Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

Purpose We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis

Fabrication de capteurs pyroelectriques comprenant une couche pyroelectrique mince necessitant une polarisation electrique

The method for group manufacturing of pyroelectric sensors by forming a thin pyroelectric layer on the upper side of a silicon wafer, where each sensor comprises several pixels (4) and each pixel is defined by an upper electrode (6) situated on the face side and a lower electrode on the rear side of the layer, includes the following steps: (a) The formation of electrical connections in the form of strip conductors (28,30) between the upper electrodes and a contact pad (32), and the formation of resistances (36) connected in series with the upper electrodes, as a protection against a short-circuit. (b) The electric polarization of the pyroelectric layer by applying a voltage between the contact pad (32) of upper electrodes and the lower electrodes. (c) The electrical insulation of upper and/or lower electrodes of one or more sensors by cutting the strip conductors (28) along dotted lines (44) and separating sensors, so that each pixel can deliver an elementary electrical signal. The lower electrodes are also in the form of proper electrodes that are mutually connected by strip conductors (24) and to a contact pad (26). The upper and lower electrical connections present intersections (40) when projected onto the plane of wafer, and the lower connections are laid out so that the intersections are between the electrodes and the resistances. The resistances and electrical connections are laid out on the thin layer substantially horizontal on the upper side of wafer. In the second embodiment, the first electrical connections are formed in part by strip conductors on the lower side of wafer and feedthroughs, and the resistances are associated at least in part at the level of feedthroughs. The sensors are formed each by a two-dimensional array of pixels. The contact pads (38) connect the electrodes to the resistances, and the pads are the contacts of pixels in functioning when the resistances are inactive. The values of resistances are substantially equal and define an impedance of pixels allowing a uniform deposition of an absorption layer of e.g. platinum black on the pixels by electrochemical method

Photoakustisches Gasmesssystem zur Bestimmung des Schwefeldioxidgehaltes in Schiffsabgasen

Ab dem Jahr 2020 gelten weltweit auf den Ozeanen strengere Grenzwerte für die Emission von SO2 in Schiffsabgasen. Diese können entweder über schwefelarmen Treibstoff oder durch den Einbau von Filteranlagen erreicht werden, wobei in letzteren der SO2-Ausstoß permanent gemessen werden muss. Wir präsentieren erste Feldtest-Messungen eines photoakustischen SO2-Messsystems, das seit August 2018 auf einem Schiff auf der Ostsee unterwegs ist

Photoacoustic gas detector for the monitoring of sulfur dioxide content in ship emissions

Ship emissions heavily pollute marine ecosystems and are extremely detrimental to the health of humans in harbour areas. From 2020 on, the International Maritime Organization (IMO) is imposing tighter limits on global sulphur emissions. Although shipping companies can continue using heavy fuel oils, they are then obligated by international maritime law to install gas scrubbers for the purification of the exhaust gas. In addition, special exhaust gas measuring technology must be installed subsequent to the gas scrubber to detect the actually emitted SO2. We present the development of a low-cost, resonant photoacoustic (PA) gas detector for the monitoring of SO2 in marine vessels. A UV LED at 285 nm is used as light source in combination with a microphone as acoustic detector. In first experiments, we used acetone gas as a substitution for the harmful SO2 for sensor characterization. The results of the experiments show that SO2 concentrations between 0 and 111 ppm should be detectable with 2 ppm accuracy

Resonant photoacoustic gas monitoring of combustion emissions

Since the entrance into the industrial era and the increasing demand for energy due to global economic growth and development, the amount of energy-related emissions have continuously grown every year to significantly high levels. Greenhouse gases like carbon dioxide, nitrous oxide or methane cause an increase in the earth’s temperature. Toxic gases like nitrous oxides, Sulphur dioxide and carbon monoxide are extremely detrimental to the health of all living beings. Over the past few years, global organizations are imposing tighter limits by international laws for flue-gas emissions from fossil-fuel combustion. Emission-limiting techniques like filter and scrubber systems have to be installed for waste gas treatment in the exhaust gas streams. In addition, exhaust gas measuring technologies detect the actual emission values of the respective target gases. We present the development of a low-cost and highly sensitive photoacoustic gas detector for the monitoring of emitted combustion gases. First tests were carried out with the toxic Sulphur dioxide (SO2) in secure lab conditions, where a sensitivity below 1 part per million (ppm) was achieved during continuous flow of the gas

Atividades de controle do dengue na visão de seus agentes e da população atendida, São José do Rio Preto, São Paulo, Brasil Dengue control as viewed by agents and the target population in São José do Rio Preto, São Paulo, Brazil

O objetivo foi identificar, no contexto da atuação dos agentes responsáveis pelo controle do dengue e na sua relação com moradores, situações vivenciadas no dia-a-dia de suas funções. Realizou-se estudo transversal com aplicação de questionários à população dos agentes de controle de vetores (ACV), à dos agentes comunitários de saúde (ACS) e a uma amostra de mulheres. As respostas dadas pelos agentes foram agrupadas nos âmbitos do trabalho, particular e coletivo. As mulheres foram abordadas sobre a relação mantida com os agentes. As dificuldades citadas nos âmbitos particular e trabalho pelos ACV diferiram das citadas pelos ACS. No coletivo foram coincidentes e mostraram que ambos não estão preparados para lidar com estas questões. Das mulheres entrevistadas, 87,0% afirmaram estar bem ou muito bem informadas sobre dengue, 84,0% afirmaram que os trabalhos dos agentes ajudam sempre e 54,0% apontaram como dificuldade o horário impróprio da visita realizada pelo agente. Identificou-se a necessidade de um novo profissional que reconheça e respeite as particularidades dos locais onde atua e desenvolva suas atividades de forma integrada às questões sócio-ambientais da comunidade.<br>The aim of this article was to identify daily situations experienced by dengue control agents in their relationship to local residents. A cross-sectional study applied questionnaires among vector control agents, community health workers, and a sample of local women. The answers by the dengue control agents and community health workers were grouped in the categories of work, private life, and community. The women were asked about the relationship with the vector control and community health workers. The difficulties cited in the private and work areas by the vector control agents were different from those reported by community health workers. At the community level they coincided and showed that neither group is adequately prepared to deal with these issues. Of the local women interviewed, 87.0% reported that they were well-informed or very well-informed about dengue, 84.0% stated that the work by the vector control agents and community health workers was always helpful, and 54.0% identified inappropriate visiting hours by vector control agents and community health workers as a difficulty. The study identified the need for a new job profile that would recognize and respect the specificities of the areas where their activities are conducted, integrating the community's socio-environmental issues

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

International audienc

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

PURPOSE: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. METHODS: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. RESULTS: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. CONCLUSION: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Accepted version (6 month embargo), submitted versio