Dissection of local and systemic transcriptional responses to phosphate starvation in Arabidopsis.

Phosphate is a crucial and often limiting nutrient for plant growth. To obtain inorganic phosphate (P(i) ), which is very insoluble, and is heterogeneously distributed in the soil, plants have evolved a complex network of morphological and biochemical processes. These processes are controlled by a regulatory system triggered by P(i) concentration, not only present in the medium (external P(i) ), but also inside plant cells (internal P(i) ). A 'split-root' assay was performed to mimic a heterogeneous environment, after which a transcriptomic analysis identified groups of genes either locally or systemically regulated by P(i) starvation at the transcriptional level. These groups revealed coordinated regulations for various functions associated with P(i) starvation (including P(i) uptake, P(i) recovery, lipid metabolism, and metal uptake), and distinct roles for members in gene families. Genetic tools and physiological analyses revealed that genes that are locally regulated appear to be modulated mostly by root development independently of the internal P(i) content. By contrast, internal P(i) was essential to promote the activation of systemic regulation. Reducing the flow of P(i) had no effect on the systemic response, suggesting that a secondary signal, independent of P(i) , could be involved in the response. Furthermore, our results display a direct role for the transcription factor PHR1, as genes systemically controlled by low P(i) have promoters enriched with P1BS motif (PHR1-binding sequences). These data detail various regulatory systems regarding P(i) starvation responses (systemic versus local, and internal versus external P(i) ), and provide tools to analyze and classify the effects of P(i) starvation on plant physiology.

Factors predisposing to dislocation after primary total hip arthroplasty: a multivariate analysis.

We conducted this study to determine the relative influence of various mechanical and patient-related factors on the incidence of dislocation after primary total hip asthroplasty (THA). Of 2,023 THAs, 21 patients who had at least 1 dislocation were compared with a control group of 21 patients without dislocation, matched for age, gender, pathology, and year of surgery. Implant positioning, seniority of the surgeon, American Society of Anesthesiologists (ASA) score, and diminished motor coordination were recorded. Data analysis included univariate and multivariate methods. The dislocation risk was 6.9 times higher if total anteversion was not between 40 degrees and 60 degrees and 10 times higher in patients with high ASA scores. Surgeons should pay attention to total anteversion (cup and stem) of THA. The ASA score should be part of the preoperative assessment of the dislocation risk.

Jasmonic acid and the THO/TREX complex participate in phosphate starvation response

