Expression of genes encoding the pre-TCR and CD3 complex during thymus development.

The mature TCR is composed of a clonotypic heterodimer (alpha beta or gamma delta) associated with the invariant CD3 components (gamma, delta, epsilon and zeta). There is now considerable evidence that more immature forms of the TCR-CD3 complex (consisting of either CD3 alone or CD3 associated with a heterodimer of TCR beta and pre-T alpha) can be expressed at the cell surface on early thymocytes. These pre-TCR complexes are believed to be necessary for the ordered progression of early T cell development. We have analyzed in detail the expression of both the pre-TCR and CD3 complex at various stages of adult thymus development. Our data indicate that all CD3 components are already expressed at the mRNA level by the earliest identifiable (CD4lo) thymic precursor. In contrast, genes encoding the pre-TCR complex (pre-T alpha and fully rearranged TCR beta) are first expressed at the CD44loCD25+CD4-CD8- stage. Detectable surface expression of both CD3 and TCR beta are delayed relative to expression of the corresponding genes, suggesting the existence of other (as yet unidentified) components of the pre-TCR complex.

Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases

AbstractBACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult.PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell.CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases.AVAILABILITY: The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download

Complex suicide with homemade nicotine patches.

Suicide by self-poisoning is rather common around the world. This paper presents an exceptional complex suicide in which nicotine was applied in the form of self-made patches soaked with an extraction from fine-cut tobacco. In addition, the 51-year-old suicide victim took a lethal dose of diphenhydramine. Toxicological analysis also revealed the presence of tetrazepam in subtherapeutic concentrations. The scene of death suggested an autoerotic accident at first, as the body was tied with tapes, cables and handcuffs. As a result of the entire investigations, the fatality had to be classified as a suicidal intoxication by nicotine and diphenhydramine.

Complex formation by the human RAD51C and XRCC3 recombination repair proteins.

In vertebrates, the RAD51 protein is required for genetic recombination, DNA repair, and cellular proliferation. Five paralogs of RAD51, known as RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3, have been identified and also shown to be required for recombination and genome stability. At the present time, however, very little is known about their biochemical properties or precise biological functions. As a first step toward understanding the roles of the RAD51 paralogs in recombination, the human RAD51C and XRCC3 proteins were overexpressed and purified from baculovirus-infected insect cells. The two proteins copurify as a complex, a property that reflects their endogenous association observed in HeLa cells. Purified RAD51C--XRCC3 complex binds single-stranded, but not duplex DNA, to form protein--DNA networks that have been visualized by electron microscopy.

Human-to-bovine jump of Staphylococcus aureus CC8 is associated with the loss of a β-hemolysin converting prophage and the acquisition of a new staphylococcal cassette chromosome.

Staphylococcus aureus can colonize and infect both humans and animals, but isolates from both hosts tend to belong to different lineages. Our recent finding of bovine-adapted S. aureus showing close genetic relationship to the human S. aureus clonal complex 8 (CC8) allowed us to examine the genetic basis of host adaptation in this particular CC. Using total chromosome microarrays, we compared the genetic makeup of 14 CC8 isolates obtained from cows suffering subclinical mastitis, with nine CC8 isolates from colonized or infected human patients, and nine S. aureus isolates belonging to typical bovine CCs. CC8 isolates were found to segregate in a unique group, different from the typical bovine CCs. Within this CC8 group, human and bovine isolates further segregated into three subgroups, among which two contained a mix of human and bovine isolates, and one contained only bovine isolates. This distribution into specific clusters and subclusters reflected major differences in the S. aureus content of mobile genetic elements (MGEs). Indeed, while the mixed human-bovine clusters carried commonly human-associated β-hemolysin converting prophages, the bovine-only isolates were devoid of such prophages but harbored an additional new non-mec staphylococcal cassette chromosome (SCC) unique to bovine CC8 isolates. This composite cassette carried a gene coding for a new LPXTG-surface protein sharing homologies with a protein found in the environmental bacterium Geobacillus thermoglucosidans. Thus, in contrast to human CC8 isolates, the bovine-only CC8 group was associated with the combined loss of β-hemolysin converting prophages and gain of a new SCC probably acquired in the animal environment. Remaining questions are whether the new LPXTG-protein plays a role in bovine colonization or infection, and whether the new SCC could further acquire antibiotic-resistance genes and carry them back to human.

