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1.
Sci Bull (Beijing) ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38702277

ABSTRACT

Heparan sulfate proteoglycan 2 (HSPG2) gene encodes the matrix protein Perlecan, and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects (NTDs). We discovered rare genetic variants of HSPG2 in 10% cases compared to only 4% in controls among a cohort of 369 NTDs. Endorepellin, a peptide cleaved from the domain V of Perlecan, is known to promote angiogenesis and autophagy in endothelial cells. The roles of enderepellin in neurodevelopment remain unclear so far. Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the neuroepithelia receptor neurexin in vivo. Through the endocytic pathway, the interaction of endorepellin and neurexin physiologically triggers autophagy and appropriately modulates the differentiation of neural stem cells into neurons as a blocker, which is necessary for normal neural tube closure. We created knock-in (KI) mouse models with human-derived HSPG2 variants, using sperm-like stem cells that had been genetically edited by CRISPR/Cas9. We realized that any HSPG2 variants that affected the function of endorepellin were considered pathogenic causal variants for human NTDs given that the severe NTD phenotypes exhibited by these KI embryos occurred in a significantly higher response frequency compared to wildtype embryos. Our study provides a paradigm for effectively confirming pathogenic mutations in other genetic diseases. Furthermore, we demonstrated that using autophagy inhibitors at a cellular level can repress neuronal differentiation. Therefore, autophagy agonists may prevent NTDs resulting from failed autophagy maintenance and neuronal over-differentiation caused by deleterious endorepellin variants.

2.
Forensic Sci Res ; 9(2): owad052, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38765700

ABSTRACT

Insertion/Deletion (InDel) polymorphisms, characterized by their smaller amplicons, reduced mutation rates, and compatibility with the prevalent capillary electrophoresis (CE) platforms in forensic laboratories, significantly contribute to the advancement and application of genetic analysis. Guizhou province in China serves as an important region for investigating the genetic structure, ethnic group origins, and human evolution. However, DNA data and the sampling of present-day populations are lacking, especially about the InDel markers. Here, we reported data on 47 autosomal InDels from 592 individuals from four populations in Guizhou (Han, Dong, Yi, and Chuanqing). Genotyping was performed with the AGCU InDel 50 kit to evaluate their utility for forensic purposes and to explore the population genetic structure. Our findings showed no significant deviations from Hardy-Weinberg and linkage equilibriums. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) for each population demonstrated that the kit could be applied to forensic individual identification and was an effective supplement for parentage testing. Genetic structure analyses, including principal component analysis, multidimensional scaling, genetic distance calculation, STRUCTURE, and phylogenetic analysis, highlighted that the genetic proximity of the studied populations correlates with linguistic, geographical, and cultural factors. The observed genetic variances within four research populations were less pronounced than those discerned between populations across different regions. Notably, the Guizhou Han, Dong, and Chuanqing populations showed closer genetic affiliations with linguistically similar groups than the Guizhou Yi. These results underscore the potential of InDel markers in forensic science and provide insights into the genetic landscape and human evolution in multi-ethnic regions like Guizhou. Key points: InDel markers show promise for forensic individual identification and parentage testing via the AGCU InDel 50 kit.Genetic analysis of Guizhou populations reveals correlations with linguistic, geographical, and cultural factors.Guizhou Han, Dong, and Chuanqing populations showed closer genetic affiliations with linguistically similar groups than the Guizhou Yi.

