Methamphetamine exposure increases cardiac microvascular permeability by activating the VEGF-PI3K-Akt-eNOS signaling pathway, reversed by Bevacizumab.

Methamphetamine (METH) is an illicit amphetamine-like psychostimulant that is commonly abused. However, the modulation of METH-induced cardiac microvascular permeability is still not completely known. Previously, we discovered that the vascular endothelial growth factor (VEGF) regulated the cardiotoxicity produced by METH. In this work, we looked into the effect of METH exposure on cardiac microvascular permeability via the VEGF-PI3K-Akt-eNOS signaling pathway, as well as the efficacy of Bevacizumab treatment in reducing this effect. The findings revealed that METH exposure enhanced cardiac microvascular permeability while also activating the VEGF-PI3K-Akt-eNOS signaling pathway. Furthermore, treatment with Bevacizumab has been shown to be effective in reversing the METH-induced phenomena. Briefly stated, our research may provide fresh insight into the molecular underpinnings of METH-induced cardiac microvascular permeability, and it may also provide evidence for a relationship between METH misuse and Bevacizumab medication.

Analyzing genetic polymorphism and mutation of 44 Y-STRs in a Chinese Han population of Southern China.

Short tandem repeat on the non-recombining part of chromosome Y with paternally inheritable capability is a valuable tool in the studies of forensic genetics, population genetics and anthropology. The mutation rate of Y-STR is an important parameter in the applications. A total of 629 haplotypes at 44 Y-STR markers were found in 629 unrelated males of our population. Mutation rates at 44 Y-STR loci ranged from 0 (CI: 0-5.70 × 10-3) to 40.63 × 10-3 (25.90 × 10-3-57.2 × 10-3) in our population. A higher mutation rate was noted at DYS612, DYS449, DYS547, DYS518, DYS576, DYS627, DYF403S1b, DYF387S1, DYS385a/b, DYS527a/b, DYF404S1, DYF403S1a and DYF399S1 in this population. The Y-STR set showed a higher discrimination capacity in forensic applications, and the present study provided reference data for the application of forensic and population genetics.

Revisiting the male genetic landscape of China: a multi-center study of almost 38,000 Y-STR haplotypes.

China has repeatedly been the subject of genetic studies to elucidate its prehistoric and historic demography. While some studies reported a genetic distinction between Northern and Southern Han Chinese, others showed a more clinal picture of small differences within China. Here, we investigated the distribution of Y chromosome variation along administrative as well as ethnic divisions in the mainland territory of the People's Republic of China, including 28 administrative regions and 19 recognized Chinese nationalities, to assess the impact of recent demographic processes. To this end, we analyzed 37,994 Y chromosomal 17-marker haplotype profiles from the YHRD database with respect to forensic diversity measures and genetic distance between groups defined by administrative boundaries and ethnic origin. We observed high diversity throughout all Chinese provinces and ethnicities. Some ethnicities, including most prominently Kazakhs and Tibetans, showed significant genetic differentiation from the Han and other groups. However, differences between provinces were, except for those located on the Tibetan plateau, less pronounced. This discrepancy is explicable by the sizeable presence of Han speakers, who showed high genetic homogeneity all across China, in nearly all studied provinces. Furthermore, we observed a continuous genetic North-South gradient in the Han, confirming previous reports of a clinal distribution of Y chromosome variation and being in notable concordance with the previously observed spatial distribution of autosomal variation. Our findings shed light on the demographic changes in China accrued by a fast-growing and increasingly mobile population.

Using whole exome sequencing and bioformatics in the molecular autopsy of a sudden unexplained death syndrome (SUDS) case.

Whole exome sequencing (WES) and bioinformatics analysis were used to investigate potential disease-causing gene mutations in a sudden unexplained death syndrome (SUDS) case after autopsy and pathology tests failed to suggest an obvious disease mechanism. Following whole exome sequencing, a 3-step bioinformatics filtering procedure was carried out to identify possible pathogenic genomic features. Single nucleotide variations (SNVs) were analyzed and ranked by likely mutation impact using various open online tools. After screening, we identified G643S as a putative causative heterozygous mutation in the KCNQ1 gene. This mutation has been reported in abnormalities consistent with SUDS, such as IKs in cardiac myocytes, a condition that predisposes for arrhythmias. Our work demonstrates the application of sequencing technology at the whole exome level for determining potential causes of an otherwise unexplained death.

