Sample records for targeted gene neighborhoods
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G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes
Directory of Open Access Journals (Sweden)
Lemay Danielle G
2012-09-01
Full Text Available Abstract Background In previous studies, gene neighborhoods—spatial clusters of co-expressed genes in the genome—have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Scoring Tool (G-NEST which combines genomic location, gene expression, and evolutionary sequence conservation data to score putative gene neighborhoods across all possible window sizes simultaneously. Results Using G-NEST on atlases of mouse and human tissue expression data, we found that large neighborhoods of ten or more genes are extremely rare in mammalian genomes. When they do occur, neighborhoods are typically composed of families of related genes. Both the highest scoring and the largest neighborhoods in mammalian genomes are formed by tandem gene duplication. Mammalian gene neighborhoods contain highly and variably expressed genes. Co-localized noisy gene pairs exhibit lower evolutionary conservation of their adjacent genome locations, suggesting that their shared transcriptional background may be disadvantageous. Genes that are essential to mammalian survival and reproduction are less likely to occur in neighborhoods, although neighborhoods are enriched with genes that function in mitosis. We also found that gene orientation and protein-protein interactions are partially responsible for maintenance of gene neighborhoods. Conclusions Our experiments using G-NEST confirm that tandem gene duplication is the primary driver of non-random gene order in mammalian genomes. Non-essentiality, co-functionality, gene orientation, and protein-protein interactions are additional forces that maintain gene neighborhoods, especially those formed by tandem duplicates. We expect G-NEST to be useful for other applications such as the identification of core regulatory modules, common transcriptional backgrounds, and chromatin domains. The
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G-NEST: A gene neighborhood scoring tool to identify co-conserved, co-expressed genes
In previous studies, gene neighborhoods--spatial clusters of co-expressed genes in the genome--have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Sc...
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Drug-Target Interaction Prediction through Label Propagation with Linear Neighborhood Information.
Zhang, Wen; Chen, Yanlin; Li, Dingfang
2017-11-25
Interactions between drugs and target proteins provide important information for the drug discovery. Currently, experiments identified only a small number of drug-target interactions. Therefore, the development of computational methods for drug-target interaction prediction is an urgent task of theoretical interest and practical significance. In this paper, we propose a label propagation method with linear neighborhood information (LPLNI) for predicting unobserved drug-target interactions. Firstly, we calculate drug-drug linear neighborhood similarity in the feature spaces, by considering how to reconstruct data points from neighbors. Then, we take similarities as the manifold of drugs, and assume the manifold unchanged in the interaction space. At last, we predict unobserved interactions between known drugs and targets by using drug-drug linear neighborhood similarity and known drug-target interactions. The experiments show that LPLNI can utilize only known drug-target interactions to make high-accuracy predictions on four benchmark datasets. Furthermore, we consider incorporating chemical structures into LPLNI models. Experimental results demonstrate that the model with integrated information (LPLNI-II) can produce improved performances, better than other state-of-the-art methods. The known drug-target interactions are an important information source for computational predictions. The usefulness of the proposed method is demonstrated by cross validation and the case study.
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Neighborhood Regularized Logistic Matrix Factorization for Drug-Target Interaction Prediction.
Liu, Yong; Wu, Min; Miao, Chunyan; Zhao, Peilin; Li, Xiao-Li
2016-02-01
In pharmaceutical sciences, a crucial step of the drug discovery process is the identification of drug-target interactions. However, only a small portion of the drug-target interactions have been experimentally validated, as the experimental validation is laborious and costly. To improve the drug discovery efficiency, there is a great need for the development of accurate computational approaches that can predict potential drug-target interactions to direct the experimental verification. In this paper, we propose a novel drug-target interaction prediction algorithm, namely neighborhood regularized logistic matrix factorization (NRLMF). Specifically, the proposed NRLMF method focuses on modeling the probability that a drug would interact with a target by logistic matrix factorization, where the properties of drugs and targets are represented by drug-specific and target-specific latent vectors, respectively. Moreover, NRLMF assigns higher importance levels to positive observations (i.e., the observed interacting drug-target pairs) than negative observations (i.e., the unknown pairs). Because the positive observations are already experimentally verified, they are usually more trustworthy. Furthermore, the local structure of the drug-target interaction data has also been exploited via neighborhood regularization to achieve better prediction accuracy. We conducted extensive experiments over four benchmark datasets, and NRLMF demonstrated its effectiveness compared with five state-of-the-art approaches.
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Smith, Jennifer A; Zhao, Wei; Wang, Xu; Ratliff, Scott M; Mukherjee, Bhramar; Kardia, Sharon L R; Liu, Yongmei; Roux, Ava V Diez; Needham, Belinda L
2017-08-01
Living in a disadvantaged neighborhood is associated with poor health outcomes even after accounting for individual-level socioeconomic factors. The chronic stress of unfavorable neighborhood conditions may lead to dysregulation of the stress reactivity and inflammatory pathways, potentially mediated through epigenetic mechanisms such as DNA methylation. We used multi-level models to examine the relationship between 2 neighborhood conditions and methylation levels of 18 genes related to stress reactivity and inflammation in purified monocytes from 1,226 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of US adults. Neighborhood socioeconomic disadvantage, a summary of 16 census-based metrics, was associated with DNA methylation [False discovery rate (FDR) q-value ≤ 0.1] in 2 out of 7 stress-related genes evaluated (CRF, SLC6A4) and 2 out of 11 inflammation-related genes (F8, TLR1). Neighborhood social environment, a summary measure of aesthetic quality, safety, and social cohesion, was associated with methylation in 4 of the 7 stress-related genes (AVP, BDNF, FKBP5, SLC6A4) and 7 of the 11 inflammation-related genes (CCL1, CD1D, F8, KLRG1, NLRP12, SLAMF7, TLR1). High socioeconomic disadvantage and worse social environment were primarily associated with increased methylation. In 5 genes with significant associations between neighborhood and methylation (FKBP5, CD1D, F8, KLRG1, NLRP12), methylation was associated with gene expression of at least one transcript. These results demonstrate that multiple dimensions of neighborhood context may influence methylation levels and subsequent gene expression of stress- and inflammation-related genes, even after accounting for individual socioeconomic factors. Further elucidating the molecular mechanisms underlying these relationships will be important for understanding the etiology of health disparities.
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The drug target genes show higher evolutionary conservation than non-target genes.
Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie
2016-01-26
Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.
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Healy-Profitós, Jessica; Lee, Seungjun; Mouhaman, Arabi; Garabed, Rebecca; Moritz, Mark; Piperata, Barbara; Lee, Jiyoung
2016-06-01
This study examined the spatial variation of potential gastrointestinal pathogens within drinking water sources and home storage containers in four neighborhoods in Maroua, Cameroon. Samples were collected from source (n = 28) and home containers (n = 60) in each study neighborhood. Pathogen contamination was assessed using quantitative polymerase chain reaction, targeting Campylobacter spp., Shiga toxin producing Escherichia coli (virulence genes, stx1 and stx2), and Salmonella spp. Microbial source tracking (MST) targeted three different host-specific markers: HF183 (human), Rum2Bac (ruminant) and GFD (poultry) to identify contamination sources. Staphylococcus aureus and the tetracycline-resistance gene (tetQ) were assessed to measure human hand contact and presence of antibiotic-resistant bacteria. Pathogen/MST levels were compared statistically and spatially, and neighborhood variation was compared with previously collected demographic information. All the test fecal markers and pathogens (except Arcobacter) were detected in home and source samples. Two neighborhoods tested positive for most pathogens/MST while the others only tested positive for one or two. Spatial variation of pathogens/MST existed between sources, storage containers, and neighborhoods. Differing population density and ethno-economic characteristics could potentially explain variation. Future research should explore the influence of demographic and ethno-economic factors on water quality during microbial risk assessments in urban Africa.
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Network neighborhood analysis with the multi-node topological overlap measure.
Li, Ai; Horvath, Steve
2007-01-15
The goal of neighborhood analysis is to find a set of genes (the neighborhood) that is similar to an initial 'seed' set of genes. Neighborhood analysis methods for network data are important in systems biology. If individual network connections are susceptible to noise, it can be advantageous to define neighborhoods on the basis of a robust interconnectedness measure, e.g. the topological overlap measure. Since the use of multiple nodes in the seed set may lead to more informative neighborhoods, it can be advantageous to define multi-node similarity measures. The pairwise topological overlap measure is generalized to multiple network nodes and subsequently used in a recursive neighborhood construction method. A local permutation scheme is used to determine the neighborhood size. Using four network applications and a simulated example, we provide empirical evidence that the resulting neighborhoods are biologically meaningful, e.g. we use neighborhood analysis to identify brain cancer related genes. An executable Windows program and tutorial for multi-node topological overlap measure (MTOM) based analysis can be downloaded from the webpage (http://www.genetics.ucla.edu/labs/horvath/MTOM/).