3.
Sci Total Environ ; 930: 172034, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38657806

ABSTRACT

Due to their assembly properties and variable molecular weights, the potential biological toxicity effects of macromolecular organic ligand heavy metal complexes are more difficult to predict and their mechanisms are more complex. This study unraveled the toxicity response and metabolic compensation mechanism of tannic acid-Cr(III) (TA-Cr(III)) complex on alga Raphidocelis subcapitata using multi-omics approaches. Results showed TA-Cr(III) complex caused oxidative damage and photosystem disruption, destroying the cell morphology and inhibiting algal growth by >80 % at high exposure levels. TA-Cr(III) complex stress down-regulated proteins linked to proliferation, photosynthesis and antioxidation while upregulating carbon fixation, TCA cycle and amino acid metabolism. The increase of fumarate, citrate, isocitrate and semialdehyde succinate was validated by metabolomics analysis, which improved the TCA cycle, amino acid metabolism and carbon fixation. Activation of the above cellular processes somewhat compensated for the inhibition of algal photosynthesis by TA-Cr(III) complex exposure. In conclusion, physiological toxicity coupled with downstream metabolic compensation in response to Cr(III) complex of macromolecular was characterized in Raphidocelis subcapitata, unveiling the adaptive mechanism of algae under the stress of heavy metal complexes with macromolecular organic ligands.


Subject(s)
Tannins , Chromium/toxicity , Photosynthesis/drug effects , Water Pollutants, Chemical/toxicity , Polyphenols
4.
BMC Genomics ; 25(1): 395, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649810

ABSTRACT

The testes are the organs of gamete production and testosterone synthesis. Up to date, no model system is available for mammalian testicular development, and only few studies have characterized the mouse testis transcriptome from no more than three postnatal ages. To describe the transcriptome landscape of the developing mouse testis and identify the potential molecular mechanisms underlying testis maturation, we examined multiple RNA-seq data of mouse testes from 3-week-old (puberty) to 11-week-old (adult). Sperm cells appeared as expected in 5-week-old mouse testis, suggesting the proper sample collection. The principal components analysis revealed the genes from 3w to 4w clustered away from other timepoints, indicating they may be the important nodes for testicular development. The pairwise comparisons at two adjacent timepoints identified 7,612 differentially expressed genes (DEGs), resulting in 58 unique mRNA expression patterns. Enrichment analysis identified functions in tissue morphogenesis (3-4w), regulation of peptidase activity (4-5w), spermatogenesis (7-8w), and antigen processing (10-11w), suggesting distinct functions in different developmental periods. 50 hub genes and 10 gene cluster modules were identified in the testis maturation process by protein-protein interaction (PPI) network analysis, and the miRNA-lncRNA-mRNA, miRNA-circRNA-mRNA and miRNA-circRNA-lncRNA-mRNA competing endogenous RNA (ceRNA) networks were constructed. The results suggest that testis maturation is a complex developmental process modulated by various molecules, and that some potential RNA-RNA interactions may be involved in specific developmental stages. In summary, this study provides an update on the molecular basis of testis development, which may help to understand the molecular mechanisms of mouse testis development and provide guidance for mouse reproduction.


Subject(s)
Gene Expression Profiling , Testis , Animals , Male , Testis/metabolism , Testis/growth & development , Mice , Gene Expression Regulation, Developmental , Transcriptome , Gene Regulatory Networks , Protein Interaction Maps , MicroRNAs/genetics , MicroRNAs/metabolism
5.
Fa Yi Xue Za Zhi ; 40(1): 50-58, 2024 Feb 25.
Article in English, Chinese | MEDLINE | ID: mdl-38500461

ABSTRACT

OBJECTIVES: To establish and forensically verify a 42 microhaplotypes (mircohaps, MHs) multiplex assay system based on next-generation sequencing (NGS), and to explore the application value of this system in the practice of forensic genetics. METHODS: A total of 42 highly polymorphic MHs were selected from previous studies, and sequenced by the MiSeq FGxTM platform to verify the repeata-bility, sensitivity, specificity, stability, and mixture analysis ability of the detection system. Through population genetic investigation of 102 unrelated Chinese Han individuals in Liyang City, Jiangsu Province, China, the application value of this system in forensic genetics was evaluated. RESULTS: The sequencing repeatability of the 42-plex MHs assay was 100% and the sensitivity was as low as 0.062 5 ng. The system had the ability to withstand the interference of indigo (≤2 500 ng/µL), humic acid (≤9 ng/µL), hemoglobin(≤20 µmol), and urea (≤200 ng/µL) and to detect mixtures of 2 people (1∶19), 3 people (1∶1∶9) and 4 people (1∶1∶1∶9). Based on 102 individual data, the combined power of discrimination and the combined power of exclusion were 1-3.45×10-30 and 1-3.77×10-11, respectively, and the average effect value of alleles was 2.899. CONCLUSIONS: The 42-plex MHs assay was successfully established in this study and this system has high repeatability and sensitivity, good anti-jamming ability and mixture analysis ability. The 42 MHs are highly polymorphism and have good application value in individual identification and paternity testing.


