Identification of clustered microRNAs using an ab initio prediction method

BACKGROUND: MicroRNAs (miRNAs) are endogenous 21 to 23-nucleotide RNA molecules that regulate protein-coding gene expression in plants and animals via the RNA interference pathway. Hundreds of them have been identified in the last five years and very recent works indicate that their total number is still larger. Therefore miRNAs gene discovery remains an important aspect of understanding this new and still widely unknown regulation mechanism. Bioinformatics approaches have proved to be very useful toward this goal by guiding the experimental investigations. RESULTS: In this work we describe our computational method for miRNA prediction and the results of its application to the discovery of novel mammalian miRNAs. We focus on genomic regions around already known miRNAs, in order to exploit the property that miRNAs are occasionally found in clusters. Starting with the known human, mouse and rat miRNAs we analyze 20 kb of flanking genomic regions for the presence of putative precursor miRNAs (pre-miRNAs). Each genome is analyzed separately, allowing us to study the species-specific identity and genome organization of miRNA loci. We only use cross-species comparisons to make conservative estimates of the number of novel miRNAs. Our ab initio method predicts between fifty and hundred novel pre-miRNAs for each of the considered species. Around 30% of these already have experimental support in a large set of cloned mammalian small RNAs. The validation rate among predicted cases that are conserved in at least one other species is higher, about 60%, and many of them have not been detected by prediction methods that used cross-species comparisons. A large fraction of the experimentally confirmed predictions correspond to an imprinted locus residing on chromosome 14 in human, 12 in mouse and 6 in rat. Our computational tool can be accessed on the world-wide-web. CONCLUSION: Our results show that the assumption that many miRNAs occur in clusters is fruitful for the discovery of novel miRNAs. Additionally we show that although the overall miRNA content in the observed clusters is very similar across the three considered species, the internal organization of the clusters changes in evolution

Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

Tumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.</p

Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders

Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approach-in a limited number of patients and controls-to investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology

Développement de nouvelles applications en criblage virtuel

Basé sur le docking moléculaire, le criblage virtuel devient de plus en plus utilisé dans la recherche pharmaceutique. En vue d'améliorer les résultats de docking, nous avons développé Consdock, outil d'analyse des interactions Ligand - Récepteur. Appliqué à trois outils de docking, Gold, FlexX et Gold pour un ensemble de 100 complexes, ConsDock a pu générer des résultats meilleurs que ceux obtenus par chacun des outils utilisés, avec une précision avoisinant 1 Å. Par ailleurs, nous nous sommes intéressés à une application moins connue du criblage virtuel, le criblage inverse. Celui-ci consiste à chercher des cibles pour une petite molécule donnée. Pour cela, nous avons construit sc-PDB (screening PDB) une base de données de cibles à partir de la Protein Data Bank. Pour utiliser la base, nous avons développé une stratégie de criblage inverse basée sur Gold. Dans les tests que nous avons réalisés, les cibles recherchées de molécules connues ont pu toujours être trouvées parmi les meilleures solutions générées. Enfin, nous avons entrepris la simulation du repliement des Récepteurs couplés aux protéines G ou RCPG en présence de ligand par algorithmes génétiques. Nous avons choisi et construit des méthodes de sélection susceptibles de donner de bons résultats, lorsqu'elles sont employées en concordance avec des opérateurs génétiques adéquats sur un nombre suffisant de générationsBased on molecular docking, virtual screening or in silico screening becomes of increasing interest in the pharmaceutical industry. In this study, we propose ConsDock a consensus docking program that takes advantage of three widely used docking tools Dock, Gold and FlexX. ConsDock significantly outperforms single docking with respect to the docking accuracy of the top-ranked pose. Then, for inverse screening purpose, we develop a protein database based on the Protein data Bank (sc-PDB). This database has been used to recover target of known ligands by using an in-house inverse screening process based on Gold. At last, as we were interested in developing activated models of G Protein-Coupled Receptors or GPCRs, we present a simulation process of ligand-based GPCR folding. The simulation is performed by genetic algorithms. By using a GPCR and a ligand, the algorithm tries to find stable conformations of GPCR by rotating and translating helices. Movement is performed according experimental observations. We tested the method on the X-ray structure of rhodopsin complexed with the cis-retinal. We got some good results when used specific genetic operators for a sufficient number of generations.STRASBOURG ILLKIRCH-Pharmacie (672182101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Trade-Offs of Flowering and Maturity Synchronisation for Pineapple Quality.

