The evolution of purinergic receptors involved in recognition of a blood meal by hematophagous insects

Many blood feeders use adenine nucleotides as cues for locating blood meal. Structure-activity relationship of adenine nucleotides as phagostimulants varies between closely-related species of blood feeders. It is suggested that a preexisting diverse pool of nucleotide-binding proteins present in all living cells, serves as a source of receptor proteins for the gustatory receptors involved in blood detection. It is proposed that the selection of any such nucleotide-binding protein is random.

Le suicide comme langage de l'oppression. Ethnographie d'un service d'urgences psychiatriques

Ce travail s'intéresse à la problématique du suicide à partir de l'émergence en Suisse, vers la fin des années '90, de la prévention du suicide comme préoccupation sociale et politique. Au début, ce sont les milieux associatifs qui ont soulevé à cette question en percevant le suicide comme le reflet d'une souffrance d'origine sociale. Par la suite, la prévention du suicide est progressivement devenue une problématique de santé publique appréhendée essentiellement sous le registre médical comme étant le symptôme d'une pathologie psychiatrique. Après une première partie consacrée aux processus sociopolitiques et aux transformations morales touchant le suicide et sa prévention, ce travail approfondit, au travers d'un terrain ethnographique, la prise en charge des personnes présentant des problématiques suicidaires au sein d'un service d'urgences psychiatriques.Malgré une approche se voulant biopsychosociale, l'analyse des discours et des pratiques soignantes montre que la dimension sociale est largement négligée, conduisant à une médicalisation de situations de détresse qui sont principalement de nature sociale. En effet, parmi la population qui fréquente le service, on observe une surreprésentation de personnes issues des classes sociales défavorisées présentant souvent des trajectoires biographiques particulièrement difficiles. Au fil des entretiens avec les patients émerge une analyse voyant la souffrance psychique et la prise en charge psychiatrique comme étant aujourd'hui une manière d'obtenir une reconnaissance sociale et symbolique. Les problématiques suicidaires peuvent ainsi être interprétées comme une forme d'expression, un langage au travers duquel s'exprime la position sociale défavorisée.En adoptant une posture militante construite à partir de la réalité ethnographique, les problématiques suicidaires sont analysées comme l'expression d'une condition d'oppression liée à un cadre social et économique de plus en plus contraignant, à des rapports de pouvoir inégaux ainsi qu'à une lecture individualisante, médicalisante et pathologisante des problèmes sociaux.The present thesis discusses suicide prevention in Switzerland, which emerged as a social and political issue at the end of the '90s. At first, this question was taken up by associations considering suicide as a reflection of social suffering. Thereafter, suicide prevention gradually became a public health matter conceived with a medical approach as a symptom of a psychiatric disease. The first part of this work analyzes the sociopolitical process and moral transformations concerning suicide and its prevention. The second part is based on an ethnographic fieldwork conducted in a psychiatric emergency unit that attends people who have tried to attempt their life or consider doing it. Through the analysis of discourses and practices of the medical staff, this research shows that the social aspect of suicide is widely neglected, leading to a medicalization of social problems. In fact, amongst patients attending the emergency unit, there is an over-­-representation of people from disadvantaged classes having very difficult life stories. Interviews with patients also revealed that psychic suffering and psychiatric treatment is nowadays a way to get social and symbolical recognition. Suicidal problems can be understood as a language expressing a disadvantaged social position. By adopting a militant position constructed from the ethnographic reality, suicide is analyzed as the expression of an oppressed condition related to a more and more restricted social and economic situation, to unequal power relations as well as to an individualistic, medical and pathological interpretation of social problems.

Object recognition for autonomous objects: comparison of two approaches

Report for the scientific sojourn at the Swiss Federal Institute of Technology Zurich, Switzerland, between September and December 2007. In order to make robots useful assistants for our everyday life, the ability to learn and recognize objects is of essential importance. However, object recognition in real scenes is one of the most challenging problems in computer vision, as it is necessary to deal with difficulties. Furthermore, in mobile robotics a new challenge is added to the list: computational complexity. In a dynamic world, information about the objects in the scene can become obsolete before it is ready to be used if the detection algorithm is not fast enough. Two recent object recognition techniques have achieved notable results: the constellation approach proposed by Lowe and the bag of words approach proposed by Nistér and Stewénius. The Lowe constellation approach is the one currently being used in the robot localization project of the COGNIRON project. This report is divided in two main sections. The first section is devoted to briefly review the currently used object recognition system, the Lowe approach, and bring to light the drawbacks found for object recognition in the context of indoor mobile robot navigation. Additionally the proposed improvements for the algorithm are described. In the second section the alternative bag of words method is reviewed, as well as several experiments conducted to evaluate its performance with our own object databases. Furthermore, some modifications to the original algorithm to make it suitable for object detection in unsegmented images are proposed.