Subject(s)
Forensic Genetics , Genetics, Population , Humans , Gene Frequency , Genotype , Polymorphism, Genetic , High-Throughput Nucleotide Sequencing , Polymorphism, Single Nucleotide , DNA Fingerprinting , Microsatellite Repeats
6.
Mol Genet Genomics ; 299(1): 9, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38374461

ABSTRACT

Currently, the most commonly used method for human identification and kinship analysis in forensic genetics is the detection of length polymorphism in short tandem repeats (STRs) using polymerase chain reaction (PCR) and capillary electrophoresis (CE). However, numerous studies have shown that considerable sequence variations exist in the repeat and flanking regions of the STR loci, which cannot be identified by CE detection. Comparatively, massively parallel sequencing (MPS) technology can capture these sequence differences, thereby enhancing the identification capability of certain STRs. In this study, we used the ForenSeq™ DNA Signature Prep Kit to sequence 58 STRs and 94 individual identification SNPs (iiSNPs) in a sample of 220 unrelated individuals from the Eastern Chinese Han population. Our aim is to obtain MPS-based STR and SNP data, providing further evidence for the study of population genetics and forensic applications. The results showed that the MPS method, utilizing sequence information, identified a total of 486 alleles on autosomal STRs (A-STRs), 97 alleles on X-chromosome STRs (X-STRs), and 218 alleles on Y-chromosome STRs (Y-STRs). Compared with length polymorphism, we observed an increase of 260 alleles (157, 31, and 72 alleles on A-STRs, X-STRs, and Y-STRs, respectively) across 36 STRs. The most substantial increments were observed in DYF387S1 and DYS389II, with increases of 287.5% and 250%, respectively. The most increment in the number of alleles was found at DYF387S1 and DYS389II (287.5% and 250%, respectively). The length-based (LB) and sequence-based (SB) combined random match probability (RMP) of 27 A-STRs were 6.05E-31 and 1.53E-34, respectively. Furthermore, other forensic parameters such as total discrimination power (TDP), cumulative probability of exclusion of trios (CPEtrio), and duos (CPEduo) were significantly improved when using the SB data, and informative data were obtained for the 94 iiSNPs. Collectively, these findings highlight the advantages of MPS technology in forensic genetics, and the Eastern Chinese Han genetic data generated in this study could be used as a valuable reference for future research in this field.


Subject(s)
DNA Fingerprinting , Ethnicity , Humans , DNA Fingerprinting/methods , Ethnicity/genetics , Genetics, Population , Polymorphism, Single Nucleotide/genetics , Microsatellite Repeats/genetics , High-Throughput Nucleotide Sequencing/methods , China , DNA , Sequence Analysis, DNA/methods
7.
Plant Physiol Biochem ; 207: 108430, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38364632

ABSTRACT

Copper oxide nanoparticles (CuO NPs) influence the uptake of heavy metal ions by plants, but molecular mechanism is still unknown. Here, we proved the mechanism of CuO NPs affecting Cd absorption in Arabidopsis root. 4-d-old seedlings were treated by 10 and 20 mg/L CuO NPs for 3 d, which decreased the contents of cellulose and hemicellulose in roots. Moreover, the contents of some important monosaccharides were altered by CuO NPs, including arabinose, glucose and mannose. Biosynthesis of cellulose and hemicellulose is regulated by cellulose synthase A complexe (CSC) dynamics. The synthesis of tubulin cytoskeleton was inhibited by CuO NPs, which resulted in the decrease of CSCs bidirectional velocities. Furthermore, the arrangement and network of cellulose fibrillar bundles were disrupted by CuO NPs. CuO NPs treatment significantly increased the influx of Cd2+. The accumulation and translocation of Cd were increased by 10 and 20 mg/L CuO NPs treatment. The subcellular distribution of Cd in root cells indicated CuO NPs decrease the enrichment of Cd in cell wall, but increase the enrichment of Cd in soluble fraction and organelle. In light of these findings, we proposed a mechanistic model in which CuO NPs destroy the ordered structure of the cell wall, alter the uptake and distribution of Cd in Arabidopsis.


