Publications by authors named "Yanrui Wu"

29 Publications

  • Page 1 of 1

An efficient multi-path 3D convolutional neural network for false-positive reduction of pulmonary nodule detection.

Int J Comput Assist Radiol Surg 2021 Aug 27. Epub 2021 Aug 27.

Faculty of Information Technology, Beijing University of Technology, Beijing, 100124, People's Republic of China.

Purpose: Considering that false-positive and true pulmonary nodules are highly similar in shapes and sizes between lung computed tomography scans, we develop and evaluate a false-positive nodules reduction method applied to the computer-aided diagnosis system.

Methods: To improve the pulmonary nodule diagnosis quality, a 3D convolutional neural networks (CNN) model is constructed to effectively extract spatial information of candidate nodule features through the hierarchical architecture. Furthermore, three paths corresponding to three receptive field sizes are adopted and concatenated in the network model, so that the feature information is fully extracted and fused to actively adapting to the changes in shapes, sizes, and contextual information between pulmonary nodules. In this way, the false-positive reduction is well implemented in pulmonary nodule detection.

Results: Multi-path 3D CNN is performed on LUNA16 dataset, which achieves an average competitive performance metric score of 0.881, and excellent sensitivity of 0.952 and 0.962 occurs to 4, 8 FP/Scans.

Conclusion: By constructing a multi-path 3D CNN to fully extract candidate target features, it accurately identifies pulmonary nodules with different sizes, shapes, and background information. In addition, the proposed general framework is also suitable for similar 3D medical image classification tasks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11548-021-02478-yDOI Listing
August 2021

Polymorphism of Antifolate Drug Resistance in From Local Residents and Migrant Workers Returned From the China-Myanmar Border.

Front Cell Infect Microbiol 2021 24;11:683423. Epub 2021 Jun 24.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.

Drug-resistant  malaria impedes efforts to control, eliminate, and ultimately eradicate malaria in Southeast Asia. resistance to antifolate drugs derives from point mutations in specific parasite genes, including the dihydropteroate synthase (), dihydrofolate reductase (), and GTP cyclohydrolase I () genes. This study aims to investigate the prevalence and spread of drug resistance markers in populating the China-Myanmar border. Blood samples were collected from symptomatic patients with acute infection. Samples with single-clone infections were sequenced for and genesand genotyped for 6 flanking microsatellite markers. Copy number variation in the gene was also examined. Polymorphisms were observed in six different codons of the  gene (382, 383, 512, 549, 553, and 571) and six different codons of the  gene (13, 57, 58, 61, 99, 117) in two study sites. The quadruple mutant haplotypes 57I/L/58R/61M/117T of gene were the most common (comprising 76% of cases in Myitsone and 43.7% of case in Laiza). The double mutant haplotype 383G/553G of  gene was also prevalent at each site (40.8% and 31%). Microsatellites flanking the gene differentiated clinical samples from wild type and quadruple mutant genotypes ( = 0.259-0.3036), as would be expected for a locus undergoing positive selection. The lack of copy number variation of suggests that SP-resistant may harbor alternative mechanisms to secure sufficient folate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.683423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265503PMC
July 2021

On the relationship between pollution reduction and export product quality: Evidence from Chinese firms.

J Environ Manage 2021 Mar 18;281:111883. Epub 2021 Jan 18.

School of Economics and Trade, Hunan University, Changsha, PR China. Electronic address:

Chinese government adopted a new environmental program during "Eleventh Five-Year Plan" period. Whether this program can achieve its goal of pollution reduction and quality improvement for exports is of vital importance for China's sustainable development. This paper constructs a quasi-difference-in-difference (DID) framework to identify the effects of the new environmental policy on export product quality by using highly disaggregated trade transaction data at the product level. Empirical results show that the implementation of pollution reduction targets is negatively correlated with export product quality. This negative impact is more profound in western regions, capital-intensive industries, privately owned firms and firms exporting to countries which are not members of Organization for Economic Co-operation and Development group. In addition, our extended analysis shows that the negative effects can be mitigated through product switching within the firms. The major policy implication is that local governments should take proper measures to strengthen the effects of innovation offsets caused by environmental regulation and effectively utilize the induced effects of environmental regulation on product switching. The goal is to achieve a win-win outcome for environmental protection and improvement in export product quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jenvman.2020.111883DOI Listing
March 2021

Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China.

J Renin Angiotensin Aldosterone Syst 2020 Oct-Dec;21(4):1470320320981316

School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan Province, P. R. China.

Objective: Prolylcarboxypeptidase (PRCP) is both involved in the Kallikrein-Kinin system (KKS) and renin-angiotensin-aldosterone system (RAAS). This study aimed to determine the genetic impact of PRCP gene polymorphisms on essential hypertension (EH) in an isolated population from a remote region of China.

Methods: A haplotype-based study was investigated in 346 EH patients and 346 normal subjects and all samples were Hani minority residents in Southwest China. A total of 11 tag single nucleotide polymorphisms (SNPs) in PRCP gene were tested by polymerase chain reaction-restriction fragment length polymorphism method.

Results: Single site analysis found that PRCP gene 3'UTR SNP rs3750931 was associated with EH. The minor allele G of rs3750931 was more prevalent in the EH patients compared to control subjects after Bonferroni correction ( < 0.05). Moreover, the rs3750931 G allele carriers showed higher average blood pressure (BP) level among the subjects. The H2 (GAGCACTAACA) haplotype without rs3750931 G allele showed the protective effect for EH (OR = 0.68, 95 CI 0.54-0.85,  = 0.001).

Conclusion: The present study indicated PRCP gene rs3750931 was associated with the risk of EH. This SNP G allele could be considered as one of risk markers for EH in Hani population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1470320320981316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745576PMC
September 2021

Fiscal Decentralization and Local Environmental Pollution in China.

Int J Environ Res Public Health 2020 11 21;17(22). Epub 2020 Nov 21.

Cooperative Innovation Center for Transition of Resource-Based Economies, Shanxi University of Finance and Economics, Taiyuan 030006, China.