Hand exposure in diagnostic nuclear medicine with 18F- and 99mTc-labelled radiopharmaceuticals - Results of the ORAMED project

Workers performing preparation and administration of radiopharmaceuticals in NM departments are likely to receive high local skin doses to the hands which may even surpass the dose limit of 500 mSv whenever radiation protection standards are insufficient. A large measurement campaign was organised within the framework of the ORAMED project to determine the dose distribution across the hands received during preparation and administration of 18F- and 99mTc-labelled radiopharmaceuticals. The final data, collected over almost 3 years, include 641 measurements from 96 workers in 30 NM departments from 6 European countries. Results have provided levels of reference doses for the considered standard NM diagnostic procedures (mean maximum normalised skin dose of 230 μSv/GBq, 430 μSv/GBq, 930 μSv/GBq and 1200 μSv/GBq for the administration of 99mTc, preparation of 99mTc, administration of 18F and preparation of 18F, respectively). Finger dose was analysed as a function of the potential parameters of influence showing that shielding is the most efficient means of radiation protection to reduce skin dose. An appropriate method for routine monitoring of the extremities is also proposed: the base of the index finger of the non-dominant hand is a suitable position to place the ring dosemeter, with its sensitive part oriented towards the palm side; its reading may be multiplied by a factor of 6 to estimate the maximum local skin dose. Finally, results were compared to earlier published data, which correspond mostly to individual works with a reduced number of workers and measurements.

Brittle cornea syndrome: recognition, molecular diagnosis and management.

Brittle cornea syndrome (BCS) is an autosomal recessive disorder characterised by extreme corneal thinning and fragility. Corneal rupture can therefore occur either spontaneously or following minimal trauma in affected patients. Two genes, ZNF469 and PRDM5, have now been identified, in which causative pathogenic mutations collectively account for the condition in nearly all patients with BCS ascertained to date. Therefore, effective molecular diagnosis is now available for affected patients, and those at risk of being heterozygous carriers for BCS. We have previously identified mutations in ZNF469 in 14 families (in addition to 6 reported by others in the literature), and in PRDM5 in 8 families (with 1 further family now published by others). Clinical features include extreme corneal thinning with rupture, high myopia, blue sclerae, deafness of mixed aetiology with hypercompliant tympanic membranes, and variable skeletal manifestations. Corneal rupture may be the presenting feature of BCS, and it is possible that this may be incorrectly attributed to non-accidental injury. Mainstays of management include the prevention of ocular rupture by provision of protective polycarbonate spectacles, careful monitoring of visual and auditory function, and assessment for skeletal complications such as developmental dysplasia of the hip. Effective management depends upon appropriate identification of affected individuals, which may be challenging given the phenotypic overlap of BCS with other connective tissue disorders.

Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production.

Interleukin 1 beta (IL-1 beta) is a potent proinflammatory factor during viral infection. Its production is tightly controlled by transcription of Il1b dependent on the transcription factor NF-kappaB and subsequent processing of pro-IL-1 beta by an inflammasome. However, the sensors and mechanisms that facilitate RNA virus-induced production of IL-1 beta are not well defined. Here we report a dual role for the RNA helicase RIG-I in RNA virus-induced proinflammatory responses. Whereas RIG-I-mediated activation of NF-kappaB required the signaling adaptor MAVS and a complex of the adaptors CARD9 and Bcl-10, RIG-I also bound to the adaptor ASC to trigger caspase-1-dependent inflammasome activation by a mechanism independent of MAVS, CARD9 and the Nod-like receptor protein NLRP3. Our results identify the CARD9-Bcl-10 module as an essential component of the RIG-I-dependent proinflammatory response and establish RIG-I as a sensor able to activate the inflammasome in response to certain RNA viruses.

Theoretical study on receptor-G protein recognition: new insights into the mechanisms of the alpha1b-adrenergic recptor activation

This work compares the structural/dynamics features of the wild-type alb-adrenergic receptor (AR) with those of the D142A active mutant and the agonist-bound state. The two active receptor forms were compared in their isolated states as well as in their ability to form homodimers and to recognize the G alpha q beta 1 gamma 2 heterotrimer. The analysis of the isolated structures revealed that, although the mutation- and agonist-induced active states of the alpha 1b-AR are different, they, however, share several structural peculiarities including (a) the release of some constraining interactions found in the wild-type receptor and (b) the opening of a cytosolic crevice formed by the second and third intracellular loops and the cytosolic extensions of helices 5 and 6. Accordingly, also their tendency to form homodimers shows commonalties and differences. In fact, in both the active receptor forms, helix 6 plays a crucial role in mediating homodimerization. However, the homodimeric models result from different interhelical assemblies. On the same line of evidence, in both of the active receptor forms, the cytosolic opened crevice recognizes similar domains on the G protein. However, the docking solutions are differently populated and the receptor-G protein preorientation models suggest that the final complexes should be characterized by different interaction patterns.

