Insight into topological and functional relationships of cytochrome c oxidase subunit I of Saccharomyces cerevisiae by means of intragenic complementation

AbstractIn yeast, revertants were selected from four respiratory deficient mutants carrying mutations in the cytochrome c oxidase subunit I gene. Intragenic second site mutations revealed amino acids which are functionally complementary to the original mutated position and may be in topological interaction with it. The results provide additional data in favour of the model proposed for the structure of the binuclear centre in proton-motive oxidases

Mapping adolescent health and lifestyles in a multi-state country: methodological aspects and first results

Summary: Objectives: To explore the feasibility of a geographical analysis (mapping) of data from a national adolescent survey. Methods: Teenagers 15 to 19 years in high school or apprenticeship (N=5275 boys and 3993 girls) answered a self-administered anonymous questionnaire targeting health and lifestyles. Switzerland was divided in 14 subunits, each one including at least 400 subjects: large cantons were isolated by themselves whereas smaller ones were aggregated taking into account common cultural, geographical and health characteristics. To minimise the impact of sample differences across the cantons, subsamples were weighted according to age, sex, and professional background. For each variable, the discretisation of the values in five classes was performed using the threshold approach which maximises intergroup differences and minimises the intragroup differences. Results: The analysis suggests different patterns of distribution depending on the type of variable studied: substance use differs mostly between urban and rural cantons, while mental health differs between French and German-speaking cantons. Conclusions: Whereas most available atlases are derived from population-based data (i.e., mortality rates), this research demonstrates the feasibility of using self-reported data from school-based survey samples. The presentation of data on attractive maps provides a unique opportunity for generating hypotheses as to the causes of differences across cantons in a multi-ethnic, multicultural countr

Biodistribution and clearance of instilled carbon nanotubes in rat lung

<p>Abstract</p> <p>Background</p> <p>Constituted only by carbon atoms, CNT are hydrophobic and hardly detectable in biological tissues. These properties make biokinetics and toxicology studies more complex.</p> <p>Methods</p> <p>We propose here a method to investigate the biopersistence of CNT in organism, based on detection of nickel, a metal present in the MWCNT we investigated.</p> <p>Results and conclusion</p> <p>Our results in rats that received MWCNT by intratracheal instillation, reveal that MWCNT can be eliminated and do not significantly cross the pulmonary barrier but are still present in lungs 6 months after a unique instillation. MWCNT structure was also showed to be chemically modified and cleaved in the lung. These results provide the first data of CNT biopersistence and clearance at 6 months after respiratory administration.</p

vanA in Enterococcus faecium, Enterococcus faecalis, and Enterococcus casseliflavus detected in French cattle.

The goal of this study was to assess the presence of enterococci species presenting van-mediated glycopeptide resistance in French cattle. Fecal samples were collected from healthy and sick animals, and enterococci were screened for vancomycin resistance. Vancomycin resistance was principally encountered in Enterococcus gallinarum and Enterococcus casseliflavus strains. However, glycopeptide resistance was detected in three different species of enterococci (E. faecalis, E. faecium, and E. casseliflavus). Molecular characterization of the genetic support proved that they all presented the prototypic VanA element. Interestingly, the E. casseliflavus strain displayed a remarkable VanB phenotype/vanA-vanC genotype. Transferability, associated resistances, and factors of vanA cotransfer were sought. This study proved that acquired vanA genes can still be detected in food-producing animals more than a decade after the avoparcin ban. Indeed, calves, which are recurrently exposed to antibiotics in France, may allow the re-emergence of glycopeptide resistance through coselection factors, and this might potentially be concerning for human health

Challenges and solutions to embed cancer survivorship research and innovation within the EU Cancer Mission

We have reached a watershed moment in Europe in our efforts to ensure increased survival and better outcomes for cancer patients. The EU Cancer Mission and the European Beating Cancer Plan together provide an unrivalled opportunity to make significant inroads into a disease that kills over 1.7 million European citizens annually. Harnessing these twin pillars of cancer research and cancer control can be transformative for the European cancer community and in particular for the European cancer patient. However, from a research perspective, in order to fully realise these benefits, we need to ensure that all aspects of the cancer continuum are addressed. Previous research efforts have focussed more on the diagnosis and treatment of cancer, whereas cancer survivorship, to date, has been overlooked. Here, we aim to redress this balance, by identifying the key challenges in cancer survivorship research that need to be addressed and proposing a series of recommended solutions, which, if acted upon, would deliver significant benefits for the nearly 20 million cancer survivors in Europe. To achieve this, we propose the development of a clearly articulated and sustainably funded European Cancer Survivorship Research and Innovation Plan. Embedding this plan within the framework of the EU Cancer Mission would be transformative for cancer survivors and society

Clinical and functional analyses of AIPL1 variants reveal mechanisms of pathogenicity linked to different forms of retinal degeneration

Disease-causing sequence variants in the highly polymorphic AIPL1 gene are associated with a broad spectrum of inherited retinal diseases ranging from severe autosomal recessive Leber congenital amaurosis to later onset retinitis pigmentosa. AIPL1 is a photoreceptor-specific co-chaperone that interacts with HSP90 to facilitate the stable assembly of retinal cGMP phosphodiesterase, PDE6. In this report, we establish unequivocal correlations between patient clinical phenotypes and in vitro functional assays of uncharacterized AIPL1 variants. We confirm that missense and nonsense variants in the FKBP-like and tetratricopeptide repeat domains of AIPL1 lead to the loss of both HSP90 interaction and PDE6 activity, confirming these variants cause LCA. In contrast, we report the association of p.G122R with milder forms of retinal degeneration, and show that while p.G122R had no effect on HSP90 binding, the modulation of PDE6 cGMP levels was impaired. The clinical history of these patients together with our functional assays suggest that the p.G122R variant is a rare hypomorphic allele with a later disease onset, amenable to therapeutic intervention. Finally, we report the primate-specific proline-rich domain to be dispensable for both HSP90 interaction and PDE6 activity. We conclude that variants investigated in this domain do not cause disease, with the exception of p.A352_P355del associated with autosomal dominant cone-rod dystrophy

Automatized lung disease quantification in patients with COVID-19 as a predictive tool to assess hospitalization severity

peer reviewedThe pandemic of COVID-19 led to a dramatic situation in hospitals, where staff had to deal with a huge number of patients in respiratory distress. To alleviate the workload of radiologists, we implemented an artificial intelligence (AI) - based analysis named CACOVID-CT, to automatically assess disease severity on chest CT scans obtained from those patients. We retrospectively studied CT scans obtained from 476 patients admitted at the University Hospital of Liege with a COVID-19 disease. We quantified the percentage of COVID-19 affected lung area (% AA) and the CT severity score (total CT-SS). These quantitative measurements were used to investigate the overall prognosis and patient outcome: hospital length of stay (LOS), ICU admission, ICU LOS, mechanical ventilation, and in-hospital death. Both CT-SS and % AA were highly correlated with the hospital LOS, the risk of ICU admission, the risk of mechanical ventilation and the risk of in-hospital death. Thus, CAD4COVID-CT analysis proved to be a useful tool in detecting patients with higher hospitalization severity risk. It will help for management of the patients flow. The software measured the extent of lung damage with great efficiency, thus relieving the workload of radiologists