Fiscal decentralization is one of the tools for the central government to engage local governments in environment management. However, its effects are inconclusive. This paper aims to examine the impact of fiscal decentralization on environmental pollution and the role of government environmental preference in China's provinces. The results show that fiscal revenue decentralization exacerbates local environmental pollution more seriously than expenditure decentralization. This negative environmental effect of fiscal decentralization could be moderated by government environmental preference. Based on our findings, it is recommended that China's local governments should improve environmental preference so that fiscal decentralization can create a win-win situation for the economy and environment. Furthermore, the different effects of fiscal revenue and expenditure decentralization create a necessity for differentiated management of fiscal decentralization by the central and local governments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17228661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700120PMC
November 2020

Long non‑coding RNA RP11‑400N13.3 promotes the progression of colorectal cancer by regulating the miR‑4722‑3p/P2RY8 axis.

Oncol Rep 2020 11 7;44(5):2045-2055. Epub 2020 Sep 7.

Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.

Accumulating evidence has shown that long non‑coding RNAs (lncRNAs) play significant roles in the development and progression of many types of cancer including colorectal cancer. RP11‑400N13.3 is a novel lncRNA discovered recently and its biological function and underlying mechanism in colorectal cancer remain elusive. This study aimed to reveal the relationship between RP11‑400N13.3 and colorectal cancer. Our results demonstrated that the expression of RP11‑400N13.3 was significantly upregulated in both colorectal cancer tissues and cell lines as compared to normal adjacent tissues and normal colonic epithelial cells by RT‑qPCR, respectively. Upregulation of RP11‑400N13.3 was found to be correlated with a poor overall survival rate. Functional studies revealed that RP11‑400N13.3 facilitated the proliferation, migration, invasion and tumor growth of colorectal cancer cells while inhibiting the apoptosis of cancer cells in vitro and in vivo. We also observed that RP11‑400N13.3 serves as a sponge for miR‑4722‑3p, and that P2Y receptor family member 8 (P2RY8) was predicted to be a target of miR‑4722‑3p by bioinformatics analysis. Western blot assay indicated that the expression of P2RY8 was negatively or positively regulated by miR‑4722‑3p or RP11‑400N13.3. In addition, rescue experiments revealed that RP11‑400N13.3 promoted proliferation, migration and invasion by directly regulating the expression of miR‑4722‑3p and P2RY8. In conclusion, our results revealed that RP11‑400N13.3 promoted colorectal cancer progression via modulating the miR‑4722‑3p/P2RY8 axis, thus suggesting RP11‑400N13.3 as a potential therapeutic target for the treatment of colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2020.7755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551293PMC
November 2020

Efficacy of artemether-lumefantrine for treating uncomplicated Plasmodium falciparum cases and molecular surveillance of drug resistance genes in Western Myanmar.

Malar J 2020 Aug 27;19(1):304. Epub 2020 Aug 27.

Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.

Background: Currently, artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment in malaria-endemic areas. However, resistance in Plasmodium falciparum to artemisinin-based combinations emerging in the Greater Mekong Sub-region is a major problem hindering malaria elimination. To continuously monitor the potential spread of ACT-resistant parasites, this study assessed the efficacy of artemether-lumefantrine (AL) for falciparum malaria in western Myanmar.

Methods: Ninety-five patients with malaria symptoms from Paletwa Township, Chin State, Myanmar were screened for P. falciparum infections in 2015. After excluding six patients with a parasite density below 100 or over 150,000/µL, 41 P. falciparum patients were treated with AL and followed for 28 days. Molecular markers associated with resistance to 4-amino-quinoline drugs (pfcrt and pfmdr1), antifolate drugs (pfdhps and pfdhfr) and artemisinin (pfk13) were genotyped to determine the prevalence of mutations associated with anti-malarial drug resistance.

Results: For the 41 P. falciparum patients (27 children and 14 adults), the 28-day AL therapeutic efficacy was 100%, but five cases (12.2%) were parasite positive on day 3 by microscopy. For the pfk13 gene, the frequency of NN insert after the position 136 was 100% in the day-3 parasite-positive group as compared to 50.0% in the day-3 parasite-negative group, albeit the difference was not statistically significant (P = 0.113). The pfk13 K189T mutation (10.0%) was found in Myanmar for the first time. The pfcrt K76T and A220S mutations were all fixed in the parasite population. In pfmdr1, the Y184F mutation was present in 23.3% of the parasite population, and found in both day-3 parasite-positive and -negative parasites. The G968A mutation of pfmdr1 gene was first reported in Myanmar. Prevalence of all the mutations in pfdhfr and pfdhps genes assessed was over 70%, with the exception of the pfdhps A581G mutation, which was 3.3%.

Conclusions: AL remained highly efficacious in western Myanmar. Pfk13 mutations associated with artemisinin resistance were not found. The high prevalence of mutations in pfcrt, pfdhfr and pfdhps suggests high-degree resistance to chloroquine and antifolate drugs. The pfmdr1 N86/184F/D1246 haplotype associated with selection by AL in Africa reached > 20% in this study. The detection of > 10% patients who were day-3 parasite-positive after AL treatment emphasizes the necessity of continuously monitoring ACT efficacy in western Myanmar.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12936-020-03376-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450958PMC
August 2020

Genetic association study of prolylcarboxypeptidase polymorphisms with susceptibility to essential hypertension in the Yi minority of China: A case-control study based on an isolated population.

J Renin Angiotensin Aldosterone Syst 2020 Apr-Jun;21(2):1470320320919586

School of Medicine, Yunnan University, China.

Objective: Prolylcarboxypeptidase (PRCP) is a negative regulator of the pressor actions of the renin-angiotensin-aldosterone system. It is also involved in the kallikrein-kinin system. This gene has an important role in blood pressure (BP) regulation.

Methods: A case-control study was performed for 615 Yi participants (303 cases and 312 controls) from a remote mountainous area in Yunnan Province of China. For the PRCP gene, 11 tag single-nucleotide polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.

