Role of noggin as an upstream signal in the lack of neuronal derivatives found in the avian caudal-most neural crest

Neural crest cells (NCCs) arising from trunk neural tube (NT) during primary and secondary neurulation give rise to melanocytes, glia and neurons, except for those in the caudal-most region during secondary neurulation (somites 47 to 53 in the chick embryo), from which no neurons are formed, either in vivo or in vitro. To elucidate this discrepancy, we have specifically analyzed caudal-most NCC ontogeny. In this region, NCCs emerge at E5/HH26, one day after full cavitation of the NT and differentiation of flanking somites. The absence of neurons does not seem to result from a defect in NCC specification as all the usual markers, with the exception of Msx1, are expressed in the dorsal caudal-most NT as early as E4/HH24. However, Bmp4-Wnt1 signaling, which triggers trunk NCC delamination, is impaired in this region due to persistence of noggin (Nog) expression. Concomitantly, a spectacular pattern of apoptosis occurs in the NT dorsal moiety. Rostral transplantation of either the caudal-most somites or caudal-most NT reveals that the observed features of caudal-most NCCs relate to properties intrinsic to these cells. Furthermore, by forced Nog expression in the trunk NT, we can reproduce most of these particular features. Conversely, increased Bmp4-Wnt1 signaling through Nog inhibition in the caudal-most NT at E4/HH24 induces proneurogenic markers in migratory NCCs, suggesting that noggin plays a role in the lack of neurogenic potential characterizing the caudal-most NCCs.CNRS, UPMC, FCT and AFM. L.O. is a recipient of a grant from FCT (SFRH/BD/11858/2003) and from AR

Searching for a link between the magnetic nature and other observed properties of Herbig Ae/Be stars and stars with debris disks

Among the 21 Herbig Ae/Be stars studied, new detections of a magnetic field were achieved in six stars. For three Herbig Ae/Be stars, we confirm previous magnetic field detections. The largest longitudinal magnetic field, = -454+-42G, was detected in the Herbig Ae/Be star HD101412 using hydrogen lines. No field detection at a significance level of 3sigma was achieved in stars with debris disks. Our study does not indicate any correlation of the strength of the longitudinal magnetic field with disk orientation, disk geometry, or the presence of a companion. We also do not see any simple dependence on the mass-accretion rate. However, it is likely that the range of observed field values qualitatively supports the expectations from magnetospheric accretion models giving support for dipole-like field geometries. Both the magnetic field strength and the X-ray emission show hints for a decline with age in the range of ~2-14Myrs probed by our sample supporting a dynamo mechanism that decays with age. However, our study of rotation does not show any obvious trend of the strength of the longitudinal magnetic field with rotation period. Furthermore, the stars seem to obey the universal power-law relation between magnetic flux and X-ray luminosity established for the Sun and main-sequence active dwarf stars.Comment: 21 pages, 16 figures, 7 tables, accepted for publication in A&

Neural crest ontogeny during secondary neurulation: a gene expression pattern study in the chick embryo

In the prospective lumbo-sacral region of the chick embryo, neurulation is achieved by cavitation of the medullary cord, a process called secondary neurulation. Neural crest cells (NCC) are generated in this region and they give rise to the same types of derivatives as in more rostral parts of the trunk where neurulation occurs by dorsal fusion of the neural plate borders (primary neurulation). However, no molecular data were available concerning the different steps of their ontogeny. We thus performed a detailed expression study of molecular players likely to participate in the generation of secondary NCC in chick embryos between Hamburger and Hamilton stages 18-20 (HH18-20) at the level of somites 30 to 43. We found that specification of secondary NCC involves, as in primary neurulation, the activity of several transcription factors such as Pax3, Pax7, Snail2, FoxD3 and Sox9, which are all expressed in the dorsal secondary neural tube as soon as full cavitation is achieved. Moreover, once specification has occurred, emigration of NCC from the dorsal neuroepithelium starts facing early dissociating somites and involves a series of changes in cell shape and adhesion, as well as interactions with the extracellular matrix. Furthermore, Bmp4 and Wnt1 expression precedes the detection of migratory secondary NCC and is coincident with maturation of adjacent somites. Altogether, this first study of molecular aspects of secondary NCC ontogeny has revealed that the mechanisms of neural crest generation occurring along the trunk region of the chick embryo are generally conserved and independent of the type of neurulation involved.We are grateful to our colleagues for helpful discussions. We thank Dr Jean-Loup Duband for fibronectin and NC1 antibodies and Dr James Briscoe for Sox9 plasmid. This work has been supported by Centre National de la Recherche Scientifique (CNRS), University Paris 6 (UPMC), Fundacao para Ciencia e Tecnologia (FCT), Association Francaise contre les Myopathies (AFM). LO is a recipient of a grant from FCT (SFRH/BD/1185812003)

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease.

The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities

A Collaborative Patient-Carer Interface for Generating Home Based Rules for Self-Management

The wide spread prevalence of mobile devices, the decreasing costs of sensor technologies and increased levels of computational power have all lead to a new era in assistive technologies to support persons with Alzheimer’s disease. There is, however, still a requirement to improve the manner in which the technology is integrated into current approaches of care management. One of the key issues relating to this challenge is in providing solutions which can be managed by non-technically orientated healthcare professionals. Within the current work efforts have been made to develop and evaluate new tools with the ability to specify, in a non-technical manner, how the technology within the home environment should be monitored and under which conditions an alarm should be raised. The work has been conducted within the remit of a collaborative patient-carer system to support self-management for dementia. A visual interface has been developed and tested with 10 healthcare professionals. Results following a post evaluation of system usability have been presented and discussed.</p

A novel CISD2 mutation associated with a classical Wolfram syndrome phenotype alters Ca2+ homeostasis and ER-mitochondria interactions.

