Genetic Landscape of Joubert syndrome in French Canadians

Le syndrome de Joubert est une maladie récessive caractérisée par une malformation congénitale distincte du tronc cérébral et du cervelet, associée à une anomalie des mouvements oculaires (apraxie oculomotrice), une respiration irrégulière, un retard de développement, et une ataxie à la démarche. Au cours de la dernière décennie, plus de 20 gènes responsables ont été identifiés, tous ayant un rôle important dans la structure et la fonction des cils primaires. Ainsi, le syndrome de Joubert est considéré une ciliopathie. Bien que le Syndrome de Joubert ait été décrit pour la première fois dans une famille canadienne-française en 1969, le(s) gène(s) causal demeurait inconnu dans presque tous les cas de syndrome de Joubert recensés en 2010 dans la population canadienne-française, soit début de mon projet doctoral. Nous avons identifié un total de 43 individus canadiens-français (35 familles) atteints du syndrome de Joubert. Il y avait un regroupement de familles dans la région du Bas-Saint-Laurent de la province de Québec, suggérant la présence d'un effet fondateur. L’objectif de ce projet était de caractériser la génétique du syndrome de Joubert dans la population canadienne-française. Notre hypothèse était qu’il existait un effet fondateur impliquant au moins un nouveau gène JBTS. Ainsi, dans un premier temps, nous avons utilisé une approche de cartographie par homozygotie. Cependant, nous n’avons pas identifié de région d’homozygotie partagée parmi les individus atteints, suggérant la présence d’une hétérogénéité génétique ou allélique. Nous avons donc utilisé le séquençage exomique chez nos patients, ce qui représente une approche plus puissante pour l’étude de conditions génétiquement hétérogènes. Nos travaux ont permis l’identification de deux nouveaux gènes responsables du syndrome de Joubert: C5orf42 et TMEM231. Bien que la localisation cellulaire et la fonction de C5orf42 soient inconnus au moment de cette découverte, nos résultats génétiques combinés avec des études ultérieures ont établi un rôle important de C5orf42 dans la structure et la fonction ciliaire, en particulier dans la zone de transition, qui est une zone de transition entre le cil et le reste de la cellule. TMEM231 avait déjà un rôle établi dans la zone de transition ciliaire et son interaction avec d’autres protéines impliquées dans le syndrome de Joubert était connu. Nos études ont également identifié des variants rares délétères chez un patient JBTS dans le gène ciliaire CEP104. Nous proposons donc CEP104 comme un gène candidat JBTS. Nous avons identifié des mutations causales dans 10 gènes, y compris des mutations dans CC2D2A dans 9 familles et NPHP1 dans 3 familles. Au total, nous avons identifié les mutations causales définitives chez 32 des 35 familles étudiées (91% des cas). Nous avons documenté un effet fondateur complexe dans la population canadienne-française avec de multiples mutations récurrentes dans quatre gènes différents (C5orf42, CC2D2A, TMEM231, NPHP1). Au début de ce projet de recherche, l’étiologie génétique était inconnue chez les 35 familles touchées du syndrome de Joubert. Maintenant, un diagnostique moléculaire définitif est identifié chez 32 familles, et probable chez les 3 autres. Nos travaux ont abouti à la caractérisation génétique du syndrome de Joubert dans la population canadienne-française grâce au séquençage exomique, et révèlent la présence d'un effet fondateur complexe avec une l'hétérogénéité allélique et intralocus importante. Ces découvertes ont éclairé la physiologie de cette maladie. Finalement, l’identification des gènes responsables ouvre de nouvelles perspectives diagnostiques ante-natales, et de conseils génétique, très précieuses pour les familles.

Toxina botulínica en manejo de síntomas del tracto urinario bajo en pacientes con hiperplasia prostática benigna - revisión sistemática de la literatura

Revisión sistemática de la literatura tomando ensayos clínicos aleatorizados sobre el uso de la inyección intraprostática de la toxina botulínica en los pacientes con hiperplasia prostática benigna evaluando una escala validada de síntomas del tracto urinario bajo como desenlace primario

Identification of Summer Origins of Songbirds Migrating through Southern Canada in Autumn

Stable hydrogen isotopes (δD) in flight feathers were measured to investigate the summer origins of five species of boreal-breeding warblers captured during fall migration at Canadian Migration Monitoring Network (CMMN) stations spread across southern Canada. Mean δD varied among stations and species within stations, but there was broad overlap in δD values. Although isotope ratios indicate that migrants at each station come from a wide range of latitudes, they are unable to provide much longitudinal discrimination. Band recoveries are sparse, but indicate that in general western Canadian warblers move southeast in fall, eastern birds move southwest, and there is a transition zone in the Great Lakes region. Combining knowledge of migratory direction with isotope results increases discrimination of breeding areas. Isotope results support fall migratory movements by Blackpoll Warbler (Dendroica striata) and Northern Waterthrush (Seiurus novaboracensis) that are more easterly than for other species, and in all study species, birds from more northern regions passed through southern Canada later in the season. Migration monitoring stations capture birds from broad areas of latitude, and migrants passing through each province appear to come from largely different portions of the Canadian breeding range, so a few stations placed in each province should suffice collectively to sample birds from most of the boreal forest. Migration monitoring in southern Canada, therefore, has the potential to monitor status of boreal forest birds in Canada that are unsampled by other monitoring programs.

