Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies

Alcohol use disorders are influenced by many interacting genetic and environmental factors. Highlighting this complexity is the observation that large genome-wide association experiments have implicated many genes with weak statistical support. Experimental model systems, cell culture and animal, have identified many genes and pathways involved in ethanol response, but their applicability to the development of alcohol use disorders in humans is undetermined. To overcome the limitations of any single experimental system, the analytical strategy used here was to identify genes that exert common phenotypic effects across multiple experimental systems. Specifically, we (1) performed a mouse linkage analysis to identify quantitative trait loci that influence ethanol-induced ataxia; (2) performed a human genetic association analysis of the mouse-identified loci against ethanol-induced body sway, a phenotype that is not only comparable to the mouse ethanol-ataxia phenotype but is also a genetically influenced endophenotype of alcohol use disorders; (3) performed behavioral genetic experiments in Drosophila showing that fly homologs of GPC5, the member of the glypican gene family implicated by both the human and mouse genetic analyses, influence the fly’s response to ethanol; and (4) discovered data from the literature demonstrating that the genetically implicated gene’s expression is not only temporally and spatially consistent with involvement in ethanol-induced behaviors but is also modulated by ethanol. The convergence of these data provides strong support to the hypothesis that GPC5 is involved in cellular and organismal ethanol response and the etiology of alcohol use disorders in humans

La motivación personal del estudiante al servicio de la creatividad para solucionar problemas: un proyecto de extensión

En este trabajo, se aborda una experiencia de docencia universitaria basada en la motivación personal de los estudiantes al servicio de la creatividad para la resolución de problemas, en el contexto de un Proyecto de Extensión. La experiencia comprendió a tres cursos de la Universidad Nacional de la Patagonia San Juan Bosco (UNPSJB), Argentina, en los cuales las clases se imparten en modalidad presencial complementadas con entornos virtuales de aprendizaje y se utilizan metodologías activas de aprendizaje. Se describen el marco teórico, el contexto, la experiencia realizada, los resultados obtenidos y las conclusiones. La motivación de los estudiantes en participar en la solución de problemas de la comunidad y su creatividad evidenciada a través de las soluciones propuestas, ha motivado la necesidad de profundizar estos aspectos en investigaciones futuras, mediante el trabajo conjunto entre la UNPSJB y el Centro de Tecnología y Docencia (CTED) de la Universidad de Concepción (Chile)

SARS Risk Perception, Knowledge, Precautions, and Information Sources, the Netherlands

Severe acute respiratory syndrome (SARS)–related risk perceptions, knowledge, precautionary actions, and information sources were studied in the Netherlands during the 2003 SARS outbreak. Although respondents were highly aware of the SARS outbreak, the outbreak did not result in unnecessary precautionary actions or fears

Additive amelioration of ALS by co-targeting independent pathogenic mechanisms.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which glia are central mediators of motor neuron (MN) death. Since multiple cell types are involved in disease pathogenesis, the objective of this study was to determine the benefit of co-targeting independent pathogenic mechanisms in a familial ALS mouse model. METHODS: Recently, our laboratory identified that ALS microglia induce MN death in an NF-κB-dependent mechanism. We also demonstrated that a single, post-natal, intravenous injection of adeno-associated viral vector serotype 9 encoding a shRNA against mutant SOD1 is able to traverse the blood-brain barrier of ALS mice and reduce SOD1-expression in astrocytes and MNs. Reducing mutant SOD1 in MNs and astrocytes led to a robust increase in survival. To evaluate the benefit of co-targeting multiple cell types in ALS, we combined microglial NF-κB suppression with SOD1 reduction in astrocytes and MNs. RESULTS: Targeting both astrocytes and microglia resulted in an additive increase in survival and motor function by delaying both onset and progression. Strikingly, targeting all three cell types (astrocytes, motor neurons [MNs], and microglia) resulted in an additive increase in lifespan and motor function, with maximum survival reaching 204 days, 67 days longer than the mean survival of untreated control animals. INTERPRETATION: Our data suggest that a combinatorial approach co-targeting different pathogenic mechanisms in independent cell types is a beneficial therapeutic strategy for ALS

Hacia el fortalecimiento de la sociedad en el uso y aplicación de la información geospacial y las TIC

Tanto la concepción tradicional de “Sociedad Civil” como la nueva concepción de la “Sociedad del Conocimiento” tienen como eje central de desarrollo el sentido de la comunicación y el sentido de territorio. Si bien las tecnologías asociadas a cada concepción distinguen características culturales diferentes y propias en las cuales ambos conceptos fueron acuñados respectivamente, hay una comunión en ambos constructos que se basan en la comunicación y el territorio. El presente proyecto trata de acercar a toda la sociedad al uso, aplicación y conocimiento de la información a través del empleo de tecnologías y tecnologías geoespaciales. Considerando sectores gubernamentales, públicos y privados trata de integrar temáticas relevantes como: tecnologías de acceso, información territorial, ontologías, infraestructura de datos espaciales. Nuestra motivación surge del hecho que el propio territorio ha estado vinculado históricamente a la pertenencia cultural, pero hoy en día esa pertenencia se ha visto modificada con la globalización y las nuevas formas de vincularnos y comunicarnos. Hoy en día se caracteriza por las facilidades a las cuales tiene acceso el ser humano (o una institución), a qué redes y sobre qué acciones territoriales puede incidir. En el caso del gobierno, está en función también del desarrollo sustentable que fomenta a través de gestión geoespacial.Eje: Innovación en Sistemas de SoftwareRed de Universidades con Carreras en Informática (RedUNCI

