335 resultados para Functional Relations
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Objectives: The aim of this study was to assess the concomitant perioperative procedures, the causes of nasolacrimal duct obstruction, the success rate, and the complications associated with endonasal dacryocystorhinostomy (ENDCR).Methods: In this single-center retrospective study, 98 patients underwent 104 ENDCRs between January 1994 and February 2006. There were 78 patients with 84 nasolacrimal duct obstructions who were included in this study.Results: The overall functional success rate with improvement in symptoms was 94.9% for primary surgery (59 of 84 obstructions) and 63.6% for salvage surgery after failure of primary surgery performed in another hospital (25 of 84 obstructions). The mean follow-up time was 36.8 +/- 17.11 months. Primary surgery showed better results, with a complete success rate of 93.2%, than did salvage surgery, with a success rate of only 68%. Persistent symptoms, despite an open rhinostomy, were found in 1.7% of patients with primary surgery and in 12% of those with salvage surgery. Failure of ENDCR was observed in 3.4% of patients after primary surgery and in 20% after salvage surgery. We encountered only minimal perioperative complications, and these were essentially related to lacrimal intubation.Conclusions: Because of the possibility of treating concomitant sinonasal disorders, the cosmetic advantages, and the excellent results, ENDCR represents the procedure of choice for treating nasolacrimal duct obstructions. The main challenge lies in the exact preoperative assessment, as well as postoperative evaluation in case of failure.
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The autosomal recessive form of type I pseudohypoaldosteronism (PHA-I) is an inherited salt-losing syndrome resulting from diminution-of-function mutations in the 3 subunits of the epithelial Na+ channel (ENaC). A PHA-I stop mutation (alpha(R508stop)) of the ENaC alpha subunit is predicted to lack the second transmembrane domain and the intracellular COOH-terminus, regions of the protein involved in pore function. Nonetheless, we observed a measurable Na+ current in Xenopus laevis oocytes that coexpress the beta and gamma subunits with the truncated alpha subunit. The mutant alpha was coassembled with beta and gamma subunits and was present at the cell surface at a lower density, consistent with the lower Na+ current seen in oocytes with the truncated alpha subunit. The single-channel Na+ conductance for the mutant channel was only slightly decreased, and the appearance of the macroscopic currents was delayed by 48 hours with respect to wild-type. Our data suggest novel roles for the alpha subunit in the assembly and targeting of an active channel to the cell surface, and suggest that channel pores consisting of only the beta and gamma subunits can provide significant residual activity. This activity may be sufficient to explain the absence of a severe pulmonary phenotype in patients with PHA-I.
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Vitamin A is necessary for normal embryonic development, but its role in the adult brain is poorly understood. Vitamin A derivatives, retinoids, are involved in a complex signaling pathway that regulates gene expression and, in the central nervous system, controls neuronal differentiation and neural tube patterning. Although a major functional implication of retinoic signaling has been repeatedly suggested in synaptic plasticity, learning and memory, sleep, schizophrenia, depression, Parkinson disease, and Alzheimer disease, the targets and the underlying mechanisms in the adult brain remain elusive.
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? The arbuscular mycorrhizal symbiosis is arguably the most ecologically important eukaryotic symbiosis, yet it is poorly understood at the molecular level. To provide novel insights into the molecular basis of symbiosis-associated traits, we report the first genome-wide analysis of the transcriptome from Glomus intraradices DAOM 197198. ? We generated a set of 25,906 nonredundant virtual transcripts (NRVTs) transcribed in germinated spores, extraradical mycelium and symbiotic roots using Sanger and 454 sequencing. NRVTs were used to construct an oligoarray for investigating gene expression. ? We identified transcripts coding for the meiotic recombination machinery, as well as meiosis-specific proteins, suggesting that the lack of a known sexual cycle in G. intraradices is not a result of major deletions of genes essential for sexual reproduction and meiosis. Induced expression of genes encoding membrane transporters and small secreted proteins in intraradical mycelium, together with the lack of expression of hydrolytic enzymes acting on plant cell wall polysaccharides, are all features of G. intraradices that are shared with ectomycorrhizal symbionts and obligate biotrophic pathogens. ? Our results illuminate the genetic basis of symbiosis-related traits of the most ancient lineage of plant biotrophs, advancing future research on these agriculturally and ecologically important symbionts.