Results: The PRCP gene rs12290550 was associated with the occurrence of essential hypertension (EH) and BP traits. Logistic regression analysis indicated that the rs12290550 T allele was significantly linked to the risk of EH (odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.44-2.39, p = 0.2 × 10). Under Bonferroni correction, the H7 TAGCACTAACA haplotype containing the risk allele rs12290550 T increased the risk of EH (OR = 4.53, 95% CI 2.29-8.93, p = 0.2×10).

Conclusions: The findings of this study demonstrate the strong association of the PRCP gene with EH. rs12290550 may be a useful genetic predictor of EH in the Yi minority.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1470320320919586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249571PMC
May 2021

Consumer-perceived risks of genetically modified food in China.

Appetite 2020 04 18;147:104520. Epub 2019 Nov 18.

College of Economics and Management, Anhui Agricultural University, Hefei, China.

This paper analyses the factors influencing consumer-perceived risks of genetically modified (GM) food by using a structural equation model and survey data of urban residents in China. The sample is divided into the acquainted and unacquainted groups according to consumers' objective knowledge level. An integrated analytical framework is developed. The results show that consumers' positive attitude towards GM technology has a significant negative effect on consumer-perceived risks and that more information reaching consumers significantly reduces consumer-perceived risks of GM food only for the unacquainted group. Consumers' trust in government, biotechnology scientists, press media and food companies does not significantly influence consumer-perceived risks of GM food. This is likely because consumers have low trust in the abovementioned stakeholders of GM food. Consumers think that the information reaching them is limited and does not clearly show the advantages and disadvantages of GM food. Consumers' objective knowledge of GM food is also limited. The health risks of GM food are of high concern for both consumer groups. These findings imply that the commercialization of GM crops in China is dependent on providing consumers with adequate and understandable information about GM food and strict supervision measures for food safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.appet.2019.104520DOI Listing
April 2020

On the convergence of per capita carbon dioxide emission: a panel unit root test with sharp and smooth breaks.

Authors:
Yifei Cai Yanrui Wu

Environ Sci Pollut Res Int 2019 Dec 17;26(36):36658-36679. Epub 2019 Nov 17.

Economics, Business School, The University of Western Australia, Perth, Australia.

This study aims to examine the stochastic convergence of per capita carbon dioxide (CO2) emissions in 21 OECD countries and 19 emerging market economies. After approximating both sharp and smooth breaks, the panel unit root tests are performed to test the convergence. The empirical results suggest stochastic convergence for the two groups of countries. However, the results are different when tests for individual countries are conducted separately. Specifically, CO2 emissions of only four OECD countries and four emerging market economies show evidence of convergence if smooth breaks are not considered. With the inclusion of both sharp and smooth breaks, convergence is observed for 11 OECD countries and 10 emerging market economies. These findings may have implications for climate change policy making in selected economies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-019-06786-4DOI Listing
December 2019

The glucose-6-phosphate dehydrogenase Mahidol variant protects against uncomplicated Plasmodium vivax infection and reduces disease severity in a Kachin population from northeast Myanmar.

Infect Genet Evol 2019 11 24;75:103980. Epub 2019 Jul 24.

Department of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, Yunnan Province, China. Electronic address:

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common red cell disorders in the world. The aim of this study was to investigate whether the G6PD Mahidol variant and haplotype 1311 T/93C, which are prevalent in the Kachin ethnic population along the China-Myanmar border area, offer protection against Plasmodium vivax infection. Malaria was monitored in nine villages near the Laiza township, Kachin State, Myanmar, where 258 cases of uncomplicated P. vivax were identified in 2013-2017. From the same villages, 250 unrelated, malaria-free participants were recruited to serve as the control cohort. Quantitative enzyme activity analysis in 100 healthy individuals identified that both male hemizygotes and female heterozygotes of the G6PD Mahidol variant had on average ~40% lower enzyme activity relative to the wild-type individuals. Compared with the overall prevalence of 25.2% in the control cohort, the G6PD Mahidol variant had a significantly lower prevalence (7.0%) among the 258 vivax patients (P <  .0001, χ test). Logistic regression analysis of G6PD genotypes stratified by sex showed that the individuals with the Mahidol 487A allele had dramatically reduced odds of having acute vivax malaria (adjusted odds ratio = 0.213 for male 487A hemizygotes, P < .0001, and 0.248 for female 487GA heterozygotes, P < .001). Furthermore, both 487A hemizygous male and 487GA heterozygous female patients had significantly lower asexual parasitemias than the wild-type patients, suggesting a potential effect on alleviating disease severity. In contrast, the silent mutation haplotype 1311 T/93C was highly prevalent (49.6%) in the study population, but it was not associated with altered G6PD enzymatic activities nor did it seem to provide protection against vivax infection or disease severity. Taken together, this study provided evidence that the Mahidol G > A mutation offers protection against P. vivax infection and potentially reduces disease severity in a Kachin population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2019.103980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832843PMC
November 2019

In vitro susceptibility of Plasmodium falciparum isolates from the China-Myanmar border area to artemisinins and correlation with K13 mutations.

Int J Parasitol Drugs Drug Resist 2019 08 10;10:20-27. Epub 2019 Apr 10.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, 650500, China. Electronic address:

Mutations in the Kelch domain of the K13 gene (PF3D7_1343700) were previously associated with artemisinin resistance in Plasmodium falciparum. This study followed the dynamics of the K13 polymorphisms in P. falciparum parasites from the China-Myanmar border area obtained in 2007-2016, and their in vitro sensitivities to artesunate (AS) and dihydroartemisinin (DHA). The 50% effective concentration (EC) values of 133 culture-adapted field isolates to AS and DHA, measured by the conventional 72 h SYBR Green I-based assay, varied significantly among the parasites from different years; all were significantly higher than that of the reference strain 3D7. Compared with parasites from 2007 to 2008, ring survival rates almost doubled in parasites obtained in later years. Sequencing the full-length K13 genes identified 11 point mutations present in 85 (63.9%) parasite isolates. F446I was the predominant (55/133) variant, and its frequency was increased from 17.6% (3/17) in 2007 to 55.9% (19/34) in 2014-2016. No wild-type (WT) Kelch domain sequences were found in the 34 samples obtained from 2014 to 2016. In the 2014-2016 samples, a new mutation (G533S) appeared and reached 44.1% (15/34). Collectively, parasites with the Kelch domain mutations (after amino acid 440) had significantly higher ring survival rates than the WT parasites. Individually, F446I, G533S and A676D showed significantly higher ring survival rates than the WT. Although the drug sensitivity phenotypes measured by the RSA and EC assays may be intrinsically linked to the in vivo clinical efficacy data, the values determined by these two assays were not significantly correlated. This study identified the trend of K13 mutations in parasite populations from the China-Myanmar border area, confirmed an overall correlation of Kelch domain mutations with elevated ring-stage survival rates, and emphasized the importance of monitoring the evolution and spread of parasites with reduced artemisinin sensitivity along the malaria elimination course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpddr.2019.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479106PMC
August 2019

