Snow is an efficient scavenger for the deposition of contaminants. Atmospheric transport and snow deposition jointly control the distribution of pollutants in remote mountain/polar regions. But can ...the contaminants contained within snow be used to reflect the interactions of air circulation patterns? The physicochemical properties of perfluoroalkyl substances (PFASs) are unique because of their high water solubilities. Taking advantage of this, 15 surface-snow and 3 snow-pit samples were collected across a vast area of western China (spanning 20° of latitude and 25° of longitude), to investigate the concentrations, composition profiles (fingerprints), and deposition fluxes of PFASs. Both a high concentration (3974 pg/L) and deposition flux (4.0 μg/m2/yr) for a total of 16 PFASs were found in the snow at Yulong, the most southern sample site, possibly because of its close proximity to source regions of pollutants in South Asia and high rate of snow deposition. Perfluorobutanoic acid was the most commonly found chemical in snow, but in general the PFAS composition in the snow of western China showed large spatial differences, with long-chain (C > 10) PFASs being relatively dominant in the north and west of the region and short-chain (C < 6) PFASs in the south and east. On the basis of the different compositions of PFASs in the snow of western China and the previously reported features of pollutant sources in Europe and India, we found that PFASs in snow can be used as an atmospheric tracer for tracking the interactions between westerly winds and the Indian Monsoon. The belt along 33°N is a key location where both the Indian Monsoon and westerly winds can arrive/interact; however, the contribution of the monsoon was found to be above 70%, while that of the westerly winds can be lower than 30%. The western part of the 33°N belt was found to be more vulnerable to the Indian Monsoon, and could be grouped into the monsoon domain, while the influence of the westerly winds increased from west to east along the belt. This finding is opposite to previous results, which reported that the western part of the 33°N belt was mainly under the influence of the westerly winds, and for the first time quantifies the relative contribution of westerly winds and the Indian Monsoon to the atmospheric transport of chemicals.
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•Perfluorobutanoic acid is the most commonly found chemical in snow from western China.•Long-chain PFASs are relatively dominant in north and short-chain PFASs in south.•PFASs in snow can be used as an atmospheric tracer.•The belt along 33–35°N is a key location where the Indian Monsoon interact with westerly winds.
Atmospheric wet deposition is an important process for the occurrence of perfluoroalkyl substances (PFASs) in polar/remote mountain regions; however, there are limited data on PFASs in precipitation ...from the Tibetan Plateau (TP). Precipitation (rain from May to October 2017) was therefore collected across the TP to investigate the concentrations, composition profiles, sources, and fluxes of perfluoroalkyl acids (PFAAs). The average ∑PFAA concentrations ranged from 212.3 pg L−1 to 547.7 pg L−1, and perfluoroalkyl carboxylic acids (PFCAs) accounted for 87% of the measured PFAAs (mean value). Significant positive associations (p < 0.05) were found for most PFCAs in the southeast TP, indicating that they may come from similar sources. The monthly PFAA deposition flux ranged from 12.6 to 68.9 ng m−2 month−1, decreasing from east to west. As climate of the eastern TP is controlled mainly by the Indian monsoon, indicating that the Indian monsoon plays an important role in delivering PFAAs to the TP. PCA (principal component analysis) combined with back-trajectory analysis was used to estimate the atmospheric transport pathways, and the PSCF (potential source contribution function) model was applied to define the potential source regions of individual PFAAs. The results suggested that northeast India, Bangladesh, and southern Nepal are the potential sources of C4–C7 PFCAs; C8–C10 PFCAs are more influenced by emissions from southern Nepal and Bhutan; while the source regions of long-chain PFCAs (C11–C12) can be attributed to northern India and Pakistan. Specifically, PFOS (perfluorooctane sulfonic acid) has a local contribution from the central TP.
•The mean PFAA concentrations are higher in the eastern Tibetan Plateau (TP).•The ∑PFAAs flux (12.6–68.9 ng m−2 month−1), decreasing from east to west of the TP.•South Asia offers the important sources of PFAAs on the TP, especially for PFCAs.•The Indian monsoon plays an important role in delivering PFAAs to the TP in summer.
