Preventing Societal Health Risks Emerging in the Development Of Nanomedicine - What Should Prevail?

International audienc

Hydrogenation of solid hydrogen cyanide HCN and methanimine CH2NH at low temperature

International audienceContext. Hydrogenation reactions dominate grain surface chemistry in dense molecular clouds and lead to the formation of complex saturated molecules in the interstellar medium. Aims. We investigate in the laboratory the hydrogenation reaction network of hydrogen cyanide HCN. Methods. Pure hydrogen cyanide HCN and methanimine CH2NH ices are bombarded at room temperature by H-atoms in an ultra-high vacuum experiment. Warm H-atoms are generated in an H2 plasma source. The ices are monitored with Fourier-transform infrared spectroscopy in reflection absorption mode. The hydrogenation products are detected in the gas phase by mass spectroscopy during temperature-programmed desorption experiments. Results. HCN hydrogenation leads to the formation of methylamine CH3NH2, and CH2NH hydrogenation leads to the formation of methylamine CH3NH2, suggesting that CH2NH can be a hydrogenation-intermediate species between HCN and CH3NH2. Conclusions. In cold environments the HCN hydrogenation reaction can produce CH3NH2, which is known to be a glycine precursor, and to destroy solid-state HCN, preventing its observation in molecular clouds ices

Homo cerevisiae-Leveraging Yeast for Investigating Protein-Protein Interactions and Their Role in Human Disease.

peer reviewedUnderstanding how genetic variation affects phenotypes represents a major challenge, particularly in the context of human disease. Although numerous disease-associated genes have been identified, the clinical significance of most human variants remains unknown. Despite unparalleled advances in genomics, functional assays often lack sufficient throughput, hindering efficient variant functionalization. There is a critical need for the development of more potent, high-throughput methods for characterizing human genetic variants. Here, we review how yeast helps tackle this challenge, both as a valuable model organism and as an experimental tool for investigating the molecular basis of phenotypic perturbation upon genetic variation. In systems biology, yeast has played a pivotal role as a highly scalable platform which has allowed us to gain extensive genetic and molecular knowledge, including the construction of comprehensive interactome maps at the proteome scale for various organisms. By leveraging interactome networks, one can view biology from a systems perspective, unravel the molecular mechanisms underlying genetic diseases, and identify therapeutic targets. The use of yeast to assess the molecular impacts of genetic variants, including those associated with viral interactions, cancer, and rare and complex diseases, has the potential to bridge the gap between genotype and phenotype, opening the door for precision medicine approaches and therapeutic development

Qu’en est-il de l’état de santé des myes au Saguenay ? Un bilan d’études sur plus d’une décennie

