Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a

Voltage-gated sodium channels drive the initial depolarization phase of the cardiac action potential and therefore critically determine conduction of excitation through the heart. In patients, deletions or loss-of-function mutations of the cardiac sodium channel gene, SCN5A, have been associated with a wide range of arrhythmias including bradycardia (heart rate slowing), atrioventricular conduction delay, and ventricular fibrillation. The pathophysiological basis of these clinical conditions is unresolved. Here we show that disruption of the mouse cardiac sodium channel gene, Scn5a, causes intrauterine lethality in homozygotes with severe defects in ventricular morphogenesis whereas heterozygotes show normal survival. Whole-cell patch clamp analyses of isolated ventricular myocytes from adult Scn5a(+/-) mice demonstrate a approximate to50% reduction in sodium conductance. Scn5a(+/-) hearts have several defects including impaired atrioventricular conduction, delayed intramyocardial conduction, increased ventricular refractoriness, and ventricular tachycardia with characteristics of reentrant excitation. These findings reconcile reduced activity of the cardiac sodium channel leading to slowed conduction with several apparently diverse clinical phenotypes, providing a model for the detailed analysis of the pathophysiology of arrhythmias.

Analysis of the mouse transcriptome for genes involved in the function of the nervous system

We analyzed the mouse Representative Transcript and Protein Set for molecules involved in brain function. We found full-length cDNAs of many known brain genes and discovered new members of known brain gene families, including Family 3 G-protein coupled receptors, voltage-gated channels, and connexins. We also identified previously unknown candidates for secreted neuroactive molecules. The existence of a large number of unique brain ESTs suggests an additional molecular complexity that remains to be explored. A list of genes containing CAG stretches in the coding region represents a first step in the potential identification of candidates for hereditary neurological disorders.

The mouse secretome: functional classification of the proteins secreted into the extracellular environment

We have developed a computational strategy to identify the set of soluble proteins secreted into the extracellular environment of a cell. Within the protein sequences predominantly derived from the RIKEN representative transcript and protein set, we identified 2033 unique soluble proteins that are potentially secreted from the cell. These proteins contain a signal peptide required for entry into the secretory pathway and lack any transmembrane domains or intracellular localization signals. This class of proteins, which we have termed the mouse secretome, included >500 novel proteins and 92 proteins

Effects of combined low-density lipoprotein apheresis and aggressive statin therapy on coronary calcified plaque as measured by computed tomography

Eight patients with heterozygous familial hypercholesterolemia who received combined long-term low-density lipoprotein apheresis and high-dose statin therapy showed a significant decrease in volume of coronary calcium over a period of 29 months as measured by, computed tomography. This suggests that the effects of aggressive lipid-lowering therapy can be assessed non-invasively and may be used as surrogate end points when testing new therapies.

Graduate entry to medical studies: thoughts from 'down under' (editorial)

This invited editorial, reflecting on expectations of changing to graduate entry, eg enhanced maturity in the student cohort with greater self-sufficiency and taking of responsibility for learning in the context of adoption of a problem-based learning model, examines experiences of early post-change years and raises questions for contemplation by medical schools considering graduate entry.

Dos clássicos aos hereges : Keynes e a economia de seu tempo

O artigo trata da posição teórica de Keynes relativamente à economia clássica e à abordagem denominada herética. A primeira seção resgata os traços distintivos das escolas clássica e neoclássica segundo a demarcação proposta por Keynes, bem como as críticas por ele dirigidas às principais teses defendidas por essas linhagens teóricas. A seguir, retoma-se a sua avaliação dos argumentos subconsumistas, indicando-se os seus pontos de convergência e distanciamento dessa visão econômica. Na continuação, apresentam-se as interpretações neoclássicas ao problema da demanda, comentando-se a relação da obra de Keynes com a tradição marshalliana. A última seção avalia a teoria neoclássica do produto real sob condições cíclicas e introduz a versão de Keynes para o equilíbrio agregado definido pelas propensões a gastar e a investir, além de indicar o componente de fragilidade da leitura marshalliana de sua estrutura teórica. Por fim, comenta-se a contribuição de Keynes ao conhecimento econômico da época perante a escola clássica e os hereges.

