Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

An analysis of naturally occurring radionuclides and Cs-137 in the soils of urban areas using gamma-ray spectrometry

This study of environmental radioactivity was carried out in the soils of an urban area. Naturally occurring gamma-emitting radionuclides and man-made Cs-137 were found in the soil profiles collected from four parks in the central Belgrade city area and the soil layer was examined every 10 cm and to a depth of 50 cm. Radioisotope activity concentrations (Bq kg(-1)) in the samples of urban soil using the gamma-ray spectrometry method were in the range of 14-46 for U-238, 33-50 for Ra-226, 29-63 for Pb-210, 1.2-3.4 for U-235, 28-50 for Th-232, 424-576 for K-40 and 0.7-35.8 for Cs-137. Some of the basic physicochemical soil properties (pH, organic matter content, calcium-carbonate content, particle size distribution) were determined to investigate the impact on the vertical distribution of radionuclides. The results of this investigation showed that variations of activity concentration ratios of radionuclides that belong to the same (U-238/Ra-226) or different radioactive series (Th-232/Ra-226; U-235/U-238), including Pb-210/Cs-137 ratios could well be explained by the properties of the soil. Alkaline pH reaction, the accumulation of organic matter in the uppermost and of carbonates in the deepest layers of urban soil had an effect on U-238/Ra-226, and Pb-210/Cs-137 activity concentration ratio values, while Th-232/Ra-226 and partially U-235/U-238 ratios were associated with the particle sizes vertical distribution. A study of radionuclides in the samples of leaves of two deciduous tree species common for these parks was also conducted and Pb-210 and K-40 were found concentrated in leaves rather than other investigated radionuclides

Radionuclides in the soil around the largest coal-fired power plant in Serbia: radiological hazard, relationship with soil characteristics and spatial distribution

Primordial radionuclides, U-238, Th-232 and K-40 were determined in soil samples collected at two depths (0-10 and 10-20 cm) in the vicinity of the largest coal-fired power plant in Serbia, and their spatial distribution was analysed using ordinary kriging. Mean values of activity concentrations for these depths were 50.7 Bq kg(-1) for U-238, 48.7 Bq kg(-1) for Th-232 and 560 Bq kg(-1) for K-40. Based on the measured activity concentrations, the radiological hazard due to naturally occurring radionuclides in soil was assessed. The value of the mean total absorbed dose rate was 76.3 nGy h(-1), which is higher than the world average. The annual effective dose due to these radionuclides ranged from 51.4 to 114.2 mu Sv. Applying cluster analysis, correlations between radionuclides and soil properties were determined. The distribution pattern of natural radionuclides in the environment surrounding the coal-fired power plant and their enrichment in soil at some sampling sites were in accordance with dispersion models of fly ash emissions. From the results obtained, it can be concluded that operation of the coal-fired power plant has no significant negative impact on the surrounding environment with regard to the content of natural radionuclides

Evaluation of virtual screening performance of support vector machines trained by sparsely distributed active compounds

10.1021/ci800022eJournal of Chemical Information and Modeling4861227-123