On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

Dietary inflammatory index and anthropometric measures of obesity in a population sample at high cardiovascular risk from the PREDIMED trial

The dietary inflammatory index (DII) is a new tool to assess the inflammatory potential of diet. We aimed to determine the association between the DII and body mass index (BMI), waist circumference and waist to height ratio (WHtR). We conducted a cross-sectional study of 7,236 participants recruited into the PREDIMED trial (PREvención con DIeta MEDiterránea). Information from a validated 137-item food frequency questionnaire was used to calculate energy, foods and nutrients. A 14-item dietary screener was used to assess adherence to the Mediterranean diet (MeDiet). Sex-specific multivariable linear regression models were fitted to estimate differences (and 95% confidence intervals) in BMI, waist circumference and WHtR across quintiles of the DII. All nutrient intakes, healthy foods and adherence to the MeDiet were higher in the quintile with lowest DII score (more anti-inflammatory values) except for animal protein, saturated and monounsaturated fat. Though an inverse association between DII and total energy was apparent, the DII was associated with higher average BMI, waist circumference and WHtR after adjusting for known risk factors. The adjusted difference in WHtR for women and men between the highest and lowest quintile of DII was 1.60% (95% CI 0.87-2.33) and 1.04% (95% CI 0.35-1.74), respectively. Pro-inflammatory scores remained associated with obesity after controlling for the effect that adherence to a MeDiet had on inflammation. In conclusion, this study shows a direct association between the DII and indices of obesity and supports the hypothesis that diet may have a role in the development of obesity through inflammatory modulation mechanisms

Changes in Dynamics upon Oligomerization Regulate Substrate Binding and Allostery in Amino Acid Kinase Family Members

Oligomerization is a functional requirement for many proteins. The interfacial interactions and the overall packing geometry of the individual monomers are viewed as important determinants of the thermodynamic stability and allosteric regulation of oligomers. The present study focuses on the role of the interfacial interactions and overall contact topology in the dynamic features acquired in the oligomeric state. To this aim, the collective dynamics of enzymes belonging to the amino acid kinase family both in dimeric and hexameric forms are examined by means of an elastic network model, and the softest collective motions (i.e., lowest frequency or global modes of motions) favored by the overall architecture are analyzed. Notably, the lowest-frequency modes accessible to the individual subunits in the absence of multimerization are conserved to a large extent in the oligomer, suggesting that the oligomer takes advantage of the intrinsic dynamics of the individual monomers. At the same time, oligomerization stiffens the interfacial regions of the monomers and confers new cooperative modes that exploit the rigid-body translational and rotational degrees of freedom of the intact monomers. The present study sheds light on the mechanism of cooperative inhibition of hexameric N-acetyl-L-glutamate kinase by arginine and on the allosteric regulation of UMP kinases. It also highlights the significance of the particular quaternary design in selectively determining the oligomer dynamics congruent with required ligand-binding and allosteric activities

Fecundación in vitro y transferencia de embriones (FIVET)

The epidemological analysis of data regarding the efficacy of artificial reproduction techniques reveáis certain problems in those most widely used. Aside from these empirical difficulties comes the affront on human dignity that some of them entail. It is necessary to deal with the problem of sterility in a manner that safeguards the excellence of the human being

Planificación familiar natural

Family planning through natural means is the result of previous ethical and anthropological reflection. Deprived of this foundation, one easily falls prey to widespread errors regarding its inefficacy, its scarce demand and the difficulty of its learning and utilization. Neither would it be possible here to ignore the moral dimensión of this human act

Geoquímica y mineralogía aplicadas a estudios de impacto ambiental derivado de la combustión del carbón

Los autores agradecen a E.N.D.E.S.A. las facilidades dadas para el muestreo así como por su apoyo en las investigaciones.[ES] En el presentes artículo se muestran dos ejemplos de aplicación de geoquímica y mineralogía al estudio del impacto ambiental derivado de la combustión de las centrales termoeléctricas de carbón. La investigación se centra en el estudio del comportamiento de elementos traza durante la combustión del carbón, en la determinación de balances de emisiones de elementos traza en una gran central térmica y sobre la delineación de áreas de impacto alrededor de la misma por medio del seguimiento de las cenizas volantes.[EN] The present article summarizes two studies of applications of geochemistry and mineralogy to the research on the environmental impact around coal-fired power stations. The research is focused on the behaviour of the trace elements during coa1 combustión in power stations, the determination of mass balances for trace element emissions from a large power station, and the delineation of impact areas around the power station by monitoring the fly ash distribution.Los estudios presentados en este artículo han sido financiados por la Comunidad Europea del Carbón y del Acero (contrato 7220lEDlO14) y por el Plan Nacional de Investigación y Desarrollo de la CICYT (proyecto AMB-95-1102).Peer reviewe

Methodological quality and reporting of ethical requirements in clinical trials

Objectives—To assess the relationship between the approval of trials by a research ethics committee (REC) and the fact that informed consent from participants (ICP) was obtained, with the quality of study design and methods. Design—Systematic review using a standardised checklist. Main measures—Methodological and ethical issues of all trials published between 1993 and 1995 in the New England Journal of Medicine, the Lancet, the Journal of the American Medical Association and the British Medical Journal were studied. In addition, clinical trials conducted in Spain and published by at least one Spanish author during the same period in any other journal were also included. Results—We studied the published articles of 767 trials and found the following indicators of lower methodological quality to be independent predictors for failure to disclose REC approval or ICP: absence of concealment of allocation, lack of justification for unblinded trials, not using a treatment for the patients in the control group, absent information on statistical methods, not including sample size estimation, not establishing the rules to stop the trial, and omitting the presentation of a baseline comparison of groups Conclusion—Trials of higher methodological and scientific quality were more likely to provide information about their ethical aspects. Key Words: Clinical trials • informed consent • research ethics committees • research desig