This study aimed to analyze the polymorphism of the vasoactive intestinal peptide receptor-1 (VIPR-1) gene and its association with growth traits in quail using the PCR-RFLP and sequencing ...techniques. Genomic DNA was extracted from blood samples of 36 female Savimalt (SV) quails and 49 female French Giant (FG) quails. Growth traits were measured and used for VIPR-1 gene analysis, as body weight (BW), tibia length (TL), chest width (CW), chest depth (CD), sternum length (SL), body length (BL), and tibia circumference (TC). The results showed that 2 SNPs (BsrD I and HpyCH4 IV) were detected in exon 4 to 5 and exon 6 to 7 of the VIPR-1 gene, respectively. The results of association showed that the BsrD I site was not significantly associated with growth traits at 3 or 5 wk of age in the SV strain (P < 0.05), while the BsrD I site was significantly associated with BL at 3 or 5 wk of age in FG (P < 0.05). The HpyCH4 IV site was significantly associated with TL, CW, CD, SL, and BL at 3 wk of age in the SV strain (P < 0.05), while the HpyCH4 IV site was significantly correlated with BW, CW, SL, and BL at 5 wk of age in SV (P < 0.05). The HpyCH4 IV site was significantly associated with TL and TC at 3 wk of age in FG (P < 0.05), while the HpyCH4 IV site was significantly associated with TC at 5 wk of age in FG (P < 0.05). Four haplotype combinations based on 2 SNPs showed significantly association with BW, CW, CD, SL, BL, and TC at 3 or 5 wk of age in SV (P < 0.05). There was not significant association between 3 haplotype combinations with growth trait at 3 or 5 wk of age in FG (P > 0.05). In conclusion, the VIPR-1 gene could be used as a molecular genetic marker to improve growth traits in quail.
•Chemical weathering processes and intensities are explored in a cold glacial catchment.•Sulfide oxidation is the dominant source for solutes in the glacial runoff.•Carbonate dissolution controls ...hydrochemistry of streams in the non-glacial areas.•Glaciation enhanced chemical weathering in a cold glacier catchment.•Higher chemical weathering rates are caused by higher runoff and physical erosion.
The uplift of the Tibetan Plateau (TP) not only may enhance physical denudation and chemical weathering but also makes this area contain the largest glacier storage outside the polar regions. There is an argument on whether glaciation favours chemical weathering and carbon sequestration. To explore chemical weathering processes and intensities in the cold glacial region of the central TP, hydrochemistry of the river water in two catchments, i.e. the Qugaqiong and Qugaqie, was monitored from April to September 2018 with high-frequency sampling. These two catchments share similar geographical features except there are some cold glaciers in the upper reaches of the Qugaqie. The results of chemical composition show that the river water of the Qugaqie has a lower proportion of Ca2+ and HCO3− but higher SO42− and K++Na+ compared with the Qugaqiong. The seasonal variation of ionic concentration in the Qugaqie is significant but minor in the Qugaqiong. Those differences highlight the glacial impact in the Qugaqie compared with the non-glacierized Qugaqiong. Solutes in the glacial runoff of the Qugaqie mainly derive from sulfide oxidation. Its contribution to cations in the runoff of the Zhadang glacier and the Hanging glacier reaches 39% and 36%. The second most important contribution is carbonate dissolution (32% for both glacial runoffs). Silicate weathering provides fewer solutes and its contribution is only 20% and 11% in the two glacial runoffs, respectively. River water of the Qugaqiong shares similar hydrochemical characteristics with the non-glacial tributaries draining granodiorite/biotite adamellite in the Qugaqie. The contribution of sulfide oxidation to solutes in those rivers decreases to 10% while carbonate dissolution increases to 50%. Glacial comminution exposed trace sulfide minerals, thus made sulfide oxidation became pretty active due to this reaction is much faster than other mineral dissolution. The carbonate weathering rate (CWR) and silicate weathering rate (SWR) in the Qugaqie catchment are 9.7 t/km2/y and 6.7 t/km2/y. In comparison, values in the Qugaqiong catchment are 6.9 t/km2/y and 3.8 t/km2/y, respectively, which means CWR and SWR is 1.4 and 1.8 times higher in the Qugaqie catchment, respectively. Higher runoff and physical erosion rates are considered as the main reasons for higher chemical denudation rates in the Qugaqie catchment. The drainage system of the glaciers is dominated by the distributed pattern, which caused longer residences time of water, thus further promoted chemical weathering in the glacierized region. Our observation supports the idea that glaciation in the glacierized catchment of the central TP enhances chemical weathering, especially for SWR. Chemical denudation rates in the Qugaqie catchment remain at a moderate level compared with other glacierized catchments in the world and lithology and runoff are important factors to cause this spatial heterogeneity.
