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Articles by J. Chen
Total Records ( 18 ) for J. Chen
  X Mao , X Nie , F Cao and J. Chen
 

Here we reported that, in Saccharomyces cerevisiae, deleting Swi1 (ScSwi1), a core component in Swi/Snf complex, caused defects of invasive growth, pseudohyphal growth, FLO11 expression, and proper cell separation. Re-introduction of SWI1 into the swi1 mutants could suppress all defects observed. We also showed that overproducing Swi1 could suppress the defect of flo8 cells in pseudohyphal growth in diploids, but not invasive growth in haploids. Overexpression of SWI1 could not bypass the requirement of Ste12 or Tec1 in invasive growth or pseudohyphal growth. We concluded that the Swi/Snf complex was required for FLO11 expression and proper cell separation, and both the FLO8 and STE12 genes should be present for the complex to function for the invasive growth but only the STE12 gene was required for the pseudohyphal growth. Ectopic expression of Candida albicans SWI1 (CaSWI1) could partially complement the defects examined of haploid Scswi1 mutants, but failed to complement the defects examined of diploid Scswi1/Scswi1 mutants. Overexpressing CaSwi1 mitigated invasive and pseudohyphal growth defects resulting from deletions in the MAP kinase and cAMP pathways. The integrity of S. cerevisiae Swi/Snf complex is required for invasive and filamentous growth promoted by overexpressing CaSwi1.

  X Nie , X Liu , H Wang and J. Chen
 

Phenotypic switching in Candida albicans spontaneously generates different cellular morphologies. The reversible switching between white and opaque phenotypes is regulated by multiple regulators including Efg1 and Wor1. In mating-type-like locus (MTL) homozygous cells, the Efg1 functions as a repressor, whereas the Wor1 acts as an activator in white–opaque switching. We presented evidence that switching between white and opaque in efg1/efg1 mutant is regulated by ambient pH. In pH 6.8 media, the efg1/efg1 mutant cells exhibited opaque form, but shifted to white form in pH 4.5 media. The pH-dependent morphological switching is not blocked by further deletion of WOR1 in the efg1/efg1 mutant. Correlated with the phenotype, the opaque-phase-specific gene OP4 was induced in efg1/efg1 mutant cells when cultured in pH 6.8 media, and was repressed in pH 4.5 media. Consistently, the MTLa efg1/efg1 mutant cells could mate efficiently with MTL cells in pH 6.8 media, but poorly in pH 4.5 media. Ectopic expression of the Rim101-405 allele in the efg1/efg1 mutant helped to bypass the pH restriction on white–opaque switching and show opaque form in both neutral and acidic media. We proposed that relief of the Efg1 repression enables C. albicans to undergo white–opaque switching in pH-dependent regulation mediated by Rim101-signaling pathway.

  J. Chen , E. Civerolo , K. Tubajika , S. Livingston and B. Higbee
  Xylella fastidiosa is a gram-negative plant pathogenic bacterium that causes almond leaf scorch disease (ALSD) and Pierce`s disease (PD) of grape in many regions of North America and Mexico. Of the two 16S rRNA gene genotypes described in California, A genotype strains cause ALSD only and G genotype strains cause both PD and ALSD. While G genotype strains cause two different diseases, little is known about their genetic variation. In this study, we identified a putative protease locus, PD0218 (pspB), in the genome of X. fastidiosa and evaluated the variation at this locus in X. fastidiosa populations. PD0218 contains tandem repeats of ACDCCA, translated to threonine and proline (TP), upstream of the putative protease conserved domain. Among 116 X. fastidiosa ALSD and PD strains isolated from seven locations in California, tandem repeat numbers (TRNs) varied from 9 to 47, with a total of 30 TRN genotypes, indicating that X. fastidiosa possesses an active mechanism for contracting and expanding tandem repeats at this locus. Significant TRN variation was found among PD strains (mean = 29.9), which could be further divided into two TRN groups: PD-Gsmall (mean = 17.3) and PD-Glarge (mean = 44.3). Less variation was found in ALSD strains (mean = 21.7). The variation was even smaller after ALSD strains were subdivided into the A and G genotypes (mean = 13.3, for the G genotype; mean = 27.1, for the A genotype). Genetic variation at the PD0218 locus is potentially useful for sensitive discrimination of X. fastidiosa strains. However, TRN stability, variation range, and correlation to phenotypes should be evaluated in epidemiological applications such as pathotype identification and delineation of pathogen origin.
  W. G Zhao , S. N Yu , Z. H Lu , Y. H Ma , Y. M Gu and J. Chen
 