Le fjord du Saguenay, reconnu pour sa faune diversifiée mais aussi pour la contamination reliée aux activités industrielles et anthropiques, a fait l’objet d’un vaste programme de suivi environnemental, entrepris par notre équipe et qui visait à répondre à la question fondamentale : L’état de santé des myes s’est-il modifié dans le fjord du Saguenay ? Dans cet article de synthèse, nous avons regroupé des résultats déjà publiés sur la condition physiologique de Mya arenaria ainsi que des résultats originaux pour extraire des tendances, de façon à répertorier les sites qui s’avèrent critiques pour le bien-être physiologique de la mye. Mya arenaria (LINNÉ, 1758) ou mye des sables, choisie comme espèce sentinelle, a été échantillonnée de 1994 à 2007, en période de maturité sexuelle, dans des sites situés à l’intérieur du fjord et à son embouchure. Les objectifs de cet article sont de comparer les résultats de différents indices de condition et de suivis hormonaux et de la gamétogenèse de chaque site et en fonction des sexes, pour identifier les sites moins favorables pour la croissance et la reproduction de la mye. Nous avons démontré que les myes de Baie‑Sainte-Catherine subissent des retards de gamétogenèse tandis que les niveaux d’hormones stéroïdiennes sont très bas à Tadoussac. Ces deux sites sont soumis à des influences portuaires et à la circulation navale. Le site de Baie‑Éternité, plus en amont, se caractérise par des influences portuaires (huiles et peintures antisalissures) et une forte contamination métallique de sources urbaines et terrigènes. Anse‑aux‑Érables est un site près des influences industrielles, tandis que Anse‑Saint‑Jean est fortement influencée par les effluents municipaux et domestiques. D’amont en aval sur la rivière Saguenay, les myes des sites Anse‑à‑la‑Croix, Anse‑aux‑Érables, Petit‑Saguenay, Anse‑à‑la‑Barque, Tadoussac et Pointe‑aux‑Alouettes ont montré une croissance moindre. Les sites de Baie‑Éternité, Anse‑aux‑Érables, Anse‑Saint‑Jean et Baie-Sainte-Catherine ont un indice de maturité sexuelle moindre qu’aux autres sites, les données regroupées démontrant que ce sont les sites les plus influencés dans le fjord du Saguenay, résultats corroborés par les résultats de phagocytose. Toutes ces données démontrent que l’état physiologique de la mye répond à différents facteurs, anthropiques, biotiques et abiotiques, et que les sources ponctuelles de contamination viennent renforcer les effets négatifs de paramètres abiotiques telles la température et les conditions trophiques.The Saguenay fjord has been submitted for many years to anthropogenic influences. We surveyed this ecosystem between 1994 and 2007 to assess if Mya arenaria health status was altered by the contamination present in this ecosystem. The physiological condition of clams was determined using grouped annual data from sites at the mouth and in the Saguenay fjord. The results were analyzed according to sex and sites for all the samplings done during the active gametogenesis. The aims of this paper are to compare results of condition signs, gametogenesis stages and hormonal levels between sites and according to sex, to finally identify which sites were less favorable for the growth and reproduction of clams. We have shown that clams from Baie-Sainte-Catherine had delayed gametogenesis while those from Tadoussac showed very low steroid hormonal levels. Portuary and naval circulation influences could explain these particular results that also correspond to those from phagocytosis. Upstream in Baie‑Éternité, portuary influences (oils, anti-fouling paints) and metallic inputs from urban and terrigenous sources were reported. In Anse-aux-Érables, metallic contamination comes from industrial sources, while Anse-Saint‑Jean is influenced by sewage discharges from domestic and urban origin. From upstream to downstream, clams from Anse‑à‑la‑Croix, Anse‑aux‑Érables, Petit‑Saguenay, Anse‑à‑la‑Barque, Tadoussac and Pointe‑aux‑Alouettes showed decreased growth. Baie‑Éternité, Anse‑aux‑Érables, Anse‑Saint‑Jean and Baie-Sainte-Catherine sites, with their lower sexual maturity index and decreased phagocytosis, were shown to be the more influenced by contamination. All these data show that physiological condition of Mya arenaria reflects the combined effects of abiotic factors such as contamination, trophic conditions and site characteristics

Les paysages boisés sont-ils propices aux syrphidés auxiliaires du blé?

Les éléments semi-naturels des paysages agricoles (bois, haies, bandes enherbées, autres bords de champs) seraient favorables aux insectes auxiliaires des cultures présents naturellement dans les paysages agricoles. Ce « réseau vert » offrirait : i) des abris pour passer l’hiver, ii) des ressources complémentaires et des hôtes de substitution. Dans cette étude, nous avons testé l’hypothèse selon laquelle les syrphes prédateurs des pucerons du blé seraient plus abondants dans des paysages boisés. Ainsi, les pucerons et les syrphes (oeufs, larves, pupes) présents dans les parcelles de blé de deux paysages différant par leur taux de boisement (Boisé : 28%, Peu Boisé : 16%) ont été échantillonnés durant les printemps 2003-2004-2005. De plus, un modèle multi-agent simulant la dynamique hivernale d’une espèce de syrphe (Episyrphus balteatus), a été utilisé sur ces deux paysages. Globalement, les abondances de pucerons et de syrphes prélevés sur le terrain ne diffèrent pas significativement entre les deux paysages. Par contre, les syrphes sont présents plus tôt et sont significativement plus nombreux en paysage boisé. Les simulations de la dynamique hivernale sur le modèle ont montré que les taux de survie hivernale sont plus forts dans les paysages boisés grâce à la présence de prairies et de lisières boisées orientées au Sud. En conclusion, les paysages boisés permettraient une survie plus importante en hiver qui expliquerait des abondances printanières plus fortes. Cet effet disparaîtrait avec l’avancée du printemps. Cette fenêtre temporelle courte (hiver / début du printemps) pourrait être décisive dans la régulation précoce des populations de pucerons

Cytopathological Aspects of Breast Discharge in Women without Palpable Breast Mass in Yaounde, Cameroon

Objective: Describe cytopathological characteristics of nipple discharge.Methods: Four years retrospective cross- sectional study in Yaounde, Cameroon. We included all complete files of adult women with cytopathological analyses of breast discharge without palpable mass. Exclusion Criteria: Pregnant or breastfeeding women, puerperium and first 4 weeks post- abortum. Cytological modifications were classified as benign or malignant. Results: We retained 153 cases. Mean age was 41.2+/-14.4 years. Cytological modifications were malignant in 27 (17.65%) and benign in 126 (82.35%) cases. Of the 27 malignant cases, 18 (11.77%) were carcinomas and 9 (5.88%) were lymphomas. Upon histological analyses, all suspected lymphomas were confirmed while only 1 case of suspected carcinoma turned to be an atypical ductal hyperplasia. Of the 126 cases with benign modifications, 54 (35.29%) had inflammatory lesions, 48 (31.38%) had non inflammatory lesions and 24 (15.69%) had papillomas. Conclusion: Cytology of breast discharge can enhance early detection of breast cancers