Subject(s)
Arabidopsis , Metal Nanoparticles , Nanoparticles , Copper/pharmacology , Copper/chemistry , Cadmium/pharmacology , Nanoparticles/chemistry , Oxides , Cellulose , Metal Nanoparticles/chemistry
8.
Nat Commun ; 15(1): 1071, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38316797

ABSTRACT

While significant advances have been made in predicting static protein structures, the inherent dynamics of proteins, modulated by ligands, are crucial for understanding protein function and facilitating drug discovery. Traditional docking methods, frequently used in studying protein-ligand interactions, typically treat proteins as rigid. While molecular dynamics simulations can propose appropriate protein conformations, they're computationally demanding due to rare transitions between biologically relevant equilibrium states. In this study, we present DynamicBind, a deep learning method that employs equivariant geometric diffusion networks to construct a smooth energy landscape, promoting efficient transitions between different equilibrium states. DynamicBind accurately recovers ligand-specific conformations from unbound protein structures without the need for holo-structures or extensive sampling. Remarkably, it demonstrates state-of-the-art performance in docking and virtual screening benchmarks. Our experiments reveal that DynamicBind can accommodate a wide range of large protein conformational changes and identify cryptic pockets in unseen protein targets. As a result, DynamicBind shows potential in accelerating the development of small molecules for previously undruggable targets and expanding the horizons of computational drug discovery.


Subject(s)
Molecular Dynamics Simulation , Proteins , Ligands , Proteins/metabolism , Protein Conformation , Drug Discovery , Protein Binding , Molecular Docking Simulation
9.
Forensic Sci Int Genet ; 69: 102979, 2024 03.
Article in English | MEDLINE | ID: mdl-38043150

ABSTRACT

Biological traces discovered at crime scenes hold significant significance in forensic investigations. In cases involving mixed body fluid stains, the evidentiary value of DNA profiles depends on the type of body fluid from which the DNA was obtained. Recently, coding region polymorphism analysis has proved to be a promising method for directly linking specific body fluids to their respective DNA contributors in mixtures, which may help to avoid "association fallacy" between separate DNA and RNA evidence. In this study, we present an update on previously reported coding region Single Nucleotide Polymorphisms (cSNPs) by exploring the potential application of coding region Insertion/Deletion polymorphisms (cInDels). Nine promising cInDels, selected from 70 mRNA markers based on stringent screening criteria, were integrated into an existing mRNA profiling assay. Subsequently, the body fluid specificity of our cInDel assay and the genotyping consistency between complementary DNA (cDNA) and genomic DNA (gDNA) were examined. Our study demonstrates that cInDels can function as important multifunctional genetic markers, as they provide not only the ability to confirm the presence of forensically relevant body fluids, but also the ability to associate/dissociate specific body fluids with particular donors.


Subject(s)
Body Fluids , Humans , RNA, Messenger/genetics , RNA , Genetic Markers , DNA/genetics , Forensic Genetics/methods , Semen , Saliva
10.
Fa Yi Xue Za Zhi ; 39(5): 441-446, 2023 Oct 25.
Article in English, Chinese | MEDLINE | ID: mdl-38006262

