activitat, la taxa d’ocupació i la taxa d’atur a Catalunya i Bèlgica. Aquestes taxes ens permeten quantificar clarament les diferencies existents en el mercat laboral entre homes i dones. A més, realitzarem un anàlisis per conèixer la jornada que predomina a Catalunya i Bèlgica per sexes. Una manifestació de la desigualtat laboral es la distribució dels treballadors en les diverses branques d’activitat i ocupació. Per això, ens hem proposat identificar la distribució dels treballadors per sexe en els diversos sectors econòmics. D’aquesta manera, podrem conèixer la feminització dels sectors. Finalment analitzarem els salaris per sexes, tant a Catalunya com a Bèlgica. Així mateix, podrem esbrinar en quin mercat laboral, si a Catalunya o a Bèlgica, els salaris són més alts. Al mateix temps que realitzem una comparació entre el guany real d’un treballador i el salari mínim interprofessional.

Socio-economic benefits of using space technologies to monitor and respond to earthquakes

Earthquakes represent a major hazard for populations around the world, causing frequent loss of life,human suffering and enormous damage to homes, other buildings and infrastructure. The Technology Resources forEarthquake Monitoring and Response (TREMOR) Team of 36 space professionals analysed this problem over thecourse of the International Space University Summer Session Program and published their recommendations in the formof a report. The TREMOR Team proposes a series of space- and ground-based systems to provide improved capabilityto manage earthquakes. The first proposed system is a prototype earthquake early-warning system that improves theexisting knowledge of earthquake precursors and addresses the potential of these phenomena. Thus, the system willat first enable the definitive assessment of whether reliable earthquake early warning is possible through precursormonitoring. Should the answer be affirmative, the system itself would then form the basis of an operational earlywarningsystem. To achieve these goals, the authors propose a multi-variable approach in which the system will combine,integrate and process precursor data from space- and ground-based seismic monitoring systems (already existing andnew proposed systems) and data from a variety of related sources (e.g. historical databases, space weather data, faultmaps). The second proposed system, the prototype earthquake simulation and response system, coordinates the maincomponents of the response phase to reduce the time delays of response operations, increase the level of precisionin the data collected, facilitate communication amongst teams, enhance rescue and aid capabilities and so forth. It isbased in part on an earthquake simulator that will provide pre-event (if early warning is proven feasible) and post-eventdamage assessment and detailed data of the affected areas to corresponding disaster management actors by means of ageographic information system (GIS) interface. This is coupled with proposed mobile satellite communication hubs toprovide links between response teams. Business- and policy-based implementation strategies for these proposals, suchas the establishment of a non-governmental organisation to develop and operate the systems, are included.

Aportacions per a una bibliografia de l'exili republicà català, valencià i balear als Estats Units d'Amèrica

This article attempts to gather together the work published in the United States and Puerto Rico by Spanish Civil War exiles of Catalan, Valencia and Balearic origin. Included are books, serials, sheet music, sound recordings and domestic movie videos, which have appeared in US territory from 1936 through 2004. The objective of the bibliography is to provide both an overview and a starting point for recovering the intellectual effort carried out by these exiles because this first inventory must still be completed with the addition of journal articles, contributions to monographs, and conference proceedings. There have also been exiles for whom books, music or videos have not been found, but for whom a certain level of intellectual activity is known or suspected. Such potential work would include articles and other contributions to journals in the US or cultural and membership activities of Catalan communities in that country. Without being able to offer definitive conclusions, it appears that exile in North America was a solitary experience, and never as a cohesive group or with the ties of mutual interests as was the case in Mexico or even in France. There were neither readers nor publishers to facilitate publication and to serve for creating group cohesiveness.

Els Factors competitius de les pimes a Catalunya

El principal objectiu d'aquest estudi és reflectir quins són els principals factors competitius per a les pymes a Catalunya. Per això, es va escollir una mostra de 1000 empreses de diferents sectors i amb els límits que marca la Unió Europea per a definir una pyme. A partir d'aquí, es va analitzar la informació financera. Amb aquesta font d'informació, es va poder arribar a la conclusió que tots aquells aspectes relacionats amb el personal i reflectits a través de ràtios, eren els més significatius estadísticament per a poder explicar la rendibilitat en les empreses. També es va enviar un qüestionari a la mostra esmentada i es va preguntar el punt de vista del gestor o empresari. Només 50 empreses van contestar, i una vegada més, el factor humà es va revelar com el més important. S'ha d'assenyalar que altres elements tals com la inversió en tecnologia, que s'esperava fossin significatius, no van donar els resultats esperats en el sentit que cap altre fos considerat tan rellevant com els recursos humans.

Els Factors competitius de les pimes a Catalunya

El principal objectiu d'aquest estudi és reflectir quins són els principals factors competitius per a les pymes a Catalunya. Per això, es va escollir una mostra de 1000 empreses de diferents sectors i amb els límits que marca la Unió Europea per a definir una pyme. A partir d'aquí, es va analitzar la informació financera. Amb aquesta font d'informació, es va poder arribar a la conclusió que tots aquells aspectes relacionats amb el personal i reflectits a través de ràtios, eren els més significatius estadísticament per a poder explicar la rendibilitat en les empreses. També es va enviar un qüestionari a la mostra esmentada i es va preguntar el punt de vista del gestor o empresari. Només 50 empreses van contestar, i una vegada més, el factor humà es va revelar com el més important. S'ha d'assenyalar que altres elements tals com la inversió en tecnologia, que s'esperava fossin significatius, no van donar els resultats esperats en el sentit que cap altre fos considerat tan rellevant com els recursos humans.

Neck pounding during sinus rhythm: a new clinical manifestation of dual atrioventricular nodal pathways

Objective To determine the clinical and electrophysiological characteristics of patients with paroxysmal palpitations and neck pounding during sinus rhythm. Methods Clinical, electrocardiographic, and electrophysiological characteristics of six patients with paroxysmal palpitations and neck pounding during sinus rhythm were studied in basal conditions and when symptomatic. Response to treatment was observed. Results Baseline ECGs were normal (four patients) or had first degree atrioventricular block with intermittent PR shortening. During symptoms, narrow QRS rhythms were seen without visible P waves (three patients) or with P waves partially hidden in the QRS complex (three patients). Dual atrioventricular nodal pathways were found in all five patients who had electrophysiological studies. In these patients the slow pathway conduction time was long enough (mean (SD), 425 (121)¿ms) for ventricular activation after slow pathway conduction during sinus rhythm to coincide with the next atrial depolarisation, causing neck pounding during exercise (four patients) or at rest (two patients). Tachycardia was not induced in any patient. Medical treatment aggravated symptoms in three patients. A pacemaker was successfully used in two. Conclusions Neck pounding during sinus rhythm is a clinical manifestation of dual atrioventricular nodal pathways. Medical treatment may aggravate symptoms but a pacemaker may offer definitive relief.