Disruption of regulatory domains and novel transcripts as disease-causing mechanisms

Deletions, duplications, insertions, inversions, and translocations, collectively called structural variations (SVs), affect more base pairs of the genome than any other sequence variant. The recent technological advancements in genome sequencing have enabled the discovery of tens of thousands of SVs per human genome. These SVs primarily affect non-coding DNA sequences, but the difficulties in interpreting their impact limit our understanding of human disease etiology. The functional annotation of non-coding DNA sequences and methodologies to characterize their three-dimensional (3D) organization in the nucleus have greatly expanded our understanding of the basic mechanisms underlying gene regulation, thereby improving the interpretation of SVs for their pathogenic impact. Here, we discuss the various mechanisms by which SVs can result in altered gene regulation and how these mechanisms can result in rare genetic disorders. Beyond changing gene expression, SVs can produce novel gene-intergenic fusion transcripts at the SV breakpoints

Phenetic and genetic structure of tsetse fly populations (Glossina palpalis palpalis) in southern Ivory Coast

Background: Sleeping sickness, transmitted by G. p. palpalis, is known to be present in the Ivory Coast. G. p. palpalis has recently been reported to occur in several places within the town of Abidjan, including: (i) the Banco forest, (ii) the Abobo Adjame University campus and (iii) the zoological park. Could these three places be treated sequentially, as separate tsetse populations, or should they be taken as one area comprising a single, panmictic population? Methods: The amount of gene flow between these places provides strategic information for vector control. It was estimated by the use of both microsatellite DNA and morphometric markers. The idea was to assess the interest of the faster and much less expensive morphometric approach in providing relevant information about population structure. Thus, to detect possible lack of insect exchange between these neighbouring areas of Abidjan, we used both genetic (microsatellite DNA) and phenetic (geometric morphometrics) markers on the same specimens. Using these same markers, we also compared these samples with specimens from a more distant area of south Ivory Coast, the region of Aniassue (186 km north from Abidjan). Results: Neither genetic nor phenetic markers detected significant differentiation between the three Abidjan G. p. palpalis samples. Thus, the null hypothesis of a single panmictic population within the city of Abidjan could not be rejected, suggesting the control strategy should not consider them separately. The markers were also in agreement when comparing G. p. palpalis from Abidjan with those of Aniassue, showing significant divergence between the two sites. Conclusions: Both markers suggested that a successful control of tsetse in Abidjan would require the three Abidjan sites to be considered together, either by deploying control measures simultaneously in all three sites, or by a continuous progression of interventions following for instance the "rolling carpet" principle. To compare the geometry of wing venation of tsetse flies is a cheap and fast technique. Agreement with the microsatellite approach highlights its potential for rapid assessment of population structure

Lippia multiflora (verbenaceae) en Côte d’Ivoire : point des premiers resultats de recherche et Enjeu cultural

Lippia multiflora (Verbenaceae) ou thé de savane pousse naturellement dans les régions de savane en Côte d’Ivoire. Dans le cadre de la diversification des cultures en Côte d’Ivoire, des recherches récentes ont été conduites en vue de la caractérisation de sa composition, sa domestication et sa valorisation, ont abouti à des résultats. Des résultats de recherche couvrant les années 1996 à 2009 de travaux sur Lippia multiflora ont concerné cette analyse. Ceux-ci concernent différents champs disciplinaires dont des évaluationspédologiques, agrophysiologiques, physicochimiques et médicinales effectués en Côte d’Ivoire. Les particularités de cette plante en interaction avec les paramètres environnementaux de sa culture mises en valeur sont discutées

Décomposition des tourteaux de coprah et de palmiste et effets sur la croissance des cocotiers (Cocos nucifera L.) en pépinière et la nutrition minérale des cocotiers adultes en Côte-d\'Ivoire