ABSTRACT

OBJECTIVES: To evaluate the forensic application value of an age estimation model based on DNA methylation in eastern Chinese Han population, and to provide a theoretical basis for exploring age estimation models suitable for different detection platforms. METHODS: According to the 6 age-related methylation sites in the published blood DNA methylation age estimation models of Chinese Han population, the DNA methylation level of 48 samples was detected by pyrosequencing and next-generation sequencing (NGS). After submitting DNA methylation levels to the age estimation model, the DNA methylation ages were predicted and compared with their real ages. RESULTS: The 6 DNA methylation sites in both detection techniques were age-related, with an R2 of 0.85 and a median absolute deviation (MAD) of 4.81 years when using pyrosequencing;with an R2 of 0.84 and MAD of 4.41 years when using NGS. CONCLUSIONS: The blood DNA methylation age estimation model can be used under pyrosequencing and multi-purpose regional methylation enrichment sequencing technology based on NGS and it can accurately estimate the age.


Subject(s)
DNA Methylation , East Asian People , Humans , Aging/genetics , CpG Islands , Forensic Genetics/methods
11.
Fa Yi Xue Za Zhi ; 39(5): 465-470, 2023 Oct 25.
Article in English, Chinese | MEDLINE | ID: mdl-38006266

ABSTRACT

OBJECTIVES: To explore the feasibility of genetic marker detection of semen-specific coding region single nucleotide polymorphism (cSNP) based on SNaPshot technology in semen stains and mixed body fluid identification. METHODS: Genomic DNA (gDNA) and total RNA were extracted from 16 semen stains and 11 mixtures composed of semen and venous blood, and the total RNA was reverse transcribed into complementary DNA (cDNA). The cSNP genetic markers were screened on the validated semen-specific mRNA coding genes. The cSNP multiplex detection system based on SNaPshot technology was established, and samples were genotyped by capillary electrophoresis (CE). RESULTS: A multiplex detection system containing 5 semen-specific cSNPs was successfully established. In 16 semen samples, except the cSNP located in the TGM4 gene showed allele loss in cDNA detection results, the gDNA and cDNA typing results of other cSNPs were highly consistent. When detecting semen-venous blood mixtures, the results of cSNP typing detected were consistent with the genotype of semen donor and were not interfered by the genotype of venous blood donor. CONCLUSIONS: The method of semen-specific cSNPs detection by SNaPshot technology method can be applied to the genotyping of semen (stains) and provide information for determining the origin of semen in mixed body fluids (stains).


Subject(s)
Body Fluids , Semen , Genetic Markers , Polymorphism, Single Nucleotide , DNA, Complementary/genetics , RNA, Messenger/genetics , DNA , Saliva , Forensic Genetics/methods
12.
Am J Cardiol ; 202: 90-99, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37423176

ABSTRACT

Despite recent advances in the prevention of coronary heart disease, the mortality rate of sudden cardiac death (SCD) remains high, which has become a substantial public health issue. Methyltransferase-like protein 16 (METTL16), as a newly discovered m6A methyltransferase, may be related to cardiovascular diseases. In the present study, a 6-base-pair insertion/deletion (del) polymorphism (rs58928048) in the METTL16 3'untranslated region (3'UTR) region was chosen as a candidate variant based on the findings of systematic screening. Then, the association between rs58928048 and susceptibility to SCD originating from coronary artery disease (SCD-CAD) in the Chinese population was investigated by conducting a case-control study that included 210 SCD-CAD cases and 644 matched healthy controls. Logistic regression analysis showed that the del allele of rs58928048 significantly reduced the SCD risk (odds ratio 0.69, 95% confidence interval 0.55 to 0.87, p = 0.00177). Genotype-phenotype correlation studies in human cardiac tissue samples demonstrated that the lower messenger RNA and protein expression levels of METTL16 were associated with the del allele of rs58928048. In the dual-luciferase activity assay, the del/del genotype exhibited lower transcriptional competence. Further bioinformatic analysis showed that the rs58928048 del variant may create transcription factor binding sites. Finally, pyrosequencing showed that the genotype of rs58928048 was related to the methylation status of the 3'UTR region of METTL16. Taken together, our findings provide evidence that rs58928048 may affect the methylation status of the 3'UTR region of METTL16 and subsequently affect its transcriptional activity thus as a potential genetic risk marker for SCD-CAD.