All plants are typically confronted to simultaneous biotic and abiotic stress throughout their life cycle. Low inorganic phosphate (Pi) is the most common nutrient deficiency limiting plant growth in natural and agricultural ecosystems while insect herbivory accounts for major losses in plant productivity and impacts on ecological and evolutionary changes in plant populations. Here we report that plants experiencing Pi deficiency induce the jasmonic acid (JA) pathway and enhance their defence against insect herbivory. The phol mutant is impaired in the translocation of Pi from roots to shoots and shows the typical symptoms associated with Pi deficiency, including high anthocyanin and poor shoot growth. These phol shoot phenotypes were significantly attenuated by blocking the JA biosynthesis or signalling pathways. Wounded phol leaves hyper-accumulated JA in comparison to wild type, leading to increased resistance against the generalist herbivore Spodoptera littoralis. Pi deficiency also triggered enhanced resistance to herbivory in wild-type Arabidopsis as well as tomato and tobacco, revealing that the link between Pi deficiency and JA-mediated herbivory resistance is conserved in a diversity of plants, including crops. We performed a phol suppressor screen to identify new components involved in the adaptation of plants to Pi deficiency. We report that the THO RNA TRANSCRIPTION AND EXPORT (THO/TREX) complex is a crucial component involved in modulating the Pi- deficiency response. Knockout mutants of at least three members of the THO/TREX complex, including TEX1, HPR1, and TH06, can suppress the phol shoot phenotype. Grafting experiments showed that loss of function of TEX1 only in the root was sufficient to suppress the reduced shoot growth phenotype of phol while maintaining low Pi contents. This indicates that TEX1 is involved in a long distance root-to-shoot signalling component of the Pi-deficiency response. We identified a small MYB-like transcription factor, RAD LIKE 3 (RL3), as a potential downstream target of the THO/TREX complex. RL3 expression is induced in phol mutants but attenuated in phol-7 texl-4 double mutants. Identical to knockout mutants of the THO/TREX complex, rl3 mutants can suppress the phol shoot phenotypes. Interestingly, RL3 is induced during Pi deficiency and is described in the literature as likely being mobile. It is therefore a promising new candidate involved in the root-to-shoot Pi-deficiency signalling response. Finally, we report that PHOl and its homologue PH01:H3 are involved in the co-regulation of Pi and zinc (Zn) homeostasis. PH01;H3 is up-regulated in response to Zn deficiency and, like PHOl, is expressed in the root vascular cylinder and localizes to the Golgi when expressed transiently in tobacco cells. The phol;h3 mutant accumulates more Pi as compared to wild-type when grown in Zn-deficient medium, but this increase is abolished in the phol phol;h3 double mutant. These results suggest that PH01;H3 restricts the PHOl-mediated root-to-shoot Pi transfer in responsé to Zn deficiency. Résumé Au cours de leur cycle de vie, toutes les plantes sont généralement confrontées à divers stress biotiques et abiotiques. La carence nutritionnelle la plus fréquente, limitant la croissance des plantes dans les écosystèmes naturels et agricoles, est la faible teneur en phosphate inorganique (Pi). Au niveau des stress biotiques, les insectes herbivores sont responsables de pertes majeures de rendement et ont un impact considérable sur les changements écologiques et évolutifs dans les populations des plantes. Au cours de ce travail, nous avons mis en évidence que les plantes en situation de carence en Pi induisent la voie de l'acide jasmonique (JA) et augmentent leur défense contre les insectes herbivores. Le mutant phol est déficient dans le transport du phosphate des racines aux feuilles et démontre les symptômes typiques associés à la carence, tels que la forte concentration en anthocyane et une faible croissance foliaire. Ces phénotypes du mutant phol sont significativement atténués lors d'un blocage de la voie de la biosynthèse ou des voies de signalisation du JA. La blessure des feuilles induit une hyper-accumulation de JA chez phol, résultant en une augmentation de la résistance contre l'herbivore généraliste Spodoptera littoralis. Outre Arabidopsis, la carence en Pi induit une résistance accrue aux insectes herbivores aussi chez la tomate et le tabac. Cette découverte révèle que le lien entre la carence en Pi et la résistance aux insectes herbivores via le JA est conservé dans différentes espèces végétales, y compris les plantes de grandes cultures. Nous avons effectué un crible du suppresseur de phol afin d'identifier de nouveaux acteurs impliqués dans l'adaptation de la plante à la carence en Pi. Nous rapportons que le complexe nommé THO RNA TRANSCRIPTION AND EXPORT (THO/TREX) est un élément crucial participant à la réponse des feuilles à la carence en Pi. Les mutations d'au moins trois des membres que composent le complexe THO/TREX, incluant TEX1, HPR1 et 77/06, peuvent supprimer le phénotype de phol. Des expériences de greffes ont montré que la perte de fonction de TEX1, seulement dans la racine, est suffisante pour supprimer le phénotype de la croissance réduite des parties aériennes observé chez le mutant phol, tout en maintenant de faibles teneurs en Pi foliaire. Ceci indique que TEX1 est impliqué dans la signalisation longue distance entre les racines et les parties aériennes. Nous avons identifié un petit facteur de transcription proche de la famille des MYB, RAD LIKE 3 (RL3), comme une cible potentielle en aval du complexe THO / TREX. L'expression du gène RL3 est induite dans le mutant phol mais atténuée dans le double mutant phol-7 texl-4. Exactement comme les plantes mutées d'un des membres du complexe THO/TREX, le mutant rl3 peut supprimer le phénotype foliaire de phol. RL3 est induit au cours d'une carence en Pi et est décrit dans la littérature comme étant potentiellement mobile. Par conséquent, il serait un nouveau candidat potentiellement impliqué dans la réponse longue distance entre les racines et les parties aériennes lors d'un déficit en Pi. Enfin, nous reportons que PHOl et son homologue PHOl: H3 sont impliqués dans la co- régulation de l'homéostasie du Pi et du zinc (Zn). PHOl; H3 est sur-exprimé en réponse au déficit en Zn et, comme PHOl, est exprimé dans les tissus vasculaires des racines et se localise dans l'appareil de Golgi lorsqu'il est exprimé de manière transitoire dans des cellules de tabac. Le mutant phol; h3 accumule plus de Pi par rapport aux plantes sauvages lorsqu'il est cultivé sur un milieu déficient en Zn, mais cette augmentation en Pi est abolie dans le double mutant phol phol; h3. Ces résultats suggèrent qu'en réponse à une carence en Zn, PHOl; H3 limite l'action de PHOl et diminue le transfert du Pi des racines aux parties aériennes.

