Solution Structure of Human p8 MTCP1 , a Cysteine-rich Protein Encoded by the MTCP1 Oncogene, Reveals a New a a a-Helical Assembly Motif

International audienceMature-T-Cell Proliferation) is the ®rst gene unequivocally identi®ed in the group of uncommon leukemias with a mature phenotype. The three-dimensional solution structure of the human p8 MTCP1 protein encoded by the MTCP1 oncogene was determined by homonuc-lear proton two-dimensional NMR methods at 600 MHz. After sequence speci®c assignments, a total of 931 distance restraints and 57 dihedral restraints were collected. The location of the three previously unassigned disul®de bridges was determined from preliminary DIANA structures, using a statistical analysis of intercystinyl distances. The solution structure of p8 MTCP1 is presented as a set of 30 DIANA structures, further re®ned by restrained molecular dynamics using a simulated annealing protocol with the AMBER force ®eld. The r.m.s.d. values with respect to the mean structure for the backbone and all heavy atoms for a family of 30 structures are 0.73(AE0.28) and 1.17(AE0.23) A Ê , when the structured core of the protein (residues 5 to 63) is considered. The solution structure of p8 MTCP1 reveals an original scaffold consisting of three a helices, associated with a new cysteine motif. Two of the helices are covalently paired by two disul®de bridges, forming an a-hairpin which resembles an antiparallel coiled-coil. The third helix is oriented roughly parallel to the plane de®ned by the a-antiparallel motif and its axis forms an angle of %60 with respect to the main axis of this motif

A high-temperature furnace for in situ synchrotron X-ray spectroscopy under controlled atmospheric conditions.

A high-temperature furnace with an induction heater coil has been designed and constructed for in situ X-ray spectroscopic experiments under controlled atmospheric conditions and temperatures up to 3275 K. The multi-purpose chamber design allows working in backscattering and normal fluorescence mode for synchrotron X-ray absorption and emission spectroscopy. The use of the furnace is demonstrated in a study of the in situ formation of Cr oxide between 1823 K and 2023 K at logPO(2) values between -10.0 and -11.3 using X-ray absorption near-edge spectroscopy. The set-up is of particular interest for studying liquid metals, alloys and other electrically conductive materials under extreme conditions

Modelling the distribution of the Ocellated Lizard in France : implications for conservation

The Ocellated Lizard, Timon lepidus (Daudin 1802) occupies the Mediterranean regions of southwestern Europe (Portugal, Spain, France, and the extreme northwest of Italy). Over the last decades, a marked decline in its population has been observed, particularly on the northern edge of its distribution. As a result, it is currently considered a threatened species, especially in France and Italy. In France, a national action plan for its conservation has been put in place. In this study, ecological niche modelling (ENM) was carried out over the entire area of France in order to evaluate the species' potential distribution, more accurately define its ecological niche, guide future surveys, and inform land use planning so this species can be better taken into consideration. The modelling used data representing 2,757 observation points spread over the known range of the species, and 34 ecogeographical variables (climate, topography, and vegetation cover) were evaluated. After removing correlated variables, models were fitted with several combinations of variables using eight species distribution model (SDM) algorithms, and then their performance was assessed using three model accuracy metrics. Iterative trials changing the input variables were used to obtain the best model. The optimized model included nine determining variables. The results indicate the presence of this species is linked primarily to three climate variables: precipitation in the driest month, precipitation seasonality, and mean temperature in the driest quarter. The model was checked by a sample dataset that was not used to fit the model, and this validation dataset represented 25% of the overall field observations. Of the known occurrence locations kept aside to check the results, 94% fell within the presence area predicted by the modelled map with a presence probability greater than 0.7, and 90% fell within the area with a presence probability ranging from 0.8 to 1, which represents a very high predictive value. These results indicate that the models closely matched the observed distribution, suggesting a low impact of either geographical factors (barriers to dispersal), historical factors (dispersal process), or ecological factors (e.g., competition, trophic resources). The overlap between the predicted distribution and protected areas for this species reveals that less than 1% of the potential distribution area is protected by strong regulatory measures (e.g., national parks and natural reserves). The knowledge obtained in this study allows us to recommend some guidelines that would favor the conservation of this species.Peer reviewe

A Machine Checked Model of Idempotent MGU Axioms For Lists of Equational Constraints

We present formalized proofs verifying that the first-order unification algorithm defined over lists of satisfiable constraints generates a most general unifier (MGU), which also happens to be idempotent. All of our proofs have been formalized in the Coq theorem prover. Our proofs show that finite maps produced by the unification algorithm provide a model of the axioms characterizing idempotent MGUs of lists of constraints. The axioms that serve as the basis for our verification are derived from a standard set by extending them to lists of constraints. For us, constraints are equalities between terms in the language of simple types. Substitutions are formally modeled as finite maps using the Coq library Coq.FSets.FMapInterface. Coq's method of functional induction is the main proof technique used in proving many of the axioms.Comment: In Proceedings UNIF 2010, arXiv:1012.455