[Analysis of linkage disequilibrium and linkage for 12 short tandem repeat loci on chromosome X].

OBJECTIVE: To analyze linkage disequilibrium of 12 short tandem repeat loci on chromosome X (X-STR) among an ethnic Han population from Guilin, Guangxi, and to study the genetic linkage and haplotype distributions of such loci in 2 linkage groups. METHODS: 12 X-STR loci including DXS8378, DXS10159, DXS10162, DXS10164, DXS981, DXS6789, DXS7424, DXS101, DXS7133, GATA165B12, GATA31E08 and DXS7423 were genotyped using an AGCU X12 STR PCR Amplification kit. A total of 119 pedigrees were analyzed for linkage and linkage disequilibrium. RESULTS: Two mutations were found at DXS7424, and 1 mutation was found at DXS10164. A total of 93 haplotypes of DXS10159-DXS10162-DXS10164 were constructed for 261 unrelated males and females, in addition with 167 haplotypes of DXS6789-DXS7424-DXS101-DXS7133. The values of recombination fraction between DXS10159 and DXS10162, DXS10162 and DXS10164, DXS6789 and DXS7424, and DXS7424 and DXS101 were 0.0269, 0.0236, 0.0505 and 0.0438, respectively. CONCLUSION: Linkage disequilibrium of X-STR does not only depend on physical and genetic distances. There was incomplete linkage relationship between loci on DXS10159-DXS1016-DXS10164 and DXS6789-DXS7424-DXS101 linkage groups.

[A population genetic study of 22 autosomal loci of single nucleotide polymorphisms].

OBJECTIVE: To evaluate polymorphisms and forensic efficiency of 22 non-binary single nucleotide polymorphism (SNP) loci. METHODS: One hundred ethnic Han Chinese individuals were recruited from Dongguan, Guangdong. The 22 loci were genotyped with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). RESULTS: Nine loci were found with a single allele, 4 loci were found to be biallelic, whilst 9 loci were found to have 3 alleles. For 13 polymorphic loci, the combined discrimination power and power of exclusion were 0.999 98 and 0.9330, respectively. For the 9 non-biallelic loci, the combined discrimination power and power of exclusion were 0.9998 and 0.8956, respectively. For motherless cases, the combined power of exclusion was 0.6405 for 13 polymorphic SNPs and 0.6405 for 9 non-binary SNPs. CONCLUSION: Non-binary loci have a greater discrimination power and exclusion power per SNP.

Stature estimation from hand dimensions in a Han population of Southern China.

To analyze the relationship between stature and hand dimensions for forensic applications, the stature and hand dimensions of 400 healthy adults aged between 20 and 25 years were measured in a Han population of Southern China. The mean values of the stature are 170.49 and 159.72 cm in the men and the women, respectively. The statistically significant differences between the right- and the left-hand dimensions were not observed in the men, whereas the bilateral differences are statistically significant in female hand dimensions. The correlation coefficients were found to be statistically significant for the hand dimensions in both the sexes. The hand length showed higher correlation coefficients than the hand breadth in both sexes. Linear and multiple regressions were developed in this study; multiple regressions showed higher correlation coefficients than linear regressions. Two regression models could be used to estimate the stature from the hand dimensions in this population.

A study on the influence of ethanol over the primary cultured rat cortical neurons by using the scanning electron microscopy.

As an inhibitor and toxic factor of central nervous system, ethanol inhibits the action of the neurons and causes various kinds of neuronal damage. However, the precise mechanisms that ethanol-induced neuronal damage in the central nervous system remain unclear. In spite of thousands of published studies, little information is available on the neurons' morphological alteration in the central nervous system. In this study, we investigated the morphological alterations of the primary cultured rat cortical neurons after they were treated by different concentrations of ethanol using the scanning electron microscopy. Our results showed that the moderate or high concentration of ethanol could lead to morphological changes of these cultured rat cortical neurons, and they were closely associated with the duration of time. Our study will provide a new base for further studies on the effects of ethanol in the central nervous system.

