Human and microbial genetic factors contributions to the development of HIV-associated neurocognitive disorder

Years of research and the development of effective therapeutic treatments, have dramatically improved the life expectancy rates for HIV-infected individuals. However, there is a subpopulation of aging, infected individuals who have experienced an adverse impact on their long-term health and quality of life, the mechanism of which has become an increasing concern of public health importance. The counteractive outcomes of aging within the infected population leaves many susceptible to developing age related morbidities in the form of cognitive impairment, brain atrophy, and other neurocognitive disorders at an earlier age then those within the non-infected population. These symptoms manifest in the form of HIV-associated Neurocognitive Disorder or HAND in infected individuals. Fully understanding the process in which HAND can occur has been a striving goal within the Public Health community. Our goal is to determine if there are specific genetic and/or microbial factors within individuals that may be contributing to their development of cognitive decline. All these efforts could provide comprehensive insight at an endophenotypic level into the pathological mechanism of HAND, and a better understanding of how diversity in the gut microbiome can affect health and aging. Subsequently, this information could lead to the identification of genetic biomarkers, development of treatments, and therapeutic options for regulating chronic HIV infection and neuropathology. We hypothesize that inherited SNPs in genes of the folate metabolism pathway affect the availability of methyl groups within the cell, and consequently influence DNA methylation, leading to the development of HAND in seropositive individuals, and neurocognitive decline in seronegative individuals. We also hypothesize that there is an altered composition of the microbiome within the gut of infected individuals, the presence of which directs the level of HIV pathogenesis and HAND development. In comparing HIV+ and Cognitive Decline groups against control groups, we do not have sufficient evidence to conclude that there is an increased risk of adverse outcome in association with any of the folate genes that we observed. Isolation of bacterial genome produced expected PCR product, and data interpretation following 16S rRNA sequencing will soon yield definitive microbial composition analysis

Network-Guided Analysis of Genes with Altered Somatic Copy Number and Gene Expression Reveals Pathways Commonly Perturbed in Metastatic Melanoma

Cancer genomes frequently contain somatic copy number alterations (SCNA) that can significantly perturb the expression level of affected genes and thus disrupt pathways controlling normal growth. In melanoma, many studies have focussed on the copy number and gene expression levels of the BRAF, PTEN and MITF genes, but little has been done to identify new genes using these parameters at the genome-wide scale. Using karyotyping, SNP and CGH arrays, and RNA-seq, we have identified SCNA affecting gene expression (‘SCNA-genes’) in seven human metastatic melanoma cell lines. We showed that the combination of these techniques is useful to identify candidate genes potentially involved in tumorigenesis. Since few of these alterations were recurrent across our samples, we used a protein network-guided approach to determine whether any pathways were enriched in SCNA-genes in one or more samples. From this unbiased genome-wide analysis, we identified 28 significantly enriched pathway modules. Comparison with two large, independent melanoma SCNA datasets showed less than 10% overlap at the individual gene level, but network-guided analysis revealed 66% shared pathways, including all but three of the pathways identified in our data. Frequently altered pathways included WNT, cadherin signalling, angiogenesis and melanogenesis. Additionally, our results emphasize the potential of the EPHA3 and FRS2 gene products, involved in angiogenesis and migration, as possible therapeutic targets in melanoma. Our study demonstrates the utility of network-guided approaches, for both large and small datasets, to identify pathways recurrently perturbed in cancer

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Co-construction of a local fish culture system : case study in Western Cameroon

National audienceFish culture can be an important food source as well as a way to increase employment and income of rural populations in Africa. In most countries, however, it is not considered to be a full share activity, and, in most cases, the fish culture systems implemented by rural production do not reach their economic viability. In order to promote sustainable fish culture as well as flexible and innovative production systems, it is important that the socio-technical and organizational innovations be codesigned. To study this issue a research program in Western Cameroon developed a project with two fish farming groups organized into Common Initiative Groups. Two theoretical approaches are used: the sociology of translation and sciences - which considers that innovations are socially built and that the role of the research is not only to produce new techniques but to translate the different issues, so as to enrol the actors around a common question; and both action-research and intervention-research developed by sociologists and management researchers. We presented the results of the diagnosis to three groups of farmers gathered by local leaders. During these meetings, we were able to identify the actors concerned, the requests, and the stakes. We will present here the first two phases of what we describe as a Partnership-based Action-Research. The first phase consists of exploring and formalizing how the different actors will commit themselves to work together and to reach an agreement. In the second phase the co-conception of the fish culture innovation is implemented. The main result is the groups (CIG) which were set up. They not only enable the experimental protocols but also build a language, a representation and a common way of working, as a necessary passage point (NPP), essential to any socio-technical and organisational innovation. Another important result is how the experimental protocols helped formalize the ethical framework necessary to work in partnership. In conclusion, it is important for us to learn from the methodological work accomplished - in particular to reflect on the competencies the researchers ought to develop to work with farmers. Researchers act as mediators, facilitators, translators and spokesmen of a hybrid actorresearcher group. The “technical” work is carried out according to a co-defined action plan, generally to solve a problem. The production of action-based scientific knowledge becomes a true task of the research group