In the pineapple sector of Benin, poor fruit quality prevents pineapple producers to enter the European market. We investigated effects of common cultural practices, flowering and maturity synchronisation, (1) to quantify the trade-offs of flowering and maturity synchronisation for pineapple quality and the proportion of fruits exportable to European markets, and (2) to determine the effect of harvesting practice on quality attributes. Four on-farm experiments were conducted during three years using cultivars Sugarloaf and Smooth Cayenne. A split-split plot design was used in each experiment, with flowering induction practice as main factor (artificial or natural flowering induction), maturity induction practice as split factor (artificial or natural maturity induction) and harvesting practice as the split-split factor (farmers' harvest practice or individual fruit harvesting at optimum maturity). Artificial flowering induction gave fruits with lower infructescence weight, higher ratio crown: infructescence length, and a lower proportion of fruits exportable to European markets than natural flowering induction. The costs of the improvements by natural flowering induction were huge: the longer durations from planting to flowering induction and harvesting, the higher number of harvestings of the fruits increasing the labour cost and the lower proportion of plants producing fruits compared with crops from artificially flowering-induced plants. Artificial maturity induction decreased the total soluble solids concentration in the fruits compared with natural maturity induction thus decreasing the proportion of fruits exportable to European markets, at a benefit of only a slightly shorter time from flowering induction to harvesting. Harvesting individual fruits at optimum maturity gave fruits with higher total soluble solids in naturally maturity induced fruits compared with the farmers' harvest practice. Given the huge costs of natural flowering induction, options to use artificial flowering induction effectively for obtaining high fruit quality are discussed

Marketing of fish caught by enclosure fishing in South Ubangi, Democratic Republic of the Congo

Une étude relative à la commercialisation des poissons capturés par la pêche aux claies a été menée entre août 2021 et novembre 2022 dans le Sud-Ubangi, en République démocratique du Congo pour évaluer le niveau de profitabilité du commerce en gros. Les résultats ont montré que le fumage est le mode de conservation le plus pratiqué&nbsp; pour les poissons destinés à la commercialisation dans les marchés éloignés. Le coût de commercialisation en gros d’un kilogramme de poissons fumés de Bomboma à Zongo est en moyenne de 6 222,2FC/Kg&nbsp; (±1344,3FC) soit 2.8$Kg (au taux de 1$ = 2 200FC). Ce commerce génère un profit moyen de 1 599,4FC/Kg de poissons (±1 904,7) (équivalent de 0.727/Kg). Les plus gros bénéfices sont réalisés par les grossistes dont les gains nets sont compris entre 5 003,1FC/Kg et 6 058,7FC/Kg. Mais cette catégorie ne représente que 4% des répondants. Le prix de vente accuse une variation à la hausse de 3 060FC le Kg (± 1 898,6FC) (équivalent de 1.39)&nbsp;soit un taux d’accroissement moyen de&nbsp; 74,7%&nbsp; (±57,5%) de prix de vente bord capture qui est en moyenne de 4 761,6 FC/Kg (±1263,2) soit 2.16$(au taux de 1$=2 200FC).&nbsp; Cette augmentation n’est pas profitable à tous les grossistes car 26,5% d’entre eux enregistrent une rentabilité négative suite au coût élevé de transport. En conséquence, le revenu brut engendrés par cette pêche n’est pas équitablement répartis entre les deux premiers maillons de ladite filière&nbsp;: la part revenant à la capture (pêcheur) représente en moyenne 62,9% (±18,2%) contre 37,1% (±18,3%) pour la vente en gros, en majeur partie dominé par le coût de transaction. Autrefois considérée comme une pêche de subsistance, elle constitue une source non négligeable des revenus et peut faire l’objet d’insertion dans le circuit de commercialisation à l’échelle tant nationale qu’internationale. Mots clés: Répartition, Revenu, Claies, Halieutique, Profitabilité, BombomaA study relating to the marketing of fish caught by fishing with racks was carried out between August 2021 and November 2022 in Sud-Ubangi province, in the Democratic Republic of Congo to evaluate the level of profitability of the wholesale trade. The results showed that the smoking is the most practiced method of conservation for fish intended for sale in the distant market. The cost of wholesale marketing of one kilogram of smoked fish from Bomboma to Zongo is on average 6,222.2FC/Kg (±1,344.3FC) or 2.8$/Kg (at the rate of 1$=2,200FC). This trade generates an average profit of 1 599.4FC/Kg of fish (±1,904.7FC) (equivalent to 0.727$/Kg). The biggest profits made by wholesales whose net earnings are between 5,003.1FC and 6,058.7FC/Kg. but this category represents only 4$1.39) about a rate of average increase of 74.7% (±57.5%) in the selling price on board catch which is on average 4761.6FC/Kg (±1,263.2FC) or 2.16$(at the rate of 1$=2,200FC). This increase is not beneficial to all wholesalers because 26.5% of them record negative profitability due to the high cost of transport. So the gross income generated by this fishery is not equitably distributed between the first two links of the said sector: the share going to the capture (fisherman) represents on average 62.9% (±18.2%) against 37.1% (±18.3%) for the wholesale, mainly dominated by the transaction cost. Thus, once considered as subsistence fishing, this seasonal activity is a significant source of income and can therefore be included in the marketing circuit both nationally and internationally. Keywords: Distribution, Income, Racks, Fishery, Profitability, Bombom