The role of host genetic factors in COVID-19 outcomes remains unclear despite various genome-wide association studies (GWAS). We annotate all significant variants and those variants in high LD (R2 > ...0.8) from the COVID-19 host genetics initiative (HGI) and identify risk genes by recognizing genes intolerant nonsynonymous mutations in coding regions and genes associated with cis-expression quantitative trait loci (cis-eQTL) in non-coding regions. These genes are enriched in the immune response pathway and viral life cycle. It has been found that host RNA binding proteins (RBPs) participate in different phases of the SARS-CoV-2 life cycle. We collect 503 RBPs that interact with SARS-CoV-2 RNA concluded from in vitro studies. Combining risk genes from the HGI with RBPs, we identify two COVID-19 risk loci that regulate the expression levels of FUBP1 and RAB2A in the lung. Due to the risk allele, COVID-19 patients show downregulation of FUBP1 and upregulation of RAB2A. Using single-cell RNA sequencing data, we show that FUBP1 and RAB2A are expressed in SARS-CoV-2-infected upper respiratory tract epithelial cells. We further identify NC_000001.11:g.77984833C>A and NC_000008.11:g.60559280T>C as functional variants by surveying allele-specific transcription factor sites and cis-regulatory elements and performing motif analysis. To sum up, our research, which associates human genetics with expression levels of RBPs, identifies FUBP1 and RAB2A as two risk genes for COVID-19 and reveals the anti-viral role of FUBP1 and the pro-viral role of RAB2A in the infection of SARS-CoV-2.
Insulin-like growth factor 1 receptor (IGF-1R) gene is the main effector of insulin-like growth factor (IGF), which plays an important role in growth, development and reproduction of the animal ...organism. This study aimed to investigate the association of IGF-1R gene single nucleotide polymorphisms (SNPs) with egg quality and carcass traits of quail by direct sequencing. In this study, genomic DNA was extracted from quail blood samples of 46 Chinese yellow (CY) quail, 49 Beijing white (BW) quail and 48 Korean (KO) quail strains. Egg quality and carcass traits were measured and used for IGF-1R gene analysis in 3 quail strains. The results showed that 2 SNPs (A57G and A72T) of the IGF-1R gene were detected in 3 quail strains. The A57G was significantly associated with yolk width (YWI) in BW strain (P < 0.05). Whereas A72T was significantly associated with egg shell thickness (EST) in BW strain (P < 0.05), and significantly associated with egg weight (EW), egg long (EL), and egg short (ES) in KO strain (P < 0.05). Haplotypes based on 2 SNPs showed significant effect on EST in 3 quail strains (P < 0.05), it also has a significant effect on EW in KO strain (P < 0.05). Meanwhile, A72T was significantly associated with liver weight (LW) and dressing percentage (DP) in 3 strains (P < 0.05). Haplotypes showed significant effect on LW (P < 0.05). Therefore, the IGF-1R gene may be a molecular genetic marker to improve egg quality and carcass traits in quails.
This study aimed to identify polymorphisms of gonadotropin-releasing hormone (GnRH) gene and their association with growth traits in quail by PCR and direct sequencing. Genomic DNA was extracted from ...quail blood samples of 36 from Savimalt (SV) and 49 from French Giant (FG). Growth traits were measured and used for candidate gene analysis, as body weight (BW), shank length (SL), chest width (CW), chest depth (CD), breastbone length (BBL), body length (BL), and shank circumference (SC). The results showed that a total of 20 SNPs were detected in GnRH gene, whereas 8 SNPs were significantly associated with growth traits (P < 0.05). The T215C, G279A, C458T, A520G, and C547G were significantly associated with SL at 3 wk of age in the FG strain, whereas A583T was significantly related to BBL and BL, and C591T was significantly related to SL, BBL, and BL, whereas A592G was significantly correlated with SL, CW, CD, BBL, and BL (P < 0.05). The 8 SNPs were significantly related to CW, CD, and BBL at 3 wk of age in the SV strain, whereas A583T, C591T, and A592G were significantly associated with BW (P < 0.05). The G279A showed significant correlations with SL at 5 wk of age in FG, whereas A583T showed significant associations with SC in FG, and C591T was significantly associated with BW and SC in FG, whereas A592T was significantly related to BW, SL, and CD in FG (P < 0.05). The T215C, G279A, C458T, A520G, and C547G were significantly correlated with BW, CW, BBL, and BL at 5 wk of age in SV, whereas A583T, C591T, and A592G were significantly related to BW, SL, CW, BBL, and BL (P < 0.05). Haplotypes based on 8 SNPs showed significant correlation with BW, SL, CW, CD, BBL, BL, and SC in FG (P < 0.05). In conclusion, the GnRH gene could be used as a molecular genetic marker to provide theoretical foundation to improve growth traits in quail.