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Henriksen, Lisa; Schleicher, Nina C; Dauphinee, Amanda L; Fortmann, Stephen P
2012-01-01
To describe advertising, promotions, and pack prices for the leading brands of menthol and nonmenthol cigarettes near California high schools and to examine their associations with school and neighborhood demographics. In stores (n = 407) within walking distance (0.8 km [1/2 mile]) of California high schools (n = 91), trained observers counted ads for menthol and nonmenthol cigarettes and collected data about promotions and prices for Newport and Marlboro, the leading brand in each category. Multilevel modeling examined the proportion of all cigarette advertising for any menthol brand, the proportion of stores with sales promotions, and the lowest advertised pack price in relation to store types and school/neighborhood demographics. For each 10 percentage point increase in the proportion of Black students, the proportion of menthol advertising increased by 5.9 percentage points (e.g., from an average of 25.7%-31.6%), the odds of a Newport promotion were 50% higher (95% CI = 1.01, 2.22), and the cost of Newport was 12 cents lower (95% CI = -0.18, -0.06). By comparison, the odds of a promotion and the price for Marlboro, the leading brand of nonmenthol cigarettes, were unrelated to any school or neighborhood demographics. In high school neighborhoods, targeted advertising exposes Blacks to more promotions and lower prices for the leading brand of menthol cigarettes. This evidence contradicts the manufacturer's claims that the availability of its promotions is not based on race/ethnicity. It also highlights the need for tobacco control policies that would limit disparities in exposure to retail marketing for cigarettes.
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Schleicher, Nina C.; Dauphinee, Amanda L.; Fortmann, Stephen P.
2012-01-01
Objectives: To describe advertising, promotions, and pack prices for the leading brands of menthol and nonmenthol cigarettes near California high schools and to examine their associations with school and neighborhood demographics. Methods: In stores (n = 407) within walking distance (0.8 km [1/2 mile]) of California high schools (n = 91), trained observers counted ads for menthol and nonmenthol cigarettes and collected data about promotions and prices for Newport and Marlboro, the leading brand in each category. Multilevel modeling examined the proportion of all cigarette advertising for any menthol brand, the proportion of stores with sales promotions, and the lowest advertised pack price in relation to store types and school/neighborhood demographics. Results: For each 10 percentage point increase in the proportion of Black students, the proportion of menthol advertising increased by 5.9 percentage points (e.g., from an average of 25.7%–31.6%), the odds of a Newport promotion were 50% higher (95% CI = 1.01, 2.22), and the cost of Newport was 12 cents lower (95% CI = −0.18, −0.06). By comparison, the odds of a promotion and the price for Marlboro, the leading brand of nonmenthol cigarettes, were unrelated to any school or neighborhood demographics. Conclusions: In high school neighborhoods, targeted advertising exposes Blacks to more promotions and lower prices for the leading brand of menthol cigarettes. This evidence contradicts the manufacturer’s claims that the availability of its promotions is not based on race/ethnicity. It also highlights the need for tobacco control policies that would limit disparities in exposure to retail marketing for cigarettes. PMID:21705460
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COGNAT: a web server for comparative analysis of genomic neighborhoods.
Klimchuk, Olesya I; Konovalov, Kirill A; Perekhvatov, Vadim V; Skulachev, Konstantin V; Dibrova, Daria V; Mulkidjanian, Armen Y
2017-11-22
In prokaryotic genomes, functionally coupled genes can be organized in conserved gene clusters enabling their coordinated regulation. Such clusters could contain one or several operons, which are groups of co-transcribed genes. Those genes that evolved from a common ancestral gene by speciation (i.e. orthologs) are expected to have similar genomic neighborhoods in different organisms, whereas those copies of the gene that are responsible for dissimilar functions (i.e. paralogs) could be found in dissimilar genomic contexts. Comparative analysis of genomic neighborhoods facilitates the prediction of co-regulated genes and helps to discern different functions in large protein families. We intended, building on the attribution of gene sequences to the clusters of orthologous groups of proteins (COGs), to provide a method for visualization and comparative analysis of genomic neighborhoods of evolutionary related genes, as well as a respective web server. Here we introduce the COmparative Gene Neighborhoods Analysis Tool (COGNAT), a web server for comparative analysis of genomic neighborhoods. The tool is based on the COG database, as well as the Pfam protein families database. As an example, we show the utility of COGNAT in identifying a new type of membrane protein complex that is formed by paralog(s) of one of the membrane subunits of the NADH:quinone oxidoreductase of type 1 (COG1009) and a cytoplasmic protein of unknown function (COG3002). This article was reviewed by Drs. Igor Zhulin, Uri Gophna and Igor Rogozin.
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International Nuclear Information System (INIS)
Liu Bing; Chinese Academy of Sciences, Beijing; Zhang Hong
2005-01-01
Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)
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DEFF Research Database (Denmark)
2016-01-01
The present invention relates to a dual cassette reporter system capable of assessing target gene translation and target gene product folding. The present invention further relates to vectors and host cells comprising the dual cassette reporter system. In addition the invention relates to the use...... of the dual cassette reporter system for assessing target gene translation and target gene product folding....
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A Systematic Review of Neighborhood Disparities in Point-of-Sale Tobacco Marketing.
Lee, Joseph G L; Henriksen, Lisa; Rose, Shyanika W; Moreland-Russell, Sarah; Ribisl, Kurt M
2015-09-01
We systematically reviewed evidence of disparities in tobacco marketing at tobacco retailers by sociodemographic neighborhood characteristics. We identified 43 relevant articles from 893 results of a systematic search in 10 databases updated May 28, 2014. We found 148 associations of marketing (price, placement, promotion, or product availability) with a neighborhood demographic of interest (socioeconomic disadvantage, race, ethnicity, and urbanicity). Neighborhoods with lower income have more tobacco marketing. There is more menthol marketing targeting urban neighborhoods and neighborhoods with more Black residents. Smokeless tobacco products are targeted more toward rural neighborhoods and neighborhoods with more White residents. Differences in store type partially explain these disparities. There are more inducements to start and continue smoking in lower-income neighborhoods and in neighborhoods with more Black residents. Retailer marketing may contribute to disparities in tobacco use. Clinicians should be aware of the pervasiveness of these environmental cues.
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A Systematic Review of Neighborhood Disparities in Point-of-Sale Tobacco Marketing
Henriksen, Lisa; Rose, Shyanika W.; Moreland-Russell, Sarah; Ribisl, Kurt M.
2015-01-01
We systematically reviewed evidence of disparities in tobacco marketing at tobacco retailers by sociodemographic neighborhood characteristics. We identified 43 relevant articles from 893 results of a systematic search in 10 databases updated May 28, 2014. We found 148 associations of marketing (price, placement, promotion, or product availability) with a neighborhood demographic of interest (socioeconomic disadvantage, race, ethnicity, and urbanicity). Neighborhoods with lower income have more tobacco marketing. There is more menthol marketing targeting urban neighborhoods and neighborhoods with more Black residents. Smokeless tobacco products are targeted more toward rural neighborhoods and neighborhoods with more White residents. Differences in store type partially explain these disparities. There are more inducements to start and continue smoking in lower-income neighborhoods and in neighborhoods with more Black residents. Retailer marketing may contribute to disparities in tobacco use. Clinicians should be aware of the pervasiveness of these environmental cues. PMID:26180986
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Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S
2017-06-01
In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.