Investigation of Field Corrosion Performance and Bond/Development Length of Galvanized Reinforcing Steel, TR-666, 2014

In reinforced concrete systems, ensuring that a good bond between the concrete and the embedded reinforcing steel is critical to long-term structural performance. Without good bond between the two, the system simply cannot behave as intended. The bond strength of reinforcing bars is a complex interaction between localized deformations, chemical adhesion, and other factors. Coating of reinforcing bars, although sometimes debated, has been commonly found to be an effective way to delay the initiation of corrosion in reinforced concrete systems. For many years, the standard practice has been to coat reinforcing steel with an epoxy coating, which provides a barrier between the steel and the corrosive elements of water, air, and chloride ions. Recently, there has been an industry-led effort to use galvanizing to provide the protective barrier commonly provided by traditional epoxy coatings. However, as with any new structural product, questions exist regarding both the structural performance and corrosion resistance of the system. In the fall of 2013, Buchanan County, Iowa constructed a demonstration bridge in which the steel girders and all internal reinforcing steel were galvanized. The work completed in this project sought to understand the structural performance of galvanized reinforcing steel as compared to epoxy-coated steel and to initiate a long-term corrosion monitoring program. This work consisted of a series of controlled laboratory tests and the installation of a corrosion monitoring system that can be observed for years in the future. The results of this work indicate there is no appreciable difference between the bond strength of epoxy-coated reinforcing steel and galvanized reinforcing steel. Although some differences were observed, no notable difference in either peak load, slip, or failure mode could be identified. Additionally, a long-term monitoring system was installed in this Buchanan County bridge and, to date, no corrosion activity has been identified.

Kernel-based Mapping of Meteorological Fields in Complex Orography

Due to the advances in sensor networks and remote sensing technologies, the acquisition and storage rates of meteorological and climatological data increases every day and ask for novel and efficient processing algorithms. A fundamental problem of data analysis and modeling is the spatial prediction of meteorological variables in complex orography, which serves among others to extended climatological analyses, for the assimilation of data into numerical weather prediction models, for preparing inputs to hydrological models and for real time monitoring and short-term forecasting of weather.In this thesis, a new framework for spatial estimation is proposed by taking advantage of a class of algorithms emerging from the statistical learning theory. Nonparametric kernel-based methods for nonlinear data classification, regression and target detection, known as support vector machines (SVM), are adapted for mapping of meteorological variables in complex orography.With the advent of high resolution digital elevation models, the field of spatial prediction met new horizons. In fact, by exploiting image processing tools along with physical heuristics, an incredible number of terrain features which account for the topographic conditions at multiple spatial scales can be extracted. Such features are highly relevant for the mapping of meteorological variables because they control a considerable part of the spatial variability of meteorological fields in the complex Alpine orography. For instance, patterns of orographic rainfall, wind speed and cold air pools are known to be correlated with particular terrain forms, e.g. convex/concave surfaces and upwind sides of mountain slopes.Kernel-based methods are employed to learn the nonlinear statistical dependence which links the multidimensional space of geographical and topographic explanatory variables to the variable of interest, that is the wind speed as measured at the weather stations or the occurrence of orographic rainfall patterns as extracted from sequences of radar images. Compared to low dimensional models integrating only the geographical coordinates, the proposed framework opens a way to regionalize meteorological variables which are multidimensional in nature and rarely show spatial auto-correlation in the original space making the use of classical geostatistics tangled.The challenges which are explored during the thesis are manifolds. First, the complexity of models is optimized to impose appropriate smoothness properties and reduce the impact of noisy measurements. Secondly, a multiple kernel extension of SVM is considered to select the multiscale features which explain most of the spatial variability of wind speed. Then, SVM target detection methods are implemented to describe the orographic conditions which cause persistent and stationary rainfall patterns. Finally, the optimal splitting of the data is studied to estimate realistic performances and confidence intervals characterizing the uncertainty of predictions.The resulting maps of average wind speeds find applications within renewable resources assessment and opens a route to decrease the temporal scale of analysis to meet hydrological requirements. Furthermore, the maps depicting the susceptibility to orographic rainfall enhancement can be used to improve current radar-based quantitative precipitation estimation and forecasting systems and to generate stochastic ensembles of precipitation fields conditioned upon the orography.