Aberrantly expressed microRNA (miRNA) is frequently associated with a variety of cancers, including pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the expression and possible role of miR-217 in PDAC. Data obtained by locked nucleic acid in situ hybridization and real-time quantitative polymerase chain reaction showed that miR-217 was downregulated in 76.2% (16/21) of PDAC tissues and in all tested PDAC cell lines when compared with the corresponding normal pancreatic tissue. Overexpression of miR-217 in PDAC cells inhibited tumor cell growth and anchorage-independent colony formation and miR-217 decreased tumor cell growth in nude mouse xenografts in vivo. Using in silico predictions, KRAS was defined as a potential direct target of miR-217. Data from the dual-luciferase reporter gene assay showed that KRAS was a direct target of miR-217. Upregulation of miR-217 could decrease KRAS protein levels and reduce the constitutive phosphorylation of downstream AKT. Downregulation of miR-217 expression in PDAC cells could increase cell anchorage-independent colony formation and KRAS protein levels. Furthermore, miR-217 expression was observed to be negatively correlated with KRAS protein expression in PDAC cell lines. We conclude that the frequently downregulated miR-217 can regulate KRAS and function as a tumor suppressor in PDAC. Therefore, miR-217 may serve as a useful therapeutic agent for miRNA-based PDAC therapy.

  X. Liang , Q. Wang , X. Yang , J. Cao , J. Chen , X. Mo , J. Huang , L. Wang and D. Gu
  Aims  To assess the effect of mobile phone intervention on glycaemic control in diabetes self-management. Methods We searched three electronic databases (PubMed, EMBASE and Cochrane Library) using the following terms: diabetes or diabetes mellitus and mobile phone or cellular phone, or text message. We also manually searched reference lists of relevant papers to identify additional studies. Clinical studies that used mobile phone intervention and reported changes in glycosylated haemoglobin (HbA1c) values in patients with diabetes were reviewed. The study design, intervention methods, sample size and clinical outcomes were extracted from each trial. The results of the HbA1c change in the trials were pooled using meta-analysis methods.

Results  A total of 22 trials were selected for the review. Meta-analysis among 1657 participants showed that mobile phone interventions for diabetes self-management reduced HbA1c values by a mean of 0.5% [6 mmol/mol; 95% confidence interval, 0.3-0.7% (4-8 mmol/mol)] over a median of 6 months follow-up duration. In subgroup analysis, 11 studies among Type 2 diabetes patients reported significantly greater reduction in HbA1c than studies among Type 1 diabetes patients [0.8 (9 mmol/mol) vs. 0.3% (3 mmol/mol); P = 0.02]. The effect of mobile phone intervention did not significantly differ by other participant characteristics or intervention strategies.

Conclusions  Results pooled from the included trials provided strong evidence that mobile phone intervention led to statistically significant improvement in glycaemic control and self-management in diabetes care, especially for Type 2 diabetes patients.

  K. Pottie , A. Hadi , J. Chen , V. Welch and K. Hawthorne
 

Aims

Minority populations often face linguistic, cultural and financial barriers to diabetes education and care. The aim was to understand why culturally appropriate diabetes education interventions work, when they work best and for whom they are most effective.

Methods

This review used a critical realist approach to examine culturally appropriate diabetes interventions. Beginning with the behavioural model and access to medical care, it reanalysed 11 randomized controlled trials from a Cochrane systematic review and related programme and training documents on culturally appropriate diabetes interventions. The analysis examined context and mechanism to understand their relationship to participant retention and statistically improved outcomes.

Results

Minority patients with language barriers and limited access to diabetes programmes responded to interventions using health workers from the same ethnic group and interventions promoting culturally acceptable and financially affordable food choices using local ingredients. Programme incentives improved retention in the programmes and this was associated with improved HbA1c levels at least in the short term. Adopting a positive learning environment, a flexible and less intensive approach, one-to-one teaching in informal settings compared with a group approach in clinics led to improved retention rates.

Conclusions

Minority and uninsured migrants with unmet health needs showed the highest participation and HbA1c responses from culturally appropriate programmes.

  F. Bragg , L. Li , M. Smith , Y. Guo , Y. Chen , I. Millwood , Z. Bian , R. Walters , J. Chen , L. Yang , R. Collins , R. Peto , Y. Lu , B. Yu , X. Xie , Y. Lei , G. Luo and Z. Chen
 

Aims

To examine the relationship of self-reported diabetes, and of random blood glucose levels among individuals without known diabetes, with the prevalence of cardiovascular disease in Chinese adults.