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BACKGROUND:: Although cell therapy is a promising approach after cerebral cortex lesion, few studies assess quantitatively its behavioral gain in non-human primates. Furthermore, implantations of fetal grafts of exogenous stem cells are limited by safety and ethical issues. OBJECTIVE:: To test in non-human primates the transplantation of autologous adult neural progenitor cortical cells with assessment of functional outcome. METHODS:: Seven adult macaque monkeys were trained to perform a manual dexterity task, before the hand representation in motor cortex was chemically lesioned unilaterally. Five monkeys were used as control, compared to two monkeys subjected to different autologous cells transplantation protocols performed at different time intervals. RESULTS:: After lesion, there was a complete loss of manual dexterity in the contralesional hand. The five "control" monkeys recovered progressively and spontaneously part of their manual dexterity, reaching a unique and definitive plateau of recovery, ranging from 38% to 98% of pre-lesion score after 10 to 120 days. The two "treated" monkeys reached a first spontaneous recovery plateau at about 25 and 40 days post-lesion, representing 35% and 61% of the pre-lesion performance, respectively. In contrast to the controls, a second recovery plateau took place 2-3 months after cell transplantation, corresponding to an additional enhancement of functional recovery, representing 24 and 37% improvement, respectively. CONCLUSIONS:: These pilot data, derived from two monkeys treated differently, suggest that, in the present experimental conditions, autologous adult brain progenitor cell transplantation in non-human primate is safe and promotes enhancement of functional recovery.
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Functional connectivity (FC) as measured by correlation between fMRI BOLD time courses of distinct brain regions has revealed meaningful organization of spontaneous fluctuations in the resting brain. However, an increasing amount of evidence points to non-stationarity of FC; i.e., FC dynamically changes over time reflecting additional and rich information about brain organization, but representing new challenges for analysis and interpretation. Here, we propose a data-driven approach based on principal component analysis (PCA) to reveal hidden patterns of coherent FC dynamics across multiple subjects. We demonstrate the feasibility and relevance of this new approach by examining the differences in dynamic FC between 13 healthy control subjects and 15 minimally disabled relapse-remitting multiple sclerosis patients. We estimated whole-brain dynamic FC of regionally-averaged BOLD activity using sliding time windows. We then used PCA to identify FC patterns, termed "eigenconnectivities", that reflect meaningful patterns in FC fluctuations. We then assessed the contributions of these patterns to the dynamic FC at any given time point and identified a network of connections centered on the default-mode network with altered contribution in patients. Our results complement traditional stationary analyses, and reveal novel insights into brain connectivity dynamics and their modulation in a neurodegenerative disease.
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Y chromosomes underlie sex determination in mammals, but their repeat-rich nature has hampered sequencing and associated evolutionary studies. Here we trace Y evolution across 15 representative mammals on the basis of high-throughput genome and transcriptome sequencing. We uncover three independent sex chromosome originations in mammals and birds (the outgroup). The original placental and marsupial (therian) Y, containing the sex-determining gene SRY, emerged in the therian ancestor approximately 180 million years ago, in parallel with the first of five monotreme Y chromosomes, carrying the probable sex-determining gene AMH. The avian W chromosome arose approximately 140 million years ago in the bird ancestor. The small Y/W gene repertoires, enriched in regulatory functions, were rapidly defined following stratification (recombination arrest) and erosion events and have remained considerably stable. Despite expression decreases in therians, Y/W genes show notable conservation of proto-sex chromosome expression patterns, although various Y genes evolved testis-specificities through differential regulatory decay. Thus, although some genes evolved novel functions through spatial/temporal expression shifts, most Y genes probably endured, at least initially, because of dosage constraints.
