Genomic mosaicism arising from mosaic variants is a phenomenon that describes the presence of a cell or cell populations with different genome compositions from the germline cells of an individual. ...It comprises all types of genetic variants. A large proportion of childhood genetic disorders are defined as being de novo, meaning that the disease-causing mutations are only detected in the proband, not in any of the parents. Population studies show that 80% of the de novo mutations arise from the paternal haplotype, that is, from paternal sperm mosaicism. This review provides a summary of the types and detection strategies of sperm mosaicism. In addition, it provides discussions on how recent studies demonstrated that genomic mosaic mutations in parents, especially those in the paternal sperms, could be inherited by the offspring and cause childhood disorders. According to the previous findings of the author's research team, sperm mosaicism derived from early embryogenesis and primordial germ cell stages can exp
Abstract
Polyborylated organic compounds have been emerging as versatile building blocks in chemical synthesis. Here we report a selective cobalt-catalyzed deoxygenative 1,1,3-triborylation reaction ...of allylic ethers with pinacolborane to prepare 1,1,3-triborylalkane compounds. With naturally abundant and/or synthetic cinnamic methyl ethers as starting materials, we have achieved the synthesis of a variety of 1,1,3-triborylalkanes (25 examples). The synthetic utility of these 1,1,3-triborylalkanes is demonstrated through site-selective allylation, protodeborylation, and consecutive carbon-carbon bond-forming reactions. Mechanistic studies including deuterium-labeling and control experiments suggest that this 1,1,3-triborylation reaction proceeds through initial cobalt-catalyzed deoxygenative borylation of allylic ethers to form allylic boronates followed by cobalt-catalyzed 1,1-diborylation of the resulting allylic boronates.
Transient receptor potential vanilloid subtype 1 (TRPV1), a member of the transient receptor potential vanilloid (TRPV) channel family, is a nonselective cation channel that is widely expressed in ...sensory nerve fibers and nonneuronal cells, including certain vascular endothelial cells and smooth muscle cells. The activation of TRPV1 may be involved in the regulation of various physiological functions, such as the release of inflammatory mediators in the body, gastrointestinal motility function, and temperature regulation. In recent years, a large number of studies have revealed that TRPV1 plays an important role in the physiological and pathological conditions of the digestive system, cardiovascular system, and respiratory system, but there is no systematic report on TRPV1. The objective of this review is to explain the function and effects of TRPV1 on specific diseases, such as irritable bowel syndrome, hypertension, and asthma, and to further investigate the intrinsic relationship between the expression and function of TRPV1 in those diseases to find new therapeutic targets for the cure of related diseases.
The burgeoning development of railway construction in plateau regions of southwest China necessitates innovative and environmentally sustainable approaches, particularly in the realm of tunnel ...construction, where the transfer of muck poses significant operational and environmental challenges. This research, pivoting around the application and configuration of electric muck transfer equipment in plateau railway tunnels, seeks to dissect the potentialities and impediments of transitioning from conventional diesel-powered machinery to electric alternatives, with a spotlight on mitigating environmental impacts and enhancing operational efficiency. Through an analytical lens, the study employs a case study methodology, leveraging data and insights from existing electric equipment models and their applications, provided by major manufacturers in China, to weave a comprehensive narrative around the practicalities, specifications, and challenges embedded in the adoption of electric machinery in plateau environments. The findings unveil a nuanced landscape, where the environmental and operational advantages of electric equipment are juxtaposed against a backdrop of technological, financial, and infrastructural hurdles, thereby crafting a complex tapestry of opportunities and challenges. The research further extrapolates policy recommendations and practical guidelines, advocating for a harmonized amalgamation of governmental policies, technological advancements, and strategic planning to navigate through the identified challenges and optimize the integration of electric equipment in tunnel construction practices. Envisaging future research pathways, the study underscores the criticality of perpetuating technological innovations, policy adaptations, and interdisciplinary research to further refine and enhance the application of electric muck transfer equipment in plateau railway tunnel projects, thereby contributing to the broader narrative of sustainable construction practices in challenging terrains.
Cold temperatures can be detrimental to crop survival and productivity. Breeding progress can be improved by understanding the molecular basis of low temperature tolerance. We investigated the key ...routes and critical metabolites related to low temperature resistance in cold-tolerant and -sensitive common bean cultivars 120 and 093, respectively. Many potential genes and metabolites implicated in major metabolic pathways during the chilling stress response were identified through transcriptomics and metabolomics research. Under chilling stress, the expression of many genes involved in lipid, amino acid, and flavonoid metabolism, as well as metabolite accumulation increased in the two bean types. Malondialdehyde (MDA) content was lower in 120 than in 093. Regarding amino acid metabolism, 120 had a higher concentration of acidic amino acids than 093, whereas 093 had a higher concentration of basic amino acids. Methionine accumulation was clearly higher in 120 than in 093. In addition, 120 had a higher concentration of many types of flavonoids than 093. Flavonoids, methionine and malondialdehyde could be used as biomarkers of plant chilling injury. Transcriptome analysis of hormone metabolism revealed considerably greater, expression of abscisic acid (ABA), gibberellin (GA), and jasmonic acid (JA) in 093 than in 120 during chilling stress, indicating that hormone regulation modes in 093 and 120 were different. Thus, chilling stress tolerance is different between 093 and 120 possibly due to transcriptional and metabolic regulation.
