Report on the Fourth Excavation Season (2011) of the Madâ'in Sâlih Archaeological Project

This volume is the report on the results of the fourth excavation season of the Saudi-French Archaeological Project at Madâ'in Sâlih, ancient Hegra in the Nabataean kingdom, in north-west Saudi Arabia (MAEE, SCTA, CNRS, Univ Paris 1, IFPO). Apart from the results obtained in the different excavation areas (both in the residential area and in tomb IGN 117), the reader will find a study on the cairns/tumuli of the site (W. Abu-Azizeh) as well as intermediary reports on the geophysical detection (Chr. Benech), the fauna (J. Studer) and the pottery (C. Durand).Ce volume constitue le rapport sur les résultats de la quatrième campagne de fouilles de la mission archéologique franco-saoudienne de Madâ'in Sâlih, l'ancienne Hégra des Nabatéens, dans le nord-ouest de l'Arabie Saoudite (MAEE, SCTA, CNRS, Univ. Paris 1, IFPO). Outre les résultats obtenus dans les différents chantiers (dans la zone résidentielle et dans le tombeau IGN 117), le lecteur trouvera une étude synthétique sur les cairns/tumuli du site (W. Abu-Azizeh) ainsi que des rapports intermédiaires sur la détection géophysique (Chr. Benech), la faune (J. Studer) et la céramique (C. Durand)

Implementation of a standardized protocol to manage elderly patients with low energy pelvic fractures: can service improvement be expected?

Purpose: The incidence of low energy pelvic fractures (FPFs) in the elderly is increasing. Comorbidities, decreased bone-quality, problematic fracture fixation and poor compliance represent some of their specific difficulties. In the absence of uniform management, a standard operating procedure (SOP) was introduced to our unit, aiming to improve the quality of services provided to these patients. Methods: A cohort study was contacted to test the impact of (1) using a specific clinical algorithm and (2) using different antiosteoporotic drugs. Multivariate regression analysis was used to determine prognostic factors. Study endpoints were the time-to-healing, length-of-stay, return to pre-injury mobility, union status, mortality and complications. Results: A total of 132 elderly patients (≥65 years) admitted during the period 2012–2014 with FPFs were enrolled. High-energy fractures, acetabular fractures, associated trauma affecting mobility, pathological pelvic lesions and operated FPFs were used as exclusion criteria. The majority of included patients were females (108/132; 81.8%), and the mean age was 85.8 years (range 67–108). Use of antiosteoporotics was associated with a shorter time of healing (p = 0.036). Patients treated according to the algorithm showed a significant protection against malunion (p < 0.001). Also, adherence to the algorithm allowed more patients to return to their pre-injury mobility status (p = 0.039). Conclusions: The use of antiosteoporotic medication in elderly patients with fragility pelvic fractures was associated with faster healing, whilst the adherence to a structured clinical pathway led to less malunions and non-unions and return to pre-injury mobility state

Treatment results for hypopharyngeal cancer by different treatment strategies and its secondary primary- an experience in Taiwan

<p>Abstract</p> <p>Purpose</p> <p>The aim of this study was to evaluate treatment results in our hypopharyngeal cancer patients.</p> <p>Patients and Methods</p> <p>A total of three hundred and ninety five hypopharyngeal cancer patients received radical treatment at our hospital; 96% were male. The majority were habitual smokers (88%), alcohol drinkers (73%) and/or betel quid chewers (51%). All patients received a CT scan or MRI for tumor staging before treatment. The stage distribution was stage I: 2 (0.5%); stage II: 22 (5.6%); stage III: 57 (14.4%) and stage IV: 314 (79.5%). Radical surgery was used first in 81 patients (20.5%), and the remaining patients (79.5%) received organ preservation-intended treatment (OPIT). In the OPIT group, 46 patients received radiotherapy alone, 156 patients received chemotherapy followed by radiotherapy (CT/RT) and 112 patients received concomitant chemo-radiotherapy (CCRT).</p> <p>Results</p> <p>The five-year overall survival rates for stages I/II, III and IV were 49.5%, 47.4% and 18.6%, respectively. There was no significant difference in overall and disease-specific survival rates between patients who received radical surgery first and those who received OPIT. In the OPIT group, CCRT tended to preserve the larynx better (p = 0.088), with three-year larynx preservation rates of 44.8% for CCRT and 27.2% for CT/RT. Thirty-seven patients developed a second malignancy, with an annual incidence of 4.6%.</p> <p>Conclusions</p> <p>There was no survival difference between OPIT and radical surgery in hypopharyngeal cancer patients at our hospital. CCRT may offer better laryngeal preservation than RT alone or CT/RT. However, prospective studies are still needed to confirm this finding. Additionally, second primary cancers are another important issue for hypopharyngeal cancer management.</p

TMFoldRec: a statistical potential-based transmembrane protein fold recognition tool.

