The Penicillium chrysogenum aclA gene encodes a broad-substrate-specificity acyl-coenzyme A ligase involved in activation of adipic acid, a side-chain precursor for cephem antibiotics

Activation of the cephalosporin side-chain precursor to the corresponding CoA-thioester is an essential step for its incorporation into the P-lactam backbone. To identify an acyl-CoA ligase involved in activation of adipate, we searched in the genome database of Penicillium chrysogenum for putative structural genes encoding acyl-CoA ligases. Chemostat-based transcriptome analysis was used to identify the one presenting the highest expression level when cells were grown in the presence of adipate. Deletion of the gene renamed aclA, led to a 32% decreased specific rate of adipate consumption and a threefold reduction of adipoyl-6-aminopenicillanic acid levels, but did not affect penicillin V production. After overexpression in Escherichia coli, the purified protein was shown to have a broad substrate range including adipate. Finally, protein-fusion with cyan-fluorescent protein showed co-localization with microbody-borne acyl-transferase. Identification and functional characterization of aclA may aid in developing future metabolic engineering strategies for improving the production of different cephalosporins. (C) 2009 Elsevier Inc. All rights reserved.

Validity of self-reported hysterectomy and tubal sterilisation

Both hysterectomy and tubal sterilisation offer significant protection from ovarian cancer, and the risk of cardiovascular disease in women is lowered after hysterectomy. Since little is known about the accuracy of women's self-reports of these procedures, we assessed their reliability and validity using data obtained in a case-control study of ovarian cancer. There was 100 per cent repeatability for both positive and negative histories of hysterectomy and tubal sterilisation among a small sample of women on reinterview. Verification of surgery was sought against surgeons' or medical records, or if these were unavailable, from randomly selected current general practitioners for 51 cases and 155 controls reporting a hysterectomy and 73 cases and 137 controls reporting a tubal sterilisation. Validation rate for self-reported hysterectomy against medical reports (32 cases, 96 controls) was 96 per cent (95 per cent confidence interval (CI) 91 to 99) and for tubal sterilisation (32 cases, 77 controls) it was 88 per cent (CI 81 to 93), which is likely to be an underestimate. Although findings are based on small numbers of women for whom medical reports could be ascertained, they are consistent with other findings that suggest women have good recall of past histories of hysterectomy and tubal sterilisation; this allows long-term effects of these procedures to be studied with reasonable accuracy from self-reports.

Short-Term Carbohydrate-Restricted Diet for Weight Loss in Severely Obese Women

Weight loss in bariatric pre-surgery period reduces surgical complications, surgery time, blood loss, and length of hospital stay. Carbohydrate-restricted diets have been used as an alternative for weight loss. We tested the efficacy of a low-calorie carbohydrate-restricted diet (RD) for short-term weight loss in women with severe obesity and evaluate its metabolic effects in relation to a conventional low-calorie diet (CD). The subjects received a 1,200-kcal diet with or without carbohydrate restriction for a period of 1 week in the hospital. Nineteen obesity class III women were distributed into two groups: experimental (n = 10) and control (n = 9). The following variables were assessed at the beginning and end of the study: anthropometric measurements, body composition, resting energy expenditure, substrate oxidation, and biochemical tests. Compared with CD, RD led to larger weight loss (2.6 and 4.4 kg, respectively; p = 0.01) and waist circumference reduction (p < 0.01). Among the assessed biochemical indicators, only plasma and urine acetone levels were different (p < 0.01); higher values were found in the experimental group with no symptoms and other diet-related complaints. There was also a significant decrease in triglycerides and carbohydrate oxidation, as well as a significant enhancement in lipid oxidation in the RD group. Short-term RD was more efficient than CD regarding quick weight loss and waist circumference reduction, which may favor gastroplasty. Also, RD did not lead adverse metabolic effects.

Knowledge and practices of medical students to prevent tuberculosis transmission in Rio de Janeiro, Brazil

Objectives. To describe knowledge, practices, and associated factors of medical students to prevent transmission of tuberculosis (TB) in five medical schools. Methods. Cross-sectional survey of undergraduate medical students in preclinical and in early and late clinical years. Information was obtained on sociodemographic profile, previous lectures on TB, knowledge about TB transmission, exposure to patients with active pulmonary TB, and use of respiratory protective masks. Results. Among 1 094 respondents, 575 (52.6%) correctly answered that coughing, speaking, and sneezing can transmit TB. Early [adjusted odds ratio = 4.0 (3.0, 5.5)] and late [adjusted odds ratio = 4.2 (3.1, 5.8)] clinical years were associated with correct answers, but having had previous lectures on TB was not. Among those who had previous lectures on TB, the rate of correct answers increased from 42.1% to 61.6%. Among 332 medical students who reported exposure to TB patients, 194 (58.4%) had not used protective masks. More years of clinical experience was associated with the use of masks [adjusted odds ratio = 2.9 (1.4, 6.1)], while knowledge was inversely associated with the use of masks [adjusted odds ratio = 0.4 (0.2, 0.6)]. Conclusions. Many medical students are not aware of the main routes of TB infection, and lectures on TB are not sufficient to change knowledge and practices. Regardless of knowledge about TB transmission, students engage in risky behaviors: more than two-thirds do not use a protective mask when examining an active TB case. We suggest innovative, effective active learning experiences to change this scenario.

