207 research outputs found

    The promoter for intestinal cell kinase is head-to-head with F-Box 9 and contains functional sites for TCF7L2 and FOXA factors

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    <p>Abstract</p> <p>Background</p> <p>Intestinal cell kinase (ICK; GeneID 22858) is a conserved MAPK and CDK-like kinase that is widely expressed in human tissues. Data from the Cancer Genome Anatomy Project indicated ICK mRNA is increased in cancer, and that its expression correlated with expression of mRNA for an uncharacterized F-box protein, FBX9 (GeneID: 26268). <it>ICK </it>and <it>FBX9 </it>genes are arranged head-to-head on opposite strands, with start sites for transcription separated by ~3.3 kb. We hypothesized ICK and FBX9 are potentially important genes in cancer controlled by a bidirectional promoter.</p> <p>Results</p> <p>We assessed promoter activity of the intergenic region in both orientations in cancer cell lines derived from breast (AU565, SKBR3), colon (HCT-15, KM12), and stomach (AGS) cancers, as well as in embryonic human kidney (HEK293T) cells. The intergenic segment was active in both orientations in all of these lines, and ICK promoter activity was greater than FBX9 promoter activity. Results from deletions and truncations defined a minimal promoter for ICK, and revealed that repressors and enhancers differentially regulate ICK versus FBX9 promoter activity. The ICK promoter contains consensus motifs for several FOX-family transcription factors that align when mouse and human are compared using EMBOSS. FOXA1 and FOXA2 increase luciferase activity of a minimal promoter 10-20 fold in HEK293T cells. Consensus sites for TCF7L2 (TCF4) (Gene Id: 6934) are also present in both mouse and human. The expression of β-catenin increased activity of the minimal promoter ~10 fold. ICK reference mRNAs (NM_014920.3, NM_016513) are expressed in low copy number and increased in some breast cancers, using a ten base tag 5'-TCAACCTTAT-3' specific for both ICK transcripts.</p> <p>Conclusion</p> <p><it>ICK </it>and <it>FBX9 </it>are divergently transcribed from a bidirectional promoter that is GC-rich and contains a CpG island. A minimal promoter for <it>ICK </it>contains functional sites for β-cateinin/TCF7L2 and FOXA. These data are consistent with functions that have been proposed for ICK in development and in proliferation or survival of some breast and colon cancers.</p

    Epidemiology of Dengue Virus in Iquitos, Peru 1999 to 2005: Interepidemic and Epidemic Patterns of Transmission

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    To develop prevention (including vaccines) and control programs for dengue fever, a significant mosquito-borne disease in the tropics, there is an urgent need for comprehensive long term field epidemiological studies. We report results from a study that monitored ∼2,400 school children and some adult family members for dengue infection at 6 month intervals from 1999 to 2005, in the Amazonian city of Iquitos, Peru. At enrollment, ∼80% of the participants had a previous infection with DENV serotypes 1 and 2 or both. During the first 15 months, about 3 new infections for every 100 participants were observed among the study participants. In 2001, DENV-3, a serotype not previously observed in the region, invaded Iquitos in a process characterized by 3 distinct periods: amplification over at least a 5–6 month period, replacement of previously circulating serotypes, and epidemic transmission when incidence peaked. Incidence patterns of new infections were geographically distinct from baseline prevalence rates prior to arrival of DENV-3, but closely mirrored them during the invasion. DENV transmission varied geographically corresponding to elevated mosquito densities. The invasion of a novel serotype is often characterized by 5–6 months of silent transmission before traditional surveillance programs detect the virus. This article sets the stage for subsequent publications on dengue epidemiology