Minimal invasive surgery for coronoid fracture: technical note.

Operative treatment of coronoid fracture often requires a large dissection of soft tissue, resulting in elbow stiffness and functional limitation. The authors present a minimal invasive, safe technique, useful in the case of isolated coronoid fracture associated with elbow dislocation. This technique does not require soft tissue dissection and allows an early unlimited resumption of sports activities.

Expression analysis of the AtPHO1 gene family in Arabidopsis thaliana and the involvement of AtPHO1 in the regulation of stomatal movements

Résumé Le transfert du phosphate des racines vers les feuilles s'effectue par la voie du xylème. Il a été précédemment démontré que la protéine AtPHO1 était indispensable au transfert du phosphate dans les vaisseaux du xylème des racines chez la plante modèle Arabidopsis thaliana. Le séquençage et l'annotation du génome d'Arabidopsis ont permis d'identifier dix séquences présentant un niveau de similarité significatif avec le gène AtPHO1 et constituant une nouvelle famille de gène appelé la famille de AtPHO1. Basée sur une étude moléculaire et génétique, cette thèse apporte des éléments de réponse pour déterminer le rôle des membres de ia famille de AtPHO1 chez Arabidopsis, inconnue à ce jour. Dans un premier temps, une analyse bioinformatique des séquences protéiques des membres de la famille de AtPHO1 a révélé la présence dans leur région N-terminale d'un domaine nommé SPX. Ce dernier est conservé parmi de nombreuses protéines impliquées dans l'homéostasie du phosphate chez la levure, renforçant ainsi l'hypothèse que les membres de la famille de AtPHO1 auraient comme AtPHO1 un rôle dans l'équilibre du phosphate dans la plante. En parallèle, la localisation tissulaire de l'expression des gènes AtPHO dans Arabidopsis a été identifiée par l'analyse de plantes transgéniques exprimant le gène rapporteur uidA sous le contrôle des promoteurs respectifs des gènes AtPHO. Un profil d'expression de chaque gène AtPHO au cours du développement de la plante a été obtenu. Une expression prédominante au niveau des tissus vasculaires des racines, des feuilles, des tiges et des fleurs a été observée, suggérant que les gènes AtPHO pourraient avoir des fonctions redondantes au niveau du transfert de phosphate dans le cylindre vasculaire de ces différents organes. Toutefois, plusieurs régions promotrices des gènes AtPHO contrôlent également un profil d'expression GUS non-vasculaire, indiquant un rôle putatif des gènes AtPHO dans l'acquisition ou le recyclage de phosphate dans la plante. Dans un deuxième temps, l'analyse de l'expression des gènes AtPHO durant une carence en phosphate a établi que seule l'expression des gènes AtPHO1, AtPHO1; H1 et AtPHO1; H10 est régulée par cette carence. Une étude approfondie de leur expression en réponse à des traitements affectant l'homéostasie du phosphate dans la plante a ensuite démontré leur régulation par différentes voies de signalisation. Ensuite, une analyse détaillée de la régulation de l'expression du gène AtPHO1; H1O dans des feuilles d'Arabidopsis blessées ou déshydratées a révélé que ce gène constitue le premìer gène marqueur d'une nouvelle voie de signalisation induite par l'OPDA, pas par le JA et dépendante de la protéine COI1. Ces résultats démontrent pour la première fois que l'OPDA et le JA peuvent activer différents gènes via des voies de signalisation dépendantes de COI1. Enfin, cette thèse révèle l'identification d'un nouveau rôle de la protéine AtPHO1 dans la régulation de l'action de l'ABA au cours des processus de fermeture stomatique et de germination des graines chez Arabidopsis. Bien que les fonctions exactes des protéines AtPHO restent à être déterminées, ce travail de thèse suggère leur implication dans la propagation de différents signaux dans la plante via la modulation du potentiel membranaire et/ou l'affectation de la composition en ions des cellules comme le font de nombreux transporteurs ou régulateur