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Biomedical subjects

Jun Zhu

Publications and source records attributed to Jun Zhu.

At least 37 records · Page 2Linked to original sources
PubMed2006

A Vibrio cholerae protease needed for killing of Caenorhabditis elegans has a role in protection from natural predator grazing.

Vibrio cholerae is the causal bacterium of the diarrheal disease cholera, and its growth and survival are thought to be curtailed by bacteriovorous predators, e.g., ciliates and flagellates. We explored Caenorhabditis elegans as a test organism after finding that V. cholerae can cause lethal infection of this nematode. By reverse genetics we identified an extracellular protease, the previously uncharacterized PrtV protein, as being necessary for killing. The killing effect is associated with the colonization of bacteria within the Caenorhabditis elegans intestine. We also show that PrtV is essential for V. cholerae in the bacterial survival from grazing by the flagellate Cafeteria roenbergensis and the ciliate Tetrahymena pyriformis. The PrtV protein appears to have an indirect role in the interaction of V. cholerae with mammalian host cells as judged from tests with tight monolayers of human intestinal epithelial cells. Our results demonstrate a key role for PrtV in V. cholerae interaction with grazing predators, and we establish Caenorhabditis elegans as a convenient organism for identification of V. cholerae factors involved in host interactions and environmental persistence.

Animals↗
PubMed2006

Screening rates and characteristics of health plan members who respond to screening reminders.

INTRODUCTION: Preventive screening is widely recognized as a key component of cost-effective, high-quality health care. Even so, national screening for cancer, diabetes, and cholesterol falls far short of U.S. Preventive Services Task Force recommendations. Although evidence has shown that reminder programs improve preventive screening rates, this study is one of the first to examine the characteristics of health plan members who respond to screening reminders. METHODS: The study sample included active members of a large health plan in Hawaii who were identified by an algorithm as not having received one or more recommended screenings based on age and sex criteria (2000-2003) for breast cancer (n = 44,331), cervical cancer (n = 73,875), colon cancer (n = 131,860), diabetes (n = 86,216), and cholesterol (n = 54,843). Statistical analyses were conducted using Cox proportional hazard and logistic regression models. In the proportional hazard models, reminder letters were treated as time-varying exposures. Hazard ratios, or rate ratios, were used to examine the relationship between health plan member and physician characteristics and the likelihood of responding to the reminders. The effects of additional or multiple reminders among health plan members receiving more than one reminder were examined in multivariable regression models. RESULTS: The impact of health plan member characteristics and number of office visits on the response to reminders varied among the five health-screening types. Health plan members responded better to reminders for diabetes screening than for colon cancer screening. Members sent their second annual reminders were less likely to obtain screening than members sent their first reminder. Members receiving their third (or more) annual reminder were especially recalcitrant. CONCLUSION: Our findings suggest that the response to reminders differs according to patient characteristics. In particular, targeted interventions may be needed to encourage screening for younger and healthier members whose response rate to reminders was low. Further research is needed to determine how health plans can best reach members who do not respond to patient reminders.

Aged↗
PubMed2006

Genome-wide investigation of intron length polymorphisms and their potential as molecular markers in rice (Oryza sativa L.).

Intron length polymorphisms (ILPs) have been used as genetic markers in some studies. However, a systematic investigation and large-scale exploitation of ILP markers has not been reported. In this study, we performed a genome-wide search of ILPs between two subspecies (indica and japonica) in rice using the draft genomic sequences of cultivars 93-11 (indica) and Nipponbare (japonica) and 32,127 full-length cDNA sequences of Nipponbare obtained from public databases. We identified 13,308 putative ILPs. Based on these putative ILPs, we developed 5811 candidate ILP markers via electronic-PCR with primers designed in flanking exons. We further conducted experiment to verify the candidate ILP markers. Out of 215 candidate ILP markers tested on 93-11, Nipponbare and their hybrid, we successfully exploited 173 codominant ILP markers. Further analyses on 10 rice accessions showed that these ILP markers were widely applicable and most (71.1%) exhibited subspecies specificity. This feature suggests that ILPs would be useful for the studies of genome evolution and inter-subspecies heterosis and for cross-subspecies marker-assisted selection in rice. In addition, by testing 51 pairs of the ILP primers on five Gramineae plants and three dicot plants, we found another desirable characteristic of rice ILP markers that they have high transferability to other plants.

