Redox and ion-exchange properties in surface-tethered DNA-conducting polymers

A poly(cyclopentadithiophene) matrix modified by DNA covalently fixed to the surface has been designed to study the redox and ion-exchange properties in surface-tethered DNA-conducting polymers. Voltammetric investigations show an improvement in conductivity, originating from DNA modification, probably due to changes in charged-density and size of dopant species. Cyclic voltammetry with concomitant QCM measurements indicate that the mass changes are consistent with an ejection of Na+ cations associated to the anionic phosphate groups, attesting a DNA contribution to the p-doping process. So, in contrast to the classic doping patterns, the p-doping process of surface-tethered DNA-copolymer exhibits a cation-controlled transport mechanism. Impedimetric investigations indicate that for long enough DNA target sequence, nucleic acid preserves certain flexibility and is involved in the p-doping process through a diffusion-like motion. These results give new opportunities for genesensors development and for a better understanding of bioactive conducting surfaces

Création d’un score d’évaluation du risque de symptômes musculo-squelettiques basé sur des facteurs professionnels

Objectif L’objectif de ce travail est la création d’un score d’évaluation du risque de symptômes musculo-squelettiques (SMS) chroniques des membres supérieurs, uniquement basé sur des données d’exposition professionnelle aux déterminants biomécaniques, psychosociaux et organisationnels. Ce score ne prenant pas en compte les facteurs individuels, permettra de classer les situations de travail devant bénéficier d’une action de prévention. Méthodes L’échantillon d’étude était constitué de 1749 salariés recrutés lors de la phase d’inclusion de la cohorte des salariés ligériens (COSALI). Les facteurs organisationnels, biomécaniques et psychosociaux et les variables associées aux SMS chroniques ont été recueillis par auto-questionnaire. Un score a été créé selon trois méthodes statistiques : une régression logistique binaire, une analyse en clusters suivie d’une analyse par arbre de décision et une modélisation par classes latentes. Chacune de ces méthodes est susceptible d’entraîner la création de scores différents. Résultats L’area under the curve (AUC) obtenu par la régression logistique était de 0,75 contre 0,66 pour l’analyse en clusters et 0,65 pour l’analyse en classes latentes. La régression logistique a donc été retenue pour la création du score. Les facteurs associés aux SMS chroniques des membres supérieurs étaient l’intensité élevée des efforts physiques ressentie (échelle RPE de Borg), la répétitivité des gestes plus de 4 h/j, la flexion du coude plus de 2 h/j, l’utilisation de la pince pouce-index plus de 4 h/j, la possibilité d’influencer le déroulement de son travail et l’aide des collègues. Le score a ensuite été créé à partir des paramètres estimés de la régression logistique, il s’étend de −1 à 15. Par exemple, 66 % de l’échantillon a un score supérieur ou égal à deux. Pour ce seuil, la valeur prédictive négative est de 93,4 %. Conclusions Selon le seuil choisi, le score aboutit à une forte valeur prédictive négative. Il pourrait constituer un outil utile aux préventeurs en entreprise afin de cibler l’effectif pour lequel il n’est pas indispensable de mettre en place des actions de prévention. Néanmoins ce score ne permet pas de prédire avec confiance les salariés qui seront atteints de SMS. Pour avoir un score plus performant, il faudrait intégrer des facteurs individuels tels que l’âge et le sexe, mais la caractérisation par situation de travail n’est alors plus envisageable

Hybridization-induced interfacial changes detected by non-Faradaic impedimetric measurements compared to Faradaic approach

A biosensor for direct label-free DNA detection based on a polythiophene matrix is investigated by electrochemical impedance spectroscopy (EIS). Impedimetric experiments are performed with and without redox probe in solution. The non-Faradaic impedance measurements reveal two relaxation processes located at 50 Hz and 5 kHz, respectively. The first relaxation process, located at low frequencies, allows to detect biorecognition events by measuring the phase angle decrease, in accordance with a hindrance of the polaronic conduction. The second relaxation process, located at 5 kHz and originating from DNA modification, seems to increase with the length of the target sequence. These results suggest that this loaded support provides a platform for impedimetric detection of hybridization at high frequencies, leading to less time-consuming detection procedure. For a better understanding, results obtained in non-Faradaic mode are compared with Faradaic approach

The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3

OBJECTIVE—The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS—We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS—Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10−4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS—These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors

Lipid droplet analysis in caveolin-deficient adipocytes: alterations in surface phospholipid composition and maturation defects.