du transport d'ions. Summary Phosphate is transferred from the roots to the shoot via the xylem. The requirement for AtPHO1 protein to transfer phosphate to the xylem vessels of the root has been previously demonstrated in Arabidopsis thaliana. The sequencing and the annotation of the Arabidopsis genome had allowed the identification of ten sequences that show a significant level of similarity with the AtPHO1 gene. These 10 genes, of unknown functions, constitute a new gene family called the AtPHO1 gene family. Based on a molecular and genetics study, this thesis reveals some information needed to understand the role of the AtPHO1 family members in the plant Arabidopsis. First, a bioinformatics study revealed that the AtPHO sequences contained, in the N-terminal hydrophilic region, a motif called SPX and conserved among multiple proteins involved in phosphate homeostasis in yeast. This finding reinforces the hypothesis that all AtPHO1 family members have, as AtPHO1, a role in phosphate homeostasis. In parallel, we identified the pattern of expression of AtPHO genes in Arabidopsis via analysis of transgenic plants expressing the uidA reporter gene under the control of respective AtPHO promoter regions. The results exhibit a predominant expression of AtPHO genes in vascular tissues of all organs of the plant, implying that these AtPHO genes could have redundant functions in the transfer of phosphate to the vascular cylinder of various organs. The GUS expression pattern for several AtPHO promoter regions was also detected in non-vascular tissue indicating a broad role of AtPHO genes in the acquisition or in the recycling of phosphate in the plant. In a second step, the analysis of the expression of AtPHO genes during phosphate starvation established that only the expression of the AtPHO1, AtPHO1; H1 and AtPHO1; H10 genes were regulated by Pi starvation. Interestingly, different signalling pathways appeared to regulate these three genes during various treatments affecting Pi homeostasis in the plant. The third chapter presents a detailed analysis of the signalling pathways regulating the expression of the AtPHO1; H10 gene in Arabidopsis leaves during wound and dehydrated stresses. Surprisingly, the expression of AtPHO1; H10 was found to be regulated by OPDA (the precursor of JA) but not by JA itself and via the COI1 protein (the central regulator of the JA signalling pathway). These results demonstrated for the first time that OPDA and JA could activate distinct genes via COI1-dependent pathways. Finally, this thesis presents the identification of a novel role of the AtPHO1 protein in the regulation of ABA action in Arabidopsis guard cells and during seed germination. Although the exact role and function of AtPHO1 still need to be determined, these last findings suggest that AtPHO1 and by extension other AtPHO proteins could mediate the propagation of various signals in the plant by modulating the membrane potential and/or by affecting cellular ion composition, as it is the case for many ion transporters or regulators of ion transport.

Diagnostic et traitement de l'instabilité rotulienne [Diagnosis and treatment of patellar instability].

Patellar instability concerns mostly young and active patients. Because of the condition's multifactorial origin, knowledge about the risk factors of patella instability and the biomechanics of the femoropatellar joint are necessary to understand this disorder. Most of the patellar dislocations are spontaneously reduced. Only the patient's history, clinical examination and appropriate imaging lead to the correct diagnosis. If haemarthrosis is present, MRI is recommended to rule out concomitant injuries. A traumatic patellar dislocation without history of prior dislocation is treated conservatively. Surgical treatment is indicated in presence of intra-articular injury or for recurrent dislocations. The surgical procedure should correct the different factors of patella instability identified by preoperative analysis.

