Changes in air quality in Mexico City, London and Delhi in response to various stages and levels of lockdowns and easing of restrictions during COVID-19 pandemic

The impacts of COVID-19 lockdown restrictions have provided a valuable global experiment into the extent of improvements in air quality possible with reductions in vehicle movements. Mexico City, London and Delhi all share the problem of air quality failing WHO guideline limits, each with unique situations and influencing factors. We determine, discuss and compare the air quality changes across these cities during the COVID-19, to understand how the findings may support future improvements in their air quality and associated health of citizens. We analysed ground-level PM10, PM2.5, NO2, O3 and CO changes in each city for the period 1st January to August 31, 2020 under different phases of lockdown, with respect to daily average concentrations over the same period for 2017 to 2019. We found major reductions in PM10, PM2.5, NO2 and CO across the three cities for the lockdown phases and increases in O3 in London and Mexico City but not Delhi. The differences were due to the O3 production criteria across the cities, for Delhi production depends on the VOC-limited photochemical regime. Levels of reductions were commensurate with the degree of lockdown. In Mexico City, the greatest reduction in measured concentration was in CO in the initial lockdown phase (40%), in London the greatest decrease was for NO2 in the later part of the lockdown (49%), and in Delhi the greatest decrease was in PM10, and PM2.5 in the initial lockdown phase (61% and 50%, respectively). Reduction in pollutant concentrations agreed with reductions in vehicle movements. In the initial lockdown phase vehicle movements reduced by up to 59% in Mexico City and 63% in London. The cities demonstrated a range of air quality changes in their differing geographical areas and land use types. Local meteorology and pollution events, such as forest fires, also impacted the results

Identification of De Novo Copy Number Variants Associated with Human Disorders of Sexual Development

Disorders of sexual development (DSD), ranging in severity from genital abnormalities to complete sex reversal, are among the most common human birth defects with incidence rates reaching almost 3%. Although causative alterations in key genes controlling gonad development have been identified, the majority of DSD cases remain unexplained. To improve the diagnosis, we screened 116 children born with idiopathic DSD using a clinically validated array-based comparative genomic hybridization platform. 8951 controls without urogenital defects were used to compare with our cohort of affected patients. Clinically relevant imbalances were found in 21.5% of the analyzed patients. Most anomalies (74.2%) evaded detection by the routinely ordered karyotype and were scattered across the genome in gene-enriched subtelomeric loci. Among these defects, confirmed de novo duplication and deletion events were noted on 1p36.33, 9p24.3 and 19q12-q13.11 for ambiguous genitalia, 10p14 and Xq28 for cryptorchidism and 12p13 and 16p11.2 for hypospadias. These variants were significantly associated with genitourinary defects (P = 6.08×10−12). The causality of defects observed in 5p15.3, 9p24.3, 22q12.1 and Xq28 was supported by the presence of overlapping chromosomal rearrangements in several unrelated patients. In addition to known gonad determining genes including SRY and DMRT1, novel candidate genes such as FGFR2, KANK1, ADCY2 and ZEB2 were encompassed. The identification of risk germline rearrangements for urogenital birth defects may impact diagnosis and genetic counseling and contribute to the elucidation of the molecular mechanisms underlying the pathogenesis of human sexual development

Differential Proteomic Analysis of Mammalian Tissues Using SILAM

Differential expression of proteins between tissues underlies organ-specific functions. Under certain pathological conditions, this may also lead to tissue vulnerability. Furthermore, post-translational modifications exist between different cell types and pathological conditions. We employed SILAM (Stable Isotope Labeling in Mammals) combined with mass spectrometry to quantify the proteome between mammalian tissues. Using 15N labeled rat tissue, we quantified 3742 phosphorylated peptides in nuclear extracts from liver and brain tissue. Analysis of the phosphorylation sites revealed tissue specific kinase motifs. Although these tissues are quite different in their composition and function, more than 500 protein identifications were common to both tissues. Specifically, we identified an up-regulation in the brain of the phosphoprotein, ZFHX1B, in which a genetic deletion causes the neurological disorder Mowat–Wilson syndrome. Finally, pathway analysis revealed distinct nuclear pathways enriched in each tissue. Our findings provide a valuable resource as a starting point for further understanding of tissue specific gene regulation and demonstrate SILAM as a useful strategy for the differential proteomic analysis of mammalian tissues