Développement de la petite pisciculture marchande au Cameroun : la recherche-action en partenariat

SAD CT1 Numéro thématique "Piscicultures : le poisson de demain" coordonné par J. Lazard et R. Lésel Etude originale dans partie "Nouvelles approches du développement de la pisciculture" mars-juin 2009 FI 2008 0.304National audienceIn Cameroon, fish farming represents the only alternative to fill in the deficit in fish and to decrease the importation levels. It is also a new source of income for the rural farmers. However, the fish farming systems that have been put forward are note efficient enough on the biotechnical and economical levels to drive commercial dynamics. Several approaches to the development of fish farming have been applied since the nineties: after a systemic agronomic approach implemented in development projects, a participatory approach emerged. This article introduces a new approach based on action research in partnership (ARP) to contribute to fish farming development. We intend to present here the first results achieved in the Cameroonian field.La pisciculture représente, au Cameroun, la seule alternative pour combler le déficit en poissons et réduire le niveau des importations. C'est aussi une nouvelle source de revenu pour des producteurs ruraux. Cependant, les systèmes piscicoles proposés ne sont pas assez performants sur le plan biotechnique et économique pour impulser des dynamiques marchandes. Différentes approches pour développer la pisciculture ont été appliquées, depuis les années 1990 : à une démarche agronomique de type systémique mise en oeuvre dans des projets de développement est venue s'ajouter une démarche participative. Cet article propose une nouvelle approche pour contribuer au développement de la pisciculture basée sur une démarche de recherche-action en partenariat (RAP). Nous présenterons les premiers résultats obtenus sur le terrain camerounais

Development of eco-efficient smart electronics for anticounterfeiting and shock detection based on printable inks

Printed electronics are expected to meet an increasing demand for improved functionality and autonomy of products in the context of Internet-of-Things. With this trend, the environmental performance of novel technologies is of growing importance. The current study presents the life cycle assessment of two novel devices: an anticounterfeit label based on the electrochromic display and a shock-detection tag based on the piezoelectric sensor, designed for the use in packaging of pharmaceuticals and luxury items to improve the safety and accountability in the supply chain. The devices are manufactured by means of energy-efficient printing techniques on a low-cost flexible and recyclable paper substrate. Comprehensive cradle-to-grave analysis contributes to industrial-scale energy and material life cycle inventories and identifies the main impact hotspots evaluated for a broad range of categories of the ReCiPe midpoint (H) impact assessment method. Results show that major impact burdens are associated with the near-field communication chip and radio-frequency identification antenna, while the impacts of solvents, process energy, electrochromic display/piezoelectric sensor, Li-ion battery, and substrate are comparatively small. In terms of their global warming potential, both the anticounterfeit label and shock-detection tag embody around 0.23 kg of CO2-equiv. Several material-use reduction and material-substitution strategies are quantified and discussed for their potential to reduce high impacts of the antenna.Expertise hub for a market uptake of energy-efficient supermarkets by awareness raising, knowledge transfer and pre-preparation of an EU Ecolabe

Isotope-assisted metabolomics for the quantification of plasma metabolites: A preliminary inter-laboratory trial

International audienceHuman Large-scale metabolomics analysis is facing important challenges to increase its robustness, reproducibility and interoperability. In this context, stable-isotope labeled compounds are increasingly used for identification and quantification of their unlabeled homologs.In this study, two laboratories were involved in an inter-laboratory absolute quantification trial of amino and organic acids in the reference human plasma sample (NIST-SRM-1950) using 24 commercially-available stable-isotope (13C/15N/D) labeled standards, among the 416 identified level-1 metabolites. A pool of the labeled compounds was prepared in concentrations similar to what is expected in human plasma (0.12-67.25 mg/L). The labeled pool, the NIST-SRM-1950 and the spiked NIST-SRM-1950 were analyzed by LC-HRMS using HILIC and C18 chromatography along with QToF instruments in positive and negative modes.Regardless of chromatography or detection mode, above 19 endogenous metabolites and their labeled homologs were detected without any effects on retention times of spiking and matrix. MS-peak areas of endogenous metabolites in spiked NIST-SRM-1950 were not impacted by the isotope addition. Compared to the analysis in buffer, the intensity of the labeled compounds was impacted (attenuation>1 log for half of them) by the dilution in plasma. Calculated absolute concentration of endogenous metabolites were in accordance (±30%) with expected values for 35-58% of metabolites identified with C18 and 18-25% with HILIC. Results obtained for C18 in positive mode were consistent between the two laboratories. HILIC results complemented those from C18 by allowing quantification of metabolites not detected by C18.This preliminary trial demonstrated that isotope-assisted metabolomics could provide comparable and reliable results across laboratories