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CcrM is a DNA methyltransferase that methylates the adenine in GANTC motifs in the chromo-some of the bacterial model Caulobacter crescentus. The loss of the CcrM homolog is lethal in C. crescentus and in several other species of Alphaproteobacteria. In this research, we used different experimental and bioinformatic approaches to determine why CcrM is so critical to the physiology of C. crescentus. We first showed that CcrM is a resident orphan DNA methyltransferase in non-Rickettsiales Alphaproteobacteria and that its gene is strictly conserved in this clade (with only one ex¬ception among the genomes sequenced so far). In C. crescentus, cells depleted in CcrM in rich medium quickly lose viability and present an elongated phenotype characteristic of an im¬pairment in cell division. Using minimal medium instead of rich medium as selective and main¬tenance substrate, we could generate a AccrM mutant that presents a viability comparable to the wild type strain and only mild morphological defects. On the basis of a transcriptomic ap¬proach, we determined that several genes essential for cell division were downregulated in the AccrM strain in minimal medium. We offered decisive arguments to support that the efficient transcription of two of these genes, ftsZ and mipZ, coding respectively for the Z-ring forming GTPase FtsZ and an inhibitor of FtsZ polymerization needed for the correct positioning of the Z- ring at mid-cell, requires the methylation of an adenine in a conserved GANTC motif located in their core promoter region. We propose a model, according to which the genome of C. crescentus encodes a transcriptional activator that requires a methylated adenine in a GANTC context to bind to DNA and suggest that this transcriptional regulator might be the global cell-cycle regulator GcrA. In addition, combining a classic genetic approach and in vitro evolution experiments, we showed that the mortality and cell division defects of the AccrM strain in rich medium are mainly due to limiting intracellular levels of the FtsZ protein. We also studied the dynamics of GANTC methylation in C. crescentus using the SMRT technol¬ogy developed by Pacific Biosciences. Our findings support the commonly accepted model, accord¬ing to which the methylation state of GANTC motifs varies during the cell cycle of C. crescentus: before the initiation of DNA replication, the GANTC motifs are fully-methylated (methylated on both strands); when the DNA gets replicated, the GANTC motifs become hemi-methylated (methyl¬ated on one strand only) and this occurs at different times during replication for different loci along the chromosome depending on their position relative to the origin of replication; the GANTC mo¬tifs are only remethylated after DNA replication has finished as a consequence of the massive and short-lived expression of CcrM in predivisional cells. About 30 GANTC motifs in the C. crescentus chromosome were found to be undermethylated in most of the bacterial population; these might be protected from CcrM activity by DNA binding proteins and some of them could be involved in methylation-based bistable transcriptional switches. - CcrM est une ADN méthyltransférase qui méthyle les adénines dans le contexte GANTC dans le génome de la bactérie modèle Caulobacter crescentus. La perte de l'homologue de CcrM chez C. crescentus et chez plusieurs autres espèces d'Alphaproteobactéries est létale. Dans le courant de cette recherche, nous tentons de déterminer pourquoi la protéine CcrM est cruciale pour la survie de C. crescentus. Nous démontrons d'abord que CcrM est une adénine méthyltransférase orpheline résidente, dont le gène fait partie du génome minimal partagé par les Alphaprotéobactéries non-Rickettsiales (à une exception près). Lorsqu'une souche de C. crescentus est privée de CcrM, sa viabilité décroît rapi¬dement et ses cellules présentent une morphologie allongée qui suggère que la division cellulaire est inhibée. Nous sommes parvenus à créer une souche AccrM en utilisant un milieu minimum, au lieu du milieu riche classiquement employé, comme milieu de sélection et de maintenance pour la souche. Lorsque nous avons étudié le transcriptome de cette souche de C. crescentus privée de CcrM, nous avons pu constater que plusieurs gènes essentiels pour le bon déroulement de la division cellulaire bactérienne étaient réprimés. En particulier, l'expression adéquate des gènes ftsZ et mipZ - qui codent, respectivement, pour FtsZ, la protéine qui constitue, au milieu de la cellule, un anneau protéique qui initie le processus de division et pour MipZ, un inhibiteur de la polymérisation de FtsZ qui est indispensable pour le bon positionnement de l'anneau FtsZ - est dépendante de la présence d'une adénine méthylée dans un motif GANTC conservé situé dans leur région promotrice. Nous présentons un modèle selon lequel le génome de C. crescentus code pour un facteur de transcription qui exige la présence d'une adénine méthylée dans un contexte GANTC pour s'attacher à l'ADN et nous suggérons qu'il pourrait s'agir du régulateur global du cycle cellulaire GcrA. En outre, nous montrons, en combinant la génétique classique et une approche basée sur l'évolution expérimentale, que la mortalité et l'inhibition de la division cellulaire caractéristiques de la souche àccrMeη milieu riche sont dues à des niveaux excessivement bas de protéine FtsZ. Nous avons aussi étudié la dynamique de la méthylation du chromosome de C. crescentus sur la base de la technologie SMRT développée par Pacific Biosciences. Nous confirmons le modèle communément accepté, qui affirme que l'état de méthylation des motifs GANTC change durant le cycle cellulaire de C. crescentus: les motifs GANTC sont complètement méthylés (méthylés sur les deux brins) avant de début de la réplication de l'ADN; ils deviennent hémi-méthylés (méthylés sur un brin seulement) une fois répliqués, ce qui arrive à différents moments durant la réplication pour différents sites le long du chromosome en fonction de leur position par rapport à l'origine de répli-cation; finalement, les motifs GANTC sont reméthylés après la fin de la réplication du chromosome lorsque la protéine CcrM est massivement, mais très transitoirement, produite. Par ailleurs, nous identifions dans le chromosome de C. crescentus environ 30 motifs GANTC qui restent en perma-nence non-méthylés dans une grande partie de la population bactérienne; ces motifs sont probable-ment protégés de l'action de CcrM par des protéines qui s'attachent à l'ADN et certains d'entre eux pourraient être impliqués dans des mécanismes de régulation générant une transcription bistable.