Ghosts in contemporary African diasporic literature : re-visioning history, memory and identity

Starting from the observation that ghosts are strikingly recurrent and prominent figures in late-twentieth African diasporic literature, this dissertation proposes to account for this presence by exploring its various functions. It argues that, beyond the poetic function the ghost performs as metaphor, it also does cultural, theoretical and political work that is significant to the African diaspora in its dealings with issues of history, memory and identity. Toni Morrison's Beloved (1987) serves as a guide for introducing the many forms, qualities and significations of the ghost, which are then explored and analyzed in four chapters that look at Fred D'Aguiar's Feeding the Ghosts (1998), Gloria Naylor's Mama Day (1988), Paule Marshall's Praisesong for the Widow (1983) and a selection of novels, short stories and poetry by Michelle Cliff. Moving thematically through these texts, the discussion shifts from history through memory to identity as it examines how the ghost trope allows the writers to revisit sites of trauma; revise historical narratives that are constituted and perpetuated by exclusions and invisibilities; creatively and critically repossess a past marked by violence, dislocation and alienation and reclaim the diasporic culture it contributed to shaping; destabilize and deconstruct the hegemonic, normative categories and boundaries that delimit race or sexuality and envision other, less limited and limiting definitions of identity. These diverse and interrelated concerns are identified and theorized as participating in a project of "re-vision," a critical project that constitutes an epistemological as much as a political gesture. The author-based structure allows for a detailed analysis of the texts and highlights the distinctive shapes the ghost takes and the particular concerns it serves to address in each writer's literary and political project. However, using the ghost as a guide into these texts, taken collectively, also throws into relief new connections between them and sheds light on the complex ways in which the interplay of history, memory and identity positions them as products of and contributions to an African diasporic (literary) culture. If it insists on the cultural specificity of African diasporic ghosts, tracing its origins to African cultures and spiritualities, the argument also follows gothic studies' common view that ghosts in literary and cultural productions-like other related figures of the living dead-respond to particular conditions and anxieties. Considering the historical and political context in which the texts under study were produced, the dissertation makes connections between the ghosts in them and African diasporic people's disillusionment with the broken promises of the civil rights movement in the United States and of postcolonial independence in the Caribbean. It reads the texts' theoretical concerns and narrative qualities alongside the contestation of traditional historiography by black and postcolonial studies as well as the broader challenge to conventional notions such as truth, reality, meaning, power or identity by poststructuralism, postcolonialism or queer theory. Drawing on these various theoretical approaches and critical tools to elucidate the ghost's deconstructive power for African diasporic writers' concerns, this work ultimately offers a contribution to "speciality studies," which is currently emerging as a new field of scholarship in cultural theory.

Synthèse de l'évolution de la plateforme Urgonienne (Barrémien tardif à Aptien précoce) du Sud-Est de la France : facies, micropaléontologie, géochimie, géométries, paléotectonique et géomodélisation

