Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome

Aberrant activation or inhibition of potassium (K+) currents across the plasma membrane of cells has been causally linked to altered neurotransmission, cardiac arrhythmias, endocrine dysfunction, and (more rarely) perturbed developmental processes. The K+ channel subfamily K member 4 (KCNK4), also known as TRAAK (TWIK-related arachidonic acid-stimulated K+ channel), belongs to the mechano-gated ion channels of the TRAAK/TREK subfamily of two-pore-domain (K2P) K+ channels. While K2P channels are well known to contribute to the resting membrane potential and cellular excitability, their involvement in pathophysiological processes remains largely uncharacterized. We report that de novo missense mutations in KCNK4 cause a recognizable syndrome with a distinctive facial gestalt, for which we propose the acronym FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth). Patch-clamp analyses documented a significant gain of function of the identified KCNK4 channel mutants basally and impaired sensitivity to mechanical stimulation and arachidonic acid. Co-expression experiments indicated a dominant behavior of the disease-causing mutations. Molecular dynamics simulations consistently indicated that mutations favor sealing of the lateral intramembrane fenestration that has been proposed to negatively control K+ flow by allowing lipid access to the central cavity of the channel. Overall, our findings illustrate the pleiotropic effect of dysregulated KCNK4 function and provide support to the hypothesis of a gating mechanism based on the lateral fenestrations of K2P channels

Chalcogenide Glass Optical Waveguides for Infrared Biosensing

Due to the remarkable properties of chalcogenide (Chg) glasses, Chg optical waveguides should play a significant role in the development of optical biosensors. This paper describes the fabrication and properties of chalcogenide fibres and planar waveguides. Using optical fibre transparent in the mid-infrared spectral range we have developed a biosensor that can collect information on whole metabolism alterations, rapidly and in situ. Thanks to this sensor it is possible to collect infrared spectra by remote spectroscopy, by simple contact with the sample. In this way, we tried to determine spectral modifications due, on the one hand, to cerebral metabolism alterations caused by a transient focal ischemia in the rat brain and, in the other hand, starvation in the mouse liver. We also applied a microdialysis method, a well known technique for in vivo brain metabolism studies, as reference. In the field of integrated microsensors, reactive ion etching was used to pattern rib waveguides between 2 and 300 μm wide. This technique was used to fabricate Y optical junctions for optical interconnections on chalcogenide amorphous films, which can potentially increase the sensitivity and stability of an optical micro-sensor. The first tests were also carried out to functionalise the Chg planar waveguides with the aim of using them as (bio)sensors

Zumbido e intolerância a sons : evidência e experiência de um grupo brasileiro

Introdução Zumbido e intolerância a sons são queixas frequentes e subjetivas que podem ter impacto na qualidade de vida do paciente. Objetivo Apresentar uma revisão dos principais pontos, inclusive conceitos, fisiopatologia, diagnóstico e abordagem do paciente com zumbido e sensibilidade a sons. Método Revisão da literatura com levantamento bibliográfico na base de dados da LILACS, SciELO, Pubmed e MEDLINE. Foram selecionados artigos e capítulos de livros sobre zumbido e sensibilidade a sons. Os diversos tópicos foram discutidos por um grupo de profissionais brasileiros e as conclusões, descritas. Resultado A prevalência de zumbido tem aumentado ao longo dos anos, muitas vezes associado a perda auditiva, fatores metabólicos e erros alimentares. A avaliação médica deve ser feita minuciosamente no sentido de orientar a solicitação de exames subsidiários. Os tratamentos disponíveis atualmente variam de medicamentos ao uso de sons com características específicas e técnicas de meditação, com resultados variáveis. Conclusão Foi apresentada uma revisão sobre os temas que permitindo ao leitor uma visão ampla da abordagem dos pacientes com zumbido e sensibilidade auditiva baseada em evidências científicas e experiência nacional.Introduction Tinnitus and sound intolerance are frequent and subjective complaints that may have an impact on a patient's quality of life. Objective To present a review of the salient points including concepts, pathophysiology, diagnosis and approach of the patient with tinnitus and sensitivity to sounds. Methods Literature review with bibliographic survey in LILACS, SciELO, Pubmed and MEDLINE database. Articles and book chapters on tinnitus and sound sensitivity were selected. The several topics were discussed by a group of Brazilian professionals and the conclusions were described. Results The prevalence of tinnitus has increased over the years, often associated with hearing loss, metabolic factors and inadequate diet. Medical evaluation should be performed carefully to guide the request of subsidiary exams. Currently available treatments range from medications to the use of sounds with specific characteristics and meditation techniques, with variable results. Conclusion A review on tinnitus and auditory sensitivity was presented, allowing the reader a broad view of the approach to these patients, based on scientific evidence and national experience

Jardins perchés néolithiques sur le Dhar Oualata (Mauritanie). Apport d’une méthode sédimentologique à une question d’archéologie africaine

L’existence d’espaces protégés interprétés sur le plan archéologique comme étant destinés à la culture se trouve confirmée par une approche sédimentologique. L’intérêt de cette dernière, fondée sur des témoins micropaléontologiques, est également de révéler l’origine même de leurs sols. Des prélèvements réalisés, d’une part, dans les sols conservés des enclos des villages néolithiques perchés sur la falaise de Khneivissa (Dhar Oualata, Hodh mauritanien) et, d’autre part, dans les dépôts lacustres de piémont, ont livré des cortèges microfauniques (ostracodes) identiques. Cette identité d’assemblages ne s’explique que par un apport anthropique de sédiments lacustres provenant du pied de la falaise afin de constituer un sol arable sur le relief de grès paléozoïque. Ces sols artificiels protégés de l’érosion éolienne par des murets de pierres sèches constituent un ensemble de jardins à proximité immédiate des concessions habitées par les villageois.The existence of protected spaces interpreted in the archaeological sphere like being intended for the cultivation is confirmed by a sedimentologic approach. The aim of this latter, based on micropalaeontological witness, is also to revelate the formation of these soils. Sedimentological samples from the pediment lake deposits and from the preserved soils of agglomerated compounds on the cliff edge of Khneivissa (Dhar Oualata, Hodh, Mauritania), have delivered identical microfaunic assemblages (ostracoda). This identity between ostracodic assemblages can only be explained by an anthropic dressing of lacustrine sediments from the cliff foot in order to constitute a cultivated soil on the edge of palaeozoic sandstone relief. These artificial soils protected from the wind erosion by dry-stone walls form a set of gardens in the immediate vicinity of village settlements

Tuner d'antenne pour terminaux 3G intégré en technologie CMOS SOI avancée

National audienc

Tuner d'antenne pour terminaux 3G intégré en technologie CMOS SOI avancée

National audienc

Surface plasmon resonance in chalcogenide glass-based optical system

International audienceThe surface plasmon resonance phenomenon has been studied in a chalcogenide glass-based optical system. IR transmission properties of these materials combined to their high refractive indices lead to advantageous properties for sensing. In this study, numerical simulations have been carried out to investigate the potentialities of sulfide glass from the GeGaSbS system as a coupling prism material. Then, an angular modulation SPR biosensor has been set up in the Kretschmann-Raether arrangement. Experimental data are consistent with numerical calculation and the detection limit of the sensor is 3 × 10−5 RIU. These preliminary results are promising. Further investigations have to be carried out to confirm the great potentialities of those materials for SPR-based biosensor

Stabilité de QTL et de composantes de résistance adulte du blé tendre à la rouille jaune.

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