Melatonin plays important roles in multiple stress responses; however, the downstream signaling pathway and molecular mechanism remain unclear. This study aimed to elucidate the transcriptional ...regulation of melatonin-induced salt stress tolerance in Phaseolus vulgaris L. and identify the key downstream transcription factors of melatonin through transcriptomic and metabolomic analyses. The melatonin-induced transcriptional network of hormones, transcription factors, and functional genes was established under both control and stress conditions. Among these, eight candidate transcription factors were identified via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, one gene related to transmembrane transport of salts (Phvul.004G177300). These genes may play a role in maintaining the cell structure and excreting sodium ions outside the cell or transporting them to the vacuoles for storage. Melatonin regulates the Phvul.009G210332 gene and metabolites C05642 (N-acetyl-N-2-formyl-5-methoxycanurine), C05643 (6-hydroxymelatonin), C05660 (5-methoxyindoleacetic acid) involved in tryptophan metabolism. The metabolites C05642 and C05643 were identified as decomposition products of tryptophan, indicating that exogenous melatonin entered the P. vulgaris tissue and was metabolized. Melatonin promotes the synthesis and metabolism of tryptophan, which is crucial to plant metabolism, growth, maintenance, and repair.
Germline mosaicisms could be inherited to offspring, which considered as "de novo" in most cases. Paternal germline MECP2 mosaicism has been reported in fathers of girls with Rett syndrome (RTT) ...previously. For further study, we focused on MECP2 germline mosaicism in males, not only RTT fathers.
Thirty-two fathers of RTT girls with MECP2 pathogenic mutations and twenty-five healthy adult males without history and family history of RTT or other genetic disorders were recruited. Sperm samples were collected and ten MECP2 hotspot mutations were detected by micro-droplet digital PCR (mDDPCR). And routine semen test was performed at the same time if the sample was sufficient. Additionally, blood samples were also detected for those with sperm MECP2 mosaicisms.
Nine fathers with RTT daughters (28.1%, 9/32) were found to have MECP2 mosaicism in their sperm samples, with the mutant allele fractions (MAFs) ranging from 0.05% to 7.55%. Only one father with MECP2 c.806delG germline mosaicism (MAF 7.55%) was found to have mosaicism in the blood sample, with the MAF was 0.28%. In the group of healthy adult males, MECP2 mosaicism was found in 7 sperm samples (28.0%, 7/25), with the MAFs ranging from 0.05% to 0.18%. None of the healthy adult males with MECP2 germline mosaicisms were found with MECP2 mosaicism in blood samples. There were no statistical differences in age, or the incidence of asthenospermia between fathers with RTT daughters and healthy adult males with MECP2 germline mosaicisms. Additionally, there was no linear correlation between MAFs of MECP2 mosaicisms and the age of males with germline MECP2 mosaicisms.
Germline MECP2 mosaicism could be found not only in fathers with RTT daughters but also in healthy adult males without family history of RTT. As germline mosaic mutations may be passed on to offspring which commonly known as "de novo", more attention should be paid to germline mosaicism, especially in families with a proband diagnosed with genetic disorders.
Pod color is a major economic trait of snap beans (
L.), among which the pod with a purple stripe is more attractive to people. A stable purple mutant with purple stripes on the pods was obtained by ...artificial mutagenesis with the high generation snap bean inbred line 'A18-1'. In order to reveal the genetic factors and pathways responsible for the purple appearance in snap bean, we performed transcriptome and metabolome analyses using the green stem and yellow pod cultivar 'A18-1' and its purple mutant '
' via
Co-γ radiation. Transcriptome analysis showed that three genes in the anthocyanin biosynthetic pathway were differentially expressed, among which the expression level of
(
) was increased in the mutant '
', while expression of
(
) and
(
) was downregulated. Anthocyanin-targeted metabonomics analysis showed significant differences in the contents of 10 metabolites between the wild type and mutant plants. Combined analysis of transcriptome and metabolomics showed that one differential metabolite, delphinidin, was related to the differential expression of
,
, and
. Based on the levels of six anthocyanins in wild type and mutant plants, we speculative that the purple appearance of the mutant '
' is caused by the increased expression of
(
), the key enzyme in the transformation from dihydroflavanol (DHK) to dihydromyricetone (DHM) in the anthocyanin biosynthetic pathway. The results lay a foundation for further studies on the molecular mechanism of anthocyanin synthesis in snap bean, and provide a framework for breeding different colors of snap bean.
The allele fraction (AF) distribution, occurrence rate, and evolutionary contribution of postzygotic single-nucleotide mosaicisms (pSNMs) remain largely unknown. In this study, we developed a ...mathematical model to describe the accumulation and AF drift of pSNMs during the development of multicellular organisms. By applying the model, we quantitatively analyzed two large-scale data sets of pSNMs identified from human genomes. We found that the postzygotic mutation rate per cell division during early embryogenesis, especially during the first cell division, was higher than the average mutation rate in either male or female gametes. We estimated that the stochastic cell death rate per cell cleavage during human embryogenesis was ∼5%, and parental pSNMs occurring during the first three cell divisions contributed to ∼10% of the de novo mutations observed in children. We further demonstrated that the genomic profiles of pSNMs could be used to measure the divergence distance between tissues. Our results highlight the importance of pSNMs in estimating recurrence risk and clarified the quantitative relationship between postzygotic and de novo mutations.
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