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Lowe, Sarah R; Pothen, John; Quinn, James W; Rundle, Andrew; Bradley, Bekh; Galea, Sandro; Ressler, Kerry J; Koenen, Karestan C
2015-11-15
Few studies have explored interactions between genes and social environmental exposures (GxSEs) for trauma-related psychopathology, including symptoms of posttraumatic stress (PTS) and major depression (MD). The extant literature suggests the possibility of a GxSE between the rs2267735 variant of the ADCYAP1R1 gene and neighborhood crime. The current study aimed to explore this possibility among a predominantly African American sample of trauma-exposed women. Female participants (N=1361) were recruited from a public hospital, and completed measures of PTS and MD symptoms and provided DNA samples. Participants' home addresses were mapped onto 300 neighborhoods (2010 census tracts), and data on crime within neighborhoods was collected. Multilevel models detected a significant GxSE between rs2267735 and neighborhood crime for MD symptoms (p=.01). Having two copies of the risk (C) allele was associated with higher MD symptoms for participants living in high-crime neighborhoods. At least six limitations are noteworthy: (1) low statistical power; (2) use of self-report symptom inventories; (3) lack of information on symptom onset; (4) homogeneous sample from a single metropolitan area; (5) non-specific index of crime; and (6) use of census tracts to define neighborhoods. The results provide further evidence of GxSEs for psychiatric outcomes among trauma-exposed populations. Further investigations of genetic factors for trauma-related psychopathology should include careful assessments of the social environment. Copyright © 2015 Elsevier B.V. All rights reserved.
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Rural Neighborhood Walkability: Implications for Assessment.
Kegler, Michelle C; Alcantara, Iris; Haardörfer, Regine; Gemma, Alexandra; Ballard, Denise; Gazmararian, Julie
2015-06-16
Physical activity levels, including walking, are lower in the southern U.S., particularly in rural areas. This study investigated the concept of rural neighborhood walkability to aid in developing tools for assessing walkability and to identify intervention targets in rural communities. Semi-structured interviews were conducted with physically active adults (n = 29) in rural Georgia. Mean age of participants was 55.9 years; 66% were male, 76% were white, and 24% were African American. Participants drew maps of their neighborhoods and discussed the relevance of typical domains of walkability to their decisions to exercise. Comparative analyses were conducted to identify major themes. The majority felt the concept of neighborhood was applicable and viewed their neighborhood as small geographically (less than 0.5 square miles). Sidewalks were not viewed as essential for neighborhood-based physical activity and typical destinations for walking were largely absent. Destinations within walking distance included neighbors' homes and bodies of water. Views were mixed on whether shade, safety, dogs, and aesthetics affected decisions to exercise in their neighborhoods. Measures of neighborhood walkability in rural areas should acknowledge the small size of self-defined neighborhoods, that walking in rural areas is likely for leisure time exercise, and that some domains may not be relevant.
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About miRNAs, miRNA seeds, target genes and target pathways.
Kehl, Tim; Backes, Christina; Kern, Fabian; Fehlmann, Tobias; Ludwig, Nicole; Meese, Eckart; Lenhof, Hans-Peter; Keller, Andreas
2017-12-05
miRNAs are typically repressing gene expression by binding to the 3' UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways. By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade. The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database (https://mpd.bioinf.uni-sb.de).
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Lynch, Michael; Manly, Jody Todd; Cicchetti, Dante
2015-11-01
Physiological response to stress has been linked to a variety of healthy and pathological conditions. The current study conducted a multilevel examination of interactions among environmental toxins (i.e., neighborhood crime and child maltreatment) and specific genetic polymorphisms of the endothelial nitric oxide synthase gene (eNOS) and GABA(A) receptor subunit alpha-6 gene (GABRA6). One hundred eighty-six children were recruited at age 4. The presence or absence of child maltreatment as well as the amount of crime that occurred in their neighborhood during the previous year were determined at that time. At age 9, the children were brought to the lab, where their physiological response to a cognitive challenge (i.e., change in the amplitude of the respiratory sinus arrhythmia) was assessed and DNA samples were collected for subsequent genotyping. The results confirmed that complex Gene × Gene, Environment × Environment, and Gene × Environment interactions were associated with different patterns of respiratory sinus arrhythmia reactivity. The implications for future research and evidence-based intervention are discussed.
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Work and Home Neighborhood Design and Physical Activity.
Carlson, Jordan A; Frank, Lawrence D; Ulmer, Jared; Conway, Terry L; Saelens, Brian E; Cain, Kelli L; Sallis, James F
2018-01-01
To investigate relations of perceived worksite neighborhood environments to total physical activity and active transportation, over and above home neighborhood built environments. Observational epidemiologic study. Baltimore, Maryland-Washington, DC, and Seattle-King County, Washington metropolitan areas. One thousand eighty-five adults (mean age = 45.0 [10.2]; 46% women) recruited from 32 neighborhoods stratified by high/low neighborhood income and walkability. The Neighborhood Environment Walkability Survey assessed perceptions of worksite and home neighborhood environments. Accelerometers assessed total moderate-to-vigorous physical activity (MVPA). The International Physical Activity Questionnaire assessed total active transportation and active transportation to and around work. Mixed-effects regression tested relations of home and worksite neighborhood environments to each physical activity outcome, adjusted for demographics. Home and worksite mixed land use and street connectivity had the most consistent positive associations with physical activity outcomes. Worksite traffic and pedestrian safety were also associated with multiple physical activity outcomes. The worksite neighborhood explained additional variance in physical activity outcomes than explained by the home neighborhood. Worksite and home neighborhood environments interacted in explaining active transportation to work, with the greatest impacts occurring when both neighborhoods were activity supportive. Both worksite and home neighborhood environments were independently related to total MVPA and active transportation. Community design policies should target improving the physical activity supportiveness of worksite neighborhood environments and integrating commercial and residential development.
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Slutske, Wendy S; Deutsch, Arielle R; Piasecki, Thomas M
2018-05-07
Genetic influences on alcohol involvement are likely to vary as a function of the 'alcohol environment,' given that exposure to alcohol is a necessary precondition for genetic risk to be expressed. However, few gene-environment interaction studies of alcohol involvement have focused on characteristics of the community-level alcohol environment. The goal of this study was to examine whether living in a community with more alcohol outlets would facilitate the expression of the genetic propensity to drink in a genetically-informed national survey of United States young adults. The participants were 2434 18-26-year-old twin, full-, and half-sibling pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health. Participants completed in-home interviews in which alcohol use was assessed. Alcohol outlet densities were extracted from state-level liquor license databases aggregated at the census tract level to derive the density of outlets. There was evidence that the estimates of genetic and environmental influences on alcohol use varied as a function of the density of alcohol outlets in the community. For example, the heritability of the frequency of alcohol use for those residing in a neighborhood with ten or more outlets was 74% (95% confidence limits = 55-94%), compared with 16% (95% confidence limits = 0-34%) for those in a neighborhood with zero outlets. This moderating effect of alcohol outlet density was not explained by the state of residence, population density, or neighborhood sociodemographic characteristics. The results suggest that living in a neighborhood with many alcohol outlets may be especially high-risk for those individuals who are genetically predisposed to frequently drink.
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Targeting the human lysozyme gene on bovine αs1- casein gene ...
African Journals Online (AJOL)
Targeting an exogenous gene into a favorable gene locus and for expression under endogenous regulators is an ideal method in mammary gland bioreactor research. For this purpose, a gene targeting vector was constructed to targeting the human lysozyme gene on bovine αs1-casein gene locus. In this case, the ...
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Nearest Neighbor Networks: clustering expression data based on gene neighborhoods
Directory of Open Access Journals (Sweden)
Olszewski Kellen L
2007-07-01
Full Text Available Abstract Background The availability of microarrays measuring thousands of genes simultaneously across hundreds of biological conditions represents an opportunity to understand both individual biological pathways and the integrated workings of the cell. However, translating this amount of data into biological insight remains a daunting task. An important initial step in the analysis of microarray data is clustering of genes with similar behavior. A number of classical techniques are commonly used to perform this task, particularly hierarchical and K-means clustering, and many novel approaches have been suggested recently. While these approaches are useful, they are not without drawbacks; these methods can find clusters in purely random data, and even clusters enriched for biological functions can be skewed towards a small number of processes (e.g. ribosomes. Results We developed Nearest Neighbor Networks (NNN, a graph-based algorithm to generate clusters of genes with similar expression profiles. This method produces clusters based on overlapping cliques within an interaction network generated from mutual nearest neighborhoods. This focus on nearest neighbors rather than on absolute distance measures allows us to capture clusters with high connectivity even when they are spatially separated, and requiring mutual nearest neighbors allows genes with no sufficiently similar partners to remain unclustered. We compared the clusters generated by NNN with those generated by eight other clustering methods. NNN was particularly successful at generating functionally coherent clusters with high precision, and these clusters generally represented a much broader selection of biological processes than those recovered by other methods. Conclusion The Nearest Neighbor Networks algorithm is a valuable clustering method that effectively groups genes that are likely to be functionally related. It is particularly attractive due to its simplicity, its success in the
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Clark, Cheryl R.; Ommerborn, Mark J.; Hickson, DeMarc A.; Grooms, Kya N.; Sims, Mario; Taylor, Herman A.; Albert, Michelle A.