Il y a environ 125 millions d'années, au Crétacé inférieur, la position des continents et le climat terrestre étaient bien différents de ce que l'on connait aujourd'hui. Le Sud-Est de la France, secteur de cette étude, était alors recouvert d'eau, sous un climat chaud et humide. Sur la bordure de cette étendue d'eau (appelée bassin Vocontien), qui correspond aujourd'hui aux régions de la Provence, du Vaucluse, du Gard, de l'Ardèche et du Vercors, des plateformes carbonatées, (telles que les Bahamas), se développaient. Le calcaire, formé à partir des sédiments accumulés sur ces plateformes, est appelé Urgonien. L'objectif de cette étude est de définir les facteurs qui ont influencé le développement de cette plateforme carbonatée dite « urgonienne » et dans quelle mesure. Plusieurs missions de terrain ont permis de récolter de nombreux échantillons de roche en 52 lieux répartis sur l'ensemble du Sud-Est de la France. Les observations réalisées sur le terrain ainsi que les données acquises en laboratoire (microfaune, microfacies et données géo-chimiques) ont permis, de subdiviser chacune des 52 séries urgoniennes en séquences stratigraphiques et cortèges sédimentaires. La comparaison des épaisseurs et des faciès de chaque cortège sédimentaire permet de concevoir la géométrie et l'évolution paléogéographique de la plateforme urgonienne. Les résultats de cette étude démontrent que son organisation est principalement dirigée par des failles qui ont jouées pendant le dépôt des sédiments. Sur la bordure nord du bassin Vocontien, trois failles subméridiennes contrôlent la géométrie et la répartition des environnements de dépôt. Sur sa bordure sud, ces failles synsédimentaires d'orientation N30° et N110° délimitent des blocs basculés. En tête de bloc, des séries d'épaisseurs réduites à faciès de lagon interne se sont déposées alors que les pieds de blocs sont caractérisés par des épaisseurs importantes et la présence de faciès plus externes. Ces concepts ont ensuite été testés en construisant un modèle numérique en trois dimensions de l'Urgonien du Sud-Est de la France. Sa cohérence avec les données acquises tout au long de cette étude d'une part, et sa cohérence géométrique d'autre part, valide les théories avancées. Des formations équivalentes à l'Urgonien sont réparties dans le monde entier et notamment au Moyen-Orient où elles constituent les réservoirs pétroliers les plus importants. Etre capable de caractériser les facteurs ayant influencé son architecture permet par la suite une meilleure exploitation de ses ressources énergétiques. -- Au Crétacé inférieur, l'intense activité magmatique due à la dislocation du super-continent Pangée influence fortement les conditions environnementales globales. Au Barrémien terminal et Aptien basal, période géologique dont fait l'objet cette étude, le bassin Vocontien, puis Bédoulien, recouvre le Sud-Est de la France, sous un climat chaud et humide. Sur les bordures de ces bassins, des plateformes carbonatées se mettent en place. Les sédiments qui se déposent sur ces plateformes sont à l'origine de la formation urgonienne. Afin d'étudier cette formation, une charte biostratigraphique, principalement basée sur les Orbitolinidés, et un modèle de faciès ont été développés. Les assemblages faunistiques, la succession des faciès, les observations de terrain ainsi que l'étude de signaux géochimiques ont permis le découpage séquentiel de la série urgonienne le long de 54 coupes et puis, répartis sur l'ensemble du Sud-Est de la France. Les corrélations induites par cette étude stratigraphique ont mis en évidence d'importantes variations d'épaisseur et d'environnements de dépôt au sein même de la plateforme urgonienne. Ces variations sont expliquées par le jeu de failles syn-sédimentaires qui ont compartimentées la plateforme urgonienne en blocs. Sur la bordure sud du bassin Vocontien, ces failles d'orientation N30° et N110° délimitent six blocs basculés. Au sommet du Barrémien terminal, la subsidence des blocs situés le plus au sud s'amplifie jusqu'à provoquer l'ouverture du bassin de la Bédoule au sud du secteur d'étude. Cette théorie d'évolution a ensuite été testée par l'élaboration d'un modèle numérique en trois dimensions de l'Urgonien du Sud-Est de la France. Sa cohérence avec les données acquises tout au long de cette étude d'une part, et sa cohérence géométrique d'autre part, valide les théories avancées. Des analogues de l'Urgonien sont répartis dans le monde entier et notamment au Moyen-Orient où ils représentent d'importants réservoirs pétroliers. Être capable de caractériser les facteurs ayant influencé l'architecture de l'Urgonien du Sud-Est de la France permet par la suite une meilleure exploitation de ses ressources énergétiques. -- During the Early Cretaceous epoch, intensive magmatic activity due to the dislocation of the super-continent Pangaea, highly influenced global environmental conditions, which were characterized by a warm and generally humic climate. In this context, carbonate platforms were important in tropical and subtropical shallow-water regions, and especially during the late Barremian and early Aptian, platform carbonates of so-called Urgonian affinity are widespread. In southeastern France, the Urgonian platform was part of the northern Tethyan margin and bordered the Vocontian and the Bedoulian basins. The goal of this thesis was the systematic study of the Urgonian Formation in this region, and in order to achieve this goal, a biostratigraphic chart and a facies model were developed. The faunistic assemblages, the facies succession, the field observations and the study of geochemical signals lead to a sequential subdivision of the Urgonian series along 54 sections and wells allocated in five different regions in southeastern France (Gard, Ardèche, Vercors, Vaucluse and Provence). Correlations from this stratigraphic study highlight important variations in thickness and depositional environments of the Urgonian series. These variations are explained by relative movements induced by syn-sedimentary faults, which divided the Urgonian platforms into blocks. On the southern border of the Vocontian basin, these faults, oriented N30° and N110°, delineate six tilted blocks. At the top of the upper Barremian carbonates, subsidence of the two southern blocks accelerated leading to the opening of the Bedoulian basin. The reconstruction of the sequence-stratigraphic and paleoenvironmental evolution of the Urgonian platforms was then tested by the construction of a 3D numerical model of the Urgonian formation of southeastern France. Firstly, its consistency with the data collected during this study, and secondly, its geometrical coherence validate the proposed theory. Urgonian analogs exist all over the world and particularly in Middle East where they constitute important oil reservoirs. The exact reconstruction of the major factors, which influenced the architecture of these formations, will allow for a better exploitation of these energy resources.