Longitudinal surveillance of drug resistance in Plasmodium falciparum isolates from the China-Myanmar border reveals persistent circulation of multidrug resistant parasites.

Int J Parasitol Drugs Drug Resist 2018 08 22;8(2):320-328. Epub 2018 May 22.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China; Department of Entomology, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address:

Multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion of Southeast Asia is a major threat to malaria elimination and requires close surveillance. In this study, we collected 107 longitudinal clinical samples of P. falciparum in 2007-2012 from the malaria hypoendemic region of the China-Myanmar border and measured their in vitro susceptibilities to 10 antimalarial drugs. Overall, parasites had significantly different IC values to all the drugs tested as compared to the reference 3D7 strain. Parasites were also genotyped in seven genes that were associated with drug resistance including pfcrt, pfmdr1, pfmrp1, pfdhfr, pfdhps, pfnhe1, and PfK13 genes. Despite withdrawal of chloroquine and antifolates from treating P. falciparum, parasites remained highly resistant to these drugs and mutations in pfcrt, pfdhfr, and pfdhps genes were highly prevalent and almost reached fixation in the study parasite population. Except for pyronaridine, quinine and lumefantrine, all other tested drugs exhibited significant temporal variations at least between some years, but only chloroquine and piperaquine had a clear temporal trend of continuous increase of ICs. For the pfmrp1 gene, several mutations were associated with altered sensitivity to a number of drugs tested including chloroquine, piperaquine, lumefantrine and dihydroartemisinin. The association of PfK13 mutations with resistance to multiple drugs suggests potential evolution of PfK13 mutations amid multidrug resistance genetic background. Furthermore, network analysis of drug resistance genes indicated that certain haplotypes associated multidrug resistance persisted in these years, albeit there were year-to-year fluctuations of the predominant haplotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpddr.2018.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039318PMC
August 2018

Genetic diversity of Plasmodium falciparum populations in southeast and western Myanmar.

Parasit Vectors 2017 Jul 4;10(1):322. Epub 2017 Jul 4.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.

Background: The genetic diversity of malaria parasites reflects the complexity and size of the parasite populations. This study was designed to explore the genetic diversity of Plasmodium falciparum populations collected from two southeastern areas (Shwekyin and Myawaddy bordering Thailand) and one western area (Kyauktaw bordering Bangladesh) of Myanmar.

Methods: A total of 267 blood samples collected from patients with acute P. falciparum infections during 2009 and 2010 were used for genotyping at the merozoite surface protein 1 (Msp1), Msp2 and glutamate-rich protein (Glurp) loci.

Results: One hundred and eighty four samples were successfully genotyped at three genes. The allelic distributions of the three genes were all significantly different among three areas. MAD20 and 3D7 were the most prevalent alleles in three areas for Msp1 and Msp2, respectively. The Glurp allele with a bin size of 700-750 bp was the most prevalent both in Shwekyin and Myawaddy, whereas two alleles with bin sizes of 800-850 bp and 900-1000 bp were the most prevalent in the western site Kyauktaw. Overall, 73.91% of samples contained multiclonal infections, resulting in a mean multiplicity of infection (MOI) of 1.94. Interestingly, the MOI level presented a rising trend with the order of Myawaddy, Kyauktaw and Shwekyin, which also paralleled with the increasing frequencies of Msp1 RO33 and Msp2 FC27 200-250 bp alleles. Msp1 and Msp2 genes displayed higher levels of diversity and higher MOI rates than Glurp. PCR revealed four samples (two from Shwekyin and two from Myawaddy) with mixed infections of P. falciparum and P. vivax.

Conclusions: This study genotyped parasite clinical samples from two southeast regions and one western state of Myanmar at the Msp1, Msp2 and Glurp loci, which revealed high levels of genetic diversity and mixed-strain infections of P. falciparum populations at these sites. The results indicated that malaria transmission intensity in these regions remained high and more strengthened control efforts are needed. The genotypic data provided baseline information for monitoring the impacts of malaria elimination efforts in the region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13071-017-2254-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496439PMC
July 2017

Association of CYP17A1 Genetic Polymorphisms and Susceptibility to Essential Hypertension in the Southwest Han Chinese Population.

Med Sci Monit 2017 May 24;23:2488-2499. Epub 2017 May 24.

School of Medicine, Yunnan University, Kunming, Yunnan, China (mainland).

BACKGROUND The CYP17A1 gene encodes for cytochrome P450 enzyme CYP17A1, which is involved with the steroidogenic pathway including mineralocorticoids. The CYP17A1 polymorphisms might affect enzyme activity, then leading to a state of mineralocorticoid 11-deoxycorticosterone excess characterized by hypertension, suppressed plasma renin activity, and low aldosterone concentrations. The aim of this study was to investigate the contribution of CYP17A1 polymorphisms in inducing the susceptibility to essential hypertension among the Southwest Han Chinese population. MATERIAL AND METHODS Eight single nucleotide polymorphisms of CYP17A1 were genotyped in a case-control study for samples by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS The polymorphisms rs11191548 and rs4919687 were significantly associated with hypertension risk, which was confirmed by systolic and diastolic blood pressure distribution analyses between different genotype groups, and these two polymorphisms were found in linkage disequilibrium. The rs4919687 polymorphism was estimated to cause the destruction of exonic splicing silencer (ESR and Motif 3) sites and to transform the transcription factor AREB6 binding site, respectively, in the bioinformatics analyses. The haplotypes rs4919686A-rs3740397G -rs4919687C-rs743572C-rs11191548C and rs4919686A-rs3740397G-rs4919687T-rs743572C- rs11191548T were found to be susceptible to essential hypertension. CONCLUSIONS Our findings suggest that the CYP17A1 polymorphisms could be a genetic risk factor for essential hypertension among the Yunnan Han Chinese population, which would have implications for the treatment of this complex disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450854PMC
http://dx.doi.org/10.12659/msm.902109DOI Listing
May 2017

Co-inheritance of glucose-6-phosphate dehydrogenase deficiency mutations and hemoglobin E in a Kachin population in a malaria-endemic region of Southeast Asia.

