Full informatiu. Cultius extensius - Febrer 2008

- Recomanacions de fertilització per a la sembra del blat de moro. - Dosis agronòmiques d’aplicació de fems i purins. - Jornada sobre fertilització nitrogenada.

The role of circadian timing system on drug metabolism and detoxification.

INTRODUCTION: It has been known for a long time that the efficiency and toxicity of drugs change during a 24-h period. However, the molecular mechanisms involved in these processes have started to emerge only recently. AREAS COVERED: This review aims to highlight recent discoveries showing the direct role of the molecular circadian clock in xenobiotic metabolism at the transcriptional and post-transcriptional levels in the liver and intestine, and the different ways of elimination of these metabolized drugs via biliary and urine excretions. Most of the related literature focuses on transcriptional regulation by the circadian clock of xenobiotic metabolism in the liver; however, the role of this timing system in the excretion of metabolized drugs and the importance of the kidney in this phenomenon are generally neglected. The goal of this review is to describe the molecular mechanisms involved in rhythmic drug metabolism and excretion. EXPERT OPINION: Chronopharmacology is used to analyze the metabolism of drugs in mammals according to the time of day. The circadian timing system plays a key role in the changes of toxicity of drugs by influencing their metabolisms in the liver and intestine in addition to their excretion via bile flow and urine.

Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound.

Aquaporins (AQPs) are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III) complexes screened on human red blood cells (hRBC) and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC(50) = 0.8±0.08 µM in hRBC). Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III) to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III) complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range) together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development.

Investigation of memory, executive functions, and anatomic correlates in asymptomatic FMR1 premutation carriers.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset movement disorder associated with FMR1 premutation alleles. Asymptomatic premutation (aPM) carriers have preserved cognitive functions, but they present subtle executive deficits. Current efforts are focusing on the identification of specific cognitive markers that can detect aPM carriers at higher risk of developing FXTAS. This study aims at evaluating verbal memory and executive functions as early markers of disease progression while exploring associated brain structure changes using diffusion tensor imaging. We assessed 30 aPM men and 38 intrafamilial controls. The groups perform similarly in the executive domain except for decreased performance in motor planning in aPM carriers. In the memory domain, aPM carriers present a significant decrease in verbal encoding and retrieval. Retrieval is associated with microstructural changes of the white matter (WM) of the left hippocampal fimbria. Encoding is associated with changes in the WM under the right dorsolateral prefrontal cortex, a region implicated in relational memory encoding. These associations were found in the aPM group only and did not show age-related decline. This may be interpreted as a neurodevelopmental effect of the premutation, and longitudinal studies are required to better understand these mechanisms.

Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.

BACKGROUND Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. METHODS AND FINDINGS The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction  = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction  = 1.50×10-3) and waist circumference (p for interaction  = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Motor Vehicle Accident Fatalities for the Week Ending, August 10, 2007

Record of the Fatalities for Motor Vehicle Accidents in Iowa per week.

The permeability P-glycoprotein: a focus on enantioselectivity and brain distribution.

IMPORTANCE OF THE FIELD: The permeability glycoprotein (P-gp) is an important protein transporter involved in the disposition of many drugs with different chemical structures, but few studies have examined a possible stereoselectivity in its activity. P-gp can have a major impact on the distribution of drugs in selected organs, including the brain. Polymorphisms of the ABCB1 gene, which encodes for P-gp, can influence the kinetics of several drugs. AREAS COVERED IN THIS REVIEW: A search including publications from 1990 up to 2009 was performed on P-gp stereoselectivity and on the impact of ABCB1 polymorphisms on enantiomer brain distribution. WHAT THE READER WILL GAIN: Despite stereoselectivity not being expected because of the large variability of chemical structures of P-gp substrates, structure-activity relationships suggest different P-gp-binding sites for enantiomers. Enantioselectivity in the activity of P-gp has been demonstrated by in vitro studies and in animal models (preferential transport of one enantiomer or different inhibitory potencies towards P-gp activity between enantiomers). There is also in vivo evidence of an enantioselective drug transport at the human blood-brain barrier. TAKE HOME MESSAGE: The significant enantioselective activity of P-gp might be clinically relevant and must be taken into account in future studies.

Coeficiente de determinação genotípica e de diversidade genética em topocruzamentos de soja tipo alimento com tipo grão

As estimativas do coeficiente de herdabilidade são importantes para a escolha de uma estratégia eficaz de seleção. Quando os tratamentos são considerados fixos, a herdabilidade é denominada coeficiente de determinação genotípica. Os objetivos do presente trabalho foram estimar, através de topocruzamentos obtidos entre soja tipo alimento e soja tipo grão, o coeficiente de determinação genotípica e avaliar a diversidade genética de modo a se distinguir diferenças de contribuição dos parentais de soja tipo alimento com sementes grandes e com sementes pequenas usados nos topocruzamentos, assim como avaliar a interação de cada grupo com o ambiente. Os resultados de determinação genotípica obtidos nas médias de topocruzamentos foram: 90,51% com relação ao número de dias para maturidade (NDM); 93,92% com relação à altura da planta na maturidade (APM); 79,52% com relação ao acamamento (AC); 91,37% ao valor agronômico (VA); 95,55% ao peso de cem sementes (PCS); 57,57% à produtividade de grãos (PG), e 91,18% à largura visual das vagens (LVV), enquadrando-se aos valores encontrados na literatura. Em relação às estimativas de diversidade genética, que representam a disponibilidade de diferenças genéticas para seleção, os caracteres NDM, APM e AC apresentaram valores maiores nos topocruzamentos envolvendo parentais exóticos de sementes pequenas e para VA, PCS, PG e LVV nos topocruzamentos envolvendo parentais exóticos de sementes grandes.

