Further information on the origin of the Yale and Oak Ridge wild-type strains of Neurospora crassa

Further information on the origin of the Yale and Oak Ridge wild-type strains of Neurospora crass

A new uvs mutant

A new uvs mutan

Alpha-1 antitrypsin deficiency in Italy: regional differences of the PIS and PIZ deficiency alleles

Background. Critical to the effective diagnosis and management of disease is information on its prevalence in a particular geographic area such as Italy. Alpha-1- antitrypsin deficiency (AAT Deficiency) is one of the most common serious hereditary diseases in the world, but its prevalence varies markedly from one country to another. AAT Deficiency affects at least 120.5 million carriers and deficient subjects worldwide for the two most prevalent deficiency alleles PIS and PIZ. This genetic disease is known to exist in Italy and is related to a high risk for development of jaundice in infants, liver disease in children and adults, and pulmonary emphysema in adults. Methods. Studies on the genetic epidemiology of AAT Deficiency has resulted in the development of a unique database that permits a unique analysis of the geographic distribution in 14 different regions located at random from Piemonte to Sicilia. Results. The use of Hardy-Weinberg statistical analysis to evaluate the distribution of these two deficiency alleles has demonstrated striking differences in the frequencies of these two deficiency alleles in these 14 different regions with 23/84 pair wise combinations significantly different (P=0.05) for PIS, and 5/84 combinations for PIZ. Conclusions. These findings demonstrate differences that impact the standards of care and diagnosis of AAT Deficiency in Italy since the prevalence of these deficiency alleles is not uniform throughout the country

Leitura e escrita em ambientes virtuais de aprendizagem cooperativa : o uso de pbwikis nas práticas pedagógicas

Este trabalho apresenta a experiência desenvolvida com alunos do terceiro ano do ensino médio, utilizando um ambiente virtual (pbwiki), constroem um espaço no qual expõem suas idéias sobre os conteúdos matemáticos, bem como discutem, negociam, reformulam suas concepções a partir do confronto com as idéias dos colegas. Nessa proposta, a principal função do professor é problematizar, apresentar desafios e questionar as soluções apresentadas, estimulando o debate e a capacidade argumentativa dos alunos. Constatamos que essa proposta, que visa o trabalho cooperativo, estimulou a autonomia e a argumentação constituindo alternativas viáveis ao atual modelo usualmente encontrado em nossas escolas

Large-scale comparative phenotypic and genomic analyses reveal ecological preferences of Shewanella species and identify metabolic pathways conserved at the genus level

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of American Society for Microbiology for personal use, not for redistribution. The definitive version was published in Applied and Environmental Microbiology 77 (2011): 5352-5360, doi:10.1128/AEM.00097-11.The use of comparative genomics among different microbiological species has increased substantially as sequence technologies become more affordable. However, efforts to fully link a genotype to its phenotype remain limited to the development of one mutant at the time. In this study, we provide a high throughput alternative to this limiting step by coupling comparative genomics to phenotype arrays for five sequenced Shewanella strains. Positive phenotypes were obtained for 441 nutrients (C, N, P, and S sources), with N-based compounds being the most utilized for all strains. Many genes and pathways predicted by genome analyses were confirmed with the comparative phenotype assay, and three degradation pathways believed to be missing in Shewanella were confirmed. A number of previously unknown gene products were predicted to be part of pathways or to have a function, expanding the number of gene targets for future genetic analyses. Ecologically, the comparative high throughput phenotype analysis provided insights into niche specialization within the five different strains. For example, Shewanella amazonensis strain SB2B, isolated from the Amazon River delta, was capable of utilizing 60 C compounds, whereas Shewanella sp. strain W3-18-1, from the deep marine sediment, utilized only 25 of them. In spite of the large number of nutrient sources yielding positive results, our study indicated that except for the N-sources they were not sufficiently informative to predict growth phenotypes from increasing evolutionary distances. Our results indicate the importance of phenotypic evaluation for confirming genome predictions. This strategy will accelerate the functional discovery of genes and provide an ecological framework for microbial genome sequencing projects.The work conducted by the U.S. Department of Energy Joint Genome Institute is supported by the Office of Science of the U.S. Department of Energy under Contract numbers DE-AC02-05CH11231 and DE-FG02-08ER64511

Humoral Responses against BQ.1.1 Elicited after Breakthrough Infection and SARS-CoV-2 mRNA Vaccination.

The Omicron BQ.1.1 variant is now the major SARS-CoV-2 circulating strain in many countries. Because of the many mutations present in its Spike glycoprotein, this variant is resistant to humoral responses elicited by monovalent mRNA vaccines. With the goal to improve immune responses against Omicron subvariants, bivalent mRNA vaccines have recently been approved in several countries. In this study, we measure the capacity of plasma from vaccinated individuals, before and after a fourth dose of mono- or bivalent mRNA vaccine, to recognize and neutralize the ancestral (D614G) and the BQ.1.1 Spikes. Before and after the fourth dose, we observe a significantly better recognition and neutralization of the ancestral Spike. We also observe that fourth-dose vaccinated individuals who have been recently infected better recognize and neutralize the BQ.1.1 Spike, independently of the mRNA vaccine used, than donors who have never been infected or have an older infection. Our study supports that hybrid immunity, generated by vaccination and a recent infection, induces higher humoral responses than vaccination alone, independently of the mRNA vaccine used

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk

During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in influenza-naïve, systematically-infected ferrets may not replicate the human experience. While they cannot be considered conclusive to explain human observations, these ferret findings are consistent with direct, adverse effect of prior 2008–09 TIV receipt on A(H1N1)pdm09 illness. As such, they warrant further in-depth investigation and search for possible mechanistic explanations

Children with pertussis inform the investigation of other pertussis cases among contacts

BACKGROUND: The number of reported pertussis has increased in the last two decades. However, many cases of pertussis may be underreported or not diagnosed. The World Health Organization estimates that pertussis causes 200,000-400,000 deaths each year, most deaths are in infants and in developing countries. Infants with pertussis can indicate an undetected source cases in the community. METHODS: At a University Hospital in Brazil individuals that had frequent contacts with a child with confirmed pertussis (the index case) and had recent history of cough were enrolled into the study. Nasopharyngeal swabs were collected from every contact that had cough within the last 21 days. Cases confirmation followed the guidelines of the Center for Disease Control and Prevention-Atlanta, USA. RESULTS: Pertussis diagnosis was confirmed in 51 children, (considered the index cases). Among the index cases, 72.5% (37/51) were under 6 months of age; culture for Bordetella pertussis was positive in 78.4% (40/51). Pertussis was confirmed in 39% (107/276) of the contacts of 51 index cases. Among these contacts identified as a pertussis case, 40.2% (43/107) were between 6 months and 111/2 years of age and 59.8% (64/107) were older than 111/2 years of age. Pertussis was confirmed by culture in 11.2% (12/107) of them and by epidemiologic linkage in 88.8% (95/107). Each index case allowed identifying two new cases of pertussis. CONCLUSION: Public health authorities should consider implementing early recognition of pertussis index cases and searching for pertussis cases among the contacts. Treatment of the cases and prophylaxis of the contacts is fundamental to control outbreaks in the community