2013-01-01
Objective We examined associations between neighborhood socioeconomic disadvantage, perceived neighborhood safety and cardiometabolic risk factors, adjusting for health behaviors and socioeconomic status (SES) among African Americans. Methods Study participants were non-diabetic African Americans (n = 3,909) in the baseline examination (2000–2004) of the Jackson Heart Study. We measured eight risk factors: the metabolic syndrome, its five components, insulin resistance and cardiovascular inflammation. We assessed neighborhood socioeconomic disadvantage with US Census 2000 data. We assessed perceived neighborhood safety, health behaviors and SES via survey. We used generalized estimating equations to estimate associations with a random intercept model for neighborhood effects. Results After adjustment for health behaviors and SES, neighborhood socioeconomic disadvantage was associated with the metabolic syndrome in women (PR 1.13, 95% CI 1.01, 1.27). Lack of perceived safety was associated with elevated glucose (OR 1.36, 95% CI 1.03, 1.80) and waist circumference (PR 1.06, 95% CI 1.02, 1.11) among women, and with elevated glucose (PR 1.30, 95% CI 1.02, 1.66) and insulin resistance (PR 1.25, 95% CI 1.08, 1.46) among men. Conclusions Neighborhood socioeconomic disadvantage and perceived safety should be considered as targets for intervention to reduce cardiometabolic risks among African Americans. PMID:23691005
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Osato, Naoki
2018-01-19
Transcriptional target genes show functional enrichment of genes. However, how many and how significantly transcriptional target genes include functional enrichments are still unclear. To address these issues, I predicted human transcriptional target genes using open chromatin regions, ChIP-seq data and DNA binding sequences of transcription factors in databases, and examined functional enrichment and gene expression level of putative transcriptional target genes. Gene Ontology annotations showed four times larger numbers of functional enrichments in putative transcriptional target genes than gene expression information alone, independent of transcriptional target genes. To compare the number of functional enrichments of putative transcriptional target genes between cells or search conditions, I normalized the number of functional enrichment by calculating its ratios in the total number of transcriptional target genes. With this analysis, native putative transcriptional target genes showed the largest normalized number of functional enrichments, compared with target genes including 5-60% of randomly selected genes. The normalized number of functional enrichments was changed according to the criteria of enhancer-promoter interactions such as distance from transcriptional start sites and orientation of CTCF-binding sites. Forward-reverse orientation of CTCF-binding sites showed significantly higher normalized number of functional enrichments than the other orientations. Journal papers showed that the top five frequent functional enrichments were related to the cellular functions in the three cell types. The median expression level of transcriptional target genes changed according to the criteria of enhancer-promoter assignments (i.e. interactions) and was correlated with the changes of the normalized number of functional enrichments of transcriptional target genes. Human putative transcriptional target genes showed significant functional enrichments. Functional
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Targeted gene insertion for molecular medicine.
Voigt, Katrin; Izsvák, Zsuzsanna; Ivics, Zoltán
2008-11-01
Genomic insertion of a functional gene together with suitable transcriptional regulatory elements is often required for long-term therapeutical benefit in gene therapy for several genetic diseases. A variety of integrating vectors for gene delivery exist. Some of them exhibit random genomic integration, whereas others have integration preferences based on attributes of the targeted site, such as primary DNA sequence and physical structure of the DNA, or through tethering to certain DNA sequences by host-encoded cellular factors. Uncontrolled genomic insertion bears the risk of the transgene being silenced due to chromosomal position effects, and can lead to genotoxic effects due to mutagenesis of cellular genes. None of the vector systems currently used in either preclinical experiments or clinical trials displays sufficient preferences for target DNA sequences that would ensure appropriate and reliable expression of the transgene and simultaneously prevent hazardous side effects. We review in this paper the advantages and disadvantages of both viral and non-viral gene delivery technologies, discuss mechanisms of target site selection of integrating genetic elements (viruses and transposons), and suggest distinct molecular strategies for targeted gene delivery.
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NEIGHBORHOOD CHOICE AND NEIGHBORHOOD CHANGE
Bruch, Elizabeth; Mare, Robert D.
2006-01-01
This paper examines the relationships between the residential choices of individuals and aggregate patterns of neighborhood change. We investigate the conditions under which individuals’ preferences for the race-ethnic composition of their neighborhoods produce high levels of segregation. Using computational models, we find that high levels of segregation occur only when individuals’ preferences follow a threshold function. If individuals make finer-grained distinctions among neighborhoods th...
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TBC2target: A Resource of Predicted Target Genes of Tea Bioactive Compounds
Directory of Open Access Journals (Sweden)
Shihua Zhang
2018-02-01
Full Text Available Tea is one of the most popular non-alcoholic beverages consumed worldwide. Numerous bioactive constituents of tea were confirmed to possess healthy benefits via the mechanisms of regulating gene expressions or protein activities. However, a complete interacting profile between tea bioactive compounds (TBCs and their target genes is lacking, which put an obstacle in the study of healthy function of tea. To fill this gap, we developed a database of target genes of TBCs (TBC2target, http://camellia.ahau.edu.cn/TBC2target based on a pharmacophore mapping approach. In TBC2target, 6,226 interactions between 240 TBCs and 673 target genes were documented. TBC2target contains detailed information about each interacting entry, such as TBC, CAS number, PubChem CID, source of compound (e.g., green, black, compound type, target gene(s of TBC, gene symbol, gene ID, ENSEMBL ID, PDB ID, TBC bioactivity and the reference. Using the TBC-target associations, we constructed a bipartite network and provided users the global network and local sub-network visualization and topological analyses. The entire database is free for online browsing, searching and downloading. In addition, TBC2target provides a BLAST search function to facilitate use of the database. The particular strengths of TBC2target are the inclusion of the comprehensive TBC-target interactions, and the capacity to visualize and analyze the interacting networks, which may help uncovering the beneficial effects of tea on human health as a central resource in tea health community.
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TBC2target: A Resource of Predicted Target Genes of Tea Bioactive Compounds.
Zhang, Shihua; Zhang, Liang; Wang, Yijun; Yang, Jian; Liao, Mingzhi; Bi, Shoudong; Xie, Zhongwen; Ho, Chi-Tang; Wan, Xiaochun
2018-01-01
Tea is one of the most popular non-alcoholic beverages consumed worldwide. Numerous bioactive constituents of tea were confirmed to possess healthy benefits via the mechanisms of regulating gene expressions or protein activities. However, a complete interacting profile between tea bioactive compounds (TBCs) and their target genes is lacking, which put an obstacle in the study of healthy function of tea. To fill this gap, we developed a database of target genes of TBCs (TBC2target, http://camellia.ahau.edu.cn/TBC2target) based on a pharmacophore mapping approach. In TBC2target, 6,226 interactions between 240 TBCs and 673 target genes were documented. TBC2target contains detailed information about each interacting entry, such as TBC, CAS number, PubChem CID, source of compound (e.g., green, black), compound type, target gene(s) of TBC, gene symbol, gene ID, ENSEMBL ID, PDB ID, TBC bioactivity and the reference. Using the TBC-target associations, we constructed a bipartite network and provided users the global network and local sub-network visualization and topological analyses. The entire database is free for online browsing, searching and downloading. In addition, TBC2target provides a BLAST search function to facilitate use of the database. The particular strengths of TBC2target are the inclusion of the comprehensive TBC-target interactions, and the capacity to visualize and analyze the interacting networks, which may help uncovering the beneficial effects of tea on human health as a central resource in tea health community.
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Gene transfer technology and genetic radioisotope targeting therapy
International Nuclear Information System (INIS)
Wang Jiaqiong; Wang Zizheng
2004-01-01
With deeper cognition about mechanisms of disease at the cellular and molecular level, gene therapy has become one of the most important research fields in medical molecular biology at present. Gene transfer technology plays an important role during the course of gene therapy, and further improvement should be made about vectors carrying target gene sequences. Also, gene survey is needed during gene therapy, and gene imaging is the most effective method. The combination of gene therapy and targeted radiotherapy, that is, 'Genetic Radioisotope Targeting Therapy', will be a novel approach to tumor gene therapy
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Neighborhood Disparities in the Restaurant Food Environment.