The cumulus-capped boundary layer. II: Interface fluxes

This paper considers the relationship between the mean temperature and humidity profiles and the fluxes of heat and moisture at cloud base and the base of the inversion in the cumulus-capped boundary layer. The relationships derived are based on an approximate form of the scalar-flux budget and the scaling properties of the turbulent kinetic energy (TKE) budget. The scalar-flux budget gives a relationship between the change in the virtual potential temperature across either the cloud base transition zone or the inversion and the flux at the base of the layer. The scaling properties of the TKE budget lead to a relationship between the heat and moisture fluxes and the mean subsaturation through the liquid-water flux. The 'jump relation' for the virtual potential temperature at cloud base shows the close connection between the cumulus mass flux in the cumulus-capped boundary layer and the entrainment velocity in the dry-convective boundary layer. Gravity waves are shown to be an important feature of the inversion.

Experimental determination of layer cloud edge charging from cosmic ray ionisation

The cloud-air transition zone at stratiform cloud edges is an electrically active region where droplet charging has been predicted. Cloud edge droplet charging is expected from vertical flow of cosmic ray generated atmospheric ions in the global electric circuit. Experimental confirmation of stratiform cloud edge electrification is presented here, through charge and droplet measurements made within an extensive layer of supercooled stratiform cloud, using a specially designed electrostatic sensor. Negative space charge up to 35 pC m−3 was found in a thin (<100 m) layer at the lower cloud boundary associated with the clear air-cloud conductivity gradient, agreeing closely with space charge predicted from the measured droplet concentration using ion-aerosol theory. Such charge levels carried by droplets are sufficient to influence collision processes between cloud droplets.

Spectral invariant behavior of zenith radiance around cloud edges observed by ARM SWS

The ARM Shortwave Spectrometer (SWS) measures zenith radiance at 418 wavelengths between 350 and 2170 nm. Because of its 1-sec sampling resolution, the SWS provides a unique capability to study the transition zone between cloudy and clear sky areas. A spectral invariant behavior is found between ratios of zenith radiance spectra during the transition from cloudy to cloud-free. This behavior suggests that the spectral signature of the transition zone is a linear mixture between the two extremes (definitely cloudy and definitely clear). The weighting function of the linear mixture is a wavelength-independent characteristic of the transition zone. It is shown that the transition zone spectrum is fully determined by this function and zenith radiance spectra of clear and cloudy regions. An important result of these discoveries is that high temporal resolution radiance measurements in the clear-to-cloud transition zone can be well approximated by lower temporal resolution measurements plus linear interpolation.

A global picture of the seasonal persistence of stratospheric ozone anomalies

Interannual anomalies in vertical profiles of stratospheric ozone, in both equatorial and extratropical regions, have been shown to exhibit a strong seasonal persistence, namely, extended temporal autocorrelations during certain times of the calendar year. Here we investigate the relationship between this seasonal persistence of equatorial and extratropical ozone anomalies using the SAGE‐corrected SBUV data set, which provides a long‐term ozone profile time series. For the regions of the stratosphere where ozone is under purely dynamical or purely photochemical control, the seasonal persistence of equatorial and extratropical ozone anomalies arises from distinct mechanisms but preserves an anticorrelation between tropical and extratropical anomalies established during the winter period. In the 16–10 hPa layer, where ozone is controlled by both dynamical and photochemical processes, equatorial ozone anomalies exhibit a completely different behavior compared to ozone anomalies above and below in terms of variability, seasonal persistence, and especially the relationship between equatorial and extratropical ozone. Cross‐latitude‐time correlations show that for the 16–10 hPa layer, Northern Hemisphere (NH) extratropical ozone anomalies show the same variability as equatorial ozone anomalies but lagged by 3–6 months. High correlation coefficients are observed during the time frame of seasonal persistence of ozone anomalies, which is June– December for equatorial ozone and shifts by approximately 3–6 months when going from the equatorial region to NH extratropics. Thus in the transition zone between dynamical and photochemical control, equatorial ozone anomalies established in boreal summer/autumn are mirrored by NH extratropical ozone anomalies with a time lag similar to transport time scales. Equatorial ozone anomalies established in boreal winter/spring are likewise correlated with ozone anomalies in the Southern Hemisphere extratropics with a time lag comparable to transport time scales, similar to what is seen in the NH. However, the correlations between equatorial and SH extratropical ozone in the 10–16 hPa layer are weak.