Methods

We examined cross-sectional data from the China Kadoorie Biobank of 0.5 million people aged 30-79 years recruited from 10 diverse regions of China in the period 2004-2008. Logistic regression was used to estimate the odds ratios of prevalent cardiovascular disease associated with self-reported diabetes, and with measured random blood glucose levels among participants with no history of diabetes, adjusting simultaneously for age, sex, area, education, smoking, alcohol, blood pressure and physical activity.

Results

A total of 3.2% of participants had self-reported diabetes (men 2.9%; women 3.3%) and 2.8% had screen-detected diabetes (men 2.6%; women 2.8%), i.e. they had no self-reported history of diabetes but a blood glucose level suggestive of a diagnosis of diabetes. Compared with individuals without a history of diabetes, the odds ratios associated with self-reported diabetes were 2.18 (95% CI 2.06-2.30) and 1.88 (95% CI 1.75-2.01) for prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively. Among participants without self-reported diabetes there was a positive association between random blood glucose and ischaemic heart disease and stroke/transient ischaemic attack prevalence (P for trend <0.0001). Below the diabetic threshold (<11.1 mmol/l) each additional 1 mmol/l of random blood glucose was associated with 4% (95% CI 2-5%) and 5% (95% CI 3-7%) higher odds of prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively.

Conclusions

In this adult Chinese population, self-reported diabetes was associated with a doubling of the odds of prevalent cardiovascular disease. Below the threshold for diabetes there was still a modest, positive association between random blood glucose and prevalent cardiovascular disease.

  J Yuan , G Ghosal and J. Chen
 

Mutations in HepA-related protein (HARP) are the only identified causes of Schimke immunoosseous dysplasia (SIOD). HARP has a unique annealing helicase activity in vitro, but the in vivo functional significance remains unknown. Here, we demonstrated that HARP is recruited to stalled replication forks via its direct interaction with Replication protein A (RPA). Cells with HARP depletion displayed increased spontaneous DNA damage and G2/M arrest, suggesting that HARP normally acts to stabilize stalled replication forks. Our data place the annealing helicase activity of HARP at replication forks and propose that SIOD syndrome may be caused by the destabilization of replication forks during cell proliferation.

  A Fernandez and J. Chen
 

Proteins rely on associations to improve packing quality and thus maintain structural integrity. This makes packing deficiency a likely determinant of dosage sensitivity, that is, of the fitness impact of concentration imbalances relative to the stoichiometry of the protein complexes. This hypothesis was validated by examining evolution-related dosage imbalances: Duplicates of genes encoding for deficiently packed proteins are less likely to be retained than genes coding for well-packed proteins. This selection pressure is apparent in unicellular organisms, but is mitigated in higher eukaryotes. In human, this effect reveals a capacitance toward dosage imbalance. This capacitance is not expected in organisms with larger population size, where evolutionary forces are more efficient at promoting adaptive functional innovation and purifying selection, thus curbing the concentration imbalance arising from gene duplication. By examining miRNA target dissimilarities within human gene families, we show that the capacitance is operative at a post-transcriptional regulatory level: The higher the packing deficiency of a protein, the more likely that its paralogs will be dissimilarly targeted by miRNA to mitigate dosage imbalance. For families with low capacitance, paralog sequence divergence and family size correlate tightly with packing deficiency, just like in unicellular eukaryotes. Thus, a major component of human tolerance toward dosage imbalances is rooted in the paralog-discriminating capacity of miRNA regulation. The results may clarify the evolutionary etiology of aggregation-related diseases, since aggregation is often promoted by overexpression (a dosage imbalance) and aggregation propensity is associated with extreme packing deficiency.