Base Sequence↗
PubMed2006

Long-range polony haplotyping of individual human chromosome molecules.

We report a method for multilocus long-range haplotyping on human chromosome molecules in vitro based on the DNA polymerase colony (polony) technology. By immobilizing thousands of intact chromosome molecules within a polyacrylamide gel on a microscope slide and performing multiple amplifications from single molecules, we determined long-range haplotypes spanning a 153-Mb region of human chromosome 7 and found evidence of rare mitotic recombination events in human lymphocytes. Furthermore, the parallel nature of DNA polony technology allows efficient haplotyping on pooled DNAs from a population on one slide, with a throughput three orders of magnitudes higher than current molecular haplotyping methods. Linkage disequilibrium statistics established by our pooled DNA haplotyping method are more accurate than statistically inferred haplotypes. This haplotyping method is well suited for candidate gene-based association studies as well as for investigating the pattern of recombination in mammalian cells.

Chromosome Mapping↗
PubMed2006

Functional mapping for genetic control of programmed cell death.

"Naturally occurring" or "programmed" cell death (PCD) in which the cell uses specialized cellular machinery to kill itself is a ubiquitous phenomenon that occurs early in organ development. Such a cell suicide mechanism that enables metazoans to control cell number and eliminate cells threatening the organism's survival has been thought to be under genetic control. In this report, we develop a novel statistical model for mapping specific genes or quantitative trait loci (QTL) that are responsible for the PCD process based on polymorphic molecular markers. This model incorporates the biological mechanisms of PCD that undergoes two different developmental stages, exponential growth and polynomial death. We derived a parametric approach to model the exponential growth and a nonparametric approach based on the Legendre function to model the polynomial death. A series of stationary and nonstationary models has been used to approximate the structure of the covariance matrix among cell numbers at a multitude of different times. The statistical behavior of our model is investigated through simulation studies and validated by a real example in rice.

Apoptosis↗
PubMed2006

Identification of novel in vivo Raf-1 phosphorylation sites mediating positive feedback Raf-1 regulation by extracellular signal-regulated kinase.

The Ras-Raf-mitogen-activated protein kinase cascade is a key growth-signaling pathway, which uncontrolled activation results in transformation. Although the exact mechanisms underlying Raf-1 regulation remain incompletely understood, phosphorylation has been proposed to play a critical role in this regulation. We report here three novel epidermal growth factor-induced in vivo Raf-1 phosphorylation sites that mediate positive feedback Raf-1 regulation. Using mass spectrometry, we identified Raf-1 phosphorylation on three SP motif sites: S289/S296/S301 and confirmed their identity using two-dimensional-phosphopeptide mapping and phosphospecific antibodies. These sites were phosphorylated by extracellular signal-regulated kinase (ERK)-1 in vitro, and their phosphorylation in vivo was dependent on endogenous ERK activity. Functionally, ERK-1 expression sustains Raf-1 activation in a manner dependent on Raf-1 phosphorylation on the identified sites, and S289/296/301A substitution markedly decreases the in vivo activity of Raf-1 S259A. Importantly, the ERK-phosphorylated Raf-1 pool has 4 times higher specific kinase activity than total Raf-1, and its phosphopeptide composition is similar to that of the general Raf-1 population, suggesting that the preexisting, phosphorylated Raf-1, representing the activatable Raf-1 pool, is the Raf-1 subpopulation targeted by ERK. Our study describes the identification of new in vivo Raf-1 phosphorylation sites targeted by ERK and provides a novel mechanism for a positive feedback Raf-1 regulation.

Amino Acid Sequence↗
PubMed2006

Midline NK/T-cell lymphoma nasal-type: treatment outcome, the effect of L-asparaginase based regimen, and prognostic factors.

