Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is?

The three-dimensional solution structure of the 40 residue amyloid beta-peptide, A beta(1-40), has been determined using NMR spectroscopy at pH 5.1, in aqueous sodium dodecyl sulfate (SDS) micelles, In this environment, which simulates to some extent a water-membrane medium, the peptide is unstructured between residues 1 and 14 which are mainly polar and likely solvated by water. However, the rest of the protein adopts an alpha-helical conformation between residues 15 and 36 with a kink or hinge at 25-27. This largely hydrophobic region is likely solvated by SDS. Based on the derived structures, evidence is provided in support of a possible new location for the transmembrane domain of A beta within the amyloid precursor protein (APP). Studies between pH 4.2 and 7.9 reveal a pH-dependent helix-coil conformational switch. At the lower pH values, where the carboxylate residues are protonated, the helix is uncharged, intact, and lipid-soluble. As the pH increases above 6.0, part of the helical region (15-24) becomes less structured, particularly near residues E22 and D23 where deprotonation appears to facilitate unwinding of the helix. This pH-dependent unfolding to a random coil conformation precedes any tendency of this peptide to aggregate to a beta-sheet as the pH increases. The structural biology described herein for A beta(1-40) suggests that (i) the C-terminal two-thirds of the peptide is an alpha-helix in membrane-like environments, (ii) deprotonation of two acidic amino acids in the helix promotes a helix-coil conformational transition that precedes aggregation, (iii) a mobile hinge exists in the helical region of A beta(1-40) and this may be relevant to its membrane-inserting properties and conformational rearrangements, and (iv) the location of the transmembrane domain of amyloid precursor proteins may be different from that accepted in the Literature. These results may provide new insight to the structural properties of amyloid beta-peptides of relevance to Alzheimer's disease.

Can we start to think about consensus-oriented clinical practices?

Pulmonary Vascular Research Institute

Academic dishonesty: understanding how undergraduate students think and act

The purpose of this investigation is to explore and understand the justifications given by students to the existence of dishonest behavior and understanding the extent to which the justifications given might influence denouncing and cheating behavior. 1277 undergraduate students of two Portuguese Public Universities were surveyed about their own cheating behavior, their propensity to denounce and the ―neutralizing attitudes‖. As predicted, ―neutralizing attitudes‖ was negatively correlated with self cheating behavior and positively correlated with reporting. The likelihood of copying is greater when the purpose is ―helping a friend‖, ―when the courses are more difficult‖, ―to get higher marks/grades‖, and because ―peers accept and tend to see copying practices as normal‖. Results support the notion that context emerges as a very important influence in the decision to cheating. The environment-peer pressure and the normalized attitudes towards academic dishonesty are the main influences on the propensity to cheating.

Aprendizagem baseada na resolução de problemas: uma experiência pedagógica com alunos de um Curso de Especialização Tecnológica

Relatório de estágio de mestrado em Ensino de Informática

Think and Discuss: Disseny de tasques per a la construcció de competències discursives a l’aula AICLE de matemàtiques. Un estudi de cas

L’objectiu de la present investigació és explorar des d’una perspectiva sociocultural el programa AICLE d’un centre de Barcelona, així com les opcions metodològiques adoptades pels docents, per tal d’esbrinar si les tasques interactives que es proposen als alumnes són integradores quant a l’aprenentatge de l’àrea –en el nostre cas, les matemàtiques– i l’adquisició d’una llengua estrangera –l’anglès. L’anàlisi de les dades mostra l’ús que els alumnes fan del complex dispositiu pedagògic que se’ls presenta per mitjà de les tasques i materials dissenyats ad hoc pel professorat que treballa en col•laboració. La recerca comprèn una crònica documentada del desenvolupament del programa experimental i l’estudi aprofundit de la tasca Think and Discuss.

Naturaleza e influencia de los think tanks en el proceso político en España

Este artículo examina la realidad que define la acción política de los think tanks españoles, así como su evolución durante los últimos años. En primer lugar, se analiza de un modo sistemático cuáles son las principales características, objetivos, perfiles ideológicos, funcionamiento y recursos de los think tanks que operan en España. Posteriormente, mediante la administración de un cuestionario y la realización de entrevistas en profundidad analizamos el impacto que este tipo de organizaciones tienen en el proceso político español. Nuestros resultados indican que, pese a que la mayoría de think tanks son de creación reciente y tienen una influencia limitada, su número y tamaño han aumentado de manera notable en los últimos años, convirtiéndolos en un actor relevante, que ejerce de modo creciente un impacto significativo en el proceso político español.

Think child, think parent, think family

This is an introductory update to the Mental Health and Children's Services Project of the HSCB

Think... before you drink... unpasteurised milk

Milk produced on farms on the island of Ireland is generally acknowledged to be of very high standard. The microbiological standards demanded of milk at EU level have been consistently improving over recent years. What you may not know, however, is that these routine tests do not specifically check for E. coli, Salmonella and other potentially harmful bacteria which may be present in unpasteurised milk. There are, therefore, potential risks associated with the consumption of unpasteurised milk and farming families who frequently drink unpasteurised milk produced on the farm should be aware of the possible risks.