L\'objectif de cette étude est d\'évaluer le potentiel fertilisant des tourteaux de coprah et de palmiste. Ainsi, les tourteaux ont été mis en décomposition pendant une période de 12 mois. Leurs effets sur la croissance des jeunes cocotiers ont été étudiés pendant 9 mois en comparaison à ceux de l\'engrais chimique. Une analyse foliaire a été réalisée afin d\'évaluer les effets des tourteaux sur la nutrition minérale des cocotiers adultes, 7 et 21 mois après leur épandage. Après 12 mois, les tourteaux ont libéré la totalité du potassium et plus de la moitié de l\'azote et du phosphore. Ils ont eu un effet positif sur la croissance des cocotiers en pépinière semblable à celui de la fumure chimique composée d\'urée à 46 % de N, super phosphate simple à 18 % de P2O5, chlorure de potassium à 60 % de K2O et de kiesérite à 28 % de MgO. Sept mois après l\'épandage, ils ont amélioré les teneurs foliaires en azote, en phosphore et en potassium des cocotiers adultes, mais ces teneurs ont chuté 21 mois après. Ces résultats montrent que les tourteaux sont des engrais organiques qui pourraient remplacer la fumure chimique.The objective of this study is to assess the fertilizing potential of the oil-cakes of copra and palm tree. Thus, the oilcakes were allowed to decompose for 12 months period. Their effects on the growth of young coconuts were studied for 9 months in comparison with those of chemical fertilisers. A foliar analysis was carried out in order to assess the effects of the oil-cakes on the mineral nutrition of adult coconuts 7 and 21 month after application. After 12 months, the oil-cakes released the totality of the potassium and more than half of nitrogen and phosphorus. Application of oil-cakes had a positive effect on the growth of coconuts in nursery similar to the one of the chemical fertilizer, consisted of urea (46 % of N), super simple phosphorus (18 % of P2O5), potassium chloride (60 % of K2O) and kieserite (28 % of MgO). Seven months after application, they improved the foliar contents of nitrogen, phosphorus and potassium of adult coconuts, but these contents fell 21 month later. These results show that the oil-cakes may be used as organic fertilizers that could replace the chemical fertilizers. Keywords: Coconut, nitrogen, potassium, mineral nutrition, phosphorus, oil-cakes.Sciences & Nature Vol. 5 (2) 2008: pp. 155-16

Neutrophil expression of glucocorticoid-induced leucine zipper (GILZ) anti-inflammatory protein is associated with acute respiratory distress syndrome severity

BACKGROUND: Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein involved in neutrophil apoptosis and the resolution of inflammation. Given the numerous pathophysiologic roles of neutrophils in the acute respiratory distress syndrome (ARDS), we postulated that neutrophil GILZ expression might be induced during ARDS, to modulate the inflammatory process and participate in lung repair. METHODS: This single-center, prospective, observational cohort study took place in the surgical intensive care unit of Bichat Hospital (Paris, France) and involved 17 ARDS patients meeting the Berlin criteria at inclusion, and 14 ventilated controls without ARDS. Serial blood samples were obtained every 2 days until extubation or death (from 1 to 9 samples per patient). GILZ protein and gene expression was quantified in blood neutrophils, along with markers of inflammation (CRP, extracellular DNA) or its resolution (Annexin A1). RESULTS: Neutrophil GILZ expression was detected at the transcriptional and/or translational level in 9/17 ARDS patients (in particular 7/10 severe ARDS) and in 2/14 ventilated controls. The highest mRNA levels were observed in the most severely ill patients (p < 0.028). GILZ was expressed in about ¾ of the corticosteroid-treated patients and its expression could also occur independently of corticosteroids, suggesting that inflammatory signals may also induce neutrophil GILZ expression in vivo. CONCLUSIONS: In this pilot study, we show for the first time that blood neutrophils from patients with ARDS can express GILZ, in keeping with an anti-inflammatory and regulatory endogenous role of GILZ in humans. Contrary to some markers of inflammation or its resolution, the levels of gilz gene expression were related to ARDS severity

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

publishedVersio

Different strategies for mechanical VENTilation during CardioPulmonary Bypass (CPBVENT 2014): Study protocol for a randomized controlled trial

Background: There is no consensus on which lung-protective strategies should be used in cardiac surgery patients. Sparse and small randomized clinical and animal trials suggest that maintaining mechanical ventilation during cardiopulmonary bypass is protective on the lungs. Unfortunately, such evidence is weak as it comes from surrogate and minor clinical endpoints mainly limited to elective coronary surgery. According to the available data in the academic literature, an unquestionable standardized strategy of lung protection during cardiopulmonary bypass cannot be recommended. The purpose of the CPBVENT study is to investigate the effectiveness of different strategies of mechanical ventilation during cardiopulmonary bypass on postoperative pulmonary function and complications. Methods/design: The CPBVENT study is a single-blind, multicenter, randomized controlled trial. We are going to enroll 870 patients undergoing elective cardiac surgery with planned use of cardiopulmonary bypass. Patients will be randomized into three groups: (1) no mechanical ventilation during cardiopulmonary bypass, (2) continuous positive airway pressure of 5 cmH2O during cardiopulmonary bypass, (3) respiratory rate of 5 acts/min with a tidal volume of 2-3 ml/Kg of ideal body weight and positive end-expiratory pressure of 3-5 cmH2O during cardiopulmonary bypass. The primary endpoint will be the incidence of a PaO2/FiO2ratio <200 until the time of discharge from the intensive care unit. The secondary endpoints will be the incidence of postoperative pulmonary complications and 30-day mortality. Patients will be followed-up for 12 months after the date of randomization. Discussion: The CPBVENT trial will establish whether, and how, different ventilator strategies during cardiopulmonary bypass will have an impact on postoperative pulmonary complications and outcomes of patients undergoing cardiac surgery. Trial registration: ClinicalTrials.gov, ID: NCT02090205. Registered on 8 March 2014