[Genetic polymorphisms of fifteen short tandem repeat loci in Guilin Han population].

OBJECTIVE: To investigate the genetic polymorphisms of 15 short tandem repeat (STRs) in Guilin Han population. METHODS: DNA was extracted by Chelex method, and 15 STRs were analyzed using AmpFISTR Identifiler kit. RESULTS: Four rare alleles, namely FGA * 10, D2S1338 * 10, D3S1358 * 16.2 and D3S1358 * 17.2, were observed. The combined match probability and exclusion probability for the 15 STRs were 2.89 x 10(-17) and 0.9999993, respectively. CONCLUSION: These STRs have good discrimination power and exclusion probability in Guilin Han population.

Genetic analyzing of 15 STR loci in a Han population of Jinan (northern China).

This study reports the genetic polymorphic data of 15 autosomal STRs D3S1358, TH01, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, CSF1PO, vWA, D8S1179, TPOX, D2S1338, D19S433, and FGA observed in Han ethnic group living in Jinan, Shandong, China. The combined match probability and exclusion probability for 15 loci was 3.89x10(-17) and 0.99997, respectively. No mutations at these loci were found in 78 pedigrees, and Chi-test of allelic frequencies in 420 unrelated samples showed no departure from Hardy-Weinberg equilibrium at these loci. The pairwise comparisons between Jinan and 41 reference populations were performed.

Assessing forensic applications of the frontal sinus in a Chinese Han population.

The frontal sinus is an important tool of personal identification. To assess the forensic applications of the frontal sinus patterns in a Chinese Han population, 198 individuals were analyzed. 165 individuals who have the frontal sinus were observed in this population, and 12 parameters of the frontal sinus were observed according to Yoshino's method. The same combined code was found in three persons from our samples. The unilateral frontal sinus scalloped with one arcade has few parameters applied to personal identification, and shows the poorer discrimination power. These parameters showed better discrimination power in our population, and could be applied to personal identification.

[Analysis of the genetic polymorphisms of 15 autosomal short tandem repeat in a Han population of Shandong].

OBJECTIVE: To obtain population genetic data at 15 short tandem repeat(STRs) in Shandong Han population. METHODS: Fifteen STRs were genotyped in 200 unrelated individuals from Shandong Han population using Identifiler(TM) Kit. RESULTS: In this Shandong Han population, the observed heterozygosities of the 15 loci ranged from 0.605 to 0.882, and the expected heterozygosities were 0.625-0.862, the polymorphic information contents ranged from 0.57 to 0.85, the discrimination powers ranged from 0.795 to 0.958, and the exclusion probabilities ranged from 0.297 to 0.758. The non-differentiation exact P values at TPOX loci were more than 0.05 between Shandong and Han population of Henan, Jilin, and Jiangsu. The non-differentiation exact P values between Shandong Han population and others populations were more than 0.05 at others loci. The P value at D13S317 was more than 0.05 between Shandong Han population and Ewenki population. CONCLUSION: These loci are polymorphic in Shandong Han population, and the discrimination powers and exclusion probabilities were high in the 15 STRs except TPOX and TH01.

[Polymorphism of 22 Y-STR loci in Guangdong Han population and genetic relationship with 12 populations].

To investigate the genetic polymorphisms of 22 Y-chromosomal short tandem repeats(STR) loci in Guangdong Han population, and to evaluate their forensic application values and genetic relationships with 12 other populations. These Y-STR loci (DYS19, DYS389/, DYS390, DYS391, DYS392, DYS393, DYS385, DYS437, DYS438, DYS439, DYS461, DYS481, DYS504, DYS505, DYS508, DYS533, DYS576, DYS588, DYS607, DYS634, and DYS643) were analyzed in 216 unrelated healthy Guangdong Han individuals by three multiplex PCR systems including the PowerPlex Y System. Cluster analysis and phylogenic trees were applied to show the genetic distance among the populations. As a result, a total of 214 haplotypes were identified and the overall haplotype diversity for the 22 Y-STR loci was 0.9999. The gene diversity values (GD) for each locus ranged from 0.3299 (DYS634) to 0.9425 (DYS385). Comparing with 12 other populations, the genetic distance between Guangdong and Chaoshan Han population was the smallest (-0.0030), while that between Guangdong and Northeast Han Chinese was the largest (0.0195). The phylogenetic tree was similar to the results of clustering analysis. Multiplex detection of the 22 Y-STR loci revealed a highly polymorphic genetic distribution, which would be very powerful for establishing a Y-STR database, for population genetics and forensic practice.