Seasonal persistence of ozone and zonal wind anomalies in the equatorial stratosphere

Analysis of the variability of equatorial ozone profiles in the Satellite Aerosol and Gas Experiment‐corrected Solar Backscatter Ultraviolet data set demonstrates a strong seasonal persistence of interannual ozone anomalies, revealing a seasonal dependence to equatorial ozone variability. In the lower stratosphere (40–25 hPa) and in the upper stratosphere (6–4 hPa), ozone anomalies persist from approximately November until June of the following year, while ozone anomalies in the layer between 16 and 10 hPa persist from June to December. Analysis of zonal wind fields in the lower stratosphere and temperature fields in the upper stratosphere reveals a similar seasonal persistence of the zonal wind and temperature anomalies associated with the quasi‐biennial oscillation (QBO). Thus, the persistence of interannual ozone anomalies in the lower and upper equatorial stratosphere, which are mainly associated with the well‐known QBO ozone signal through the QBO-induced meridional circulation, is related to a newly identified seasonal persistence of the QBO itself. The upper stratospheric QBO ozone signal is argued to arise from a combination of QBO‐induced temperature and NOx perturbations, with the former dominating at 5 hPa and the latter at 10 hPa. Ozone anomalies in the transition zone between dynamical and photochemical control of ozone (16–10 hPa) are less influenced by the QBO signal and show a quite different seasonal persistence compared to the regions above and below.

Lightning-induced extensive charge sheets provide long range electrostatic thunderstorm detection

By combining electrostatic measurements of lightning-induced electrostatic field changes with radio frequency lightning location, some field changes from exceptionally distant lightning events are apparent which are inconsistent with the usual inverse cube of distance. Furthermore, by using two measurement sites, a transition zone can be identified beyond which the electric field response reverses polarity. For these severe lightning events, we infer a horizontally extensive charge sheet above a thunderstorm, consistent with a mesospheric halo of several hundred kilometers’ extent.

Geophysical characterization of the complex dynamics of groundwater and seawater exchange in a highly stressed aquifer system linked to a coastal lagoon (SE Spain)

Anthropogenic pressure influences the two-way interactions between shallow aquifers and coastal lagoons. Aquifer overexploitation may lead to seawater intrusion, and aquifer recharge from rainfall plus irrigation may, in turn, increase the groundwater discharge into the lagoon. We analyse the evolution, since the 1950s up to the present, of the interactions between the Campo de Cartagena Quaternary aquifer and the Mar Menor coastal lagoon (SE Spain). This is a very heterogeneous and anisotropic detrital aquifer, where aquifer–lagoon interface has a very irregular geometry. Using electrical resistivity tomography, we clearly identified the freshwater–saltwater transition zone and detected areas affected by seawater intrusion. Severity of the intrusion was spatially variable and significantly related to the density of irrigation wells in 1950s–1960s, suggesting the role of groundwater overexploitation. We distinguish two different mechanisms by which water from the sea invades the land: (a) horizontal advance of the interface due to a wide exploitation area and (b) vertical rise (upconing) caused by local intensive pumping. In general, shallow parts of the geophysical profiles show higher electrical resistivity associated with freshwater mainly coming from irrigation return flows, with water resources mostly from deep confined aquifers and imported from Tagus river, 400 km north. This indicates a likely reversal of the former seawater intrusion process.

Fracture and fatigue of natural fiber-reinforced cementitious composites

This paper presents the results of an experimental study of resistance-curve behavior and fatigue crack growth in cementitious matrices reinforced with eco-friendly natural fibers obtained from agricultural by-products. The composites include: blast furnace slag cement reinforced with pulped fibers of sisal, banana and bleached eucalyptus pulp, and ordinary Portland cement composites reinforced with bleached eucalyptus pulp. Fracture resistance (R-curve) and fatigue crack growth behavior were studied using single-edge notched bend specimens. The observed stable crack growth behavior was then related to crack/microstructure interactions that were elucidated via scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Fracture mechanics models were used to quantify the observed crack-tip shielding due to crack-bridging. The implications of the results are also discussed for the design of natural fiber-reinforced composite materials for affordable housing. (C) 2009 Elsevier Ltd. All rights reserved.