Multiple glacial refugia and contemporary dispersal shape the genetic structure of an endemic amphibian from the Pyrenees

Historical factors (colonization scenarios, demographic oscillations) and contemporary processes (population connectivity, current population size) largely contribute to shaping species’ present-day genetic diversity and structure. In this study, we use a combination of mitochondrial and nuclear DNA markers to understand the role of Quaternary climatic oscillations and present-day gene flow dynamics in determining the genetic diversity and structure of the newt Calotriton asper (Al. Dugès, 1852), endemic to the Pyrenees. Mitochondrial DNA did not show a clear phylogeographic pattern and presented low levels of variation. In contrast, microsatellites revealed five major genetic lineages with admixture patterns at their boundaries. Approximate Bayesian computation analyses and linear models indicated that the five lineages likely underwent separate evolutionary histories and can be tracked back to distinct glacial refugia. Lineage differentiation started around the Last Glacial Maximum at three focal areas (western, central and eastern Pyrenees) and extended through the end of the Last Glacial Period in the central Pyrenees, where it led to the formation of two more lineages. Our data revealed no evidence of recent dispersal between lineages, whereas borders likely represent zones of secondary contact following expansion from multiple refugia. Finally, we did not find genetic evidence of sex-biased dispersal. This work highlights the importance of integrating past evolutionary processes and present-day gene flow and dispersal dynamics, together with multilocus approaches, to gain insights into what shaped the current genetic attributes of amphibians living in montane habitats.info:eu-repo/semantics/publishedVersio

Large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>Renal hypertrophy occurs early in diabetic nephropathy, its later value is unknown. Do large kidneys still predict poor outcome in patients with diabetes and Chronic Kidney Disease (CKD)?</p> <p>Methods</p> <p>Seventy-five patients with diabetes and CKD according to a Glomerular Filtration Rate (GFR, by 51Cr-EDTA clearance) below 60 mL/min/1.73 m²or an Albumin Excretion Rate above 30 mg/24 H, had an ultrasound imaging of the kidneys and were cooperatively followed during five years by the Diabetology and Nephrology departments of the Centre Hospitalier Universitaire de Bordeaux.</p> <p>Results</p> <p>The patients were mainly men (44/75), aged 62 ± 13 yrs, with long-standing diabetes (duration:17 ± 9 yrs, 55/75 type 2), and CKD: initial GFR: 56.5 (8.5-209) mL/min/1.73 m², AER: 196 (20-2358) mg/24 H. Their mean kidney lenght (108 ± 13 mm, 67-147) was correlated to the GFR (r = 0.23, p < 0.05). During the follow-up, 9/11 of the patients who had to start dialysis came from the half with the largest kidneys (LogRank: p < 0.05), despite a 40% higher initial isotopic GFR. Serum creatinine were initially lower (Small kidneys: 125 (79-320) μmol/L, Large: 103 (50-371), p < 0.05), but significantly increased in the "large kidneys" group at the end of the follow-up (Small kidneys: 129 (69-283) μmol/L, Large: 140 (50-952), p < 0.005 vs initial). The difference persisted in the patients with severe renal failure (KDOQI stages 4,5).</p> <p>Conclusions</p> <p>Large kidneys still predict progression in advanced CKD complicating diabetes. In these patients, ultrasound imaging not only excludes obstructive renal disease, but also provides information on the progression of the renal disease.</p

Ingénierie territoriale : des compétences construites au service du développement des territoires

International audienceDepuis une trentaine d'années, les mutations de l'action publique sur ou pour le territoire se sont accompagnées d'une recomposition des pratiques d'ingénierie et de l'émergence même de la notion d'ingénierie territoriale. Les territoires sont devenus des lieux d'interactions fortes entre initiatives locales et incitations politiques, et leur management est de plus en plus marqué par une orientation en matière de conduite de projet. L'accompagnement des acteurs dans la conception, la réalisation et l'évaluation de leurs projets de territoire est devenu une préoccupation croissante pour les acteurs du développement et un objet d'étude pour la recherche en sciences sociales. Parmi leurs interrogations, la question des compétences en ingénierie territoriale occupe une place particulière. Divers projets et programmes de recherche ainsi qu'une série de séminaires, assises et colloques, qui semblent poursuivre la dynamique amorcée par le projet de plate-forme d'ingénierie territoriale du CIADT en 2003, en témoignent. Cette contribution se nourrit des apports de trois projets de recherche afin d'apporter un nouvel éclairage récent sur la question. Composée de trois parties, elle montre tout d'abord la place centrale occupée par les compétences dans l'émergence et l'évolution de la notion d'ingénierie territoriale. Elle distingue et décrit ensuite quatre grands systèmes de compétences au service de l'action locale. Enfin, elle développe l'idée de chaîne d'ingénierie, comme compétence collective construite par le réseau adaptatif de mutualisation et de coordination de compétences individuelles au service du territoire