Carbohydrate Conformation and Lipid Condensation in Monolayers Containing Glycosphingolipid Gb3: Influence of Acyl Chain Structure

AbstractGlobotriaosylceramide (Gb3), a glycosphingolipid found in the plasma membrane of animal cells, is the endocytic receptor of the bacterial Shiga toxin. Using x-ray reflectivity (XR) and grazing incidence x-ray diffraction (GIXD), lipid monolayers containing Gb3 were investigated at the air-water interface. XR probed Gb3 carbohydrate conformation normal to the interface, whereas GIXD precisely characterized Gb3’s influence on acyl chain in-plane packing and area per molecule (APM). Two phospholipids, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), were used to study Gb3 packing in different lipid environments. Furthermore, the impact on monolayer structure of a naturally extracted Gb3 mixture was compared to synthetic Gb3 species with uniquely defined acyl chain structures. XR results showed that lipid environment and Gb3 acyl chain structure impact carbohydrate conformation with greater solvent accessibility observed for smaller phospholipid headgroups and long Gb3 acyl chains. In general, GIXD showed that Gb3 condensed phospholipid packing resulting in smaller APM than predicted by ideal mixing. Gb3’s capacity to condense APM was larger for DSPC monolayers and exhibited different dependencies on acyl chain structure depending on the lipid environment. The interplay between Gb3-induced changes in lipid packing and the lipid environment’s impact on carbohydrate conformation has broad implications for glycosphingolipid macromolecule recognition and ligand binding

BENA435, a new cell-permeant photoactivated green fluorescent DNA probe

N′-(2,8-Dimethoxy-12-methyl-dibenzo [c,h] [1,5] naphthyridin-6-yl)-N,N-dimethyl-propane-1,3-diamine (BENA435) is a new cell-membrane permeant DNA dye with absorption/emission maxima in complex with DNA at 435 and 484 nm. This new reagent is unrelated to known DNA dyes, and shows a distinct preference to bind double-stranded DNA over RNA. Hydrodynamic studies suggest that BENA435 intercalates between the opposite DNA strands. BENA435 fluoresces much stronger when bound to dA/dT rather than dG/dC homopolymers. We evaluated 14 related dibenzonaphthyridine derivatives and found BENA435 to be superior in its in vivo DNA-binding properties. Molecular modelling was used to develop a model of BENA435 intercalation between base pairs of a DNA helix. BENA435 fluorescence in the nuclei of cells increases upon illumination, suggesting photoactivation. BENA435 represents thus the first known cell-permeant photoactivated DNA-binding dye

032: Thirty months outcomes after PCI of unprotected left main coronary artery according to the SYNTAX score

AimsTo assess middle term outcomes according to SYNTAX score and rates of delayed surgical/bleeding events after unprotected left main (LM) coronary artery (ULMCA) PCI in an unselected patients population.MethodsConsecutive patients treated by PCI for ULMCA were included among a single center 3508 PCI database within 36 months. Syntax scores were calculated, post discharge extracardiac surgery or hemorrhage were recorded during follow-up as clinical outcomes (Death, TVR, MACCE=cardiovascular death+MI+stroke+TLR).Results102 (3.6%) patients underwent PCI of the LM, including 21 protected LM. Among the 81 patients with PCI of ULMCA, mean age was 65±13, 27% had urgent PCI for AMI or cardiogenic shock, 61% had DES.SYNTAX score was 28±14 in mean and ≤22 in 30 (37%), 23 to 32 in 22 (27%) and ≥33 in 29 (36%) patients.At 30±11 months follow up (98% of the patients), death occurred in 24 patients (30%), TVR in 16 (20%) and MACCE in 35 (43%). Clinical events according to the SYNTAX score are shown in figure. No cardiovascular death occurred in patients with syntax ≤22. MACCE rates were significantly lower when DES were used (24% vs. 64%, p<0.05) and in case of non-urgent PCI (36% vs. 71%, p<0.05).During follow-up, 20 (25%) and 12 (15%) patients underwent unplanned extracardiac surgery and/or hemorrhage, leading to antiplatelet withdrawal in 31% of the cases.ConclusionsIn unselected patients treated by PCI of ULMCA with Syntax score ≤22, outcomes were found to be excellent with no cardiovascular death observed at 30 months. DES and non-urgent PCI were associated with a better prognosis. One patient out of three underwent unplanned extracardiac surgery or hemorrhage during follow up.Figure: 30-months outcomes according to SYNTAX scor