A common mechanism of defective channel trafficking underlying DFNA2 hearing loss result in different cell surface expression levels of KCNQ4 mutants

KCNQ4 mutations underlie DFNA2, a subtype of autosomal dominant hearing loss. We had previously identified the pore-region p.G296S mutation that impaired channel activity in two manners: it greatly reduced surface expression and abolished channel function. Moreover, G296S mutant exerted a strong dominant-negative effect on potassium currents by reducing the channel expression at the cell surface representing the first study to identify a trafficking-dependent dominant mechanism for the loss of KCNQ4 channel function in DFNA2. Here, we have investigated the pathogenic mechanism associated with all the described KCNQ4 mutations (F182L, W242X, E260K, D262V, L274H, W276S, L281S, G285C, G285S and G321S) that are located in different domains of the channel protein. F182L mutant showed a wild type-like cell-surface distribution in transiently transfected NIH3T3 fibroblasts and the recorded currents in Xenopus oocytes resembled those of the wild-type. The remaining KCNQ4 mutants abolished potassium currents, but displayed distinct levels of defective cell-surface expression in NIH3T3 as quantified by flow citometry. Co-localization studies revealed these mutants were retained in the ER, unless W242X, which showed a clear co-localization with Golgi apparatus. Interestingly, this mutation results in a truncated KCNQ4 protein at the S5 transmembrane domain, before the pore region, that escapes the protein quality control in the ER but does not reach the cell surface at normal levels. Currently we are investigating the trafficking behaviour and electrophysiological properties of several KCNQ4 truncated proteins artificially generated in order to identify specific motifs involved in channel retention/exportation. Altogether, our results indicate that a defect in KCNQ4 trafficking is the common mechanism underlying DFNA

Internal to external platform sedimentation with development of mud-mounds during Viséan from the central area of the Sierra de la Estrella (Carboniferous, Córdoba, Spain)

[ES] En la Sierra de la Estrella (Área del Guadiato, Córdoba) se localiza una sucesión del Viseense superior, principalmente carbonatada, con desarrollo de montículos tipo mud-mound. En esta zona predominan calizas bioclásticas, brechoideas y bioconstruidas, aunque también se localizan niveles de areniscas y conglomerados. Se han identificado un total de 7 litofacies que agrupan a su vez a 9 microfacies tipo: 1.–Mudstonewackestone con cavidades estromatactoideas y fábricas fenestrales, 2.–Wackestonepackstone con algas y bioclastos, 3.1.–Packstone de pseudopeloides, 3.2.–Packstone con algas, pseudopeloides y litoclastos, 4.1.–Packstone de briozoos y crinoideos, 4.2.–Packstone con algas y espículas, 5.–Packstone-rudstone de litoclastos, 6.–Grainstone de cortoides y litoclastos, 7.–Arenitas híbridas. El ambiente de sedimentación se interpreta como una zona de transición entre rampa interna y externa carbonática con influencia de terrígenos y desarrollo de montículos microbianos.[EN] Late Viséan calcareous rocks containing buildups occur in the Sierra de la Estrella, Guadiato Valley. Bioclastic, breccioid and biohermal limestones as well as sandstones and conglomerates occur. Lithofacies analysis allow to identify 7 types, with 9 characteristic microfacies: 1.–Micropeloidal mudstone-wackestone with stromatactoid cavities and fenestral fabrics, 2.–Algal-bioclastic wackestone-packstone, 3.1.–Pseudopeloidal packstone, 3.2.–Packstone with algae, pseudopeloids and lithoclast, 4.1.–Bryozoal-crinoidal packstone, 4.2.–Packstone with algae and sponge spiculae, 5.–Packstone-rudstone with lithoclasts, 6.–Cortoid-lithoclasts grainstone, 7.–Hybrid sandstones. Sediments are attributed to a inner to outer carbonate ramp with sporadic terrigenous influence. Some microbial mounds developed in such environment.Este trabajo se enmarca en el proyecto PB 96-0842 de la DGICYT.Peer reviewe

Optical Particle Detection in Liquid Suspensions with a Hybrid Integrated Microsystem

AbstractA compact, robust and portable system for optical particle detection in liquid suspensions, achieved through the hybrid integration of commercial components, such as VCSELs and microlenses, in a silicon micromachined structure is presented. We demonstrate the feasibility of fabricating a device providing up to 4 collimated laser beams, with the ability of detecting and distinguishing microparticles of several diameters, even in mixed suspensions. This optical microsystem represents an alternative design for microflow cytometers based on optical fibres, and is aligned with the current tendency set by the Point-of-care devices

Comparation of the new rebound tonometer IOPen and the Goldmann tonometer, and their relationship to corneal properties