Subject(s)
Coronary Artery Disease , Death, Sudden, Cardiac , Genetic Predisposition to Disease , Methyltransferases , Humans , 3' Untranslated Regions , Case-Control Studies , Coronary Artery Disease/genetics , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/etiology , East Asian People , Methyltransferases/genetics , Polymorphism, Genetic
13.
Sensors (Basel) ; 23(10)2023 May 12.
Article in English | MEDLINE | ID: mdl-37430608

ABSTRACT

Unmanned aerial vehicles (UAVs) can be used to relay sensing information and computational workloads from ground users (GUs) to a remote base station (RBS) for further processing. In this paper, we employ multiple UAVs to assist with the collection of sensing information in a terrestrial wireless sensor network. All of the information collected by the UAVs can be forwarded to the RBS. We aim to improve the energy efficiency for sensing-data collection and transmission by optimizing UAV trajectory, scheduling, and access-control strategies. Considering a time-slotted frame structure, UAV flight, sensing, and information-forwarding sub-slots are confined to each time slot. This motivates the trade-off study between UAV access-control and trajectory planning. More sensing data in one time slot will take up more UAV buffer space and require a longer transmission time for information forwarding. We solve this problem by a multi-agent deep reinforcement learning approach that takes into consideration a dynamic network environment with uncertain information about the GU spatial distribution and traffic demands. We further devise a hierarchical learning framework with reduced action and state spaces to improve the learning efficiency by exploiting the distributed structure of the UAV-assisted wireless sensor network. Simulation results show that UAV trajectory planning with access control can significantly improve UAV energy efficiency. The hierarchical learning method is more stable in learning and can also achieve higher sensing performance.

14.
Forensic Sci Res ; 8(1): 70-78, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37415794

ABSTRACT

Y-chromosome short tandem repeats (Y-STRs) have a unique role in forensic investigation. However, low-medium mutating Y-STRs cannot meet the requirements for male lineage differentiation in inbred populations, whereas rapidly mutating (RM) high-resolution Y-STRs might cause unexpected exclusion of paternal lineages. Thus, combining Y-STRs with low and high mutation rates helps to distinguish male individuals and lineages in family screening and analysis of genetic relationships. In this study, a novel 6-dye, 41-plex Y-STR panel was developed and validated, which included 17 loci from the Yfiler kit, nine RM Y-STR loci, 15 low-medium mutating Y-STR loci, and three Y-InDels. Developmental validation was performed for this panel, including size precision testing, stutter analysis, species specificity analysis, male specificity testing, sensitivity testing, concordance evaluation, polymerase chain reaction inhibitors analysis, and DNA mixture examination. The results demonstrated that the novel 41-plex Y-STR panel, developed in-house, was time efficient, accurate, and reliable. It showed good adaptability to directly amplify a variety of case-type samples. Furthermore, adding multiple Y-STR loci significantly improved the system's ability to distinguish related males, making it highly informative for forensic applications. In addition, the data obtained were compatible with the widely used Y-STR kits, facilitating the search and construction of population databases. Moreover, the addition of Y-Indels with short amplicons improves the analyses of degraded samples. Key Points: A novel multiplex comprising 41 Y-STR and 3 Y-InDel was developed for forensic application.The multiplex included rapidly mutating Y-STRs and low-medium mutating Y-STRs, which is compatible with many commonly used Y-STR kits.The multiplex is a powerful tool for distinguishing related males, familial searching, and constructing DNA databases.

15.
Ultrason Sonochem ; 98: 106498, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37385045

ABSTRACT

This study used electrochemical noise technology to analyse the effects of surface damage induced by cavitation erosion (CE) on the pitting and passivation behaviours of TA31 Ti alloy. According to the results, TA31 Ti alloy exhibited high corrosion resistance in NaCl solutions. However, the residual tensile stress layer generated during grinding and polishing reduced its passivation ability. Subsequently, the residual tensile stress layer was eliminated after CE for 1 h, improving the passivation ability of the material. Thereafter, pitting corrosion was initiated on the material surface. Increasing the CE time from 1 h to 2 h gradually decreased the passivation ability of the alloy. A large number of CE holes promoted the transition from pitting initiation to metastable pitting growth. which gradually dominated the surface of TA31 Ti alloy. The damage mechanism of uniform thinning increased the passivation ability and stability of the alloy with the increase in CE time from 2 h to 6 h. Therefore, the surface of TA31 Ti alloy was dominated by the initiation of pitting corrosion.