Do brief alcohol motivational interventions work like we think they do?

BACKGROUND: Questions remain about how brief motivational interventions (BMIs) for unhealthy alcohol use work, and addressing these questions may be important for improving their efficacy. Therefore, we assessed the effects of various characteristics of BMIs on drinking outcomes across 3 randomized controlled trials (RCTs). METHODS: Audio recordings of 314 BMIs were coded. We used the global rating scales of the Motivational Interviewing Skills Code (MISC) 2.1: counselor's acceptance, empathy, and motivational interviewing (MI) spirit, and patient's self-exploration were rated. MI proficiency was defined as counselor's rating scale scores ≥5. We also used the structure, confrontation, and advice subscale scores of the Therapy Process Rating Scale and the Working Alliance Inventory. We examined these process characteristics in interventions across 1 U.S. RCT of middle-aged medical inpatients with unhealthy alcohol use (n = 124) and 2 Swiss RCTs of young men with binge drinking in a nonclinical setting: Swiss-one (n = 62) and Swiss-two (n = 128). We assessed the associations between these characteristics and drinks/d reported by participants 3 to 6 months after study entry. RESULTS: In all 3 RCTs, mean MISC counselor's rating scales scores were consistent with MI proficiency. In overdispersed Poisson regression models, most BMI characteristics were not significantly associated with drinks/d in follow-up. In the U.S. RCT, confrontation and self-exploration were associated with more drinking. Giving advice was significantly associated with less drinking in the Swiss-one RCT. Contrary to expectations, MI spirit was not consistently associated with drinking across studies. CONCLUSIONS: Across different populations and settings, intervention characteristics viewed as central to efficacious BMIs were neither robust nor consistent predictors of drinking outcome. Although there may be alternative reasons why the level of MI processes was not predictive of outcomes in these studies (limited variability in scores), efforts to understand what makes BMIs efficacious may require attention to factors beyond intervention process characteristics typically examined.

Flu is more serious than you think (general poster)

Contact your GP surgery to find out the arrangements for flu vaccination in your practice.

Flu is more serious than you think (General)

This leaflet encourages uptake of the flu vaccine for those people in at-risk groups. Most children aged 2 years up to less than 18 years in at risk groups will receive a nasal spray vaccine rather than an injection.

Malaise du nourrisson pensez à une intoxication à l'anis étoil [Apparent life-threatening event in infants: think about star anise intoxication!].

In previous years, several publications have reported cases of infants presenting neurological and gastrointestinal symptoms after ingestion of star anise tea. Such teas are sometimes given in various cultures for the treatment of infant colic pains. In most cases, the cause of intoxication was contamination of Chinese star anise (Illicium verum) by Japanese star anise (Illicium anisatum). Indeed, the toxicity of Illicium anisatum, also known as Shikimi, is caused by its content in potent neurotoxins (anisatin, neoanisatin, and pseudoanisatin), due to their activity as non-competitive antagonists of GABA receptors. The main reasons explaining the frequent contaminations are the strong macroscopic resemblance of the 2 substances, as well as the fact that the fruits are often sold partially broken or in ground form. Therefore, in most cases, chemical analysis is required to determine the possible adulterations. CASE REPORT: A 2-month-old infant, in good general health, was brought to the emergency unit after 3 consecutive episodes of central cyanosis and tetany of the limbs with spontaneous recovery the same afternoon. The child was also very irritable, regurgitated a lot, and positioned himself in opisthotonos. Between these episodes, the neurological exam showed some perturbations (horizontal nystagmus and Bell's phenomenon, hypertony of the extensor muscles, and mild hypotony of the axial flexor muscles) with slow improvement over the following hours. The remaining clinical exam, the laboratory work (complete blood count, renal, hepatic, and muscular tests, capillary blood gas, plasmatic amino acids, and urinary organic acids), and the electroencephalogram findings were all normal. In the course of a detailed interview, the parents reported having given 3 bottles to their child, each one containing 200 mL of an infusion with 4 to 5 fruits of star anise, in the hours preceding the symptoms to relieve colic pains. The last seizure-like event took place approximately 8h after the last ingestion. We could prove the ingestion of anisatin, the toxic substance found in Japanese star anise, and the contamination of Chinese star anise by the Japanese species. Indeed, the anisatin analysis by liquid chromatography and mass spectroscopy (LC-MS) in a urine sample taken 22 h after the last infusion ingestion showed trace amounts of the substance. In another urine sample taken 33 h after ingestion, no anisatin could be detected. Furthermore, the analysis of the fruit sample gave an anisatin concentration of 7800 μg/kg while the maximum tolerance value in Switzerland is 1000 μg/kg. CONCLUSION: The evaluation of ALTE in infants should always include the possibility of intoxication. Star anise is generally considered a harmless medicine. Nevertheless, it can sometimes cause a severe intoxication resulting in various neurological and gastrointestinal symptoms. To prevent such events, not only the parents, but also the care personnel and pharmacists must be informed about the possible adverse effects caused either by the overdose of Chinese star anise or by the eventual contamination of herbal teas with Japanese star anise. A better control of the substances by the health authorities is also necessary.