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Rare disease gene association discovery in the 100,000 Genomes Project
Abstract Up to 80% of rare disease patients remain undiagnosed after genomic sequencing 1 , with many probably involving pathogenic variants in yet to be discovered disease–gene associations. To search for such associations, we developed a rare variant gene burden analytical framework for Mendelian diseases, and applied it to protein-coding variants from whole-genome sequencing of 34,851 cases and their family members recruited to the 100,000 Genomes Project 2 . A total of 141 new associations were identified, including five for which independent disease–gene evidence was recently published. Following in silico triaging and clinical expert review, 69 associations were prioritized, of which 30 could be linked to existing experimental evidence. The five associations with strongest overall genetic and experimental evidence were monogenic diabetes with the known β cell regulator 3,4 UNC13A , schizophrenia with GPR17 , epilepsy with RBFOX3 , Charcot–Marie–Tooth disease with ARPC3 and anterior segment ocular abnormalities with POMK . Further confirmation of these and other associations could lead to numerous diagnoses, highlighting the clinical impact of large-scale statistical approaches to rare disease–gene association discovery.
Breaking the Scaling Relationship for Oxygen Reduction Reaction Using Molecular Cobalt Complexes
Personalized contrast agent dosing to prevent contrast induced nephropathy in high risk populations in Guangdong, China
Asymmetric Total synthesis of Asperones A and B through Organocatalyzed Quinone [5 + 2] Cycloaddition
DFT insights into bandgap engineering of lead-free LiMCl3 (M = Mg, Be) halide perovskites for optoelectronic device applications
Abstract In this theoretical analysis, the pressure-dependent structural, electronic, mechanical, and optoelectronic properties of LiMCl3 (M = Mg, Be) have been calculated using density functional theory within the framework of the GGA PBE and hybrid HSE06 functional. At ambient pressure, the calculated lattice parameters of LiMCl3 match well with previously reported values, validating the accuracy of this study. Geometry optimization reveals that under increasing hydrostatic pressure, both the lattice parameters and the unit cell volume decrease. Additionally, the band structure exhibits notable phenomena over the pressure range from 0 to 100 GPa. For the LiMgCl3 compound, the bandgap decreases from an indirect bandgap of 4 eV to a direct bandgap of 2.563 eV. Similarly, LiBeCl3 shows an indirect bandgap that decreases from 2.388 eV to 0.096 eV over the pressure range from 0 to 100 GPa. The optical properties of LiMCl3, including absorption coefficient, reflectivity, refractive index, dielectric function, and conductivity, have been calculated throughout the study under varying pressure conditions. The analysis reveals that the optical properties of LiMCl3 (M = Be, Mg) enhance with increasing hydrostatic pressure, thereby rendering these materials more suitable for optoelectronic applications. To assess the stability of these compounds, elastic constants were analyzed, indicating that LiMCl3 exhibits ductile and anisotropic characteristics under different pressure conditions. These investigated materials are suitable for use in optoelectronic devices due to their favorable physical properties under different pressure circumstances.
Ideal Bifunctional Catalysis for Propane Dehydrogenation over Pt-Promoted Gallia-Alumina and Minimized Use of Precious Elements
Chemical signal diversity in male sand lizards (Lacerta agilis) along an urbanization gradient
Abstract Urban areas have globally expanded recently and will likely continue to do so in the near future. Although the impact of urbanization on acoustic and visual sexual signals has received considerable attention, other aspects, such as its influence on chemical signaling, remain poorly studied. Many lizard species possess femoral glands, i.e. prominent epidermal glands on the underside of the thighs producing a wide variety of compounds used in chemical signaling. Here we assessed the effect of urban, suburban and rural habitats and individual body condition on variation of chemical signal composition in the sand lizard (Lacerta agilis). By using gas chromatography coupled with mass spectrometry, we characterized chemical compounds present in secretions of lizard femoral glands. We found that lizards from suburban and urban habitats had the highest diversity of chemicals, while rural habitats showed significantly lower compound diversity. Lizards from urban and suburban habitats had high amounts of several compounds, including α-tocopherol, an antioxidant molecule that may counterbalance the damaging effects of irradiation on other pheromones. Chemical signals may not only depend on habitat characteristics but individual traits, such as body condition, may also affect chemical compound diversity. Body condition did not significantly differ across habitats, and we did not find an association between body condition and chemical composition of femoral gland secretions. We argue that environmental differences (more extreme in cities) as well as other factors such as increased stress may shape the amounts and diversity of semiochemicals in sand lizards. Our study provides insight on how environmental conditions imposed by urban–rural gradients may modulate chemical communication in vertebrates.