Sustainability reporting and financial reporting: the relevance of an integrated reporting approach

In the business world, there are issues such as globalisation, environmental awareness, and the rising expectations of public opinion which have a specific role in what is required from companies as providers of information to the market. This chapter refers to the current state of corporate reporting (financial reporting and sustainability reporting) and demonstrates the need for evolution to a more integrated method of reporting which meets the stakeholders’ needs. This research offers a reflection on how this development can be achieved, which notes the ongoing efforts by international organisations in implementing the diffusion and adoption, as well as looking at the characteristics which are needed for this type of reporting. It also makes the link between an actual case of a company that is one of the world references in sustainable development and integrated reporting. Whether or not the integrated reporting is the natural evolution of the history of financial and sustainability reporting, it still cannot yet claim to be infallible. However, it may definitely be concluded that a new approach is necessary to meet the needs which are continuously developing for a network of stakeholders.

Fluxus: do texto à acção. A cartografia de uma a(r)titude

Trabalho de Projecto em Ciências da Comunicação, variante Cultura Contemporânea e Novas Tecnologias

The words about a “sea of trees”. Colonial and post-colonial narratives about Gorongosa (Mozambique)

8º Congresso Ibérico de Estudos Africanos (CIEA8). Madrid, 2012

Estabelecimento e multiplicação in vitro de brotos no processo de micropropagação de cultivares de bananeira (Musa spp.)

A banana (Musa spp.) é uma das frutas mais consumidas no mundo, e amplamente cultivada no Brasil, porém doenças como as sigatokas, negra e amarela, vêm reduzindo a sua produção. A disponibilização imediata de novas cultivares resistentes às principais doenças é limitada pela propagação convencional. A micropropagação é uma alternativa para a produção de mudas com qualidade fitossanitária e vegetativa, mas apresenta fatores que dificultam sua aplicação como a contaminação por fungos e bactérias, associada à oxidação dos explantes. O objetivo desse trabalho foi adaptar e/ou otimizar as etapas do processo de micropropagação para diferentes cultivares de bananeira, por meio do controle de oxidação, contaminação, e multiplicação de brotos, sendo utilizadas as cultivares Caipira (AAA), BRS Caprichosa (AAAB), Pacovan Ken (AAAB), Preciosa (AAAB), PV 03-76 (AAAB), Thap Maeo (AAB). No estudo foram utilizados o antibiótico sulfato de estreptomicina e o fungicida Opera® (BASF) visando reduzir a contaminação in vitro provocada por bactérias e fungos, além do anti-oxidante PVP (polivinilpirrolidona) para controlar a oxidação. Houve redução da contaminação com uso do sulfato de estreptomicina à concentração de 100 mg L-1 e da oxidação com PVP a 4 g L-1. Na fase de multiplicação de brotos, as cultivares apresentaram médias que variaram de 1,90 a 4,75 brotos/explante. A cultivar caipira (AAA) destacou-se das demais com a maior taxa de multiplicação de brotos após três subcultivos, média de 41,50 brotos por rizoma.

Resolving the ancestry of Austronesian‑speaking populations

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The "out-of-Taiwan" model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion.

Autonomic Modulation of the Heart in Systemic Arterial Hypertension

OBJECTIVE: To analyze the heart rate variability in patients with mild to moderate systemic arterial hypertension. METHODS: Thirty-two healthy (group I) and 70 systemic arterial hypertensive (group II) individuals, divided according to age (40 to 59 and 60 to 80 years old, respectively) and with a similar distribution by sex were studied. Thirty-one had left ventricular hypertrophy (LVH), 22 were overweight, and 16 had Type II diabetes mellitus. Smoking, alcohol ingestion, and sedentary habits were the same between groups. Variability in heart rate was analyzed in the time domain, using standard deviations of normal RR intervals (SDNN) and the differences between maximal brady- and tachycardia (D-BTmax) during sustained inspiration. Analysis of the frequency band of the power spectrum between 0.05 and 0.40 Hz at rest and during controlled respiration was chosen for analysis of the frequency domain. RESULTS: In both time and frequency domains, variables were lower in group II than in group I. Within groups, statistically significant variables were only found for individuals in the 40 to 59 year old group. The presence of LVH, overweight, or diabetes mellitus did not influence the variability in heart rate to a significant extent. CONCLUSION: Variability in heart rate was a valuable instrument for analyzing autonomic modulation of the heart in arterial hypertension. The autonomic system undergoes significant losses in cardio-modulatory capacity, more evident in subjects between 40 and 59 years old. In those over 60 years old, reduced variability in heart rate imposed by aging was not significantly influenced by the presence of systemic arterial hypertension.