L'intersubjectivité en questions : agrégat ou principe organisateur en psychologie ?

La notion d'intersubjectivité est au coeur des débats contemporains dans le champ de la psychologie. L'intersubjectivité traverse en effet les différentes approches de la psychologie, des neurosciences à la psychologie sociale, des perspectives développementales aux approches psychoaffectives de la personnalité, des contextes de l'apprentissage à ceux du soin. Cet ouvrage collectif, premier volume de la collection Actualités psychologiques, se propose de faire le point sur cette notion et d'apporter des pistes actuelles de compréhension aux enjeux de la place de l'autre et de l'altérité dans la construction du sujet. Des chercheurs de renommée internationale, de Suisse et de différents pays européens, apportent ici leur contribution, dans différents domaines de la psychologie, invitant au dialogue entre les modèles théoriques qui sous-tendent la notion d'intersubjectivité et entre les méthodologies qui permettent d'en appréhender la dynamique. Contribution exceptionnelle, cet ouvrage est à destination de tous, psychologues praticiens et professionnels de la relation, chercheurs et étudiants en psychologie ou dans des disciplines connexes. Il permet d'approcher l'intersubjectivité comme une notion tout à la fois familière et complexe, au service de la rencontre de l'autre.

Segmentation of foot and ankle complex based on kinematic criteria.

Although various foot models were proposed for kinematics assessment using skin makers, no objective justification exists for the foot segmentations. This study proposed objective kinematic criteria to define which foot joints are relevant (dominant) in skin markers assessments. Among the studied joints, shank-hindfoot, hindfoot-midfoot and medial-lateral forefoot joints were found to have larger mobility than flexibility of their neighbour bonesets. The amplitude and pattern consistency of these joint angles confirmed their dominancy. Nevertheless, the consistency of the medial-lateral forefoot joint amplitude was lower. These three joints also showed acceptable sensibility to experimental errors which supported their dominancy. This study concluded that to be reliable for assessments using skin markers, the foot and ankle complex could be divided into shank, hindfoot, medial forefoot, lateral forefoot and toes. Kinematics of foot models with more segments must be more cautiously used.

Symptomatic complex partial status epilepticus manifesting as utilization behavior of a mobile phone.

Utilization behavior (UB) consists of reaching out and using objects in the environment in an automatic manner and out of context. This behavior has been correlated to frontal lobe dysfunction, especially of the right hemisphere. We describe a 60-year-old woman, affected by a glioblastoma located in the right frontal region, who presented with intermittent UB of the mobile phone as the main clinical manifestation of partial complex status epilepticus. Video/EEG studies showed a striking correlation between mobile phone utilization and ictal epileptic activity. Clinical and EEG findings were markedly reduced after the introduction of antiepileptic drugs. This case study suggests that UB may be added to the symptoms described for partial seizures originating from frontal areas.

Favorable outcome of an acute complex regional pain syndrome with immunoglobulin infusions.

OBJECTIVE: To emphasize that complex regional pain syndrome (CRPS), a disabling disorder with the implication of aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity, might be treated with a high dose of intravenous immunoglobulin infusions (IVIG). METHODS: We describe a patient who presented with CRPS in the acute phase of the disease. RESULTS: The CRPS developed secondary to sciatic compression in a young patient and was treated within 10 days by high-dose IVIG (2 g/kg). It resolved completely within days after infusions. DISCUSSION: This observational study emphasizes that high-dose IVIG may be a treatment option in the acute phase of CRPS.

Essai de morale à l'usage de l'Eglise gallicane non-assermentée ou Questions & réponses sur la conduite des ecclésiastiques & des fidèles, par rapport aux circonstances présentes ([Reprod.]) / par M. Bacth

Collection : Les archives de la Révolution française ; 8.1589