PLoS One 2017 22;12(5):e0177917. Epub 2017 May 22.

Department of Entomology, The Pennsylvania State University, Pennsylvania, United States of America.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobin E (HbE, β26 Glu-Lys) are two common red cell disorders in Southeast Asia. G6PD deficiency produces hemolytic anemia, which can be triggered by certain drugs or infections. HbE is asymptomatic or is manifested as microcytic, minimally hemolytic anemia. The association between G6PD deficiency and HbE is little understood. This study aimed to investigate G6PD deficiency and HbE in a Kachin ethnic group in the China-Myanmar border area. G6PD enzyme activity was measured using a quantitative G6PD assay, G6PD variants genotyped by the SNaPshot assay, and an HbE gene mutation identified by an amplification refractory mutation system and subsequently confirmed by using a reverse dot blot hybridization assay from 100 unrelated individuals in the study area. G6PD enzyme activity ranged from 0.4 to 24.7 U/g Hb, and six males had severe G6PD deficiency (<0.12-1.2 U/g Hb), while six males and 12 females had mild G6PD deficiency (>1.2-4.5 U/g Hb). Among the 24 G6PD-deficient subjects, 22 (92%) had the Mahidol 487G>A mutation (12 male hemizygotes, one female homozygote, and nine female heterozygotes), while the G6PD genotypes in two female subjects were unknown. HbE was identified in 39 subjects (20 males and 19 females), including 15 HbEE (seven males and eight females) and 24 HbAE (13 males and 11 females). Twenty-three subjects co-inherited both G6PD deficiency and HbE (22 with HbAE and one with HbEE). Whereas mean Hb levels were not significantly different between the HbA and HbE groups, G6PD-deficient males had significantly lower Hb levels than G6PD-normal males (P < 0.05, t-test). However, it is noteworthy that two G6PD-deficient hemizygous males with HbAE were severely anemic with Hb levels below 50 g/L. This study revealed high prevalence of co-inheritance of G6PD deficiency with HbAE in the Kachin ethnicity, and a potential interaction of the G6PD Mahidol 487G>A and HbAE in males leading to severe anemia. The presence of 6% males with severe G6PD deficiency raised a major concern in the use of primaquine for radical cure of vivax malaria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177917PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439682PMC
September 2017

Genetic diversity of the Pvk12 gene in Plasmodium vivax from the China-Myanmar border area.

Malar J 2016 Nov 4;15(1):528. Epub 2016 Nov 4.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, 650500, Yunnan Province, China.

Background: Plasmodium falciparum resistance to artemisinin emerged in the Greater Mekong Sub-region has been associated with mutations in the propeller domain of the kelch gene Pfk13.

Methods: Here the polymorphisms in Pvk12 gene, the orthologue of Pfk13 in Plasmodium vivax, were determined by PCR and sequencing in 262 clinical isolates collected in recent years (2012-2015) from the China-Myanmar border area.

Results: Sequencing of full-length Pvk12 genes from these isolates identified three synonymous mutations (N172N, S360S, S697S) and one non-synonymous mutation M124I, all of which were at very low prevalence (2.0-3.1%). Moreover, these mutations were non-overlapping between the two study sites on both sides of the border. Molecular evolutionary analysis detected signature of purifying selection on Pvk12.

Conclusions: There is no direct evidence that Pvk12 is involved in artemisinin resistance in P. vivax, but it remains a potential candidate requiring further investigation. Continuous monitoring of potential drug resistance in this parasite is needed in order to facilitate the regional malaria elimination campaign.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12936-016-1592-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096284PMC
November 2016

Seasonal dynamics and microgeographical spatial heterogeneity of malaria along the China-Myanmar border.

Acta Trop 2016 May 23;157:12-19. Epub 2016 Jan 23.

Department of Entomology, The Pennsylvania State University, University Park, PA 16802, USA.

Malaria transmission is heterogeneous in the Greater Mekong Subregion with most of the cases occurring along international borders. Knowledge of transmission hotspots is essential for targeted malaria control and elimination in this region. This study aimed to determine the dynamics of malaria transmission and possible existence of transmission hotspots on a microgeographical scale along the China-Myanmar border. Microscopically confirmed clinical malaria cases were recorded in five border villages through a recently established surveillance system between January 2011 and December 2014. A total of 424 clinical cases with confirmed spatial and temporal information were analyzed, of which 330 (77.8%) were Plasmodium vivax and 88 (20.8%) were Plasmodium falciparum, respectively. The P. vivax and P. falciparum case ratio increased dramatically from 2.2 in 2011 to 4.7 in 2014, demonstrating that P. vivax malaria has become the predominant parasite species. Clinical infections showed a strong bimodal seasonality. There were significant differences in monthly average incidence rates among the study villages with rates in a village in China being 3-8 folds lower than those in nearby villages in Myanmar. Spatial analysis revealed the presence of clinical malaria hotspots in four villages. This information on malaria seasonal dynamics and transmission hotspots should be harnessed for planning targeted control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actatropica.2016.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779690PMC
May 2016

Artemisinin resistance at the China-Myanmar border and association with mutations in the K13 propeller gene.

Antimicrob Agents Chemother 2015 Nov 31;59(11):6952-9. Epub 2015 Aug 31.

Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, USA

Artemisinin resistance in Plasmodium falciparum parasites in Southeast Asia is a major concern for malaria control. Its emergence at the China-Myanmar border, where there have been more than 3 decades of artemisinin use, has yet to be investigated. Here, we comprehensively evaluated the potential emergence of artemisinin resistance and antimalarial drug resistance status in P. falciparum using data and parasites from three previous efficacy studies in this region. These efficacy studies of dihydroartemisinin-piperaquine combination and artesunate monotherapy of uncomplicated falciparum malaria in 248 P. falciparum patients showed an overall 28-day adequate clinical and parasitological response of >95% and day 3 parasite-positive rates of 6.3 to 23.1%. Comparison of the 57 K13 sequences (24 and 33 from day 3 parasite-positive and -negative cases, respectively) identified nine point mutations in 38 (66.7%) samples, of which F446I (49.1%) and an N-terminal NN insertion (86.0%) were predominant. K13 propeller mutations collectively, the F446I mutation alone, and the NN insertion all were significantly associated with day 3 parasite positivity. Increased ring-stage survival determined using the ring-stage survival assay (RSA) was highly associated with the K13 mutant genotype. Day 3 parasite-positive isolates had ∼10 times higher ring survival rates than day 3 parasite-negative isolates. Divergent K13 mutations suggested independent evolution of artemisinin resistance. Taken together, this study confirmed multidrug resistance and emergence of artemisinin resistance in P. falciparum at the China-Myanmar border. RSA and K13 mutations are useful phenotypic and molecular markers for monitoring artemisinin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01255-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604380PMC
November 2015

Polymorphisms within angiotensin II receptor type 1 gene associated with essential hypertension in Chinese Hani and Yi minorities.

J Renin Angiotensin Aldosterone Syst 2015 Sep 26;16(3):653-9. Epub 2015 Jan 26.

Human Genetics Center of Yunnan University, China

Introduction: Angiotensin II receptor type 1 mediates the major cardiovascular effects of angiotensin II to regulate blood pressure. Polymorphisms of angiotensin II receptor type 1 are associated with essential hypertension, but the results are inconsistent and conflicting. The aim of the present study is to assess the association between angiotensin II receptor type 1 polymorphisms and essential hypertension risk in Chinese Hani and Yi minorities.

Methods: This study recruited 692 unrelated Chinese Hani subjects (case vs. control = 346:346) and 615 unrelated Chinese Yi subjects (case vs. control = 303:312). Twelve selected single nucleotide polymorphisms in the angiotensin II receptor type 1 gene were genotyped using a polymerase chain reaction-restriction fragment length polymorphism method.

Results: Statistical analysis indicated that the GC+CC genotype of rs387967 was significantly associated with the decreased susceptibility to essential hypertension compared with GG in a Yi population (odds ratio = 0.58, 95% confidence intervals 0.41-0.83, P = 0.003). Allele C was a protective allele for essential hypertension (odds ratio = 0.78, 95% confidence intervals 0.61-0.99, P = 0.040). This association was confirmed respectively by comparing systolic blood pressure and diastolic blood pressure between different genotypes and between different alleles, which indicated that the genotype (GC+CC) had a tendency of lower systolic blood pressure and diastolic blood pressure than GG (PSBP = 3.716 × 10(-4), PDBP = 1.187 × 10(-3)); Carriers with C had lower systolic blood pressure and diastolic blood pressure (PSBP = 7.301 × 10(-3), PDBP = 9.142 × 10(-4)). Another single nucleotide polymorphism (rs2638360) was analysed in a Hani minority, then replicated in a Yi minority. The C allele showed a consistent risk trend for essential hypertension in two independent populations (Hani: odds ratio = 1.74, 95% confidence intervals 1.01-2.99, P = 0.046; Yi: odds ratio = 1.27, 95% confidence intervals 0.82-1.96, P = 0.277). Meta-analysis revealed that the C allele could significantly increase the risk of essential hypertension (odds ratio = 1.44, 95% confidence intervals 1.02-2.02, P = 0.037).

Conclusion: Our findings suggest that rs387967 is associated with the susceptibility to essential hypertension in a Yi population and the tendency was replicated in systolic blood pressure and diastolic blood pressure detection. Meta-analysis revealed that C allele of rs2638360 could significantly increase the risk of essential hypertension. The two single nucleotide polymorphisms maybe play a role in the pathology of essential hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1470320314565839DOI Listing
September 2015

[Association of CMA1 gene tag single nucleotide polymorphisms with essential hypertension in Yi population from Yunnan].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2014 Aug;31(4):449-54

Cell Biology and Medical Genetics Department, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.

Objective: To assess the association of tag single nucleotide polymorphisms (tag SNPs) of chymase gene (CMA1) with essential hypertension in Yi population from Yunnan, China.

Methods: A case-control study was carried out. Four tag SNPs(rs1956921, rs1800876, rs5244 and rs1885108) were genotyped in 303 patients with essential hypertension and 312 healthy controls using polymerase chain reaction - restriction fragment length polymorphism(PCR-RFLP) method.

Results: No significant difference in genotypic and allelic distributions of the four polymorphisms was detected between the two groups(P>0.05), and the same results existed in the females. The frequencies of rs1956921 C allele and a C-T haplotype constructed with rs1956921 and rs5244 were greater in male patients compared with male controls(P<0.01).

Conclusion: The rs1956921 C allele of the CMA1 gene and the C-T haplotype constructed with rs1956921 and rs5244 may be risk factors for essential hypertension in ethnic Yi males from Yunnan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2014.04.008DOI Listing
August 2014

Competition between Plasmodium falciparum strains in clinical infections during in vitro culture adaptation.

Infect Genet Evol 2014 Jun 22;24:105-10. Epub 2014 Mar 22.