'Willy nilly' doctors, bad patients, and resistant bodies in general public explanations of antimicrobial resistance

Increased public engagement is a feature of policy and communications focussed on the reduction of antimicrobial resistance. Explaining antimicrobial resistance for general publics has proven difficult and they continue to endorse apparently mistaken knowledge, including the conflation of antimicrobial resistance with the notion of the resistant body. We interviewed members of the general public in Melbourne, Australia, to explore explanatory models for antimicrobial resistance and shed light on the persistence of the resistant body assumption and related concepts. In the face of AMR’s complexity and the portended antibiotic apocalypse, publics rely on a heavily inscribed understanding of the body defending itself against microbes. Publics also read antibiotic misuse and overuse messages as the responsibility of other patients and medical practitioners, and not themselves. Significantly, the scientific world view that has created expert knowledge about AMR hails publics in ways that discredits them and limits their capacity to take action. Increased engagement with publics will be required to ensure that collaborative and sustainable AMR approaches are fashioned for the future

Individual variation in incentive salience attribution and accumbens dopamine transporter expression and function

Cues (conditioned stimuli; CSs) associated with rewards can come to motivate behavior, but there is considerable individual variation in their ability to do so. For example, a lever-CS that predicts food reward becomes attractive, wanted, and elicits reward-seeking behavior to a greater extent in some rats (“sign-trackers”; STs), than others (“goal-trackers”; GTs). Variation in dopamine (DA) neurotransmission in the nucleus accumbens (NAc) core is thought to contribute to such individual variation. Given that the DA transporter (DAT) exerts powerful regulation over DA signaling, we characterized the expression and function of the DAT in the accumbens of STs and GTs. STs showed greater DAT surface expression in ventral striatal synaptosomes than GTs, and ex vivo fast-scan cyclic voltammetry recordings of electrically-evoked DA release confirmed enhanced DAT function in STs, as indicated by faster DA uptake, specifically in the NAc core. Consistent with this, systemic amphetamine (AMPH) produced greater inhibition of DA uptake in STs than in GTs. Furthermore, injection of AMPH directly into the NAc core enhanced lever-directed approach in STs, presumably by amplifying the incentive value of the CS, but had no effect on goal tracking behavior. On the other hand, there were no differences between STs and GTs in electrically-evoked DA release in slices, or in total ventral striatal DA content. We conclude that greater DAT surface expression may facilitate the attribution of incentive salience to discrete reward cues. Investigating this variability in animal sub-populations may help explain why some people abuse drugs, while others do not

SLC6A3 and body mass index in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

<p>Abstract</p> <p>Background</p> <p>To investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(<it>SLC6A3</it>) and body mass index (BMI), among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.</p> <p>Methods</p> <p>Four polymorphisms (rs6350, rs6413429, rs6347 and the 3' variable number of tandem repeat (3' VNTR) polymorphism) at the <it>SLC6A3 </it>gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (<18.5, 18.5–24.9, 25.0–29.9, or ≥ 30 kg/m², respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of <it>SLC6A3 </it>genotypes and haplotypes were computed using conditional logistic regression.</p> <p>Results</p> <p>Compared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the <it>3' </it>VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR_*9= 0.80, OR₉₉= 0.47, p_trend= 0.005). Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; OR_A-C-G-9= 0.80, 95% CI 0.65–0.99, p = 0.04) and obese individuals (A-C-G-* is referent; OR_A-C-G-9= 0.70, 95% CI 0.49–0.99, p = 0.04) were less likely to possess the haplotype with the 3'variant allele (A-C-G-9).</p> <p>Conclusion</p> <p>Our results support a role of genetic variation at the dopamine transporter gene, <it>SLC6A3</it>, as a modifier of BMI.</p

Theoretical considerations in reducing risk for cardiovascular disease: Implications for nursing practice

Aims and objectives: This article describes the theoretical foundation of risk perception as a key component of changing deleterious health behaviours associated with cardiovascular disease (CVD). Furthermore, perception in increasing cardiovascular risk-reducing behaviours in a socio-cultural framework is discussed, and an empirical development conceptual model presented. Background: Perception of risk is strongly linked with health-seeking behaviours. Understanding how to reduce risk and maximise cardiovascular health is an increasing focus of clinicians, researchers and policy makers. Increasing cultural diversity in contemporary society means that nurses need to develop and evaluate interventions in this context. Design: An integrative literature review. Method: An integrative literature review method was used to assess conceptual models relating to risk perception of developing CVD. On the basis of the findings, a model was developed to inform future intervention studies, considering individual, social and cultural factors. Discussion: Studies examining CVD and health behaviours report that there is limited concordance between actual and perceived risk in people with CVD. This mismatch risk likely impedes the adoption of risk-reducing behaviours. Conclusion: There is a critical need to develop interventions for enhancing an accurate perception of CVD risk considering not only individual but social factors. Relevance to clinical practice: There is limited correlation between knowledge and behaviours, and health behaviours are influenced by individual, social and cultural factors. Appraising the congruence between actual and perceived risk is an important step in developing effective care plans to reduce cardiovascular risk. © 2010 Blackwell Publishing Ltd