Purpose To compare the intraocular pressures (IOPs) obtained with the IOPen rebound tonometer, Goldmann applanation tonometer (GAT) and the ocular response analyzer (ORA) and investigate the effects of corneal biomechanical properties on IOPen measurements. Methods A total of 198 normal eyes were included in this cross-sectional and randomized study. Three measurements were taken using IOPen. Agreement between tonometers was calculated using the Bland and Altman limits of agreement (LoA) analysis. Results The median IOPen IOP was 3mmHg below the GAT (Po0.001), 3mmHg below the ORA IOP similar to Goldmann (IOPg), and 3mmHg below the ORA IOP corrected using corneal parameters (IOPcc)(Po0.01). The LoA width between the IOPen and GAT IOPs varied between 13.92 (mean IOPen IOP) and 15.99mmHg (third IOPen measurement). The central corneal thickness (CCT) was unrelated to IOPen measurements (P40.05). Corneal hysteresis (CH) and corneal rigidity factor (CRF) were correlated with IOPen and GAT. Conclusions IOPen underestimated the IOP compared with GAT and ORA. The effect of measurement quality or measurement order on IOPen was low. CCT did not affect the IOPen, but the CH and CRF did. The LoA width between the IOPen and GAT IOPs was higher than between the ORA IOPg or ORA IOPcc and GAT IOPs

Identification and characterization of the Plasmodium vivax thrombospondin-related apical merozoite protein

Background. Malaria caused by Plasmodium vivax is a major public health problem worldwide that affects 70-80 million people in the Middle East, Asia, Western Pacific, South America and the Caribbean. Despite its epidemiological importance, few antigens from this parasite species have been characterized to date compared to Plasmodium falciparum, due in part to the difficulties of maintaining an in vitro culture of P. vivax. This study describes the identification of the P. falciparum thrombospondin-related apical merozoite protein homologue in P. vivax (PvTRAMP) and examines its potential to be further evaluated as vaccine candidate. Methods. The gene encoding PvTRAMP was identified through an extensive search of the databases hosting the genome sequence of P. vivax. Genes adjacent to pvtramp were identified in silico to determine the degree of similarity between the protein sequences encoded by equivalent chromosomic fragments in P. falciparum and Plasmodium knowlesi. The pvtramp gene was amplified from cDNA of P. vivax schizont stages, cloned and expressed in Escherichia coli. Anti-PvTRAMP antisera was obtained by inoculating rabbits with PvTRAMP B cell epitopes produced as synthetic peptides in order to assess its recognition in parasite lysates by Western blot and in intact parasites by indirect immunofluorescence. The recognition of recombinant PvTRAMP by sera from P. vivax-infected individuals living in endemic areas was also assessed by ELISA. Results. The PfTRAMP homologue in P. vivax, here denoted as PvTRAMP, is a 340-amino-acid long antigen encoded by a single exon that could have a potential role in cytoadherence, as indicated by the presence of a thrombospondin structural homology repeat (TSR) domain. According to its transcription and expression profile, PvTRAMP is initially located at the parasite's apical end and later on the parasite surface. Recombinant PvTRAMP is recognized by sera from infected patients, therefore, indicating that it is targeted by the immune system during a natural infection with P. vivax. Conclusions. The results of this work support conducting further studies with PvTRAMP to evaluate its immunogenicity and protection-inducing ability in the Aotus animal model. © 2010 Mongui et al; licensee BioMed Central Ltd

Identification and characterization of the Plasmodium vivax thrombospondin-related apical merozoite protein

<p>Abstract</p> <p>Background</p> <p>Malaria caused by <it>Plasmodium vivax </it>is a major public health problem worldwide that affects 70-80 million people in the Middle East, Asia, Western Pacific, South America and the Caribbean. Despite its epidemiological importance, few antigens from this parasite species have been characterized to date compared to <it>Plasmodium falciparum</it>, due in part to the difficulties of maintaining an <it>in vitro </it>culture of <it>P. vivax</it>. This study describes the identification of the <it>P. falciparum </it>thrombospondin-related apical merozoite protein homologue in <it>P. vivax </it>(PvTRAMP) and examines its potential to be further evaluated as vaccine candidate.</p> <p>Methods</p> <p>The gene encoding PvTRAMP was identified through an extensive search of the databases hosting the genome sequence of <it>P. vivax</it>. Genes adjacent to <it>pvtramp </it>were identified <it>in silico </it>to determine the degree of similarity between the protein sequences encoded by equivalent chromosomic fragments in <it>P. falciparum </it>and <it>Plasmodium knowlesi</it>. The <it>pvtramp </it>gene was amplified from cDNA of <it>P. vivax </it>schizont stages, cloned and expressed in <it>Escherichia coli</it>. Anti-PvTRAMP antisera was obtained by inoculating rabbits with PvTRAMP B cell epitopes produced as synthetic peptides in order to assess its recognition in parasite lysates by Western blot and in intact parasites by indirect immunofluorescence. The recognition of recombinant PvTRAMP by sera from <it>P. vivax-</it>infected individuals living in endemic areas was also assessed by ELISA.</p> <p>Results</p> <p>The PfTRAMP homologue in <it>P. vivax</it>, here denoted as PvTRAMP, is a 340-amino-acid long antigen encoded by a single exon that could have a potential role in cytoadherence, as indicated by the presence of a thrombospondin structural homology repeat (TSR) domain. According to its transcription and expression profile, PvTRAMP is initially located at the parasite's apical end and later on the parasite surface. Recombinant PvTRAMP is recognized by sera from infected patients, therefore, indicating that it is targeted by the immune system during a natural infection with <it>P. vivax.</it></p> <p>Conclusions</p> <p>The results of this work support conducting further studies with PvTRAMP to evaluate its immunogenicity and protection-inducing ability in the <it>Aotus </it>animal model.</p