Department of Pathogen Biology and Immunology, Kunming Medical University, Yunnan Province 650500, China. Electronic address:

We evaluated the dynamics of parasite populations during in vitro culture adaptation in 15 mixed Plasmodium falciparum infections, which were collected from a hypoendemic area near the China-Myanmar border. Allele types at the msp1 block 2 in the initial clinical samples and during subsequent culture were quantified weekly using a quantitative PCR method. All mixed infections carried two allele types based on the msp1 genotyping result. We also genotyped several polymorphic sites in the dhfr, dhps and mdr1 genes on day 0 and day 28, which showed that most of the common sites analyzed were monomorphic. Two of the three clinical samples mixed at dhps 581 remained stable while one changed to wild-type during the culture. During in vitro culture, we observed a gradual loss of parasite populations with 10 of the 15 mixed infections becoming monoclonal by day 28 based on the msp1 allele type. In most cases, the more abundant msp1 allele types in the clinical blood samples at the beginning of culture became the sole or predominant allele types on day 28. These results suggest that some parasites may have growth advantages and the loss of parasite populations during culture adaptation of mixed infections may lead to biased results when comparing the phenotypes such as drug sensitivity of the culture-adapted parasites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2014.03.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037425PMC
June 2014

Association of polymorphisms in prolylcarboxypeptidase and chymase genes with essential hypertension in the Chinese Han population.

J Renin Angiotensin Aldosterone Syst 2013 Sep 7;14(3):263-70. Epub 2012 Jun 7.

Cell Biology and Genetics Department, Kunming Medical University, China.

Introduction: The prolylcarboxypeptidase (PRCP) gene encodes a membrane protein that acts on angiotensin II (Ang II) and kallikrein to release vasoactive peptides. The chymase (CMA1) gene is important for Ang II generation. Therefore, the two genes might be involved in the pathogenesis of essential hypertension (EH).

Materials And Methods: Eleven tag single nucleotide polymorphisms (SNPs) in the PRCP gene and four tag SNPs and G-1903A (rs1800875) polymorphism in the CMA1 gene were genotyped in the Chinese Han population (n=1020) using a polymerase chain reaction-restriction fragment length polymorphism method.

Results: In the PRCP gene, single site analyses indicated that the rs7104980 G allele was a susceptible factor for EH (adjusted odds ratio (OR)=1.98, 95% confidence interval (CI) 1.62-2.43, p=0.3×10(-10)). The protective effect of Hap3 GAGCACTAACA was observed without carrying the susceptible rs7104908 G allele (OR=0.67, 95% CI 0.56-0.81, p=0.3×10(-4)) by haplotype analyses. In the case of the CMA1 gene, no associations with EH were found through single site analyses. However, haplotype analyses showed that Hap16 TTTA significantly increased the risk of EH with OR=3.15 (p=0.0002) which may be driven by interaction with a nearby SNP combination.

Conclusions: The present results indicated PRCP rs7104980 can be considered as a marker for EH and Hap3 GAGCACTAACA (PRCP) and Hap16 TTTA (CMA1) might be associated with EH in Chinese Han population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1470320312448949DOI Listing
September 2013

α-Kinase 2 is a novel candidate gene for inherited hypertension in Dahl rats.

J Hypertens 2011 Jul;29(7):1320-6

Department of Medicine, Research Centre, Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Quebec, Canada.

Objectives: The interval harboring a quantitative trait locus for blood pressure (BP), C18QTL3, contains β-2 adrenergic receptor (Adrb2) and neural precursor cell expressed, developmentally downregulated 4-like (Nedd4l) genes. None of the other genes in the C18QTL3-residing interval is known to affect BP. The identification of C18QTL3 might uncover a brand new gene that could prosper into a novel diagnostic and/or therapeutic target for essential hypertension, if neither Adrb2 nor Nedd4l could be upheld as candidate genes.

Methods: Congenic fine resolution was combined with gene analyses.

Results: The gene encoding α-kinase 2 (Alpk2) contains a three base-pair deletion and multiple nonconserved mutations in its coding region in Dahl salt-sensitive (DSS) rats. In contrast, the gastrin-releasing peptide gene (Grp) possesses two nonconserved mutations, designated as single nucleotide polymorphisms 1 and 2 (i.e. SNP1 and SNP2), but could not be supported as a candidate gene because the C18S.L14 congenic strain displayed a homozygous DSS genotype at both SNP1 and SNP2. Furthermore, Adrb2 and Nedd4l could not account for the BP-diminishing effect of Lewis alleles in C18S.L14, as their DSS alleles bear functionally identical domains as those of Lewis, and no evidence of differential expression and splicing was evident. No significant nucleotide variations were found in 13 other genes closely linked to Alpk2.

Conclusion: Alpk2 emerged as a strong candidate gene for C18QTL3. The present study is the first to implicate Alpk2 in the genetics of polygenic hypertension and paves the way for novel gene discovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0b013e32834705e4DOI Listing
July 2011

Polymorphisms in PPARD, PPARG and APM1 associated with four types of traditional Chinese medicine constitutions.

J Genet Genomics 2010 Jun 1;37(6):371-9. Epub 2010 Jul 1.

Human Genetics Center of Yunnan University, Kunming, China.

Based on the theory of constitution of Traditional Chinese Medicine (TCM), the human population is divided into nine constitutions including one balanced constitution (Normality) and eight unbalanced constitutions (Yang-deficiency, Yin-deficiency, Phlegm-wetness, Qi-deficiency, Wetness-heat, Blood stasis, Depressed constitution, and Inherited special constitution). Different constitutions have specific metabolic features and different susceptibility to certain diseases. However, whether a genetic basis accounts for such constitution classification is yet to be determined. Here we performed a genetic study to assess the association between genetic variations of metabolic genes including PPARD, PPARG and APM1 and the constitutions. A total of 233 individuals of the Han population in China were classified into four groups, Normality, Yang-deficiency, Yin-deficiency and Phlegm-wetness with whom 23 single nucleotide polymorphisms (SNPs) in the three genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Biased distribution of PPARD rs2267669 and rs2076167, APM1 rs7627128 and rs1063539 in Yang-deficiency, PPARG Pro12Ala in Yin-deficiency and PPARD rs2076167, APM1 rs266729 and rs7627128 in Phlegm-wetness were observed. The frequencies of Haplotype13 (Hap13) of PPARG in Yin-deficiency, Hap25 of APM1 in Yang-deficiency and Hap2 of PPARD and Hap14 of PPARG in Phlegm-wetness, were significantly different from those in Normality, suggesting those might be group-associated haplotypes. These results suggested that single SNP and haplotypes of PPARD, PPARG and APM1 may underlie the genetic basis of the constitutions classified in TCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1673-8527(09)60055-2DOI Listing
June 2010

DIXDC1 co-localizes and interacts with gamma-tubulin in HEK293 cells.