Isotope-assisted metabolomics for the quantification of plasma metabolites: A preliminary inter-laboratory trial

International audienceHuman Large-scale metabolomics analysis is facing important challenges to increase its robustness, reproducibility and interoperability. In this context, stable-isotope labeled compounds are increasingly used for identification and quantification of their unlabeled homologs.In this study, two laboratories were involved in an inter-laboratory absolute quantification trial of amino and organic acids in the reference human plasma sample (NIST-SRM-1950) using 24 commercially-available stable-isotope (13C/15N/D) labeled standards, among the 416 identified level-1 metabolites. A pool of the labeled compounds was prepared in concentrations similar to what is expected in human plasma (0.12-67.25 mg/L). The labeled pool, the NIST-SRM-1950 and the spiked NIST-SRM-1950 were analyzed by LC-HRMS using HILIC and C18 chromatography along with QToF instruments in positive and negative modes.Regardless of chromatography or detection mode, above 19 endogenous metabolites and their labeled homologs were detected without any effects on retention times of spiking and matrix. MS-peak areas of endogenous metabolites in spiked NIST-SRM-1950 were not impacted by the isotope addition. Compared to the analysis in buffer, the intensity of the labeled compounds was impacted (attenuation>1 log for half of them) by the dilution in plasma. Calculated absolute concentration of endogenous metabolites were in accordance (±30%) with expected values for 35-58% of metabolites identified with C18 and 18-25% with HILIC. Results obtained for C18 in positive mode were consistent between the two laboratories. HILIC results complemented those from C18 by allowing quantification of metabolites not detected by C18.This preliminary trial demonstrated that isotope-assisted metabolomics could provide comparable and reliable results across laboratories

New chimeric TLR7/NOD2 agonist is a potent adjuvant to induce mucosal immune responses

International audienceBackground: PRR (Pattern Recognition Receptor) agonists have been widely tested as potent vaccine adjuvants. TLR7 (Toll-Like Receptor 7) and NOD2 (nucleotide-binding oligomerization domain 2) are key innate receptors widely expressed at mucosal levels.Methods: Here, we evaluated the immunostimulatory properties of a novel hybrid chemical compound designed to stimulate both TLR7 and NOD2 receptors.Finding: The combined TLR7/NOD2 agonist showed increase efficacy than TLR7L or NOD2L agonists alone or combined in different in vitro models. Dual TLR7/NOD2 agonist efficiently stimulates TLR7 and NOD2, and promotes the maturation and reprogramming of human dendritic cells, as well as the secretion of pro-inflammatory or adaptive cytokines. This molecule also strongly induces autophagy in human cells which is a major intracellular degradation system that delivers cytoplasmic constituents to lysosomes in both MHC class I and II-restricted antigen presentation. In vivo, TLR7/NOD2L agonist is a potent adjuvant after intranasal administration with NP-p24 HIV vaccine, inducing high-quality humoral and adaptive responses both in systemic and mucosal compartments. Use of TLR7/NOD2L adjuvant improves very significantly the protection of mice against an intranasal challenge with a vaccinia virus expressing the p24.Interpretation: Dual TLR7/NOD2L agonist is a very potent and versatile vaccine adjuvant and promote very efficiently both systemic and mucosal immunity

Leitfaden zur qualitätssicheren Aktenführung nach DIN ISO-15489-1 erschienen

Der Arbeitskreis Schriftgutverwaltung im DIN NABD 15 als verantwortliches Normungsgremium zur Schriftgutverwaltung/ Records Management in Deutschland hat einen Leitfaden zur qualitätssicheren Aktenführung nach DIN ISO-15489-1 veröffentlicht. Dies zeigt prägnant die rechtlichen und fachlichen Rahmenbedingungen, Verantwortlichkeiten und Prozesse sowie notwendigen Schritte zur geeigneten IT-Unterstützung auf. Ergänzt um eine umfangreiche Literaturliste kann der Leitfaden als guter Einstieg in di..