Caveolins form plasmalemnal invaginated caveolae. They also locate around intracellular lipid droplets but their role in this location remains unclear. By studying primary adipocytes that highly express caveolin-1, we characterized the impact of caveolin-1 deficiency on lipid droplet proteome and lipidome. We identified several missing proteins on the lipid droplet surface of caveolin-deficient adipocytes and showed that the caveolin-1 lipid droplet pool is organized as multi-protein complexes containing cavin-1, with similar dynamics as those found in caveolae. On the lipid side, caveolin deficiency did not qualitatively alter neutral lipids in lipid droplet, but significantly reduced the relative abundance of surface phospholipid species: phosphatidylserine and lysophospholipids. Caveolin-deficient adipocytes can form only small lipid droplets, suggesting that the caveolin-lipid droplet pool might be involved in lipid droplet size regulation. Accordingly, we show that caveolin-1 concentration on adipocyte lipid droplets positively correlated with lipid droplet size in obese rodent models and human adipocytes. Moreover, rescue experiments by caveolin- green fluorescent protein in caveolin-deficient cells exposed to fatty acid overload demonstrated that caveolin-coated lipid droplets were able to grow larger than caveolin-devoid lipid droplets. Altogether, these data demonstrate that the lipid droplet-caveolin pool impacts on phospholipid and protein surface composition of lipid droplets and suggest a functional role on lipid droplet expandability

The composition of the protosolar disk and the formation conditions for comets

Conditions in the protosolar nebula have left their mark in the composition of cometary volatiles, thought to be some of the most pristine material in the solar system. Cometary compositions represent the end point of processing that began in the parent molecular cloud core and continued through the collapse of that core to form the protosun and the solar nebula, and finally during the evolution of the solar nebula itself as the cometary bodies were accreting. Disentangling the effects of the various epochs on the final composition of a comet is complicated. But comets are not the only source of information about the solar nebula. Protostellar disks around young stars similar to the protosun provide a way of investigating the evolution of disks similar to the solar nebula while they are in the process of evolving to form their own solar systems. In this way we can learn about the physical and chemical conditions under which comets formed, and about the types of dynamical processing that shaped the solar system we see today. This paper summarizes some recent contributions to our understanding of both cometary volatiles and the composition, structure and evolution of protostellar disks.Comment: To appear in Space Science Reviews. The final publication is available at Springer via http://dx.doi.org/10.1007/s11214-015-0167-

Progress Report on Target Development

The present document is the D08 deliverable report of work package 1 (Target Development) from the MEGAPIE TEST project of the 5th European Framework Program. Deliverable D08 is the progress report on the activities performed within WP 1. The due date of this deliverable was the 5th month after the start of the EU project. This coincided with a technical status meeting of the MEGAPIE Initiative, that was held in March 2002 in Bologna (Italy). The content of the present document reflects the status of the MEGAPIE target development at that stage. It gives an overview of the Target Design, the related Design Support activities and the progress of the work done for the safety assessment and licensing of the target

Clinical Characteristics and Diagnostic Criteria of Maturity-Onset Diabetes Of The Young (MODY) due to Molecular Anomalies of the HNF1A Gene

Context: The diagnosis of maturity-onset diabetes of the young type 3 (MODY3), associated with HNF1A molecular abnormalities, is often missed.Objective: The objective of the study was to describe the phenotypes of a large series of MODY3 patients and to reassess parameters that may improve its diagnosis. Design, Setting, and Patients: This retrospective multicenter study included 487 unrelated patients referred because of suspicion of MODY3. Genetic analysis identified 196 MODY3 and 283 non-MODY3 cases. Criteria associated with MODY3 were assessed by multivariate analysis. The capacity of the model to predict MODY3 diagnosis was assessed by the area under the receiver-operating characteristic curve and was further validated in an independent sample of 851 patients (165 MODY3 and 686 non-MODY3). Results: In the MODY3 patients, diabetes was revealed by clinical symptoms in 25% of the cases and was diagnosed by screening in the others. Age at diagnosis of diabetes was more than 25 yr in 40% of the MODY3 patients. There was considerable variability and overlap of all assessed parameters in MODY3 and non-MODY3 patients. The best predictive model was based on criteria available at diagnosis of diabetes, including age, body mass index, number of affected generations, presence of diabetes symptoms, and geographical origin. The area under the curve of the receiver-operating characteristic analysis was 0.81. When sensitivity was set to 90%, specificity was 49%. Conclusions: Differential diagnosis between MODY3 and early-onset type 2 diabetes remains difficult. Whether the proposed model will improve the pick-up rate of MODY3 diagnosis needs to be confirmed in independent populations