Quantifying the legacy of the Chinese Neolithic on the maternal genetic heritage of Taiwan and Island Southeast Asia

There has been a long-standing debate concerning the extent to which the spread of Neolithic ceramics and Malay-Polynesian languages in Island Southeast Asia (ISEA) were coupled to an agriculturally driven demic dispersal out of Taiwan 4000 years ago (4 ka). We previously addressed this question using founder analysis of mitochondrial DNA (mtDNA) control-region sequences to identify major lineage clusters most likely to have dispersed from Taiwan into ISEA, proposing that the dispersal had a relatively minor impact on the extant genetic structure of ISEA, and that the role of agriculture in the expansion of the Austronesian languages was therefore likely to have been correspondingly minor. Here we test these conclusions by sequencing whole mtDNAs from across Taiwan and ISEA, using their higher chronological precision to resolve the overall proportion that participated in the "out-of-Taiwan" mid-Holocene dispersal as opposed to earlier, postglacial expansions in the Early Holocene. We show that, in total, about 20 % of mtDNA lineages in the modern ISEA pool result from the "out-of-Taiwan" dispersal, with most of the remainder signifying earlier processes, mainly due to sea-level rises after the Last Glacial Maximum. Notably, we show that every one of these founder clusters previously entered Taiwan from China, 6-7 ka, where rice-farming originated, and remained distinct from the indigenous Taiwanese population until after the subsequent dispersal into ISEA.

Manejo biotecnológico de la rizósfera en soja, maíz y maní: Control de factores bióticos y abióticos

El estudio de las relaciones entre la actividad microbiana en la rizósfera y la sanidad vegetal, así como su vigor, es esencial y básico para desarrollar un mayor rendimiento en el sistema de producción. (...) Objetivo General Dada la necesidad de aumentar la producción de los cultivos para cubrir las necesidades básicas de alimento en el mundo, tanto para destino humano como animal, como así la tendencia a reducir el uso de fertilizantes y pesticidas se propone una serie de investigaciones que permitan, a través del manejo biotecnológico de la rizósfera y exudados radiculares, obtener mayor fijación biológica del nitrógeno asegurando mayor sanidad y crecimiento del vegetal. Las posibilidades de incrementar los rendimientos y sanidad de los cultivos de soja, maíz y maní, haciendo uso de las modernas técnicas biotecnológicas de rizósfera, abren una perspectiva muy importante para la provincia de Córdoba, ya que son innovaciones tecnológicas de primer nivel que se están aplicando en países desarrollados. Objetivos Parciales - Caracterización e identificación de exudados radiculares de leguminosas de importancia regional, en distintas condiciones ambientales. - Efecto de dichos exudados sobre la trascripción de genes "nod" en Bradyrhizobium - Rhizobium. Efecto de los mismos sobre quimiotaxis y proliferación de los de los principales grupos de microorganismos rizosféricos. - Selección de genotipos vegetales con exudados que permitan nodulación en situaciones de estrés. - Identificación y caracterización de dichos perfiles rizosféricos. Determinación de grupos de microorganismos predominantes y su efecto posible para la leguminosa. - Detección de cepas PGPR y NPR que se adapten a los exudados radiculares a los efectos de obtener una rizosfera con población estable, que garantice sanidad y mayor cantidad de sitios receptores para Brady/Rhizobium. - Proyección a otros cultivos regionales.