Wolfram syndrome (WS) is a progressive neurodegenerative disease characterized by early-onset optic atrophy and diabetes mellitus, which can be associated with more extensive central nervous system and endocrine complications. The majority of patients harbour pathogenic WFS1 mutations, but recessive mutations in a second gene, CISD2, have been described in a small number of families with Wolfram syndrome type 2 (WFS2). The defining diagnostic criteria for WFS2 also consist of optic atrophy and diabetes mellitus, but unlike WFS1, this phenotypic subgroup has been associated with peptic ulcer disease and an increased bleeding tendency. Here, we report on a novel homozygous CISD2 mutation (c.215A > G; p.Asn72Ser) in a Moroccan patient with an overlapping phenotype suggesting that Wolfram syndrome type 1 and type 2 form a continuous clinical spectrum with genetic heterogeneity. The present study provides strong evidence that this particular CISD2 mutation disturbs cellular Ca2+ homeostasis with enhanced Ca2+ flux from the ER to mitochondria and cytosolic Ca2+ abnormalities in patient-derived fibroblasts. This Ca2+ dysregulation was associated with increased ER-mitochondria contact, a swollen ER lumen and a hyperfused mitochondrial network in the absence of overt ER stress. Although there was no marked alteration in mitochondrial bioenergetics under basal conditions, culture of patient-derived fibroblasts in glucose-free galactose medium revealed a respiratory chain defect in complexes I and II, and a trend towards decreased ATP levels. Our results provide important novel insight into the potential disease mechanisms underlying the neurodegenerative consequences of CISD2 mutations and the subsequent development of multisystemic disease

Safety of tongue base procedures for sleep apnoea in adults: A systematic review and metanalysis from the YO-IFOS study group.

peer reviewed[en] OBJECTIVE: Tongue base and hypopharynx are the major sites of obstruction in OSA patients with failed palatal surgery. In recent years, several minimally invasive procedures have been developed to address tongue base obstruction. However, the research focus has consistently been on the effectiveness of surgery in reducing obstructive sleep apnoea rather than on postoperative complications. In this systematic review and metanalysis we aim to review the complication rate of minimally invasive base of tongue procedures for OSAS in adults. DATA SOURCES: PubMed (Medline), the Cochrane Library, EMBASE, Scopus, SciELO and Trip Database. REVIEW METHODS: Data sources were checked by three authors of the YO-IFOS sleep apnoea study group. Three authors extracted the data. Main outcome was expressed as the complication rate and 95% confidence interval for each surgical technique. RESULTS: 20 studies (542 patients) met the inclusion criteria. The mean complication rate is 12.79%; 4.65% for minor complications, 6.42% if they are moderate, and 1.77% if severe. The most reported complication overall is infection, in 1.95% of cases, followed by transient swallowing disorder, occurring in 1.30% of the total sample. CONCLUSION: The heterogeneity amongst the included studies prevents us from obtaining solid conclusions. The available evidence suggests that minimally invasive base of tongue procedures may present a wide spectrum of complication rates, ranging from 4.4% in tongue base radiofrequency to up to 42.42% in tongue base ablation

International Consensus Statement on the Radiological Evaluation of Dysraphic Malformations of the Spine and Spinal Cord

Dysraphic malformations of the spine and spinal cord (DMSSC) represent a spectrum of common congenital anomalies typically (though not exclusively) affecting the lower spinal segments. These may be responsible for varying degrees of neurologic, orthopedic, and urologic morbidity. With advances in neuroimaging, it is now possible to better diagnose and evaluate these disorders both prenatally and postnatally. Neuroimaging, performed at the right time and with technique optimization, is integral in guiding clinical management. However, the terminology used to describe these lesions has become increasingly confusing, and there is a lack of consensus regarding the essential radiologic features and their clinical weighting. This variability in radiologic practice risks unstructured decision making and increases the likelihood of suboptimal, less informed clinical management. In this manuscript, the first of a series of consensus statements, we outline a standardized international consensus statement for the radiologic evaluation of children with suspected DMSSC derived from a critical review of the literature, and the collective clinical experience of a multinational group of experts. We provide recommendations for plain radiography, sonography, CT, and MR imaging in the evaluation of DMSSC with an emphasis on technique of imaging and imaging protocols

The spinal and cerebral profile of adult spinal-muscular atrophy:A multimodal imaging study

Spinal muscular atrophy (SMA) type III and IV are autosomal recessive, slowly progressive lower motor neuron syndromes. Nevertheless, wider cerebral involvement has been consistently reported in mouse models. The objective of this study is the characterisation of spinal and cerebral pathology in adult forms of SMA using multimodal quantitative imaging. Methods: Twenty-five type III and IV adult SMA patients and 25 age-matched healthy controls were enrolled in a spinal cord and brain imaging study. Structural measures of grey and white matter involvement and diffusion parameters of white matter integrity were evaluated at each cervical spinal level. Whole-brain and region-of-interest analyses were also conducted in the brain to explore cortical thickness, grey matter density and tract-based white matter alterations. Results: In the spinal cord, considerable grey matter atrophy was detected between C2-C6 vertebral levels. In the brain, increased grey matter density was detected in motor and extra-motor regions of SMA patients. No white matter pathology was identified neither at brain and spinal level. Conclusions: Adult forms of SMA are associated with selective grey matter degeneration in the spinal cord with preserved white matter integrity. The observed increased grey matter density in the motor cortex may represent adaptive reorganisation.</p