[Analysis of polymorphic markers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry].

With the development of genomics and the accomplishments of human genomic sequencing, polymorphic markers and their analytic approaches are more and more important, and much attention has been paid to the fact that the analysis of single nucleotide polymorphisms utilizing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS) is a high-throughput approach. MALDI-TOF MS can also mini-sequence and genotype short tandem repeat. The approaches to analyzing single nucleotide polymorphisms are primer oligonucleotide base extension, ligase reaction, peptide nucleotide acid, invader assay, and so on.

[Distributions of haplotypes for three Y-STR loci in a Tibetan ethnic group of Chinese population by using Y-STR multiplexes].

OBJECTIVE: One multiplex genotyping system was developed in using silver staining with allelic ladders for three Y-chromosome STR markers (DYS434, DYS443, and DYS456), with a view towards the application of rapid and simple genotyping assay methods for DNA profiling. The distributions of haplotypes for three Y-STR loci(DYS434, DYS443, and DYS456) was investigated in a Tibetan ethnic group of Chinese population. METHODS: Allele and haplotype frequencies at these Y-STRs loci(DYS434, DYS443, and DYS456) were analysed by PCR amplification using Y-STR multiplexes, followed by horizontal non-denaturing polyacrylamide gelelec-trophoresis in 101 unrelated males of Tibetan ethnic group in Lasa of China. RESULTS: A total of 31 different haplotypes were found, 16 of them being unique. The haplotype diversity value (which is the same as the discrimination index) calculated from all three loci combined was 0.9481, which is informative. CONCLUSION: The Y-STR multiplexes provide useful information for forensic analysis and paternity tests and can also be of great benefit for providing information not normally available from autosomal DNA systems.

[Polymorphic markers of chromosome Y and their applications for forensic science].

Chromosome Y does not recombine with any other at meiosis except that on pseudoautosomal region. Polymorphic markers on the chromosome Y are paternal inheritance and are haploidly inherited. Variance of the sequences comes from accumulated mutation. These properties make them unique and important not only to anthroponomy and genetics but also to forensic science and medicine.

[The relationship between physical distance and genetic distance on chromosome 22].

OBJECTIVE: To construct a genetic map based on data from the Chinese population in northern part of China and to compare relationship between physical distance and genetic distance on chromosome 22. METHODS: PCR amplification was employed to genotype 6 STR loci on chromosome 22, and pedigree analysis was performed. RESULTS: A genetic map of Chinese Han population in the northern part of China was constructed and a preliminary comparison of the physical and genetic distances between 6 STR loci on chromosome 22 was made. CONCLUSION: There is complex relationship between genetic distance and physical distance: the distance between STR loci is related to physical distance but also recombination fraction, and there are differences of the genetic and physical distances on chromosome 22 between Chinese and Caucasian, and between the male and female.

[Molecular genetics and clinical application of Rh blood group system].

The Rh blood group system is one of the most complex and important systems known in humans. It has two homologous structure genes in tandem on 1p34.3-36.1 that encode Rh protein. The Rh protein is a membrane in red blood cell that has 12 transmembrane spans. Rh antigens have many variants; there are three genetic polymorphisms in the RhD-negative individual. The Rh blood group system is of great significance in clinical transfusion and hemolytic disease of the newborn (HDN). Rh PCR genotyping is used for prenatal diagnosis in fetus, but still it has some defects, and in this connection further knowledge about Rh system will be necessary to solve the problem.