Martinez-Donate, Ana P; Espino, Jennifer Valdivia; Meinen, Amy; Escaron, Anne L; Roubal, Anne; Nieto, Javier; Malecki, Kristen
2016-11-01
Restaurant meals account for a significant portion of the American diet. Investigating disparities in the restaurant food environment can inform targeted interventions to increase opportunities for healthy eating among those who need them most. To examine neighborhood disparities in restaurant density and the nutrition environment within restaurants among a statewide sample of Wisconsin households. Households (N = 259) were selected from the 2009-2010 Survey of the Health of Wisconsin (SHOW), a population-based survey of Wisconsin adults. Restaurants in the household neighborhood were enumerated and audited using the Nutrition Environment Measures Survey for Restaurants (NEMS-R). Neighborhoods were defined as a 2- and 5-mile street-distance buffer around households in urban and non-urban areas, respectively. Adjusted linear regression models identified independent associations between sociodemographic household characteristics and neighborhood restaurant density and nutrition environment scores. On average, each neighborhood contained approximately 26 restaurants. On average, restaurants obtained 36.1% of the total nutrition environment points. After adjusting for household characteristics, higher restaurant density was associated with both younger and older household average age (P restaurant food environment in Wisconsin neighborhoods varies by age, race, and urbanicity, but offers ample room for improvement across socioeconomic groups and urbanicity levels. Future research must identify policy and environmental interventions to promote healthy eating in all restaurants, especially in young and/or rural neighborhoods in Wisconsin.
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Lei, Man-Kit; Beach, Steven R. H.; Simons, Ronald L.; Philibert, Robert A.
2015-01-01
Introduction Social scientists have long recognized the important role that neighborhood crime can play in stress-related disease, but very little is known about potential biosocial mechanisms that may link the experience of living in high-crime neighborhoods with depression. Objective The current study introduces an integrated model that combines neighborhood, genetic, and epigenetic factors. Methods Hypotheses were tested with a sample of 99 African American women from the Family and Community Health Study (FACHS). Results Allele variants of the serotonin transporter gene (5-HTT) interact with neighborhood crime to predict depressive symptoms in a manner consonant with the differential susceptibility perspective. Furthermore, this association is mediated by DNA methylation of the promoter region of the serotonin transporter gene. Conclusion The findings provide support for an integrated model in which changes in DNA methylation, resulting from neighborhood crime, can result in an increase or decrease in gene activity which, in turn, influences depressive symptoms. PMID:26513121
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Lei, Man-Kit; Beach, Steven R H; Simons, Ronald L; Philibert, Robert A
2015-12-01
Social scientists have long recognized the important role that neighborhood crime can play in stress-related disease, but very little is known about potential biosocial mechanisms that may link the experience of living in high-crime neighborhoods with depression. The current study introduces an integrated model that combines neighborhood, genetic, and epigenetic factors. Hypotheses were tested with a sample of 99 African American women from the Family and Community Health Study (FACHS). Allele variants of the serotonin transporter gene (5-HTT) interact with neighborhood crime to predict depressive symptoms in a manner consonant with the differential susceptibility perspective. Furthermore, this association is mediated by DNA methylation of the promoter region of the serotonin transporter gene. The findings provide support for an integrated model in which changes in DNA methylation, resulting from neighborhood crime, can result in an increase or decrease in gene activity which, in turn, influences depressive symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Characterisation of genome-wide PLZF/RARA target genes.
Directory of Open Access Journals (Sweden)
Salvatore Spicuglia
Full Text Available The PLZF/RARA fusion protein generated by the t(11;17(q23;q21 translocation in acute promyelocytic leukaemia (APL is believed to act as an oncogenic transcriptional regulator recruiting epigenetic factors to genes important for its transforming potential. However, molecular mechanisms associated with PLZF/RARA-dependent leukaemogenesis still remain unclear.We searched for specific PLZF/RARA target genes by ChIP-on-chip in the haematopoietic cell line U937 conditionally expressing PLZF/RARA. By comparing bound regions found in U937 cells expressing endogenous PLZF with PLZF/RARA-induced U937 cells, we isolated specific PLZF/RARA target gene promoters. We next analysed gene expression profiles of our identified target genes in PLZF/RARA APL patients and analysed DNA sequences and epigenetic modification at PLZF/RARA binding sites. We identify 413 specific PLZF/RARA target genes including a number encoding transcription factors involved in the regulation of haematopoiesis. Among these genes, 22 were significantly down regulated in primary PLZF/RARA APL cells. In addition, repressed PLZF/RARA target genes were associated with increased levels of H3K27me3 and decreased levels of H3K9K14ac. Finally, sequence analysis of PLZF/RARA bound sequences reveals the presence of both consensus and degenerated RAREs as well as enrichment for tissue-specific transcription factor motifs, highlighting the complexity of targeting fusion protein to chromatin. Our study suggests that PLZF/RARA directly targets genes important for haematopoietic development and supports the notion that PLZF/RARA acts mainly as an epigenetic regulator of its direct target genes.
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Prochaska, John D; Buschmann, Robert N; Jupiter, Daniel; Mutambudzi, Miriam; Peek, M Kristen
2018-06-01
Research suggests a linkage between perceptions of neighborhood quality and the likelihood of engaging in leisure-time physical activity. Often in these studies, intra-neighborhood variance is viewed as something to be controlled for statistically. However, we hypothesized that intra-neighborhood variance in perceptions of neighborhood quality may be contextually relevant. We examined the relationship between intra-neighborhood variance of subjective neighborhood quality and neighborhood-level reported physical inactivity across 48 neighborhoods within a medium-sized city, Texas City, Texas using survey data from 2706 residents collected between 2004 and 2006. Neighborhoods where the aggregated perception of neighborhood quality was poor also had a larger proportion of residents reporting being physically inactive. However, higher degrees of disagreement among residents within neighborhoods about their neighborhood quality was significantly associated with a lower proportion of residents reporting being physically inactive (p=0.001). Our results suggest that intra-neighborhood variability may be contextually relevant in studies seeking to better understand the relationship between neighborhood quality and behaviors sensitive to neighborhood environments, like physical activity. Copyright © 2017 Elsevier Inc. All rights reserved.
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DEFF Research Database (Denmark)
Pisinger, David; Røpke, Stefan
2010-01-01
Heuristics based on large neighborhood search have recently shown outstanding results in solving various transportation and scheduling problems. Large neighborhood search methods explore a complex neighborhood by use of heuristics. Using large neighborhoods makes it possible to find better...... candidate solutions in each iteration and hence traverse a more promising search path. Starting from the large neighborhood search method,we give an overview of very large scale neighborhood search methods and discuss recent variants and extensions like variable depth search and adaptive large neighborhood...
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The mechanism of gene targeting in human somatic cells.
Directory of Open Access Journals (Sweden)
Yinan Kan
2014-04-01
Full Text Available Gene targeting in human somatic cells is of importance because it can be used to either delineate the loss-of-function phenotype of a gene or correct a mutated gene back to wild-type. Both of these outcomes require a form of DNA double-strand break (DSB repair known as homologous recombination (HR. The mechanism of HR leading to gene targeting, however, is not well understood in human cells. Here, we demonstrate that a two-end, ends-out HR intermediate is valid for human gene targeting. Furthermore, the resolution step of this intermediate occurs via the classic DSB repair model of HR while synthesis-dependent strand annealing and Holliday Junction dissolution are, at best, minor pathways. Moreover, and in contrast to other systems, the positions of Holliday Junction resolution are evenly distributed along the homology arms of the targeting vector. Most unexpectedly, we demonstrate that when a meganuclease is used to introduce a chromosomal DSB to augment gene targeting, the mechanism of gene targeting is inverted to an ends-in process. Finally, we demonstrate that the anti-recombination activity of mismatch repair is a significant impediment to gene targeting. These observations significantly advance our understanding of HR and gene targeting in human cells.
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Neighborhood Influences on Vehicle-Pedestrian Crash Severity.