PURPOSE: Midline NK/T-cell lymphoma nasal-type is an aggressive neoplasm with poor prognosis in most instances. To improve the treatment outcome, we have tried using L-asparaginase based regimen as salvage regimen plus radiation in CHOP failures, and report here the therapeutic results and prognostic factors. PATIENTS AND METHODS: From March 1992 to January 2005, 46 Chinese patients with midline NK/T-cell lymphoma nasal-type were initially treated with CHOP regimen as first-line chemotherapy. The patients who failed CHOP regimens were altered to receive L-asparaginase based salvage regimen. All the patients received primary involved-field radiation after chemotherapy. RESULTS: Thirteen patients (28.3%) sensitive to CHOP regimen received CHOP regimen for 6 cycles plus locoregional radiation, and achieved complete remission (CR). Thirty-three patients failed CHOP regimen were altered to received L-asparaginase-based salvage regimen for 2 approximately 6 cycles (median 3 cycles) plus locoregional radiation, and seventeen of the 33 CHOP failures (51.5 %) (L-asparaginase group) reached CR. The CR rate for the whole group was 65.2% (30/46 cases). The 5-year overall survival (OS) rates were 64.5% for the whole group and 55.9% for L-asparaginase group, respectively. On univariate analysis, disease stage, fever symptom and performance status were significant factors influencing overall survival. On multivariate analysis, only disease stage and fever symptom remained as independently significant factors influencing OS. CONCLUSION: In this preliminary study, the results indicated that L-asparaginase based regimen might be a promising new salvage chemotherapeutic regimen in CHOP failures and conduce to improve the treatment outcome in midline NK/T-cell lymphoma, nasal-type.

Adolescent↗
PubMed2006

Map-based cloning of a novel rice cytochrome P450 gene CYP81A6 that confers resistance to two different classes of herbicides.

Development of hybrid rice has greatly contributed to increased yields during the past three decades. Two bentazon-lethal mutants 8077S and Norin8m are being utilized in developing new hybrid rice systems. When the male sterile lines are developed in such a mutant background, the problem of F1 seed contamination by self-seeds from the sterile lines can be solved by spraying bentazon at seedling stage. We first determined the sensitivity of the mutant plants to bentazon. Both mutants showed symptoms to bentazon starting from 100 mg/l, which was about 60-fold, lower than the sensitivity threshold of their wild-type controls. In addition, both mutants were sensitive to sulfonylurea-type herbicides. The locus for the mutant phenotype is bel for 8077S and bsl for Norin8m. Tests showed that the two loci are allelic to each other. The two genes were cloned by map-based cloning. Interestingly, both mutant alleles had a single-base deletion, which was confirmed by PCR-RFLP. The two loci are renamed bel ( a ) (for bel) and bel ( b ) (for bsl). The wild-type Bel gene encodes a novel cytochrome P450 monooxgenase, named CYP81A6. Analysis of the mutant protein sequence also revealed the reason for bel ( a ) being slightly tolerant than bel ( b ). Introduction of the wild-type Bel gene rescued the bentazon- and sulfonylurea-sensitive phenotype of bel ( a ) mutant. On the other hand, expression of antisense Bel in W6154S induced a mutant phenotype. Based on these results we conclude that the novel cytochrome P450 monooxygenase CYP81A6 encoded by Bel confers resistance to two different classes of herbicides.

Alleles↗
PubMed2006

Impacts of QTL x environment interactions on genetic response to marker-assisted selection.

Genotype x environment (GE) interaction is a common characteristic for quantitative traits, and has been a subject of great concern for breeding programs. Simulation studies were conducted to investigate the effects of GE interaction on genetic response to marker-assisted selection (MAS). In our study we demonstrated that MAS is generally more efficient than phenotypic selection in the presence of GE interaction, and this trend is more pronounced for developing broadly adaptable varieties. The utilization of different QTL information dramatically influences MAS efficiency. When MAS is based on QTLs evaluated in a single environment, the causal QTL x environment (QE) interactions usually reduce general response across environments, and the reduction in the cumulative general response is a function of the proportion of QE interactions for the trait studied. However, MAS using QTL information evaluated in multiple environments not only yields higher general response, but the general response obtained is also reasonably robust to QE interactions. The total response achieved by MAS in a specific environment depends largely on the total heritability of traits and is slightly subject to relative changes between general heritability and GE interaction heritability. Two breeding strategies, breeding experiments conducted in one environment throughout and in two environments alternately, were also examined for the implementation of marker-based selection. It was thus concluded that plant breeders should be cautious to utilize QTL information from only one environment and execute breeding studies in another.

Breeding↗
PubMed2006

Mapping QTL for biomass yield and its components in rice (Oryza sativa L.).