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La masse considérable de travaux publiés dans le domaine de la neuroimagerie fonctionnelle concernant les fonctions ou modalités du langage (compréhension et expression de la parole, lecture) ou les différents processus linguistiques qui les sous-tendent (sémantique, phonologie, syntaxe) permet de dégager de grandes tendances en termes de substrats anatomiques. Si les « fondamentaux » issus des origines aphasiologiques du domaine n'ont pas été bouleversés, certaines spécificités non explorées par l'approche lésionnelle sont identifiables. Les méta-analyses, en regroupant les résultats de la littérature, nous procurent aujourd'hui une vision globale des substrats cérébraux du langage. Cependant la variabilité inter-individuelle reste importante en raison de multiples facteurs dont certains sont mal identifiés ; cartographier exhaustivement les fonctions du langage à l'échelle individuelle reste une gageure. La quête des images du langage est sans doute aussi inachevable que celle de l'étude du langage lui-même.
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RÉSUMÉ : Elucider les bases moléculaires et cellulaires du fonctionnement des cellules souches s'avère crucial dans la compréhension de l'organisation cellulaire au sein des tissus et des organes ainsi que pour le développement de nouvelles stratégies thérapeutiques en médecine régénérative et en oncologie. Les cellules souches adultes les mieux connues sont celles responsables de l'hématopoïèse, les cellules souches hématopoïétiques (CSH). Durant ces dernières années, la recherche a porté une attention particulière à l'isolation prospective de CSH dérivées de la moelle osseuse de souris en utilisant des marqueurs de surface cellulaire ainsi que des propriétés fonctionnelles alléguées. Par la suite, la capacité fonctionnelle des CSH a été vérifiée classiquement par leur transplantation intraveineuse dans des souris réceptrices conditionnées et par l'analyse de leur aptitude à reconstituer le système hématopoïétique à long terme. Des études récentes suggèrent que la transplantation des cellules directement dans la moelle osseuse pourrait non seulement aboutir à une prise de greffe plus rapide et plus efficace, mais pourrait même aider à l'identification de cellules qui ont certes des propriétés intrinsèques de CSH, mais qui n'ont pas la capacité de trouver leur niche au sein de la moelle osseuse et ont donc échoué dans les analyses classiques de reconstitution. Dans cette étude, nous comparons à deux niveaux la fonction de différents sous-groupes de cellules souches de la moelle osseuse, définis par leur phénotype de surface cellulaire. Premièrement, nous étudions leur capacité à reconstituer des souris létalement irradiées après injection soit intraveineuse soit intrafémorale. Deuxièmement, par analyse cytométrique de flux à 8 couleurs, nous comparons leur activité relative de « side population » (SP) par exclusion du colorant fluorescent Hoechst 33342. Nos résultats préliminaires renforcent en effet l'idée que la transplantation intrafémorale aboutit à une greffe plus rapide et plus efficace. Par contre, en utilisant cette approche, nous n'arrivons pas à identifier des cellules capables de prendre greffe spécifiquement quand elles sont injectées en intrafémorale. Finalement, bien qu'une confirmation in vivo soit encore nécessaire, nous suggérons sur la base de nos analyses cytométriques de flux, que les cellules SP Sca1t~és éie~~ CD48t~és bas sont très enrichies en CSH. Ceci permettrait l'isolation ex vivo de CSH de la moelle osseuse de souris par une stratégie à la fois nouvelle et simple. SUMMARY : Elucidating the molecular and cellular bases of stem cell function is crucial for the understanding of cellular organisation within tissues and organs as well as for the development of new therapeutic strategies in regenerative medicine and oncology. The best-known adult stem cells are those responsible for haematopoiesis, the haematopoietic stem cells (HSCs). In recent years, much effort has been put into the prospective isolation of mouse bone marrow (BM)-derived HSCs using cell-surface markers and alleged functional properties. Upon isolation, the functional capacity of putative HSCs has been classically assessed by intravenous transplantation into conditioned recipient mice and analysis of their ability to reconstitute the haematopoietic system at long-term. It has recently been suggested that transplanting