Développement d’une approche multi-omique pour la recherche de biomarqueurs associés à la réponse au traitement dans les lymphomes

International audienc

Inventaire des poissons capturés par la pêche aux claies au Sud-Ubangi (RD Congo)

The aim of this study was to inventory the different fish species fished by using enclosure “Ndobo” in the Bomboma sector, to detect potential breeding species. The study found that 19 fish species belonging to 13 genera and 10 families dominated by Claridae with 31.6%. Only 6 species (about 31.6%) are already breeding by the pisciculturist. From an economic point of view, 3 listed species are among the species commonly bred in Democratic Republic of Congo, namely Parachanna obscura, P. insignis and Clarias gariepinus. Physical form (dimension et weight) and organoleptiques observations makes three species potential candidates for fish farming: two of Clarias genera namely C. sp (Limongo in Boba or Ngolo in Lingala) and C. sp (Okolo in Boba or Ngolo en Lingala) and one of Clariallabe genera: C. sp. (Motepa in Boba/Mongbangele in Lingala). Hence, there is a need to domesticate and to bred in ponds these species and evaluate their economic and zootechnic performances. That will enable to enrich piscicultural fauna with new species and then to diversify the fish production. Keywords: Fishing, enclosure, Ndobo, Fish, BombomaLa présente étude avait pour but d'inventorier les espèces de poissons capturés par la technique de pêche aux claies du type «Ndobo» en vue de détecter parmi ces espèces sauvages, et ce, à partir des données de la littérature sur leur comportement, celles ayant des potentialités piscicoles et ainsi proposer les stratégies de leur domestication. Il se dégage de cette étude que 19 espèces de poissons inventoriées sont réparties en 13 genres et 10 familles dont la plus représentée est celle de Claridae avec 31,6% d'espèces. Seulement 6 espèces (soit 31,6%) font déjà l’objet d’élevage parmi lesquelles, du point de vue économique, 3 espèces sont couramment élevées en RDC à savoir Parachanna obscura, P. insignis et Clarias gariepinus. Les observations morphologiques et les appréciations organoleptiques poussent à considérer que trois espèces sont potentiellement piscicoles à savoir Clariallabes sp. et deux autres du genre Clarias, communément appelées «ngolo» (en lingala) et spécifiquement Limongo et Okolo (en Boba). D'où la nécessité de procéder à leur domestication et élevage en étang en vue d'étudier leurs performances zootechniques et économiques. Ceci pourrait permettre d'enrichir localement l'ichtyofaune piscicole en nouvelles espèces sauvages et ainsi diversifier la production. Mots clés: Pêche, claies, Ndobo, Poisson, Bombom