Interfacial interactions in concretes with silica fume and SBR latex

This paper deals with the effect of silica fume and styrene-butadiene latex (SBR) on the microstructure of the interfacial transition zone (ITZ) between Portland cement paste and aggregates (basalt). Scanning electron microscope (SEM) equipped with energy dispersive X-ray analysis system (EDX) was used to determine the ITZ thickness. In the plain concrete a marked ITZ around the aggregate particles (55 mu m) was observed, while in concretes with silica fume or latex SBR the ITZ was less pronounced (35-40 mu m). However, better results were observed in concretes with silica fume and latex SBR (20-25 mu m). (C) 2008 Elsevier Ltd. All rights reserved.

Upper-mantle seismic anisotropy from SKS splitting in the South American stable platform: A test of asthenospheric flow models beneath the lithosphere

Upper-mantle seismic anisotropy has been extensively used to infer both present and past deformation processes at lithospheric and asthenospheric depths. Analysis of shear-wave splitting (mainly from core-refracted SKS phases) provides information regarding upper-mantle anisotropy. We present average measurements of fast-polarization directions at 21 new sites in poorly sampled regions of intra-plate South America, such as northern and northeastern Brazil. Despite sparse data coverage for the South American stable platform, consistent orientations are observed over hundreds of kilometers. Over most of the continent, the fast-polarization direction tends to be close to the absolute plate motion direction given by the hotspot reference model HS3-NUVEL-1A. A previous global comparison of the SKS fast-polarization directions with flow models of the upper mantle showed relatively poor correlation on the continents, which was interpreted as evidence for a large contribution of ""frozen"" anisotropy in the lithosphere. For the South American plate, our data indicate that one of the reasons for the poor correlation may have been the relatively coarse model of lithospheric thicknesses. We suggest that improved models of upper-mantle flow that are based on more detailed lithospheric thicknesses in South America may help to explain most of the observed anisotropy patterns.

Extrativismo em área de reserva da biosfera da Mata Atlântica no Rio Grande do Sul : um estudo etnobiológico em Maquiné

As frondes de Rumohra adiantiformis (G.Forest.) Ching, conhecida como “leatherleaf”, “seven-weeks-fern” ou samambaia-preta, são usadas mundialmente em arranjos florais. Na África do Sul e Brasil o comércio da espécie é baseado no extrativismo. No Brasil a coleta é realizada em áreas de Mata Atlântica, sendo que 50% da produção provém das áreas de capoeira das encostas da Serra Geral no Rio Grande do Sul (RS). Atualmente, cerca de 2.000 famílias de agricultores familiares vivem nestas áreas, tendo no extrativismo sua principal fonte de renda. No entanto no RS a coleta, o comércio e o transporte de plantas ornamentais nativas são proibidos, já que nesta zona de transição da Reserva da Biosfera da Mata Atlântica (Maquiné, RS) há grandes restrições quanto à exploração dos recursos naturais. O êxodo rural e o próprio extrativismo estabelecido a partir da década de 70, permitiram a regeneração da Floresta Ombrófila Densa. Como a espécie é característica de estágios sucessionais iniciais, a regeneração florestal está levando à diminuição dos estoques naturais. Este trabalho se propôs a identificar alternativas econômicas para diversificação da economia de famílias de extrativistas, no intuito de minimizar a tensão associada à diminuição dos estoques naturais de samambaia-preta, às dificuldades no manejo da terra e à legislação ambiental. Junto à comunidade extrativista do distrito de Solidão (Maquiné) foram coletados dados etnobiológicos sobre plantas medicinais e plantas relacionadas ao artesanato. As principais espécies identificadas foram: Bambusa tuldoides (taquareira, colmo), Clytostoma sciuripabulum (cipó-branco, caule), Cyperus prolixus (tiririca, partes aéreas), Musa acuminata (bananeira, palha), Scirpus californicus (junco, partes aéreas), Typha dominguensis (taboa, partes aéreas), sendo que Macfadyena dentata (cipó-unha-de-gato, caule), Roupala brasiliensis (carvalho-brasileiro, folhas) e Tillandsia usneoides (barbade- pau, planta inteira) são as espécies prioritárias para a avaliação da sustentabilidade do extrativismo. Os dados etnobiológicos e ecológicos mostram que é possível estabelecer o manejo sustentável da R. adiantiformis. Os maiores entraves para o estabelecimento do manejo sustentado para as espécies identificadas incluem: a) estabelecer as bases de manejo sustentável destas espécies; b) compatibilizar esta atividade extrativista com o atual Código Florestal Estadual. Plantas medicinais não parecem ser uma alternativa viável a curto prazo, enquanto o artesanato requer a adequação da atividade artesanal no meio rural com os direitos à aposentadoria rural.