Resistivity of non-Fermi liquid U2Pt2In under pressure

Non-Fermi liquid behaviour in single-crystalline U2Pt2In has been studied by means of resistivity experiments (I||c) under hydrostatic pressure (P<1.5 GPa). At ambient pressure the resistivity rho(T) follows a power law rho~T^alpha with alpha~0.5. Upon applying pressure alpha increases. For P>1 GPa a minimum develops in rho(T). A study of the field dependence of the minimum confirms its magnetic origin. The ratio c/a is proposed as the effective control parameter, rather than the unit cell volume.Comment: 5 pages (incl. 2 figures), submitted to SCES'99, Nagan

Caffeine and adenosine A 2A receptor inactivation decrease striatal neuropathology in a lentiviral-based model of Machado–Joseph disease

Objective: Machado–Joseph disease (MJD) is a neurodegenerative disorder associated with an abnormal CAG expansion, which translates into an expanded polyglutamine tract within ataxin-3. There is no therapy to prevent or modify disease progression. Because caffeine (a nonselective adenosine receptor antagonist) and selective adenosine A2A receptor (A2A R) blockade alleviate neurodegeneration in different brain diseases, namely at early stages of another polyglutamine-related disorder such as Huntington’s disease, we now tested their ability to control MJD-associated neurodegeneration. Methods: MJD was modeled by transducing the striatum of male adult C57Bl/6 mice with lentiviral vectors encoding mutant ataxin-3 in one hemisphere and wild-type ataxin-3 in the other hemisphere (as internal control). Caffeine (1g/L) was applied through the drinking water. Mice were killed at different time points (from 2 to 12 weeks) to probe for the appearance of different morphological changes using immunohistochemical analysis. Results: Mutant ataxin-3 caused an evolving neuronal dysfunction (loss of DARPP-32 staining) leading to neurodegeneration (cresyl violet and neuronal nuclei staining) associated with increased number of mutant ataxin-3 inclusions in the basal ganglia. Notably, mutant ataxin-3 triggered early synaptotoxicity (decreased synaptophysin and microtubule-associated protein-2 staining) and reactive gliosis (glial fibrillary acidic protein and CD11b staining), which predated neuronal dysfunction and damage. Caffeine reduced the appearance of all these morphological modifications, which were also abrogated in mice with a global A2A R inactivation (knockout). Interpretation: Our findings provide a demonstration that synaptotoxicity and gliosis are precocious events in MJD and that caffeine and A2A R inactivation decrease MJD-associated striatal pathology, which paves the way to consider A2A Rs as novel therapeutic targets to manage MJD

Use of laser speckle and entropy computation to segment images of diffuse objects with longitudinal motion

International audienc

Prevalência da exposição ao fumo ambiental do tabaco em casa e do tabagismo na população Portuguesa – o estudo INAsma