16.
Cell Rep ; 42(5): 112413, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37164007

ABSTRACT

Although it is widely recognized that the ancestors of Native Americans (NAs) primarily came from Siberia, the link between mitochondrial DNA (mtDNA) lineage D4h3a (typical of NAs) and D4h3b (found so far only in East China and Thailand) raises the possibility that the ancestral sources for early NAs were more variegated than hypothesized. Here, we analyze 216 contemporary (including 106 newly sequenced) D4h mitogenomes and 39 previously reported ancient D4h data. The results reveal two radiation events of D4h in northern coastal China, one during the Last Glacial Maximum and the other within the last deglaciation, which facilitated the dispersals of D4h sub-branches to different areas including the Americas and the Japanese archipelago. The coastal distributions of the NA (D4h3a) and Japanese lineages (D4h1a and D4h2), in combination with the Paleolithic archaeological similarities among Northern China, the Americas, and Japan, lend support to the coastal dispersal scenario of early NAs.


Subject(s)
Genome, Mitochondrial , Humans , Japan , Americas , China , DNA, Mitochondrial/genetics , Haplotypes/genetics , Phylogeny
17.
Fa Yi Xue Za Zhi ; 39(1): 72-82, 2023 Feb 25.
Article in English, Chinese | MEDLINE | ID: mdl-37038859

ABSTRACT

With the improvement of DNA methylation detection techniques, studies on age-related methylation sites have found more age-specific ones across tissues, which improves the sensitivity and accuracy of age estimation. In addition, the establishment of various statistical models also provides a new direction for the age estimation of tissues from different sources. This review summarizes the related studies of age estimation based on DNA methylation from the aspects of detection technology, age-related cytosine phosphate guanine site and model selection in recent years.


Subject(s)
DNA Methylation , Forensic Genetics , Forensic Genetics/methods , CpG Islands , Forensic Medicine
18.
Appl Environ Microbiol ; 89(4): e0002123, 2023 04 26.
Article in English | MEDLINE | ID: mdl-36916911

ABSTRACT

The biosynthetic pathway of eicosapentaenoic acid (EPA) has previously been reported in marine bacteria, while the regulatory mechanism remains poorly understood. In this study, a putative transcriptional regulator PfaR encoded adjacent to the PFA biosynthesis gene cluster (pfaEABCD) was computationally and experimentally characterized. Comparative analyses on the wild type (WT) strain, in-frame deletion, and overexpression mutants revealed that PfaR positively regulated EPA synthesis at low temperature. RNA-Seq and real-time quantitative PCR analyses demonstrated that PfaR stimulated the transcription of pfaABCD. The transcription start site of pfaR was mapped by using primer extension and highly conserved promoter motifs bound by the housekeeping Sigma 70 factor that were identified in the upstream of pfaR. Moreover, overexpression of PfaR in WT strain W3-18-1 at low temperature could improve EPA productivity from 0.07% to 0.13% (percentage of EPA to dry weight, mg/mg) of dry weight. Taken together, these findings could provide important implications into the transcriptional control and metabolic engineering in terms of EPA productivity for industrial strains. IMPORTANCE We have experimentally confirmed that PfaR is a positive transcription regulator that promotes EPA synthesis at low temperature in Shewanella putrefaciens W3-18-1. Overexpression of PfaR in WT strain W3-18-1 could lead to a 1.8-fold increase in EPA productivity at low temperature. It is further shown that PfaR may be regulated by housekeeping Sigma 70 factor at low temperature.