Phenotypic features of carbohydrate sulfotransferase 3 (CHST3) deficiency in 24 patients: congenital dislocations and vertebral changes as principal diagnostic features.

We recently reported on the deficiency of carbohydrate sulfotransferase 3 (CHST3; chondroitin-6-sulfotransferase) in six subjects diagnosed with recessive Larsen syndrome or humero-spinal dysostosis [Hermanns et al. (2008); Am J Hum Genet 82:1368-1374]. Since then, we have identified 17 additional families with CHST3 mutations and we report here on a series of 24 patients in 23 families. The diagnostic hypothesis prior to molecular analysis had been: Larsen syndrome (15 families), humero-spinal dysostosis (four cases), chondrodysplasia with multiple dislocations (CDMD "Megarbane type"; two cases), Desbuquois syndrome (one case), and spondylo-epiphyseal dysplasia (one case). In spite of the different diagnostic labels, the clinical features in these patients were similar and included dislocation of the knees and/or hips at birth, clubfoot, elbow joint dysplasia with subluxation and limited extension, short stature, and progressive kyphosis developing in late childhood. The most useful radiographic clues were the changes of the lumbar vertebrae. Twenty-four different CHST3 mutations were identified; 16 patients had homozygous mutations. We conclude that CHST3 deficiency presents at birth with congenital dislocations of knees, hips, and elbows, and is often diagnosed initially as Larsen syndrome, humero-spinal dysostosis, or chondrodysplasia with dislocations. The incidence of CHST3 deficiency seems to be higher than assumed so far. The clinical and radiographic pattern (joint dislocations, vertebral changes, normal carpal age, lack of facial flattening, and recessive inheritance) is characteristic and distinguishes CHST3 deficiency from other disorders with congenital dislocations such as filamin B-associated dominant Larsen syndrome and Desbuquois syndrome.

Proximale Humerusmehrfragmentfrakturen--Misserfolge nach T-Platten-Osteosynthesen [Proximal humeral multiple fragment fractures--failures after T-plate osteosynthesis].

Dislocated compound fractures of the proximal humerus are often difficult to treat. The choice of treatment influences the final functional result. From 1984-1991 108 patients with dislocated compound fractures of the proximal humerus were operated with a T-plate osteosynthesis, retrospectively examined and classified according to the Neer-Classification. At an average follow up time of 5 years 72 patients had a clinical and radiological examination. 68% of these patients with 3-fragment fractures and 80% with 4-fragment fractures showed a modest to unsatisfactory result caused by fracture biology, imprecise fracture reduction or poor surgical procedure. Incorrect position of T-plates and inadequate material were distinguishable. The T-plate which was widely used in the late eighties for internal fixation has to be considered a failure for these particular types of fractures and should be limited for Collum chirurgicum fractures.