ResumoIntroduçãoNeste estudo, pretendemos: 1) estimar a prevalência, na população portuguesa, da exposição ao fumo ambiental do tabaco em casa; 2) estimar a prevalência de tabagismo em Portugal; 3) identificar as características sociais e pessoais associadas ao tabagismo ou à exposição ao fumo ambiental do tabaco.MétodosEstudo transversal consistindo na aplicação, à população, a nível nacional, de questionário telefónico. Completaram a entrevista 6 003 indivíduos. A exposição ao fumo ambiental do tabaco em casa foi definida como a exposição, em casa, ao fumo do tabaco de, pelo menos, um fumador atual. Por fumador entendeu-se um indivíduo com ≥ 15 anos que fumou, pelo menos, um cigarro por dia durante um período de um ano; um fumador atual fumou no último mês.ResultadosReferiram exposição ao fumo ambiental do tabaco em casa 26,6% dos participantes (IC 95%: 25,5-27,7). Viver num agregado familiar constituído por ≥ 4 pessoas (OR=2,31; IC 95%: [1,81-2,96]), ser fumador atual (OR=7,29; IC 95%: [5,74-9,26]) ou ter asma atual (OR=2,06; IC 95%: [1,45-2,94]) associaram-se positivamente à exposição ao fumo ambiental do tabaco. Na análise estratificada por sexo, o efeito da asma atual manteve-se apenas nas mulheres.Atualmente, 19,0% (IC 95%: 18,0-20,0) da população portuguesa é fumadora e 17,2% (IC 95%: 16,2-18,2) são ex-fumadores. A prevalência de fumadores atuais é mais elevada nos homens do que nas mulheres (26,5 versus 12,2%, p<0,001). A probabilidade de ser um fumador atual foi maior nos homens, nas pessoas mais instruídas e nos indivíduos expostos, em casa, ao fumo ambiental do tabaco. Na análise estratificada por sexo, o efeito da escolaridade manteve-se apenas nas mulheres.ConclusãoA exposição ao fumo ambiental do tabaco em casa foi mais elevada do que a anteriormente publicada. Crianças/adolescentes e doentes com asma podem ter um risco de exposição ambiental mais elevado. Este estudo apoia uma tendência decrescente da prevalência de tabagismo nos homens portugueses, mas uma tendência crescente nas mulheres.AbstractBackgroundWe aimed to: 1) estimate the prevalence of exposure to environmental tobacco smoke (ETS) at home in the Portuguese population; 2) estimate tobacco smoking prevalence in Portugal; 3) identify social and personal characteristics associated with smoking or exposure to ETS.MethodsNationwide, cross-sectional, population-based telephone survey. Overall, 6003 individuals completed the interview. ETS exposure at home was defined as exposure to at least one current smoker at home. A smoker was defined as someone with 15 years or older, smoking at least 1 cigarette per day during a year; a current smoker (CS) smoked in the last month.ResultsExposure to ETS at home was reported by 26.6% (95%CI 25.5-27.7) of the participants. Living in households with ≥4 persons (OR=2.31; 95%CI[1.81-2.96]), being a current smoker (OR=7.29; 95%CI[5.74-9.26]) or having current asthma (OR=2.06; 95%CI[1.45-2.94]) were factors positively associated with ETS exposure. When analyzed by gender, the effect of current asthma was only relevant to females.Currently 19.0% (95%CI 18.0-20.0) of the Portuguese population smokes tobacco and 17.2% (95%CI 16.2-18.2) are ex-smokers. CS prevalence is higher in males than females (26.5%versus 12.2%, p<0,001). The odds of being a CS were higher for males, the more educated, and those exposed to ETS at home. When analyzed by gender, school education only affected females.ConclusionExposure to ETS at home was higher than previously reported. Children/adolescents and asthma patients may have a higher risk of exposure. This report endorses a decreasing trend in the prevalence of tobacco smoking in Portuguese males, but a tendency to increase in females

Calpastatin-mediated inhibition of calpains in the mouse brain prevents mutant ataxin 3 proteolysis, nuclear localization and aggregation, relieving Machado-Joseph disease

Machado-Joseph disease is the most frequently found dominantly-inherited cerebellar ataxia. Over-repetition of a CAG trinucleotide in the MJD1 gene translates into a polyglutamine tract within the ataxin 3 protein, which upon proteolysis may trigger Machado-Joseph disease. We investigated the role of calpains in the generation of toxic ataxin 3 fragments and pathogenesis of Machado-Joseph disease. For this purpose, we inhibited calpain activity in mouse models of Machado-Joseph disease by overexpressing the endogenous calpain-inhibitor calpastatin. Calpain blockage reduced the size and number of mutant ataxin 3 inclusions, neuronal dysfunction and neurodegeneration. By reducing fragmentation of ataxin 3, calpastatin overexpression modified the subcellular localization of mutant ataxin 3 restraining the protein in the cytoplasm, reducing aggregation and nuclear toxicity and overcoming calpastatin depletion observed upon mutant ataxin 3 expression. Our findings are the first in vivo proof that mutant ataxin 3 proteolysis by calpains mediates its translocation to the nucleus, aggregation and toxicity and that inhibition of calpains may provide an effective therapy for Machado-Joseph diseas