Cell Biol Int 2009 Jun 16;33(6):697-701. Epub 2009 Apr 16.

Department of Brain Protection and Plasticity Research, Beijing Institute of Basic Medical Sciences, Beijing, PR China.

DIXDC1 is a Dishevelled-Axin (DIX) domain-containing protein involved in neural development and Wnt signaling pathway. Besides the DIX domain, DIXDC1 also contains a coiled-coil domain (MTH domain), which is a common feature of centrosomal proteins. We have demonstrated that exogenously expressed GFP-tag fused DIXDC1 co-localize with gamma-tubulin both at interphase and mitotic phase in HEK293 cells. By immunostaining with anti-DIXDC1 and anti-gamma-tubulin antibody, endogenous DIXDC1 was also co-localized with gamma-tubulin at the centrosomes in HEK293 cells. We confirmed this interaction of DIXDC1 with gamma-tubulin by co-immunoprecipitation. The findings suggest that DIXDC1 might play an important role in chromosome segregation and cell cycle regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellbi.2009.04.001DOI Listing
June 2009

Sema4C expression in neural stem/progenitor cells and in adult neurogenesis induced by cerebral ischemia.

J Mol Neurosci 2009 Sep 3;39(1-2):27-39. Epub 2009 Feb 3.

Department of Brain Protection and Plasticity Research, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing, 100850, People's Republic of China.

Sema4C is a transmembrane protein that belongs to axon guidance molecules of semaphorin family. Previous reports have shown that Sema4C could interact with postsynaptic protein PSD95, etc, but the expression and the role of Sema4C in neurogenesis remains unknown. In this study, whole-mount in situ hybridization result showed that Sema4C was expressed abundantly in the areas of lateral ventricle, the striatum, the wall of midbrain, and the pons/midbrain junction of E11.5 embryos brain. Neural stem/progenitor cells (NSPs) obtained from E13.5 embryonic rat midbrain are also positive for Sema4C immunoreactivity. Sema4C expression was dramatically downregulated during induction of NSP differentiation. In order to confirm the involvement of Sema4C in neurogenesis, we used the rat global cerebral ischemia model to make adult neurogenesis in vivo. The robust proliferative NSPs were monitored by labeling with bromodeoxyuridine (BrdU) within the subventricular zone and dentate gyrus that continues for at least 2 weeks. Immunohistochemistry and Western blot analysis showed that Sema4C expression was dramatically upregulated during neurogenesis after cerebral ischemia-perfusion injury. Double immunostaining and stereologic counting analysis indicated that a high proportion of BrdU-positive proliferative cells were Nestin-positive NSPs, and also, Sema4C was highly expressed in these proliferative populations at specific stages after ischemic injury. These observations provide the evidence to support a putative role of Sema4C during neurogenesis both in vivo and in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12031-009-9177-8DOI Listing
September 2009

Localization and cellular distribution of CPNE5 in embryonic mouse brain.

Brain Res 2008 Aug 28;1224:20-8. Epub 2008 May 28.

Department of Brain Protection and Plasticity Research, Beijing Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, P.R. China.

CPNE5 is one of the ubiquitous Ca(2+)-dependent, phospholipid-binding proteins that are highly conserved in animals. It was cloned in the fetal human brain with no exact functions identified yet. We have examined the distribution pattern of CPNE5 mRNA and protein in the developing murine brain by using in situ hybridization, western blotting and immunocytochemistry. Expression of CPNE5 mRNA remains high from embryonic day 9.5 (E9.5) to E15.5 in the developing murine brain. Whole-mount in situ hybridization with the E11.5 and E12.5 embryos showed the strong positive signals in the central nervous system. Western-blot analysis showed that CPNE5 protein is expressed in the developing but not in the adult murine brain. In situ hybridization and immunohistochemistry analysis on the embryonic brain sections indicated that both at RNA and protein levels CPNE5 is mainly expressed in frontal cortex, medial nasal prominence, ganglionic eminence and medulla, particularly in the ventricular zones. Further investigation revealed the co-localization of CPNE5 with Tuj1 and Nestin on embryonic brain sections. In addition to the slight expression in primary cultured neural progenitor cells, CPNE5 is found in soma and neurite projections of primary cultured neurons where Tuj1 is co-localized. Our results demonstrate that CPNE5 is expressed in both neural progenitor cells and the differentiated neurons during the neural development, which suggests that CPNE5 might play an important role in the development of murine central nervous system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2008.05.051DOI Listing
August 2008

Sema4C participates in myogenic differentiation in vivo and in vitro through the p38 MAPK pathway.

Eur J Cell Biol 2007 Jun 10;86(6):331-44. Epub 2007 May 10.

Department of Brain Protection & Plasticity Research, Beijing Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China.

Sema4C is a member of transmembrane semaphorin proteins which regulate axonal guidance in the developing nervous system. The expression of Sema4C was dramatically induced not only during differentiation of C2C12 mouse myoblasts, but also during injury-induced skeletal muscle regeneration. C2C12 cells stably or transiently expressing Sema4C both showed increased myogenic differentiation reflected by accelerated myotube formation and expression of muscle-specific proteins. Overexpression of Sema4C elicited p38 phosphorylation directly, and the effects of Sema4C during myogenic differentiation could be abolished by the p38alpha-specific inhibitor SB203580. Knockdown of Sema4C by siRNA transfection during C2C12 myoblasts differentiation could suppress the phosphorylation of p38 followed by dramatically diminished myotube formation. Sema4C could activate the myogenin promoter during myogenic differentiation. This activation could be abolished by p38 inhibitor SB203580. Taken together, these observations reveal novel functional potentialities of Sema4C which suggest that Sema4C promotes terminal myogenic differentiation in a p38 MAPK-dependent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejcb.2007.03.002DOI Listing
June 2007
-->