    Network Properties of Robust Immunity in Plants

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    Two modes of plant immunity against biotrophic pathogens, Effector Triggered Immunity (ETI) and Pattern-Triggered Immunity (PTI), are triggered by recognition of pathogen effectors and Microbe-Associated Molecular Patterns (MAMPs), respectively. Although the jasmonic acid (JA)/ethylene (ET) and salicylic acid (SA) signaling sectors are generally antagonistic and important for immunity against necrotrophic and biotrophic pathogens, respectively, their precise roles and interactions in ETI and PTI have not been clear. We constructed an Arabidopsis dde2/ein2/pad4/sid2-quadruple mutant. DDE2, EIN2, and SID2 are essential components of the JA, ET, and SA sectors, respectively. The pad4 mutation affects the SA sector and a poorly characterized sector. Although the ETI triggered by the bacterial effector AvrRpt2 (AvrRpt2-ETI) and the PTI triggered by the bacterial MAMP flg22 (flg22-PTI) were largely intact in plants with mutations in any one of these genes, they were mostly abolished in the quadruple mutant. For the purposes of this study, AvrRpt2-ETI and flg22-PTI were measured as relative growth of Pseudomonas syringae bacteria within leaves. Immunity to the necrotrophic fungal pathogen Alternaria brassicicola was also severely compromised in the quadruple mutant. Quantitative measurements of the immunity levels in all combinatorial mutants and wild type allowed us to estimate the effects of the wild-type genes and their interactions on the immunity by fitting a mixed general linear model. This signaling allocation analysis showed that, contrary to current ideas, each of the JA, ET, and SA signaling sectors can positively contribute to immunity against both biotrophic and necrotrophic pathogens. The analysis also revealed that while flg22-PTI and AvrRpt2-ETI use a highly overlapping signaling network, the way they use the common network is very different: synergistic relationships among the signaling sectors are evident in PTI, which may amplify the signal; compensatory relationships among the sectors dominate in ETI, explaining the robustness of ETI against genetic and pathogenic perturbations

    Linking Oviposition Site Choice to Offspring Fitness in Aedes aegypti: Consequences for Targeted Larval Control of Dengue Vectors

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    Controlling the mosquito Aedes aegypti, the predominant dengue vector, requires understanding the ecological and behavioral factors that influence population abundance. Females of several mosquito species are able to identify high-quality egg-laying sites, resulting in enhanced offspring development and survival, and ultimately promoting population growth. Here, the authors investigated egg-laying decisions of Ae. aegypti. Paradoxically, they found that larval survival and development were poorest in the containers females most often selected for egg deposition. Thus, egg-laying decisions may contribute to crowding of larvae and play a role in regulating mosquito populations. The authors also tested whether removal of the containers producing the most adult mosquitoes, a World Health Organization-recommended dengue prevention strategy, changes the pattern of how females allocate their eggs. Elimination of the most productive containers led to a more even distribution of eggs in one trial, but not another. These results suggest that behavioral adjustments by egg-laying females may lessen the effectiveness of a common mosquito control tactic. The authors advocate incorporating control strategies that take advantage of the natural egg-laying preferences of this vector species, such as luring egg-laying females to traps or places where their eggs will accumulate, but not develop

    Oviposition Site Selection by the Dengue Vector Aedes aegypti and Its Implications for Dengue Control

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    Controlling the mosquito Aedes aegypti is of public health importance because, at present, it is the only means to stop dengue virus transmission. Implementing successful mosquito control programs requires understanding what factors regulate population abundance, as well as anticipating how mosquitoes may adapt to control measures. In some species of mosquitoes, females choose egg-laying sites to improve the survival and growth of their offspring, a behavior that ultimately influences population distribution and abundance. In the current study, we tested whether Ae. aegypti actively choose the containers in which they lay their eggs and determined what cues are most relevant to that process. We also explored whether females select containers that provide the most food for their larval progeny. Surprisingly, egg-laying females were most attracted to sites containing other immature Ae. aegypti, rather than to sites containing the most food. We propose that this behavior may contribute to density-dependent competition for food among larvae and play a larger role than previously thought in regulating Ae. aegypti populations. We recommend that accounting for, and even taking advantage of, this natural behavior will lead to more effective strategies for dengue prevention

    Clinical and Virological Study of Dengue Cases and the Members of Their Households: The Multinational DENFRAME Project

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    Dengue is the most important mosquito-borne viral disease in humans. This disease is now endemic in more than 100 countries and threatens more than 2.5 billion people living in tropical countries. It currently affects about 50 to 100 million people each year. It causes a wide range of symptoms, from an inapparent to mild dengue fever, to severe forms, including dengue hemorrhagic fever. Currently no specific vaccine or antiviral drugs are available. We carried out a prospective clinical study in South-East Asia and Latin America, of virologically confirmed dengue-infected patients attending the hospital, and members of their households. Among 215 febrile dengue subjects, 177 agreed to household investigation. Based on our data, we estimated the proportion of dengue-infected household members to be about 45%. At the time of the home visit, almost three quarters of (29/39) presented an inapparent dengue infection. The proportion of inapparent dengue infection was higher in South-East Asia than in Latin America. These findings confirm the complexity of dengue disease in humans and the need to strengthen multidisciplinary research efforts to improve our understanding of virus transmission and host responses to dengue virus in various human populations

    Violent aggression predicted by multiple pre-adult environmental hits

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    Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention
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