  J. Chen , Y. Lu and X. Xie
  This study proposes a testing approach of component security based on dynamic fault tree and then specifies some related definitions of fault tree, fault injection model and attack pattern. A testing algorithm of component security based on dynamic fault tree and test-case generating approach are also proposed. The proposed testing approach generates fault injection cases which can trigger component vulnerabilities in maximum probability based on fault tree. At the same time, the fault tree can be improved according to the testing results after injecting faults. The proposed approach was implemented based on research projects CSTS (Component Security Testing System). The experimental results show that the approach is effective and can trigger lots of component exceptions by using fewer test-cases.
  J. Chen , H.B. Zhu , D. Wang , F.Q. Wang , H.S. Hao , W.H. Du and X.M. Zhao
  The objective of this study was to estimate the genetic parameters for growth traits in a cross between Piedmontese and Nanyang cattle. Data from the pure Italian Piedmontese and Chinese Nanyang breeds as well as from crosses between these two breeds were used to estimate genetic parameters and variance. Data were extracted from a base data set (49,646 growth records of 9,003 animals from 13 herds). The data were analyzed using the multiple-trait Restricted Maximum Likelihood (REML) Method to estimate the variance and the genetic parameters. The multiple-trait analysis included weights at birth, 6, 12, 18, 24 months and maturity. Weight heritability ranged from 0.34±0.01-0.54±0.03; the heritabilities at 24 months and at maturity were higher than at all other time points. Results indicated that growth traits were good traits for selection and cattle genetic evaluation. The estimates obtained in this study will be used in the breeding value estimation for national genetic evaluations of the Chinese crossbreed population between Piedmontese beef cattle and Nanyang Yellow cattle.
  L. Nie , H. Chu , Y. Cheng , C. Spurney , K. Nagaraju and J. Chen
  A marginal approach and a variance-component mixed effect model approach (here called a conditional approach) are commonly used to analyze variables that are subject to limit of detection. We examine the theoretical relationship and investigate the numerical performance of these two approaches. We make some recommendations based on our results. The marginal approach is recommended for bivariate normal variables, and the variance-component mixed effect model is preferable for other multivariate analysis in most circumstances. Two approaches are illustrated through one case study from a preclinical experiment.
  D Gu , M Wang , Z Zhang and J. Chen
 

Published data regarding the association between the apurinic/apyrimidinic endonuclease 1 (APE1) T1349G (Asp148Glu) polymorphism and cancer risk show inconclusive results. To derive a more precise estimation of the relationship, we performed a meta-analysis of 27 published studies that included 12 432 cancer cases and 17 349 controls. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the strength of the associations. The overall results suggested that the variant genotypes were associated with a moderately increased risk of all cancer types (OR = 1.09, 95% CI = 1.01–1.18 for TG versus TT; OR = 1.08, 95% CI = 1.00–1.18 for GG/TG versus TT). In the stratified analyses, the risk remained for studies of colorectal cancer, European populations and population-based studies. Although some modest bias could not be eliminated, this meta-analysis supported that the APE1 T1349G polymorphism is a low-penetrance risk factor for cancer development.

  L Bergman and J. Chen
 

In order for Canada to be better prepared to respond quickly to a radiological or nuclear emergency detailed knowledge regarding the locations and capacities of hospitals, relevant medical supplies and radiological or nuclear professionals is needed. These key points of information were identified at a CRTI workshop in 2009, and it was proposed that a medical resource database (MRD) was required. This database is in addition to the development of a radiation accident registry which was also proposed at the CRTI Workshop in 2009. The MRD has been designed, built and populated where possible; it is now ready for field testing and deployment. The creation of the database is one more step towards a better and more effective response in a radiological or nuclear emergency. In order to maintain this database and keep it up to date, contributions from all levels of radiation protection professionals will be needed. In this paper, the database structure and the data collected will be presented and discussed.

  J. Chen
 

In this article, sensitivities and doses to children from intakes of radionuclides by ingestion were studied relative to adults. Generally speaking, doses to children were higher due to their higher radiosensitiveness to many radionuclides, even though they consume less food and water than adults. Therefore, the action levels in the Canadian guidelines for the restriction of radioactively contaminated food and water following a nuclear emergency were selected as the most restrictive among the six age groups that could lead to an individual receiving a dose equal to a specified intervention level of 1 mSv. For non-emergency situations, the specified intervention level is 0.1 mSv. At such a low intervention level, the maximum acceptable concentrations (MAC) in drinking water are normally derived for adults. Although this is a common practice for guidelines in non-emergency operations, for those radionuclides when the doses to children are more than 10 times higher than the doses to adults, the MAC in non-emergency situations should be limited to, at least, as restrictive as the action levels for interventional action following a nuclear emergency.