the cells directly into the BM might not only result in more rapid and more effective engraftment, but even help to identify cells that have intrinsic HSC properties but lack the ability to home to their BM niche and have thus failed to succeed in classical reconstitution assays. In this study, we compare the function of different BM cell subsets, as defined by their cell surface phenotype, on two levels. Firstly, we assess their ability to reconstitute lethally irradiated mice, when injected either intravenously or intrafemorally. Secondly, using 8-colour flow cytometric analysis, we compare their relative side population (SP) activity by exclusion of the fluorescent dye Hoechst 33342. Our preliminary results indeed reinforce the idea that intrafemoral transplantation results in faster and more effective engraftment, however, using this approach, we are unable to identify cells that are capable of engrafting specifically when injected intrafemorally. Finally, although in vivo confirmation is still required, we propose, based on the results of our flow cytometric analyses, that SP Scat Very h'9h CD48Very'°W cells should be highly enriched for HSCs. This would allow for a simple new strategy for the isolation of mouse BM HSCs ex vivo.
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Postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains are relatively small (80-120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible for communication between distant regions of the protein, in agreement with recent NMR experiments. Thus, PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbinding events.
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1. Severe environmental conditions filter community species compositions, forming clines of functional diversity along environmental gradients. Here, the changes in functional diversity in ant assemblages with severe environmental conditions in the Swiss Alps were investigated. 2. Eight sites were sampled along an elevation gradient (1800-2550 m). The variation in functional diversity was analysed along an elevation gradient considering four traits: social structure (monogynous vs. polygynous), worker size, pupal development, and nest structure. 3. Ant species richness and functional diversity decreased with decreasing temperature. Species found in colder habitats tended to live in subterranean nests rather than in mounds and exhibit a polymorphism in queen number, either within or across populations. The phylogenetic diversity did not decrease at colder temperature: Formicinae and Myrmicinae occupied the full range of elevations investigated. 4. An insulation experiment indicated that mounds are more thermally insulated against the cold compared with soil. The absence of a mound-building ant from high elevations probably results from a reduction in the amount of vegetal materials provided by coniferous trees. 5. More severe abiotic conditions at higher elevations act as a filter on ant assemblages, directly through physiological tolerances to the abiotic conditions and indirectly as the vegetation necessary for nest building shifts with elevation.</list-item
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Gaysurvey est une enquête menée périodiquement en Suisse parmi les hommes qui ont des relations sexuelles avec des hommes (HSH). Elle s'inscrit dans le dispositif de surveillance du VIH, établi par l'Office fédéral de la santé publique, en tant qu'instrument de suivi des comportements face au VIH/Sida dans ce groupe cible. Elle a déjà été réalisée à neuf reprises : en 1987, 1990, 1992, 1994, 1997, 2000, 2004, 2007 et 2009. En 2010, l'enquête européenne EMIS a permis d'obtenir certains indicateurs qui sont présentés avec les données des enquêtes Gaysurvey lorsqu'ils sont disponibles. Les résultats de cette enquête servent directement au pilotage et à l'évaluation de la stratégie de lutte contre le VIH/Sida en Suisse, telle qu'elle a été définie par l'OFSP et ses partenaires. Elle permet d'établir des tendances temporelles au niveau des pratiques sexuelles et des expositions au risque d'infection par le VIH. Elle permet, en outre, d'approfondir certaines thématiques pertinentes pour le travail de prévention (gestion du risque au sein d'une relation stable, entrée dans la sexualité, pratiques de réduction des risques). Ce rapport a pour objectif de faire la synthèse des tendances, mises à jour lors de la dernière vague d'enquête réalisée en 2012. [Introduction p. 17]