BACKGROUND: Transmembrane proteins (TMPs) are the key components of signal transduction, cell-cell adhesion and energy and material transport into and out from the cells. For the deep understanding of these processes, structure determination of transmembrane proteins is indispensable. However, due to technical difficulties, only a few transmembrane protein structures have been determined experimentally. Large-scale genomic sequencing provides increasing amounts of sequence information on the proteins and whole proteomes of living organisms resulting in the challenge of bioinformatics; how the structural information should be gained from a sequence. RESULTS: Here, we present a novel method, TMFoldRec, for fold prediction of membrane segments in transmembrane proteins. TMFoldRec based on statistical potentials was tested on a benchmark set containing 124 TMP chains from the PDBTM database. Using a 10-fold jackknife method, the native folds were correctly identified in 77 % of the cases. This accuracy overcomes the state-of-the-art methods. In addition, a key feature of TMFoldRec algorithm is the ability to estimate the reliability of the prediction and to decide with an accuracy of 70 %, whether the obtained, lowest energy structure is the native one. CONCLUSION: These results imply that the membrane embedded parts of TMPs dictate the TM structures rather than the soluble parts. Moreover, predictions with reliability scores make in this way our algorithm applicable for proteome-wide analyses. AVAILABILITY: The program is available upon request for academic use

The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala

In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medial ganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novel model of the neuronal composition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.This work was supported by Grants of the French National Research Agency (Agence Nationale de la Recherche; ANR) [ANR-13-BSV4-0011] and by the French Government through the ‘Investments for the Future’ LABEX SIGNALIFE [ANR-11-LABX-0028-01] to M.S., by the Spanish Government (BFU2007-60263 and BFU2010-17305) to A.F, and by the Medical Research Council (MR/K013750/1) to T.T. N.R.-R. is funded by a postdoctoral fellowship from the Ville de Nice, France (“Aide Individuelle aux Jeunes Chercheurs 2016”).Peer reviewe

MiR-10 Represses HoxB1a and HoxB3a in Zebrafish

BACKGROUND: The Hox genes are involved in patterning the anterior-posterior axis. In addition to the protein coding Hox genes, the miR-10, miR-196 and miR-615 families of microRNA genes are conserved within the vertebrate Hox clusters. The members of the miR-10 family are located at positions associated with Hox-4 paralogues. No function is yet known for this microRNA family but the genomic positions of its members suggest a role in anterior-posterior patterning. METHODOLOGY/PRINCIPAL FINDINGS: Using sensor constructs, overexpression and morpholino knockdown, we show in Zebrafish that miR-10 targets HoxB1a and HoxB3a and synergizes with HoxB4 in the repression of these target genes. Overexpression of miR-10 also induces specific phenotypes related to the loss of function of these targets. HoxB1a and HoxB3a have a dominant hindbrain expression domain anterior to that of miR-10 but overlap in a weaker expression domain in the spinal cord. In this latter domain, miR-10 knockdown results in upregulation of the target genes. In the case of a HoxB3a splice variant that includes miR-10c within its primary transcript, we show that the microRNA acts in an autoregulatory fashion. CONCLUSIONS/SIGNIFICANCE: We find that miR-10 acts to repress HoxB1a and HoxB3a within the spinal cord and show that this repression works cooperatively with HoxB4. As with the previously described interactions between miR-196 and HoxA7 and Hox-8 paralogues, the target genes are located in close proximity to the microRNA. We present a model in which we postulate a link between the clustering of Hox genes and post-transcriptional gene regulation. We speculate that the high density of transcription units and enhancers within the Hox clusters places constraints on the precision of the transcriptional control that can be achieved within these clusters and requires the involvement of post-transcriptional gene silencing to define functional domains of genes appropriately

Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.

Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit in autism, intellectual disability, Lennox Gastaut and West Syndromes. Here, we investigated several such mutations using a near-complete, hybrid 3D model of the human NMDAR and studied their consequences with kinetic modelling and electrophysiology. The mutants revealed reductions in glutamate potency; increased receptor desensitisation; and ablation of voltage-dependent Mg block. In addition, we provide new views on Mg and NMDA channel blocker binding sites. We demonstrate that these mutants have significant impact on excitatory transmission in developing neurons, revealing profound changes that could underlie their associated neurological disorders. Of note, the NMDAR channel mutant GluN2B unusually allowed Mg permeation, whereas nearby N615I reduced Ca permeability. By identifying the binding site for an NMDAR antagonist that is used in the clinic to rescue gain-of-function phenotypes, we show that drug binding may be modified by some GluN2B disease-causing mutations