  V.O. Adetunji and J. Chen
  This study introduced vacuum packaging into wara a West African soft cheese storage.Wara was vacuum packaged and stored in whey. Samples were taken during 5 and 21 day storage period at 15 and 28°C to determine populations of total aerobes(TA), anaerobes, Enterobacteriacea, psychrotrophs, as well as molds and yeasts(M/Y) in Log10 CFU g-1. TA increased from 2.25 and <1.00 to 7.67-8.16 and 5.82-8.33 respectively for Calotropis procera processed cheese (CPPC) and Lemon Processed Cheese(LPC) stored in whey at 28 and 15°C during the 5 day storage. Enterobacteriacea were undetectable (<1.00) during the 5 day storage at both temperatures. Anaerobes increased from 2.43 for CPPC and undetectable levels for LPC on 1day of storage to 6.91-8.68 and 5.67-9.01, respectively at 15 and 28°C storage in whey. Population s of M/Y remained undetectable until the 5d when the M/Y increased to 6.16-8.04 and 4.82-7.8, respectively for the CPPC and LPC at 28 and 15°C storage temperatures. In vacuum packaged cheese TA increased from 2.25 and <1.00 to 5.45-6.80 and 4.73-6.45, respectively for CPPC and LPC stored in whey at 28 and 15°C during the 21 day storage. Enterobacteriacea and M/Y were undetectable at the 1 day and at the end of 21 day storage at both temperatures. Anaerobes increased from 2.43 for CPPC and undetectable levels for LPC on 1 day of storage to 4.68-6.76 and 4.8-6.24, respectively at 15 and 28°C at the end of 21 day storage. The study suggests vacuum packaging can be introduced into “wara” storage to further reduce the microbial population.
  Y Ge , A. L Wu , C Warnes , J Liu , C Zhang , H Kawasome , N Terada , M. D Boppart , C. J Schoenherr and J. Chen
 

Rapamycin-sensitive signaling is required for skeletal muscle differentiation and remodeling. In cultured myoblasts, the mammalian target of rapamycin (mTOR) has been reported to regulate differentiation at different stages through distinct mechanisms, including one that is independent of mTOR kinase activity. However, the kinase-independent function of mTOR remains controversial, and no in vivo studies have examined those mTOR myogenic mechanisms previously identified in vitro. In this study, we find that rapamycin impairs injury-induced muscle regeneration. To validate the role of mTOR with genetic evidence and to probe the mechanism of mTOR function, we have generated and characterized transgenic mice expressing two mutants of mTOR under the control of human skeletal actin (HSA) promoter: rapamycin-resistant (RR) and RR/kinase-inactive (RR/KI). Our results show that muscle regeneration in rapamycin-administered mice is restored by RR-mTOR expression. In the RR/KI-mTOR mice, nascent myofiber formation during the early phase of regeneration proceeds in the presence of rapamycin, but growth of the regenerating myofibers is blocked by rapamycin. Igf2 mRNA levels increase drastically during early regeneration, which is sensitive to rapamycin in wild-type muscles but partially resistant to rapamycin in both RR- and RR/KI-mTOR muscles, consistent with mTOR regulation of Igf2 expression in a kinase-independent manner. Furthermore, systemic ablation of S6K1, a target of mTOR kinase, results in impaired muscle growth but normal nascent myofiber formation during regeneration. Therefore, mTOR regulates muscle regeneration through kinase-independent and kinase-dependent mechanisms at the stages of nascent myofiber formation and myofiber growth, respectively.

  J. Wen , L. Li , J. Chen , S. Ji , C. Zheng and Z. Liu
 

Objective: To observe the influence of the Tripterygium wilfordii Hook F (T II) on the blood concentration of tacrolimus and analyze the impact of this effect.

Method: Twenty-two renal transplant receipts taking tacrolimus combined with the T II were selected for this study. We analyzed the blood concentrations and the rate of concentration compared with dosage (C/D rate) pre- and postcombination over 6 months. All cases underwent the CYP3A5 genotype test.

Result: The concentrations of tacrolimus were raised to a certain degree after the combination in all the cases. The first-time elevation differed from 1 week to 4 months. The C/D rate increased by 1.7 to 7.2 times with most evaluated C/D rates ranging from 1.8 to 3.8. The elevated C/D rate of the subgroup of CYP3A5 1*/1* and 1*/*3 (n = 10) contrasted with the *3/*3 genotype subgroup (n = 12: 2.99 ± 1.71 vs 2.55 ± 1.07; P = .472). The mycophenolate mofetil subgroup (n = 17) was not contrasted to the mizoribine subgroup (n = 5: 2.85 ± 1.51 vs 2.31 ± 0.26; P = .498).

Conclusion: T II considerably increased the blood concentration and the C/D rate of tacrolimus. The degree of increase was probably not related to the CYP3A5 genotype and the combination of immunosuppressive agents.
 
 
 
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