Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein

To discover novel genes underlying amyotrophic lateral sclerosis (ALS), we aggregated exomes from 3,864 cases and 7,839 ancestry-matched controls. We observed a significant excess of rare protein-truncating variants among ALS cases, and these variants were concentrated in constrained genes. Through gene level analyses, we replicated known ALS genes including SOD1, NEK1 and FUS. We also observed multiple distinct protein-truncating variants in a highly constrained gene, DNAJC7. The signal in DNAJC7 exceeded genome-wide significance, and immunoblotting assays showed depletion of DNAJC7 protein in fibroblasts in a patient with ALS carrying the p.Arg156Ter variant. DNAJC7 encodes a member of the heat-shock protein family, HSP40, which, along with HSP70 proteins, facilitates protein homeostasis, including folding of newly synthesized polypeptides and clearance of degraded proteins. When these processes are not regulated, misfolding and accumulation of aberrant proteins can occur and lead to protein aggregation, which is a pathological hallmark of neurodegeneration. Our results highlight DNAJC7 as a novel gene for ALS

Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS

NanoPen: light-actuated patterning of nanoparticles

We introduce NanoPen, a novel technique for flexible, real-time reconfigurable, and large-scale light-actuated patterning of single or multiple nanoparticles such as metallic spherical nanoparticles, semiconducting and metallic nanowires, and carbon nanotubes

Beneficial and Detrimental Effects of UV on Aquatic Organisms: Implications of Spectral Variation

Solar ultraviolet radiation (UVR) may have beneficial as well as detrimental effects on living systems. For example, UV-B radiation (280¿320 nm) is generally damaging, while UV-A radiation (320¿400 nm) may cause damage or stimulate beneficial photorepair of UV-B damage. The nature of both direct and indirect effects of UVR in nature depends on both the photon flux density and the spectral composition of the radiation incident on aquatic organisms across environmental UVR gradients in space (depth, transparency, elevation) and time (diel, seasonal, interannual). Here we use the common and widespread freshwater cladoceran Daphnia pulicaria as a model organism to demonstrate the potential importance of these wavelength-specific effects of UVR to the ecology of aquatic organisms. UVR-exposure experiments are used to manipulate both natural solar and artificial UVR sources to examine the beneficial as well as detrimental effects of different wavelengths of UVR. Changes in the spectral composition of solar radiation are also examined along several natural environmental gradients including diel gradients, depth gradients, and dissolved organic carbon (DOC) gradients. The implications of variation in the spectral composition of UVR for aquatic organisms are discussed. The first biological weighting function (BWF) for a freshwater cladoceran is presented here. It demonstrates that the shortest UV-B wavelengths in sunlight are potentially the most damaging per photon. However, due to the greater photon flux density of longer wavelength UVR in sunlight, the net potential damage to Daphnia in nature is greatest for the longer wavelength UV-B and shorter wavelength UV-A radiation in the 305¿322 nm range. Overall the contribution of UV-B to the total mortality response of Daphnia exposed to full-spectrum solar radiation for 7 h on a sunny summer day is 64% while UV-A contributes 36%. The BWF for Daphnia is used with the transmission spectrum for Mylar D to demonstrate that Mylar D cuts out only about half of the damaging UVR in sunlight. Following exposure to damaging UV-B, Daphnia exhibits a dramatic increase in survival in the presence of longer wavelength UV-A and visible radiation due to the stimulation of photoenzymatic repair. We present data that demonstrate the importance of both atmospheric ozone and DOC in creating strong environmental gradients in the intensity (irradiance) and spectral composition of solar UVR in nature. The light-absorbing component of DOC, chromophoric dissolved organic matter (CDOM), is particularly important in creating depth refugia from damaging UV-B in freshwater ecosystems. CDOM may also cause intense variations in the ratio of potentially beneficial UV-A to detrimental UV-B radiation to which aquatic organisms are exposed. In addition to changes in atmospheric ozone, future changes in CDOM related to climate change or other environmental disturbances may substantially alter the underwater exposure of a variety of aquatic organisms to different wavelengths of solar UV

Combinaison de données multi-fréquence micro-ondes et optiques pour le suivi des cultures

[Departement_IRSTEA]GT [TR1_IRSTEA]GMA1-Fonctionnement hydrologique des bassins et des réseaux hydrographiquesInternational audienceThe potential for the combined use of microwave and optical data for farm management was explored based on images acquired in the visible, near-infrared, and thermal spectrum, and the synthetic aperture radar (SAR) wavelengths in the Ku (14.85 GHz) and C (5.3 GHz) bands. The images were obtained during June 1994, and covered an agricultural site composed of large fields of partial-cover cotton, near-full-cover alfalfa and bare soil fields of varying roughness. Results showed that the SAR Ku backscatter coefficient (Ku-band so) was sensitive to soil roughness and insensitive to soil moisture conditions when vegetation was present. When soil roughness conditions were relatively similar (e.g., for cotton fields of similar row direction and for all alfalfa fields), Ku-band so was sensitive to the fraction of the surface covered by vegetation. Under these conditions, the Ku-band so and the optical normalized difference vegetation index (NDVI) were generally correlated. The SAR C backscatter coefficient (C-band so) was found to be sensitive to soil moisture conditions for cotton fields with green leaf area index (GLAI) less than 1.0 and alfalfa fields with GLAI nearly 2.0. For both low-GLAI cotton and alfalfa, C-band so was correlated with measurements of surface temperature (Ts). A theoretical basis for the relations between Ku-band so and NDVI and between C-band so and Ts was presented, and supported with on-site measurements. Based on these findings, some combined optical/radar approaches were suggested for farm management applications.La possibilité de combiner des données de télédétection micro-ondes et optiques pour la suivi des cultures est étudié, en utilisant des images acquises dans le visible, le proche infrarouge, le thermique et dans les longueurs d'onde d'un SAR (radar à ouverture synthétique) dans les bandes Ku (14.85 GHz) et C (5.3 GHz). Les images ont été obtenues en juin 1994, et couvraient un site agricole composé de grandes parcelles de coton, luzerne et sol nu. Les résultats montrent que le coefficient de rétrodiffusion en bande Ku (Ku so) est sensible à la rugosité du sol et indépendant de l'humidité du sol en présence de végétation. Lorsque les conditions de rugosité du sol sont relativement similaires (p.ex. parcelles de coton dont les rangs sont orientés dans la même direction, parcelles de luzerne), Ku so est sensible au pourcentage de recouvrement de la végétation. Dans ces conditions, Ku so et l'indice de végétation NDVI sont en général corrélés. Le coefficient de rétrodiffusion en bande C (C so) est sensible aux conditions d'humidité du sol pour les parcelles de coton dont l'indice foliaire (GLAI) est inférieur à 1.0 et pour les parcelles de luzerne dont le GLAI est proche de 2 : dans les deux cas, C so est corrélé aux mesures de température de surface Ts. Une approche théorique des relations entre Ku so et NDVI, et entre C so et Ts est présentée, et validée par les mesures terrain. A partir de ces résultats, quelques approches combinant optique et radar sont proposées pour le suivi des cultures à l'échelle de l'exploitation