Toran Pour, Alireza; Moridpour, Sara; Tay, Richard; Rajabifard, Abbas
2017-12-01
Socioeconomic factors are known to be contributing factors for vehicle-pedestrian crashes. Although several studies have examined the socioeconomic factors related to the location of the crashes, limited studies have considered the socioeconomic factors of the neighborhood where the road users live in vehicle-pedestrian crash modelling. This research aims to identify the socioeconomic factors related to both the neighborhoods where the road users live and where crashes occur that have an influence on vehicle-pedestrian crash severity. Data on vehicle-pedestrian crashes that occurred at mid-blocks in Melbourne, Australia, was analyzed. Neighborhood factors associated with road users' residents and location of crash were investigated using boosted regression tree (BRT). Furthermore, partial dependence plots were applied to illustrate the interactions between these factors. We found that socioeconomic factors accounted for 60% of the 20 top contributing factors to vehicle-pedestrian crashes. This research reveals that socioeconomic factors of the neighborhoods where the road users live and where the crashes occur are important in determining the severity of the crashes, with the former having a greater influence. Hence, road safety countermeasures, especially those focussing on the road users, should be targeted at these high-risk neighborhoods.
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Incorporating Neighborhood Choice in a Model of Neighborhood Effects on Income.
van Ham, Maarten; Boschman, Sanne; Vogel, Matt
2018-05-09
Studies of neighborhood effects often attempt to identify causal effects of neighborhood characteristics on individual outcomes, such as income, education, employment, and health. However, selection looms large in this line of research, and it has been argued that estimates of neighborhood effects are biased because people nonrandomly select into neighborhoods based on their preferences, income, and the availability of alternative housing. We propose a two-step framework to disentangle selection processes in the relationship between neighborhood deprivation and earnings. We model neighborhood selection using a conditional logit model, from which we derive correction terms. Driven by the recognition that most households prefer certain types of neighborhoods rather than specific areas, we employ a principle components analysis to reduce these terms into eight correction components. We use these to adjust parameter estimates from a model of subsequent neighborhood effects on individual income for the unequal probability that a household chooses to live in a particular type of neighborhood. We apply this technique to administrative data from the Netherlands. After we adjust for the differential sorting of households into certain types of neighborhoods, the effect of neighborhood income on individual income diminishes but remains significant. These results further emphasize that researchers need to be attuned to the role of selection bias when assessing the role of neighborhood effects on individual outcomes. Perhaps more importantly, the persistent effect of neighborhood deprivation on subsequent earnings suggests that neighborhood effects reflect more than the shared characteristics of neighborhood residents: place of residence partially determines economic well-being.
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Targeted integration of genes in Xenopus tropicalis
DEFF Research Database (Denmark)
Shi, Zhaoying; Tian, Dandan; Xin, Huhu
2017-01-01
With the successful establishment of both targeted gene disruption and integration methods in the true diploid frog Xenopus tropicalis, this excellent vertebrate genetic model now is making a unique contribution to modelling human diseases. Here, we summarize our efforts on establishing homologous...... recombination-mediated targeted integration in Xenopus tropicalis, the usefulness, and limitation of targeted integration via the homology-independent strategy, and future directions on how to further improve targeted gene integration in Xenopus tropicalis....
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Active living neighborhoods: is neighborhood walkability a key element for Belgian adolescents?
De Meester, Femke; Van Dyck, Delfien; De Bourdeaudhuij, Ilse; Deforche, Benedicte; Sallis, James F; Cardon, Greet
2012-01-04
In adult research, neighborhood walkability has been acknowledged as an important construct among the built environmental correlates of physical activity. Research into this association has only recently been extended to adolescents and the current empirical evidence is not consistent. This study investigated whether neighborhood walkability and neighborhood socioeconomic status (SES) are associated with physical activity among Belgian adolescents and whether the association between neighborhood walkability and physical activity is moderated by neighborhood SES and gender. In Ghent (Belgium), 32 neighborhoods were selected based on GIS-based walkability and SES derived from census data. In total, 637 adolescents (aged 13-15 year, 49.6% male) participated in the study. Physical activity was assessed using accelerometers and the Flemish Physical Activity Questionnaire. To analyze the associations between neighborhood walkability, neighborhood SES and individual physical activity, multivariate multi-level regression analyses were conducted. Only in low-SES neighborhoods, neighborhood walkability was positively associated with accelerometer-based moderate to vigorous physical activity and the average activity level expressed in counts/minute. For active transport to and from school, cycling for transport during leisure time and sport during leisure time no association with neighborhood walkability nor, with neighborhood SES was found. For walking for transport during leisure time a negative association with neighborhood SES was found. Gender did not moderate the associations of neighborhood walkability and SES with adolescent physical activity. Neighborhood walkability was related to accelerometer-based physical activity only among adolescent boys and girls living in low-SES neighborhoods. The relation of built environment to adolescent physical activity may depend on the context.
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Peroxisome Proliferator-Activated Receptor Alpha Target Genes
Directory of Open Access Journals (Sweden)
Maryam Rakhshandehroo
2010-01-01
Full Text Available The peroxisome proliferator-activated receptor alpha (PPARα is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARα governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARα is directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARα target genes. The emphasis is on gene regulation by PPARα in liver although many of the results likely apply to other organs and tissues as well.
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Active living neighborhoods: is neighborhood walkability a key element for Belgian adolescents?
Directory of Open Access Journals (Sweden)
De Meester Femke
2012-01-01
Full Text Available Abstract Background In adult research, neighborhood walkability has been acknowledged as an important construct among the built environmental correlates of physical activity. Research into this association has only recently been extended to adolescents and the current empirical evidence is not consistent. This study investigated whether neighborhood walkability and neighborhood socioeconomic status (SES are associated with physical activity among Belgian adolescents and whether the association between neighborhood walkability and physical activity is moderated by neighborhood SES and gender. Methods In Ghent (Belgium, 32 neighborhoods were selected based on GIS-based walkability and SES derived from census data. In total, 637 adolescents (aged 13-15 year, 49.6% male participated in the study. Physical activity was assessed using accelerometers and the Flemish Physical Activity Questionnaire. To analyze the associations between neighborhood walkability, neighborhood SES and individual physical activity, multivariate multi-level regression analyses were conducted. Results Only in low-SES neighborhoods, neighborhood walkability was positively associated with accelerometer-based moderate to vigorous physical activity and the average activity level expressed in counts/minute. For active transport to and from school, cycling for transport during leisure time and sport during leisure time no association with neighborhood walkability nor, with neighborhood SES was found. For walking for transport during leisure time a negative association with neighborhood SES was found. Gender did not moderate the associations of neighborhood walkability and SES with adolescent physical activity. Conclusions Neighborhood walkability was related to accelerometer-based physical activity only among adolescent boys and girls living in low-SES neighborhoods. The relation of built environment to adolescent physical activity may depend on the context.
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Neighborhood choices, neighborhood effects and housing vouchers
Davis, Morris A.; Gregory, Jesse; Hartley, Daniel A.; Tan, Kegon T. K.
2017-01-01
We study how households choose neighborhoods, how neighborhoods affect child ability, and how housing vouchers influence neighborhood choices and child outcomes. We use two new panel data sets with tract-level detail for Los Angeles county to estimate a dynamic model of optimal tract-level location choice for renting households and, separately, the impact of living in a given tract on child test scores (which we call "child ability" throughout). We simulate optimal location choices and change...
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Van Assche, Jasper; Asbrock, Frank; Roets, Arne; Kauff, Mathias
2018-05-01
Positive neighborhood norms, such as strong local networks, are critical to people's satisfaction with, perceived disadvantage of, and intentions to stay in their neighborhood. At the same time, local ethnic diversity is said to be detrimental for these community outcomes. Integrating both frameworks, we tested whether the negative consequences of diversity occur even when perceived social norms are positive. Study 1 ( N = 1,760 German adults) showed that perceptions of positive neighborhood norms buffered against the effects of perceived diversity on moving intentions via neighborhood satisfaction and perceived neighborhood disadvantage. Study 2 ( N = 993 Dutch adults) replicated and extended this moderated mediation model using other characteristics of diversity (i.e., objective and estimated minority proportions). Multilevel analyses again revealed consistent buffering effects of positive neighborhood norms. Our findings are discussed in light of the ongoing public and political debate concerning diversity and social and communal life.
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Examination of the neighborhood activation theory in normal and hearing-impaired listeners.