Thyroid cancer is the most frequent malignancy of the endocrine system, of which papillary thyroid cancer (PTC) is the predominant form with a rapid increasing incidence worldwide. Rearranged during ...transfection (RET) fusions are common genetic drivers of PTC and the potent RET inhibitor selpercatinib has been recently approved for treating advanced or metastatic RET fusion-positive thyroid cancer. In this study we aimed to develop a droplet digital PCR (ddPCR) system to accurately detect RET fusion in PTC samples.
The frequency and distribution of RET fusions in PTC were analyzed using genomic data of 402 PTC patients in The Cancer Genome Atlas (TCGA) database. To establish the ddPCR system for detecting CCDC6::RET fusion, a plasmid containing CCDC6::RET infusion fragment was constructed as standard template, the annealing temperature and concentrations of primers and probe were optimized. The analytical performance of ddPCR and quantitative reverse transcription PCR (qRT-PCR) were assessed in standard templates and tissue samples from 112 PTC patients. Sanger sequencing was performed in all the RET fusion-positive samples identified by ddPCR.
RET fusions were observed in 25 (6.2%) of the 402 TCGA samples, and 15 (60%) of the RET fusion-positive patients had the CCDC6::RET fusion. Compared with qRT-PCR, the ddPCR method showed a lower limit of detection (128.0 and 430.7 copies/reaction for ddPCR and qRT-PCR, respectively). When applying the two methods to 112 tissue samples of PTC, eleven (9.8%) CCDC6::RET fusion-positive samples were detected by qRT-PCR, while ddPCR identified 4 additional positive samples (15/112, 13.4%). All the CCDC6::RET fusion-positive cases identified by ddPCR were confirmed by Sanger sequencing except for one case with 0.14 copies/uL of the fusion.
The accurate and sensitive ddPCR method reported here is powerful to detection CCDC6::RET fusion in PTC samples, application of this method would benefit more RET fusion-positive patients in the clinic.
Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic multisystem disease caused primarily by mutations in the PKD1 gene or PKD2 gene. There is increasing evidence that some of ...these variants, which are described as missense, synonymous or nonsense mutations in the literature or databases, may be deleterious by affecting the pre-mRNA splicing process.
This study aimed to determine the effect of these PKD1 and PKD2 variants on exon splicing combined with predictive bioinformatics tools and minigene assay. As a result, among the 19 candidate single nucleotide alterations, 11 variants distributed in PKD1 (c.7866C > A, c.7960A > G, c.7979A > T, c.7987C > T, c.11248C > G, c.11251C > T, c.11257C > G, c.11257C > T, c.11346C > T, and c.11393C > G) and PKD2 (c.1480G > T) were identified to result in exon skipping.
We confirmed that 11 variants in the gene of PKD1 and PKD2 affect normal splicing by interfering the recognition of classical splicing sites or by disrupting exon splicing enhancers and generating exon splicing silencers. This is the most comprehensive study to date on pre-mRNA splicing of exonic variants in ADPKD-associated disease-causing genes in consideration of the increasing number of identified variants in PKD1 and PKD2 gene in recent years. These results emphasize the significance of assessing the effect of exon single nucleotide variants in ADPKD at the mRNA level.
•GDC-0994 inhibits the growth of BRAF mutant cancer cells in vitro and in vivo.•GDC-0994 induces cell cycle arrest in BRAF mutation positive cancer cells.•GDC-0994 treatment affects the expressions ...of cell cycle-related genes.•BRAF mutation confers sensitivity to multiple ERK1/2 inhibitors.
BRAF or RAS mutation-induced aberrant activation of the mitogen-activated protein kinase (MAPK) pathway is frequently observed in human cancers. As the key downstream node of MAPK pathway, ERK1/2 is as an important therapeutic target. GDC-0994 (ravoxertinib), an orally bioavailable, highly selective small-molecule inhibitor of ERK1/2, showed acceptable safety and pharmacodynamic profile in a recent phase I clinical trial. In this study, we investigated dependence of the anti-tumor effect of ERK inhibitor GDC-0994 on genetic alterations in the MAPK pathway. The results showed that GDC-0994 sharply inhibited cell proliferation and colony formation and induced remarkable G1 phase cell-cycle arrest in cancer cells harboring BRAF mutation but had little effect on cell behaviors in most RAS mutant or wild-type cell lines. The expression of a large number of genes, particularly the genes in the cell cycle pathway, were significantly changed after GDC-0994 treatment in BRAF mutant cells, while no remarkable expression change of such genes was observed in wild-type cells. Moreover, GDC-0994 selectively inhibited tumor growth in a BRAF mutant xenograft mice model. Our findings demonstrate a BRAF mutation-dependent anti-tumor effect of GDC-0994 and provide a rational strategy for patient selection for ERK1/2 inhibitor treatment.
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