Additive effects, additive by additive epistatic effects, and their environmental interactions of QTLs are important genetic components of quantitative traits. Genetic architecture underlying rice biomass yield and its two component traits (straw yield and grain yield) were analyzed for a population of 125 DH lines from an inter-subspecific cross of IR64/Azucena. The mixed-model based composite interval mapping approach (MCIM) was used to detect QTLs, There were 12 QTLs detected with additive main effects, 27 QTLs involved in digenic interaction with aa and/or aae effects, and 18 QTLs affected by environments with ae and/or aae effects. It was revealed that epistatic effects and QE interaction effects existed on biomass yield and its component traits in rice. In addition, the genetic basis of relationships among these traits were investigated. Four QTLs and one pair of epistatic QTLs were detected to be responsible for the positive correlation between biomass yield and straw yield. Three QTLs might be responsible for the negative correlation between straw yield and grain yield. This result could partially explain the genetic basis of correlation among the three traits, and provide useful information for genetic improvement of these traits by marker-assisted selection.

Biomass↗
PubMed2006

The impact of seeing physicians new to a patient on the response to screening reminders.

BACKGROUND: A large insurer in Hawaii mails annual reminders to its members regarding recommended health screenings. This study examined the associations between the characteristics of physicians visited after the reminders were sent and the health screenings received for breast, cervical, and colorectal cancers, and for diabetes and cholesterol. METHODS: The study population included members identified as needing health screenings from 2000 to 2003 based on age and gender criteria. The study used a longitudinal design focusing on the 12 months after reminders were sent. Data were analyzed using logistic regression examining physician visits, other health services, and receipt of health screenings by 1-month intervals subsequent to the reminder mailings. RESULTS: In adjusted, multivariable models, members who saw physicians they had not seen in the past year had odds ratios for obtaining health screenings 6 to 8 times higher than members who only saw previously visited physicians. This enhanced response occurred among members receiving their first, second, and third (or subsequent) annual reminder letter. The more physicians that were visited and who were new to the members, the more likely the members were to obtain health screenings. CONCLUSIONS: Members seeing physicians they had not seen in the past year had significantly higher screening rates than the members only seeing physicians they had previously visited. The results suggest that healthcare screening may receive less attention at repeat visits with a physician than at visits with a physician who is new to a member.

Adult↗
PubMed2006

Bile acids stimulate biofilm formation in Vibrio cholerae.

Vibrio cholerae is a Gram-negative bacterium that causes the acute diarrhoeal disease cholera. After the bacterium is ingested, it passes through the digestive tract, encountering various environmental stresses including the acidic milieu of the stomach and the toxic effects of bile in the duodenum. While these stresses serve as part of a host defence system, V. cholerae has evolved resistance mechanisms that allow it to evade these defences and establish infection. We examined the expression profiles of V. cholerae in response to bile or bile acids and found an induction of biofilm genes. We found that V. cholerae shows significantly enhanced biofilm formation in response to bile acids, and that bacteria within the biofilm are more resistant to the toxicity of bile acids compared with planktonic cells. Bile acid induction of biofilms was found to be dependent on the vps genes (Vibrio polysaccharide synthesis) and their transcriptional activator VpsR, but VpsT is not required. These results contribute to the developing picture of a complex relationship between V. cholerae and its environment within the host during infection.

Bacterial Proteins↗
PubMed2006

Elucidating the murine brain transcriptional network in a segregating mouse population to identify core functional modules for obesity and diabetes.

Complex biological systems are best modeled as highly modular, fluid systems exhibiting a plasticity that allows them to adapt to a vast array of changing conditions. Here we highlight several novel network-based approaches to elucidate genetic networks underlying complex traits. These integrative genomic approaches combine large-scale genotypic and gene expression results in segregating mouse populations to reconstruct reliable genetic networks underlying complex traits such as disease or drug response. We apply these novel approaches to one of the most extensive surveys of gene expression studies ever undertaken in whole brain in a segregating mouse population. More than 23,000 genes were monitored in whole brain samples from more than 300 mice derived from an F2 intercross population and genotyped at over 1200 SNP markers uniformly spread over the entire genome. We explore the topological properties of the brain transcriptional network and highlight different approaches to inferring causal associations among genes by integrating genotypic and expression data. We demonstrate the utility of these approaches by identifying and experimentally validating brain gene expression traits predicted to respond to a strong expression quantitative trait locus (eQTL) for the pituitary tumor-transforming 1 gene (Pttg1) that coincides with the physical location of this gene (a cis eQTL). We identify core functional modules making up the brain transcriptional network in mice that are coherent for core biological processes associated with metabolic disease traits including obesity and diabetes.