Dirks, D D; Takayanagi, S; Moshfegh, A; Noffsinger, P D; Fausti, S A
2001-02-01
Experiments were conducted to examine the effects of lexical information on word recognition among normal hearing listeners and individuals with sensorineural hearing loss. The lexical factors of interest were incorporated in the Neighborhood Activation Model (NAM). Central to this model is the concept that words are recognized relationally in the context of other phonemically similar words. NAM suggests that words in the mental lexicon are organized into similarity neighborhoods and the listener is required to select the target word from competing lexical items. Two structural characteristics of similarity neighborhoods that influence word recognition have been identified; "neighborhood density" or the number of phonemically similar words (neighbors) for a particular target item and "neighborhood frequency" or the average frequency of occurrence of all the items within a neighborhood. A third lexical factor, "word frequency" or the frequency of occurrence of a target word in the language, is assumed to optimize the word recognition process by biasing the system toward choosing a high frequency over a low frequency word. Three experiments were performed. In the initial experiments, word recognition for consonant-vowel-consonant (CVC) monosyllables was assessed in young normal hearing listeners by systematically partitioning the items into the eight possible lexical conditions that could be created by two levels of the three lexical factors, word frequency (high and low), neighborhood density (high and low), and average neighborhood frequency (high and low). Neighborhood structure and word frequency were estimated computationally using a large, on-line lexicon-based Webster's Pocket Dictionary. From this program 400 highly familiar, monosyllables were selected and partitioned into eight orthogonal lexical groups (50 words/group). The 400 words were presented randomly to normal hearing listeners in speech-shaped noise (Experiment 1) and "in quiet" (Experiment 2) as
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Genome-wide identification of KANADI1 target genes.
Directory of Open Access Journals (Sweden)
Paz Merelo
Full Text Available Plant organ development and polarity establishment is mediated by the action of several transcription factors. Among these, the KANADI (KAN subclade of the GARP protein family plays important roles in polarity-associated processes during embryo, shoot and root patterning. In this study, we have identified a set of potential direct target genes of KAN1 through a combination of chromatin immunoprecipitation/DNA sequencing (ChIP-Seq and genome-wide transcriptional profiling using tiling arrays. Target genes are over-represented for genes involved in the regulation of organ development as well as in the response to auxin. KAN1 affects directly the expression of several genes previously shown to be important in the establishment of polarity during lateral organ and vascular tissue development. We also show that KAN1 controls through its target genes auxin effects on organ development at different levels: transport and its regulation, and signaling. In addition, KAN1 regulates genes involved in the response to abscisic acid, jasmonic acid, brassinosteroids, ethylene, cytokinins and gibberellins. The role of KAN1 in organ polarity is antagonized by HD-ZIPIII transcription factors, including REVOLUTA (REV. A comparison of their target genes reveals that the REV/KAN1 module acts in organ patterning through opposite regulation of shared targets. Evidence of mutual repression between closely related family members is also shown.
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Department of Housing and Urban Development — Choice Neighborhoods grants transform distressed neighborhoods, public and assisted projects into viable and sustainable mixed-income neighborhoods by linking...
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A new electrospray method for targeted gene delivery.
Boehringer, Stephan; Ruzgys, Paulius; Tamò, Luca; Šatkauskas, Saulius; Geiser, Thomas; Gazdhar, Amiq; Hradetzky, David
2018-03-05
A challenge for gene therapy is absence of safe and efficient local delivery of therapeutic genetic material. An efficient and reproducible physical method of electrospray for localized and targeted gene delivery is presented. Electrospray works on the principle of coulombs repulsion, under influence of electric field the liquid carrying genetic material is dispersed into micro droplets and is accelerated towards the targeted tissue, acting as a counter electrode. The accelerated droplets penetrate the targeted cells thus facilitating the transfer of genetic material into the cell. The work described here presents the principle of electrospray for gene delivery, the basic instrument design, and the various optimized parameters to enhance gene transfer in vitro. We estimate a transfection efficiency of up to 60% was achieved. We describe an efficient gene transfer method and a potential electrospray-mediated gene transfer mechanism.
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Laméris, Joran; Hipp, John R; Tolsma, Jochem
2018-05-01
This study examines the effects of neighborhood racial in-group size, economic deprivation and the prevalence of crime on neighborhood cohesion among U.S. whites. We explore to what extent residents' perceptions of their neighborhood mediate these macro-micro relationships. We use a recent individual-level data set, the American Social Fabric Study (2012/2013), enriched with contextual-level data from the U.S. Census Bureau (2010) and employ multi-level structural equation models. We show that the racial in-group size is positively related to neighborhood cohesion and that neighborhood cohesion is lower in communities with a high crime rate. Individuals' perceptions of the racial in-group size partly mediate the relationship between the objective racial in-group size and neighborhood cohesion. Residents' perceptions of unsafety from crime also appear to be a mediating factor, not only for the objective crime rate but also for the objective racial in-group size. This is in line with our idea that racial stereotypes link racial minorities to crime whereby neighborhoods with a large non-white population are perceived to be more unsafe. Residents of the same neighborhood differ in how they perceive the degree of economic decay of the neighborhood and this causes them to evaluate neighborhood cohesion differently, however perceptions of neighborhood economic decay do not explain the link between the objective neighborhood context and neighborhood cohesion. Copyright © 2018. Published by Elsevier Inc.
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Problem-Solving Test: Targeted Gene Disruption
Szeberenyi, Jozsef
2008-01-01
Mutational inactivation of a specific gene is the most powerful technique to analyze the biological function of the gene. This approach has been used for a long time in viruses, bacteria, yeast, and fruit fly, but looked quite hopeless in more complex organisms. Targeted inactivation of specific genes (also known as knock-out mutation) in mice is…
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Randall, J; Swenson, C C; Henggeler, S W
1999-12-01
Youth antisocial behavior is influenced, in part, by neighborhood context. Yet, rather than attempting to ameliorate factors contributing to youth antisocial behavior, service dollars are primarily devoted to expensive and often ineffective out-of-home placements. This article describes the development and implementation of a collaborative partnership designed to empower an economically disadvantaged neighborhood to address violent criminal behavior, substance abuse, and other serious antisocial problems of its youth while maintaining youth in the neighborhood. Through a collaboration between a university research center and neighborhood stakeholders, services are being provided to address the key priorities identified by neighborhood residents, and extensive efforts are being made to develop family and neighborhood contexts that are conducive to prosocial youth behavior.
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Performance tuning for CUDA-accelerated neighborhood denoising filters
Energy Technology Data Exchange (ETDEWEB)
Zheng, Ziyi; Mueller, Klaus [Stony Brook Univ., NY (United States). Center for Visual Computing, Computer Science; Xu, Wei
2011-07-01
Neighborhood denoising filters are powerful techniques in image processing and can effectively enhance the image quality in CT reconstructions. In this study, by taking the bilateral filter and the non-local mean filter as two examples, we discuss their implementations and perform fine-tuning on the targeted GPU architecture. Experimental results show that the straightforward GPU-based neighborhood filters can be further accelerated by pre-fetching. The optimized GPU-accelerated denoising filters are ready for plug-in into reconstruction framework to enable fast denoising without compromising image quality. (orig.)
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Ghettoizing outdoor advertising: disadvantage and ad panel density in black neighborhoods.
Kwate, Naa Oyo A; Lee, Tammy H
2007-01-01
This study investigated correlates of outdoor advertising panel density in predominantly African American neighborhoods in New York City. Research shows that black neighborhoods have more outdoor advertising space than white neighborhoods, and these spaces disproportionately market alcohol and tobacco advertisements. Thus, understanding the factors associated with outdoor advertising panel density has important implications for public health. We linked 2000 census data with property data at the census block group level to investigate two neighborhood-level determinants of ad density: income level and physical decay. Results showed that block groups were exposed to an average of four ad spaces per 1,000 residents and that vacant lot square footage was a significant positive predictor of ad density. An inverse relationship between median household income and ad density did not reach significance, suggesting that relative affluence did not protect black neighborhoods from being targeted for outdoor advertisements.
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Gene targeting in adult rhesus macaque fibroblasts
Directory of Open Access Journals (Sweden)
Wolf Don P
2008-03-01
Full Text Available Abstract Background Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in primary culture of adult rhesus macaque fibroblasts as a first step in creating nonhuman primate models of genetic disease using nuclear transfer technology. Results A primary culture of adult male fibroblasts was transfected with hTERT to overcome senescence and allow long term in vitro manipulations. Successful gene targeting of the HPRT locus in rhesus macaques was achieved by electroporating S-phase synchronized cells with a construct containing a SV40 enhancer. Conclusion The cell lines reported here could be used for the production of null mutant rhesus macaque models of human genetic disease using SCNT technology. In addition, given the close evolutionary relationship and biological similarity between rhesus macaques and humans, the protocols described here may prove useful in the genetic engineering of human somatic cells.