Optimizing multidisciplinary scaled tests in terrestrial atmosphere for extraterrestrial unmanned aerial vehicle missions

Unmanned aerial vehicles are a valid tool for exploring celestial objects that have atmosphere. The design process of these vehicles includes numerical analysis phase, which is then followed by an experimental flight test campaign in order to validate and refine the design. In terrestrial conditions, it is impossible to use the full size prototype and recreate all the conditions of extraterrestrial flight. The only option is to use a scaled model maintaining certain similarity parameters to the prototype. This would, however, not reproduce the global multidisciplinary behavior in terrestrial conditions. Alternatively, relaxing similarity constraints enables reproducing the global multidisciplinary behavior but introduces known and measurable similarity differences. The objective of this study is to provide a methodology for designing a relaxed similarity scaled model for terrestrial multidisciplinary tests for any extraterrestrial unmanned aerial vehicle. The methodology is then applied to a case scenario in order to verify its validity

Detección de Chlamydia trachomatis, Mycoplasma hominis y Ureaplasma urealyticum en mujeres entre 18 a 50 años del Centro de Salud Básico de Wichub Huala en Guna Yala, en los meses de junio a octubre del año 2019

Chlamydia trachomatis, Mycoplasma hominis y Ureaplasma urealyticum colonizan, principalmente, el tracto genital y se han asociado a diversas enfermedades como: endometritis, corioamnionitis, ruptura prematura de membranas, muerte fetal, entre otras. Este estudio descriptivo de corte transversal tuvo como objetivo la detección de C. trachomatis, M. hominis y U.urealyticum en muestras endocervicales de mujeres entre 18 a 50 años atendidas en el Centro de Salud Básico de Wichub Huala de Guna Yala. Este centro también recibe pacientes de áreas aledañas de las islas de Nalunega, Corbisky y Mamitupu. Para la detección, se utilizaron los métodos de cultivo en Agar A8 y caldo B10, y reacción en cadena de la polimerasa (PCR).  A las participantes se les aplicó una encuesta para obtener información sobre factores de riesgo asociados a estas infecciones. Como resultado, se obtuvo un 10% de casos positivos distribuidos de la siguiente manera: 6% de U. urealyticum, 2% de M. hominis y 2% de C. trachomatis. Entre los casos positivos se observó que ninguna utilizaba métodos anticonceptivos de barrera, tienen bajo nivel de escolaridad, iniciaron su vida sexual a temprana edad y se encuentran entre los 30 y 45 años de edad

Detección de Chlamydia trachomatis, Mycoplasma hominis y Ureaplasma urealyticum en mujeres entre 18 a 50 años del Centro de Salud Básico de Wichub Huala en Guna Yala, en los meses de junio a octubre del año 2019

Chlamydia trachomatis, Mycoplasma hominis y Ureaplasma urealyticum colonizan, principalmente, el tracto genital y se han asociado a diversas enfermedades como: endometritis, corioamnionitis, ruptura prematura de membranas, muerte fetal, entre otras. Este estudio descriptivo de corte transversal tuvo como objetivo la detección de C. trachomatis, M. hominis y U.urealyticum en muestras endocervicales de mujeres entre 18 a 50 años atendidas en el Centro de Salud Básico de Wichub Huala de Guna Yala. Este centro también recibe pacientes de áreas aledañas de las islas de Nalunega, Corbisky y Mamitupu. Para la detección, se utilizaron los métodos de cultivo en Agar A8 y caldo B10, y reacción en cadena de la polimerasa (PCR).  A las participantes se les aplicó una encuesta para obtener información sobre factores de riesgo asociados a estas infecciones. Como resultado, se obtuvo un 10% de casos positivos distribuidos de la siguiente manera: 6% de U. urealyticum, 2% de M. hominis y 2% de C. trachomatis. Entre los casos positivos se observó que ninguna utilizaba métodos anticonceptivos de barrera, tienen bajo nivel de escolaridad, iniciaron su vida sexual a temprana edad y se encuentran entre los 30 y 45 años de edad