Bihippocampal damage with emotional dysfunction: impaired auditory recognition of fear.

A right-handed man developed a sudden transient, amnestic syndrome associated with bilateral hemorrhage of the hippocampi, probably due to Urbach-Wiethe disease. In the 3rd month, despite significant hippocampal structural damage on imaging, only a milder degree of retrograde and anterograde amnesia persisted on detailed neuropsychological examination. On systematic testing of recognition of facial and vocal expression of emotion, we found an impairment of the vocal perception of fear, but not that of other emotions, such as joy, sadness and anger. Such selective impairment of fear perception was not present in the recognition of facial expression of emotion. Thus emotional perception varies according to the different aspects of emotions and the different modality of presentation (faces versus voices). This is consistent with the idea that there may be multiple emotion systems. The study of emotional perception in this unique case of bilateral involvement of hippocampus suggests that this structure may play a critical role in the recognition of fear in vocal expression, possibly dissociated from that of other emotions and from that of fear in facial expression. In regard of recent data suggesting that the amygdala is playing a role in the recognition of fear in the auditory as well as in the visual modality this could suggest that the hippocampus may be part of the auditory pathway of fear recognition.

Effects of unilateral motor cortex lesion on ipsilesional hand's reach and grasp performance in monkeys: relationship with recovery in the contralesional hand.

Manual dexterity, a prerogative of primates, is under the control of the corticospinal (CS) tract. Because 90-95% of CS axons decussate, it is assumed that this control is exerted essentially on the contralateral hand. Consistently, unilateral lesion of the hand representation in the motor cortex is followed by a complete loss of dexterity of the contralesional hand. During the months following lesion, spontaneous recovery of manual dexterity takes place to a highly variable extent across subjects, although largely incomplete. In the present study, we tested the hypothesis that after a significant postlesion period, manual performance in the ipsilesional hand is correlated with the extent of functional recovery in the contralesional hand. To this aim, ten adult macaque monkeys were subjected to permanent unilateral motor cortex lesion. Monkeys' manual performance was assessed for each hand during several months postlesion, using our standard behavioral test (modified Brinkman board task) that provides a quantitative measure of reach and grasp ability. The ipsilesional hand's performance was found to be significantly enhanced over the long term (100-300 days postlesion) in six of ten monkeys, with the six exhibiting the best, though incomplete, recovery of the contralesional hand. There was a statistically significant correlation (r = 0.932; P < 0.001) between performance in the ipsilesional hand after significant postlesion period and the extent of recovery of the contralesional hand. This observation is interpreted in terms of different possible mechanisms of recovery, dependent on the recruitment of motor areas in the lesioned and/or intact hemispheres.

Pyochelin enantiomers and their outer-membrane siderophore transporters in fluorescent pseudomonads: structural bases for unique enantiospecific recognition.

Pyochelin (Pch) and enantiopyochelin (EPch) are enantiomeric siderophores, with three chiral centers, produced under iron limitation conditions by Pseudomonas aeruginosa and Pseudomonas fluorescens , respectively. After iron chelation in the extracellular medium, Pch-Fe and EPch-Fe are recognized and transported by their specific outer-membrane transporters: FptA in P. aeruginosa and FetA in P. fluorescens . Structural analysis of FetA-EPch-Fe and FptA-Pch-Fe, combined with mutagenesis and docking studies revealed the structural basis of the stereospecific recognition of these enantiomers by their respective transporters. Whereas FetA and FptA have a low sequence identity but high structural homology, the Pch and EPch binding pockets do not share any structural homology, but display similar physicochemical properties. The stereospecific recognition of both enantiomers by their corresponding transporters is imposed by the configuration of the siderophore's C4'' and C2'' chiral centers. This recognition involves specific hydrogen bonds between the Arg91 guanidinium group and EPch-Fe for FetA and between the Leu117-Leu116 main chain and Pch-Fe for FptA. FetA and FptA are the first membrane receptors to be structurally described with opposite binding enantioselectivities for their ligands, giving insights into the structural basis of their enantiospecificity.