L'Univers

1882/03/30 (Numéro 5255).

Modelo pélvico sintético como uma ferramenta didática efetiva comparada à pelve cadavérica

A anatomia é considerada matéria essencial à educação médica. Aulas práticas com uso de componentes anatômicos manipuláveis são fundamentais ao ensino e à aprendizagem. O objetivo deste estudo foi avaliar o Modelo Sintético de Pelve (Masp) como ferramenta didática, comparada à pelve cadavérica (PC) tradicionalmente utilizada, bem como a satisfação dos estudantes em relação a ambos os métodos. Sessenta e sete estudantes receberam aula teórica após teste teórico preliminar (TTP). Foram randomizados em três grupos: G1 teve aula prática tradicional (APT); G2, aula prática com Masp (APM); e G3 não teve aula prática. Um teste final (TTF) foi aplicado a todos os grupos. G1 e G2 submeteram-se à avaliação do método (AM). A análise estatística foi realizada utilizando-se Anova (Análise de Variância) e teste não paramétrico Mann-Whitney. No TTF, G3 apresentou escores mais baixos do que G1 (p = 0,041) e G2 (p = 0,000). Não foi encontrada diferença estatisticamente significante entre G1 e G2 (p >0,05). G2 apresentou maior satisfação com o método (p = 0,001). Concluiu-se que PC e Masp provaram ser ferramentas didáticas efetivas e que G2 mostrou maior satisfação.

A systematic literature review on agile project

In the 21st century, agile project management (APM) has emerged as a major evolutionary step in the area of software project management. APM is defined as a conceptual framework, consisting of various methods such as Scrum, quick respond to change, better customer collaboration, minimum coverage of documentation and extreme programming (XP) that facilitates to produce working software in multiple iterations with team work. Because agile project management has become more popular in the software industry in recent years, it constitutes an interesting and comprehensive research topic. This thesis presents a systematic literature review (SLR) of published research articles concerning agile project management. Based on a predefined search strategy, 273 such articles were identified, of which 44 were included in the review. The selected 44 articles were published between years 2005 and 2012. The thesis defines a review process by developing a review protocol and presenting the results of the review. The results are expected to provide researchers, software man

Behavioral profiles displayed by rats in an elevated asymmetric plus-maze: effects of diazepam

When rats are exposed to unknown environments where novelty and fear-inducing characteristics are present (conflictive environments), some specific behaviors are induced and exploration is apparently modulated by fear. In our laboratory, a new type of plus-maze was designed as a model of conflictive exploration. The maze is composed of four arms with different geometrical characteristics, differing from each other by the presence or absence of walls. The degree of asymmetry was as follows: NW, no wall arm; SW, a single high wall present; HL, a low and a high wall present, and HH, two high walls present. The four arms were arranged at 90o angles and the apparatus was called the elevated asymmetric plus-maze (APM). The purpose of the present study was to assess the behavioral profile of rats exposed for a single time to the APM with or without treatment with benzodiazepine. Increasing doses of diazepam were injected intraperitoneally in several groups of male, 90-day-old Holtzman rats. Distilled water was injected in control animals. Thirty minutes after treatment all rats were exposed singly to a 5-min test in the APM. Diazepam induced a biphasic modification of exploration in the NW and SW arms. The increase in the exploration score was evident at low doses of diazepam (0.25-1.0 mg/kg body weight) and the decrease in exploration was found with the higher doses of diazepam (2.0-3.0 mg/kg body weight). Non-exploratory behaviors (permanency) were not affected by benzodiazepine treatment. In the HL arm, exploration was not modified but permanency was increased in a dose-dependent manner. In the HH arm, exploration and permanency were not affected. Results are compatible with the idea that exploration-processing mechanisms in conflictive environments are modulated by fear-processing mechanisms of the brain.

Análise descritiva quantitativa de edulcorantes em diferentes concentrações

Edulcorantes em solução, com a mesma equivalência de doçura, podem apresentar características sensoriais que os tornam diferentes entre si. O presente estudo teve como objetivo realizar Análise Descritiva Quantitativa de soluções de aspartame (APM), extrato de folhas de estévia (SrB) e mistura ciclamato/sacarina 2:1 (C/S) em diferentes níveis de doçura, ou seja, em equivalência de doçura a uma solução aquosa de sacarose a 3, 10, 20 e 30%. Onze provadores, pré-selecionados através de análise seqüencial, tendo como critério suas habilidades de discriminação, foram treinados após o levantamento da terminologia descritiva. Após o treinamento, os provadores foram selecionados através de seu poder de discriminação, reproducibilidade e concordância com a equipe no uso de escalas. Os termos descritivos dos edulcorantes, para todos os níveis de doçura, gerados através do método rede (Kelly's Repertory Grid Method) foram: doçura inicial, doçura residual, amargo inicial, amargo residual, residual de alcaçuz, corpo e acidez. Os resultados obtidos para cada nível de doçura foram analisados através de análise de variância, teste de Tukey e Análise de Componentes Principais. A análise descritiva foi efetiva em caracterizar o perfil sensorial dos edulcorantes em diferentes concentrações, evidenciando as mudanças no perfil com o aumento de suas concentrações.

L'Écho de Paris

1898/10/15 (Numéro 5255).

martyrologium ad usum S. Stephani Narbonensis, ad cujus marginem conjectum est obituarium ejusdem ecclesiae : praemittitur Guillclmi, Monetarii, civis Narbonensis, testamentum factum anno 1210. in quo non pauca eidem ecclesiae legata sunt ; ad calcem verò subjicitur capitulare evangeliorum per anni circulum.

Colbertinus