A mitochondrial mutator plasmid that causes senescence under dietary restricted conditions

BACKGROUND: Calorie or dietary restriction extends life span in a wide range of organisms including the filamentous fungus Podospora anserina. Under dietary restricted conditions, P. anserina isolates are several-fold longer lived. This is however not the case in isolates that carry one of the pAL2-1 homologous mitochondrial plasmids. RESULTS: We show that the pAL2-1 homologues act as 'insertional mutators' of the mitochondrial genome, which may explain their negative effect on life span extension. Sequencing revealed at least fourteen unique plasmid integration sites, of which twelve were located within the mitochondrial genome and two within copies of the plasmid itself. The plasmids were able to integrate in their entirety, via a non-homologous mode of recombination. Some of the integrated plasmid copies were truncated, which probably resulted from secondary, post-integrative, recombination processes. Integration sites were predominantly located within and surrounding the region containing the mitochondrial rDNA loci. CONCLUSION: We propose a model for the mechanism of integration, based on innate modes of mtDNA recombination, and discuss its possible link with the plasmid's negative effect on dietary restriction mediated life span extension

Two decades of tuberculosis in a city in Northeastern Brazil: advances and challenges in time and space

Abstract: INTRODUCTION This study presents two decades of epidemiological data on tuberculosis (TB), in order to understanding the disease profile and its spatiotemporal dynamics. METHODS This descriptive study was performed in the City of Olinda/Pernambuco, Brazil, from 1991-2010, and it analyzed new patients with TB living in the city. We used the χ²-test with a p-value <0.05 to identify differences in trends. Incidence and cluster distribution were identified using spatial scan statistics. RESULTS In total, 6202 new cases were recorded during the two decades. The highest incidence occurred in 1995 (110 cases/100,000 inhabitants), and the lowest occurred in 2009 (65 cases/100,000 inhabitants) (β=-1.44; R²=0.43; p=0.0018). The highest mortality occurred in 1998 (16 deaths/100,000 inhabitants), and the lowest occurred in 2008 (5 deaths/100,000 inhabitants) (β=-0.19; R²=0.17; p=0.07). There was a male predominance (65%), and ages ranged from 20-49 years (65%). There was a substantial increase in the number of patients that were cured after treatment (60% to 67%; p<0.001) as well as those tested for HIV (1.9% to 58.5%; p<0.001). During the first decade, clusters with p-values <0.05 included 29% of the total notified cases, and in the second decade, that percentage was 12%. CONCLUSIONS We observed a decreasing trend in incidence, which was significant, and mortality rates, which was not significant. The increased number of laboratory tests performed reflects advances in surveillance, and a reduction in the proportion of cases in primary clusters suggests, among other things, that the disease is spreading across the region

High frequency of resistance to the drugs isoniazid and rifampicin among tuberculosis cases in the city of Cabo de Santo Agostinho, an urban area in Northeastern Brazil.

The objective of the present study was to investigate the frequency and risk factors for developing multidrug-resistant tuberculosis in Cabo de Santo Agostinho, PE. This was a prospective study conducted from 2000 to 2003, in which suspected cases were investigated using bacilloscopy and culturing. Out of 232 confirmed cases of tuberculosis, culturing and antibiotic susceptibility tests were performed on 174. Thirty-five of the 174 cultures showed resistance to all drugs. The frequencies of primary and acquired resistance to any drug were 14% and 50% respectively, while the frequencies of primary and acquired multidrug resistance were 8.3% and 40%. Previous tuberculosis treatment and abandonment of treatment were risk factors for drug resistance. The high levels of primary and acquired resistance to the combination of isoniazid and rifampicin contributed towards the difficulties in controlling tuberculosis transmission in the city

Determination of fumonisins B1 and B2 in Portuguese maize and maize-based samples by HPLC with fluorescence detection

Abstract Fumonisins B1 (FB1) and fumonisin B2 (FB2) are the main members of a family of mycotoxins produced by Fusarium verticillioides, Fusarium proliferatum, and other fungi species of the section Liseola. The present work shows the results of comparative studies using two different procedures for the analysis of fumonisins in maize and maize-based samples. The studied analytical methods involve extraction with methanol/water, dilution with PBS, and clean-up through immunoaffinity columns. Two reagents (o-phthaldialdehyde and naphthalene-2,3-dicarboxaldehyde) were studied for formation of fluorescent derivatives. The separation and identification were carried out by high-performance liquid chromatography with fluorescence detection. The optimized method for analysis of fumonisins in maize involved extraction with methanol/water (80:20), clean-up with an immunoaffinity column, and derivatization with naphthalene-2,3-dicarboxaldehyde (NDA). The limit of detection was 20 µg kg-1 for FB1 and 15 µg kg-1 for FB2. Recoveries of FB1 and FB2 ranged from 79% to 99.6% for maize fortified at 150 µg kg-1 and 200 µg kg-1, respectively, with within-day RSDs of 3.0 and 2.7%. The proposed method was applied to 31 samples, and the presence of fumonisins was found in 14 samples at concentrations ranging from 113 to 2,026 µg kg-1. The estimated daily intake of fumonisins was 0.14 µg kg-1 body weight per day

Clinical and epidemiological characteristics of severe community-acquired pneumonia in children after introduction of the 10-valent pneumococcal vaccine

Eduardo JF Lima,1,2 Maria JG Mello,1,2 Maria FPM Albuquerque,3 Maria IL Lopes,4 George HC Serra,2 Maria AZ Abreu-Lima,2 Jailson B Correia1 1Instituto de Medicina Integral Prof. Fernando Figueira - IMIP Recife; 2Faculdade, Pernambucana de Sa&uacute;de - FPS Recife; 3Centro de Pesquisas Aggeu Magalh&atilde;es, FIOCRUZ; 4Hospital das Cl&iacute;nicas, Universidade Federal de Pernambuco - UFPE, Recife, Pernambuco, Brazil Background: Pneumonia is an important cause of morbimortality in Brazil, despite the extensive vaccination coverage and the socioeconomic improvement in the past years. Objective: To describe the epidemiological and clinical characteristics of severe community-acquired pneumonia in children after the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10). Methods: A prospective study included children &lt;5 years old hospitalized for pneumonia between October 2010 and September 2013 in a tertiary hospital. Newborns and children with comorbidities were excluded. Pneumonia classification followed the clinical and radiological criteria established by World Health Organization (WHO). Clinical history, nutritional status, immunizations, diagnosis, disease course, and prognosis were analyzed. Results: Among 452 children, almost 70% were &lt;2 years, with no sex differences, and 10% had weight-for-age z score below than -2.0. Family income was up to one minimum wage in half the households, and 40% of mothers had completed high school. The suitability of both influenza and PCV10 vaccine schedules was ~50%. The first medical care happened later than 72 hours after the onset of symptoms in 42% of cases. Pneumonia was classified as severe or very severe in 83.9% of patients and for 23% as complicated. Global mortality was 1.5%. Hypoxia, diagnosed in 51.5% of children, looked like a better prognosis predictor than the WHO classification. Conclusion: New strategies for health care are necessary, such as the incorporation of peripheral saturometry as the &ldquo;fifth signal&rdquo;, investment in vaccine coverage, and the adequacy of hospital infrastructure for assistance of severely affected patients. Keywords: respiratory tract infections, pneumonia, child, pneumococcal conjugate vaccine, descriptive epidemiolog