De Novo SOX4 variants cause a neurodevelopmental disease associated with mild dysmorphism

SOX4, together with SOX11 and SOX12, forms group C of SRY-related (SOX) transcription factors. They play key roles, often in redundancy, in multiple developmental pathways, including neurogenesis and skeletogenesis. De novo SOX11 heterozygous mutations have been shown to cause intellectual disability, growth deficiency, and dysmorphic features compatible with mild Coffin-Siris syndrome. Using trio-based exome sequencing, we here identify de novo SOX4 heterozygous missense variants in four children who share developmental delay, intellectual disability, and mild facial and digital morphological abnormalities. SOX4 is highly expressed in areas of active neurogenesis in human fetuses, and sox4 knockdown in Xenopus embryos diminishes brain and whole-body size. The SOX4 variants cluster in the highly conserved, SOX family-specific HMG domain, but each alters a different residue. In silico tools predict that each variant affects a distinct structural feature of this DNA-binding domain, and functional assays demonstrate that these SOX4 proteins carrying these variants are unable to bind DNA in vitro and transactivate SOX reporter genes in cultured cells. These variants are not found in the gnomAD database of individuals with presumably normal development, but 12 other SOX4 HMG-domain missense variants are recorded and all demonstrate partial to full activity in the reporter assay. Taken together, these findings point to specific SOX4 HMG-domain missense variants as the cause of a characteristic human neurodevelopmental disorder associated with mild facial and digital dysmorphism

Gas separations using ceramic membranes

Alcoa's commercial membrane with 40[Angstrom] pore diameter has been identified as one of the potential candidates for high temperature gas separations. This asymmetric multiple layer membrane have been well characterized and evaluated. It has excellent thermal stability and acceptably hydrothermal stability at [approximately]650[degree]C or above. Gas separations with this membrane follow Knudsen diffusion. Its selectivity is suitable for bulk separations, or for reduction/elimination of H[sub 2]S and NH[sub 3] via selective removal of hydrogen. An improved separation efficiency with this membrane is highly desirable for applications involving hydrogen separation, and the removal of trace contaminants, such as H[sub 2]S and NH[sub 3]. One of the effective avenues in improving the efficiency of the existing membrane is to narrow its pore size through surface modifications. Thus membranes with a smaller pore size can be readily available through minor modifications of the existing commercial product. In this paper focus is on the morphological characterization and performance evaluation of hydrogen-selective and zeolitic membranes developed from existing commercial membranes

Transmission pathways for the stem rust pathogen into Central and East Asia and the role of the alternate host, barberry

After many decades of effective control of stem rust caused by the Puccinia graminis f.sp. tritici, (hereafter Pgt) the reported emergence of race TTKSK/Ug99 of Pgt in Uganda reignited concerns about epidemics worldwide because similar to 90% of world wheat cultivars had no resistance to the new race. Since it was initially detected in Uganda in 1998, Ug99 variants have now been identified in thirteen countries in Africa and the Middle East. Stem rust has been a major problem in the past, and concern is increasing about the risk of return to Central and East Asia. Whilst control programs in North America and Europe relied on the use of resistant cultivars in combination with eradication of barberry (Berberis spp.), the alternate host required for the stem rust pathogen to complete its full lifecycle, the focus in East Asia was principally on the use of resistant wheat cultivars. Here, we investigate potential airborne transmission pathways for stem rust outbreaks in the Middle East to reach East Asia using an integrated modelling framework combining estimates of fungal spore deposition from an atmospheric dispersion model, environmental suitability for spore germination, and crop calendar information. We consider the role of mountain ranges in restricting transmission pathways, and we incorporate a representation of a generic barberry species into the lifecycle. We find viable transmission pathways to East Asia from the Middle East to the north via Central Asia and to the south via South Asia and that an initial infection in the Middle East could persist in East Asia for up to three years due to the presence of the alternate host. Our results indicate the need for further assessment of barberry species distributions in East Asia and appropriate methods for targeted surveillance and mitigation strategies should stem rust incidence increase in the Middle East region