Subject(s)
Shewanella putrefaciens , Shewanella , Shewanella putrefaciens/genetics , Shewanella putrefaciens/metabolism , Eicosapentaenoic Acid/metabolism , Bacteria , Sequence Deletion , Biosynthetic Pathways/genetics , Shewanella/genetics
19.
Environ Sci Pollut Res Int ; 30(19): 55649-55661, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36897451

ABSTRACT

The stress produced from biodegradable plastics on soil ecosystem is a rising global concern. However, effects of such microplastics (MPs) on soil ecology are still debatable. In this study, the biodegradable microplastic PBAT (polyadipate/butylene terephthalate) was used as the target object, compared with the traditional microplastic LDPE (low-density polyethylene). A pot experiment and was high-throughput sequencing analysis used to determine the effect of different additions of MPs on soil bacterial community structure and the correlation between soil bacterial community structure and chemical properties was investigated. Compared with LDPE, the results showed that EC, TN, TP, NH4+-N, and NO3--N changed obviously with the increasing of PBAT addition (p < 0.05), but pH changed little and the community richness was significantly higher in soils with low PBAT addition than that with higher PBAT addition. PBAT is beneficial to soil nitrogen fixation, but it will significantly reduce the soil P content and affect the nitrification and denitrification reaction. It suggested that addition of PBAT MPs and its addition amount result in changes in soil fertility, community abundance, and structure and composition of bacterial communities in soil samples, while the presence of PBAT MPs might affect soil carbon-nitrogen cycle.


Subject(s)
Biodegradable Plastics , Microplastics , Plastics/chemistry , Polyethylene , Ecosystem , Soil/chemistry
20.
Forensic Sci Int ; 343: 111563, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36630768

ABSTRACT

Sudden cardiac death (SCD) is the leading cause of natural death worldwide which is responsible for almost half of all heart disease deaths, making it a substantial public health problem. Previous epidemiological studies from different countries have demonstrated the significant SCD incident difference rate between males and females. Besides environmental and social effects, differential genetic architecture also underlines the SCD incidence discrepancy. To this end, the functional (CAG)n repeat polymorphism within Androgen Receptor (AR) gene was analyzed to evaluate its associations with SCD originated from coronary artery disease (SCD-CAD) susceptibility in Chinese populations using 182 SCD-CAD cases and 564 healthy controls. At allelic level, the (CAG)26 allele conferred a lower SCD-CAD risk in males (adjusted odds ratio [OR] = 0.428; 95% confidence interval [CI] = 0.254, 0.915; P = 0.023). On the contrary, the (CAG)26 allele was reversely associated with a higher SCD-CAD risk in females (OR = 2.581; 95% CI = 0.944, 7.056; P = 0.057). Further cutoff strategy analysis revealed that those male subjects carrying shorter allele (≤26 repeats) had significantly lower SCD-CAD risk (OR = 0.343; 95% CI = 0.221, 0.531; P = 8.1653e-7). Additionally, an allele-dependent SCD risk tendency was observed in male subjects. Specifically, compared with males carrying allele longer than 26 repeats, the SCD-CAD risk (OR value) for male subjects carrying shorter alleles (from 25 to 21) gradually increased from 0.437 to 0.533, indicating the (CAG)26 allele of the repeat polymorphism may be the watershed in male SCD etiology. Lastly, the length variations associated with multiple phenotypes were also summarized. Collectively, our results revealed for the first time that the (CAG)n repeat polymorphism within the AR gene was associated with SCD-CAD risk in Chinese populations with sex discrepancy, proposing a new candidate genetic marker for molecular diagnosis of SCD-CAD. Furthermore, a sex-dependent SCD-CAD risk stratification and prevention approach was encouraged. Further studies with more female samples were warranted to validate our findings.


Subject(s)
Coronary Artery Disease , Humans , Male , Female , Coronary Artery Disease/genetics , Coronary Artery Disease/complications , Receptors, Androgen/genetics , Alleles , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/epidemiology , Polymorphism, Genetic , Genetic Predisposition to Disease
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