Animals↗
PubMed2006

Genetic and phenotypic diversity of quorum-sensing systems in clinical and environmental isolates of Vibrio cholerae.

Vibrio cholerae is the causative agent of cholera, a severe and devastating diarrheal disease. V. cholerae lives naturally in various aquatic habitats during interepidemic periods. Recent studies reveal that quorum-sensing systems, which exist in many bacteria and help them monitor their population densities and regulate various cellular functions, control V. cholerae pathogenesis, biofilm formation, and protease production. In this study we surveyed quorum-sensing systems in 16 geographically diverse V. cholerae strains from epidemic-causing O1 and O139 strains as well as non-O1/non-O139 and environmental isolates and discovered an unexpectedly high rate of dysfunctional components. We also found that a functional quorum-sensing system conferred a survival advantage on bacteria in biofilms when the bacteria were exposed to seawater, though quorum sensing was less important to survival in a planktonic state under the same conditions. These findings suggest that variations in quorum-sensing systems are due to environmental selective pressures and might be beneficial to V. cholerae's fitness under certain conditions found in its natural reservoirs.

Amino Acid Sequence↗
PubMed2006

A LuxR/LuxI-type quorum-sensing system in a plant bacterium, Mesorhizobium tianshanense, controls symbiotic nodulation.

The ability of rhizobia to symbiotically fix nitrogen from the atmosphere when forming nodules on their plant hosts requires various signal transduction pathways. LuxR-LuxI-type quorum-sensing systems have been shown to be one of the players in a number of rhizobium species. In this study, we found that Mesorhizobium tianshanense, a moderate-growth Rhizobium that forms nodules on a number of licorice plants, produces multiple N-acyl homoserine lactone (AHL)-like molecules. A simple screen for AHL synthase genes using an M. tianshanense genomic expression library in Escherichia coli, coupled with a sensitive AHL detector, uncovered a LuxI-type synthase, MrtI, and a LuxR-type regulator, MrtR, in M. tianshanense. Deletions of the mrtI or mrtR locus completely abolished AHL production in M. tianshanense. Using lacZ transcriptional fusions, we found that expression of the quorum-sensing regulators is autoinduced, as mrtI gene expression requires MrtR and cognate AHLs and mrtR expression is dependent on AHLs. Compared with the wild-type strains, quorum-sensing-deficient mutants showed a marked reduction in the efficiency of root hair adherence and, more importantly, were defective in nodule formation on their host plant, Glycyrrhiza uralensis. These data provide strong evidence that quorum sensing plays a critical role in the M. tianshanense symbiotic process.

4-Butyrolactone↗
PubMed2006

The transcriptional regulator VqmA increases expression of the quorum-sensing activator HapR in Vibrio cholerae.

Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. A number of environmental stimuli regulate virulence gene expression in V. cholerae, including quorum-sensing signals. At high cell densities, quorum sensing in V. cholerae invokes a series of signal transduction pathways in order to activate the expression of the master regulator HapR, which then represses the virulence regulon and biofilm-related genes and activates protease production. In this study, we identified a transcriptional regulator, VqmA (VCA1078), that activates hapR expression at low cell densities. Under in vitro inducing conditions, constitutive expression of VqmA represses the virulence regulon in a HapR-dependent manner. VqmA increases hapR transcription as measured by the activity of the hapR-lacZ reporter, and it increases HapR production as measured by Western blotting. Using a heterogenous luxCDABE cosmid, we found that VqmA stimulates quorum-sensing regulation at lower cell densities and that this stimulation bypasses the known LuxO-small-RNA regulatory circuits. Furthermore, we showed that VqmA regulates hapR transcription directly by binding to its promoter region and that expression of vqmA is cell density dependent and autoregulated. The physiological role of VqmA is also discussed.

Gene Expression Regulation, Bacterial↗
PubMed2006

Hepatitis B virus inhibiting constituents from Herpetospermum caudigerum.

From the ethanol extract of the seeds of Herpetospermum caudigerum wall, one new lignan compound 1, was isolated and characterized along with three known compounds 2, 3 and 4. The structure elucidation of the isolated new compound was performed on the basis of spectroscopic and chemical evidence. The structures of known compounds were determined by comparison of spectral data and physical data with those previously reported. The activity inhibiting hepatitis b virus was evaluated. Preliminary studies showed that compound 1 and 2 displayed promising inhibitory potential against hepatitis b virus.

Antiviral Agents↗