Isolation of genetic mutation leading to abnormal phenotype in human through ultra-high-throughput sequencing (UHTS)

The introduction of Next Generation Sequencing (NGS) facilitated the task of localizing DNA variation and identifying the genetic cause of yet unsolved Mendelian disorders. Using Whole Exome Capture method and NGS, we identified the causative genetic aberration responsible for a number of monogenic disorders previously undetermined. Due to the novelty of the NGS method we benchmarked different algorithms to assess their merits and defects. This allowed us to establish a pipeline that we successfully used to pinpoint genes responsible for a form of West's syndrome, a Complex Intellectual Disability syndrome associated with patellar dislocation and celiac disease, and correcting some erroneous molecular diagnosis of Alport's syndrome in a Saudi Arabian family.

Functional assessment of chest wall integrity after methylmethacrylate reconstruction.

BACKGROUND: All patients with extensive resection of the anterolateral chest wall and the sternum followed by reconstruction with methylmethacrylate substitutes were assessed prospectively 6 months after the operation to delineate chest wall integrity with pulmonary function and cine-magnetic resonance imaging. METHODS: Twenty-six patients underwent chest wall reconstruction by use of methylmethacrylate between 1994 and 1998 due to primary tumors in 35%, metastases in 27%, T3 lung cancer in 19%, and debridement for radionecrosis and osteomyelitis in 19% of patients. Three to eight ribs were resected and additional sternum resection was performed in 39% of patients. RESULTS: There was no 30-day mortality. All patients were extubated after the operation without need for reintubation. Prosthesis dislocation occurred in 1 patient and infection in 2 patients during follow-up. Nineteen patients (73%) suffered no restrictions of daily activities. Clinical examination revealed normal shoulder girdle function in 77% of patients. There was no significant difference between preoperative and postoperative FEV1 (forced expiratory volume in 1 second) measurements in patients with lobectomy or wedge resections. Cinemagnetic resonance imaging revealed concordant chest wall movements during respiration in 92% of patients without paradoxical movements or implant dislocations being observed. CONCLUSIONS: Large defects of the anterolateral chest wall and sternum can be reconstructed efficiently with methylmethacrylate substitutes with minimal morbidity and excellent cosmetic and functional outcome.

The fou2 gain-of-function allele and the wild-type allele of Two Pore Channel 1 contribute to different extents or by different mechanisms to defense gene expression in Arabidopsis.

The fatty acid oxygenation up-regulated 2 (fou2) mutant in Arabidopsis thaliana creates a gain-of-function allele in a non-selective cation channel encoded by the Two Pore Channel 1 (TPC1) gene. This mutant genetically implicates cation fluxes in the control of the positive feedback loop whereby jasmonic acid (JA) stimulates its own synthesis. In this study we observed extensive transcriptome reprogramming in healthy fou2 leaves closely resembling that induced by treatment with methyl jasmonate, biotic stresses and the potassium starvation response. Proteomic analysis of fou2 leaves identified increased levels of seven biotic stress- and JA-inducible proteins. In agreement with these analyses, epistasis studies performed by crossing fou2 with aos indicated that elevated levels of JA in fou2 are the major determinant of the mutant phenotype. In addition, generation of fou2 aba1-5, fou2 etr1-1 and fou2 npr1-1 double mutants showed that the fou2 phenotype was only weakly affected by ABA levels and unaffected by mutations in NPR1 and ETR1. The results now suggest possible mechanisms whereby fou2 could induce JA synthesis/signaling early in the wound response. In contrast to fou2, transcriptome analysis of a loss-of-function allele of TPC1, tpc1-2, revealed no differential expression of JA biosynthesis genes in resting leaves. However, the analysis disclosed reduced mRNA levels of the pathogenesis-related genes PDF1.2a and THI2.1 in healthy and diseased tpc1-2 leaves. The results suggest that wild-type TPC1 contributes to their expression by mechanisms somewhat different from those affecting their expression in fou2.