European 1: A globally important clonal complex of Mycobacterium bovis

We have identified a globally important clonal complex of Mycobacterium bovis by deletion analysis of over one thousand strains from over 30 countries. We initially show that over 99% of the strains of M. bovis, the cause of bovine tuberculosis, isolated from cattle in the Republic of Ireland and the UK are closely related and are members of a single clonal complex marked by the deletion of chromosomal region RDEu1 and we named this clonal complex European 1 (Eu1). Eu1 strains were present at less than 14% of French, Portuguese and Spanish isolates of M. bovis but are rare in other mainland European countries and Iran. However, strains of the Eu1 clonal complex were found at high frequency in former trading partners of the UK (USA, South Africa, New Zealand, Australia and Canada). The Americas, with the exception of Brazil, are dominated by the Eu1 clonal complex which was at high frequency in Argentina, Chile, Ecuador and Mexico as well as North America. Eu1 was rare or absent in the African countries surveyed except South Africa. A small sample of strains from Taiwan were non-Eu1 but, surprisingly, isolates from Korea and Kazakhstan were members of the Eu1 clonal complex. The simplest explanation for much of the current distribution of the Eu1 clonal complex is that it was spread in infected cattle, such as Herefords, from the UK to former trading partners, although there is evidence of secondary dispersion since. This is the first identification of a globally dispersed clonal complex M. bovis and indicates that much of the current global distribution of this important veterinary pathogen has resulted from relatively recent International trade in cattle. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.

Utopia de um teatro de textura romanesca: adaptações de romances na recente cena portuguesa

Este volume tem por tema: "Transbordamentos infinitos: a dramaturgia contemporânea"

Sintomas do trato digestivo superior e distúrbios motores do esôfago em pacientes portadores da forma indeterminada da doença de Chagas crônica

O estudo descreve os sintomas referidos por portadores da forma indeterminada da doença de Chagas crônica e avalia sua associação com alterações da motilidade esofágica. Manometria do esôfago foi realizada em 50 pacientes, medindo-se a extensão e a pressão do esfíncter inferior do esôfago, o peristaltismo e a amplitude de contração do corpo esofágico. Oito (16%) pacientes apresentaram relaxamento parcial do esfíncter inferior, 13 (26%) apresentaram aperistalse parcial e 20 (40%) apresentaram hipocontratilidade no esôfago distal. Sintomas digestivos altos foram referidos por 24 (48%) pacientes, sendo mais freqüentes a pirose, a regurgitação e o desconforto intermitente à deglutição. Esses sintomas foram referidos por 17 (51,5%) de 33 pacientes com alterações motoras do esôfago e por 7 (41,2%) de 17 pacientes com manometria normal, diferença essa não estatisticamente significante (p=0,69). Esses achados sugerem que portadores da FCI apresentam sintomas inespecíficos do trato digestivo superior que podem dificultar a sua classificação com base apenas no exame clínico e radiológico, e que é alta a freqüência de portadores desta forma que apresentam distúrbios motores do esôfago.

Quiçama : um toponimo com várias grafias

Este trabalho é motivado por se verificar uma certa confusão sobre a grafia do topónimo em estudo. As diversas grafias do topónimo em estudo utilizadas em manuais escolares, em obras científicas e literárias, em placas toponímicas e em documentos oficiais da Administração Pública, constituem não só confusões toponímicas como também confusões topográficas. Entretanto, apresentamos este trabalho com a finalidade de propor uma medida de uniformização e normalização das diversas grafias utilizadas na administração pública (programa televisivo e radiofónico, jornais, conteúdo escolar, instituições públicas, etc) para se referenciar a região em estudo. Contudo, esta uniformização e normalização visa contribuir para a gestão de informação de qualidade na administração pública da região. O estudo toponímico em questão foi analisado em duas dimensões, histórica e linguística. Na dimensão histórica analisamos os aspectos históricos da região. Na dimensão linguística, analisamos a questão da estrutura morfológica do topónimo em estudo, a sua motivação semântica e a sua classificação toponímica de acordo Dick. Consideramos fundamentais para a análise do topónimo em estudo.

To be or not to be a pseudogene: a molecular epidemiological approach to the mclx genes and its impact in tuberculosis

Tuberculosis presents a myriad of symptoms, progression routes and propagation patterns not yet fully understood. Whereas for a long time research has focused solely on the patient immunity and overall susceptibility, it is nowadays widely accepted that the genetic diversity of its causative agent, Mycobacterium tuberculosis, plays a key role in this dynamic. This study focuses on a particular family of genes, the mclxs (Mycobacterium cyclase/LuxR-like genes), which codify for a particular and nearly mycobacterial-exclusive combination of protein domains. mclxs genes were found to be pseudogenized by frameshift-causing insertion(s)/deletion(s) in a considerable number of M. tuberculosis complex strains and clinical isolates. To discern the functional implications of the pseudogenization, we have analysed the pattern of frameshift-causing mutations in a group of M. tuberculosis isolates while taking into account their microbial-, patient- and disease-related traits. Our logistic regression-based analyses have revealed disparate effects associated with the transcriptional inactivation of two mclx genes. In fact, mclx2 (Rv1358) pseudogenization appears to be primarily driven by the microbial phylogenetic background, being mainly related to the Euro-American (EAm) lineage; on the other hand, mclx3 (Rv2488c) presents a higher tendency for pseudogenization among isolates from patients born on the Western Pacific area, and from isolates causing extra-pulmonary infections. These results contribute to the overall knowledge on the biology of M. tuberculosis infection, whereas at the same time launch the necessary basis for the functional assessment of these so far overlooked genes.