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Targeting trichothecene biosynthetic genes
Wei, Songhong; Lee, van der Theo; Verstappen, Els; Gent, van Marga; Waalwijk, Cees
2017-01-01
Biosynthesis of trichothecenes requires the involvement of at least 15 genes, most of which have been targeted for PCR. Qualitative PCRs are used to assign chemotypes to individual isolates, e.g., the capacity to produce type A and/or type B trichothecenes. Many regions in the core cluster
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Multi-targeted priming for genome-wide gene expression assays
Directory of Open Access Journals (Sweden)
Adomas Aleksandra B
2010-08-01
Full Text Available Abstract Background Complementary approaches to assaying global gene expression are needed to assess gene expression in regions that are poorly assayed by current methodologies. A key component of nearly all gene expression assays is the reverse transcription of transcribed sequences that has traditionally been performed by priming the poly-A tails on many of the transcribed genes in eukaryotes with oligo-dT, or by priming RNA indiscriminately with random hexamers. We designed an algorithm to find common sequence motifs that were present within most protein-coding genes of Saccharomyces cerevisiae and of Neurospora crassa, but that were not present within their ribosomal RNA or transfer RNA genes. We then experimentally tested whether degenerately priming these motifs with multi-targeted primers improved the accuracy and completeness of transcriptomic assays. Results We discovered two multi-targeted primers that would prime a preponderance of genes in the genomes of Saccharomyces cerevisiae and Neurospora crassa while avoiding priming ribosomal RNA or transfer RNA. Examining the response of Saccharomyces cerevisiae to nitrogen deficiency and profiling Neurospora crassa early sexual development, we demonstrated that using multi-targeted primers in reverse transcription led to superior performance of microarray profiling and next-generation RNA tag sequencing. Priming with multi-targeted primers in addition to oligo-dT resulted in higher sensitivity, a larger number of well-measured genes and greater power to detect differences in gene expression. Conclusions Our results provide the most complete and detailed expression profiles of the yeast nitrogen starvation response and N. crassa early sexual development to date. Furthermore, our multi-targeting priming methodology for genome-wide gene expression assays provides selective targeting of multiple sequences and counter-selection against undesirable sequences, facilitating a more complete and
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Advances in sarcoma gene mutations and therapeutic targets.
Gao, Peng; Seebacher, Nicole A; Hornicek, Francis; Guo, Zheng; Duan, Zhenfeng
2018-01-01
Sarcomas are rare and complex malignancies that have been associated with a poor prognostic outcome. Over the last few decades, traditional treatment with surgery and/or chemotherapy has not significantly improved outcomes for most types of sarcomas. In recent years, there have been significant advances in the understanding of specific gene mutations that are important in driving the pathogenesis and progression of sarcomas. Identification of these new gene mutations, using next-generation sequencing and advanced molecular techniques, has revealed a range of potential therapeutic targets. This, in turn, may lead to the development of novel agents targeted to different sarcoma subtypes. In this review, we highlight the advances made in identifying sarcoma gene mutations, including those of p53, RB, PI3K and IDH genes, as well as novel therapeutic strategies aimed at utilizing these mutant genes. In addition, we discuss a number of preclinical studies and ongoing early clinical trials in sarcoma targeting therapies, as well as gene editing technology, which may provide a better choice for sarcoma patient management. Published by Elsevier Ltd.
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Perception of neighborhood crime and drugs increases cardiometabolic risk in Chilean adolescents
Martinez, Suzanna M; Blanco, Estela; Delva, Jorge; Burrows, Raquel; Reyes, Marcela; Lozoff, Betsy; Gahagan, Sheila
2013-01-01
Purpose Studies report an association between neighborhood risk and both obesity and cardiometabolic risk factors (CMR) among adolescents. Here we describe the effect of perceived neighborhood risk on adiposity and CMR among Chilean adolescents. Methods Participants were 523 low- to middle-income Chilean adolescents. We assessed neighborhood risk in early adolescence, adiposity in childhood and in early and later adolescence, and blood pressure and fasting glucose in later adolescence. Neighborhood risk profiles were estimated using latent profile analysis (LPA) and based on reported perceptions of crime and drug sales/use. Using linear and logistic regression, we examined the effect of neighborhood risk on adiposity and CMR. Results Mean age in early and later adolescence was 14 and 17 years, respectively. Participants were 52% male, with a mean BMI z-score of 0.67, and 8% met criteria for the metabolic syndrome. LPA identified two neighborhood profiles: 61% low risk and 39% high risk. In later adolescence, being in the high risk profile predicted a higher BMI z-score, waist-to-height ratio, and fat mass index (p-values Chilean neighborhoods with high crime and drugs, targeted public health interventions and policies for youth could be beneficial. PMID:24411818
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Improving Mental Health Through the Regeneration of Deprived Neighborhoods: A Natural Experiment.
White, James; Greene, Giles; Farewell, Daniel; Dunstan, Frank; Rodgers, Sarah; Lyons, Ronan A; Humphreys, Ioan; John, Ann; Webster, Chris; Phillips, Ceri J; Fone, David
2017-08-15
Neighborhood-level interventions provide an opportunity to better understand the impact of neighborhoods on health. In 2001, the Welsh Government, United Kingdom, funded Communities First, a program of neighborhood regeneration delivered to the 100 most deprived of the 881 electoral wards in Wales. In this study, we examined the association between neighborhood regeneration and mental health. Information on regeneration activities in 35 intervention areas (n = 4,197 subjects) and 75 control areas (n = 6,695 subjects) was linked to data on mental health from a cohort study with assessments made in 2001 (before regeneration) and 2008 (after regeneration). Propensity score matching was used to estimate the change in mental health in intervention neighborhoods versus control neighborhoods. Baseline differences between intervention and control areas were of similar magnitude as produced by paired randomization of neighborhoods. Regeneration was associated with an improvement in the mental health of residents in intervention areas compared with control neighborhoods (β = 1.54, 95% confidence interval: 0.50, 2.59), suggesting a reduction in socioeconomic inequalities in mental health. There was a dose-response relationship between length of residence in regeneration neighborhoods and improvements in mental health (P-trend = 0.05). These results show that targeted regeneration of deprived neighborhoods can improve mental health. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
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Alternative epigenetic chromatin states of polycomb target genes.
Directory of Open Access Journals (Sweden)
Yuri B Schwartz
2010-01-01
Full Text Available Polycomb (PcG regulation has been thought to produce stable long-term gene silencing. Genomic analyses in Drosophila and mammals, however, have shown that it targets many genes, which can switch state during development. Genetic evidence indicates that critical for the active state of PcG target genes are the histone methyltransferases Trithorax (TRX and ASH1. Here we analyze the repertoire of alternative states in which PcG target genes are found in different Drosophila cell lines and the role of PcG proteins TRX and ASH1 in controlling these states. Using extensive genome-wide chromatin immunoprecipitation analysis, RNAi knockdowns, and quantitative RT-PCR, we show that, in addition to the known repressed state, PcG targets can reside in a transcriptionally active state characterized by formation of an extended domain enriched in ASH1, the N-terminal, but not C-terminal moiety of TRX and H3K27ac. ASH1/TRX N-ter domains and transcription are not incompatible with repressive marks, sometimes resulting in a "balanced" state modulated by both repressors and activators. Often however, loss of PcG repression results instead in a "void" state, lacking transcription, H3K27ac, or binding of TRX or ASH1. We conclude that PcG repression is dynamic, not static, and that the propensity of a target gene to switch states depends on relative levels of PcG, TRX, and activators. N-ter TRX plays a remarkable role that antagonizes PcG repression and preempts H3K27 methylation by acetylation. This role is distinct from that usually attributed to TRX/MLL proteins at the promoter. These results have important implications for Polycomb gene regulation, the "bivalent" chromatin state of embryonic stem cells, and gene expression in development.
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Neighborhood context and health: How neighborhood social capital affects individual health
Mohnen, S.M.
2012-01-01
Does it matter for my health in which neighborhood I live? The fact is, health is determined not only by individual characteristics but also by the neighborhood in which someone lives. This thesis shows that health clusters in Dutch neighborhoods and that this is not only a composition effect (that
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TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.
Directory of Open Access Journals (Sweden)
Yi-An Chen
Full Text Available Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/.
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CRISPR/Cas9-mediated gene targeting in Arabidopsis using sequential transformation.
Miki, Daisuke; Zhang, Wenxin; Zeng, Wenjie; Feng, Zhengyan; Zhu, Jian-Kang
2018-05-17
Homologous recombination-based gene targeting is a powerful tool for precise genome modification and has been widely used in organisms ranging from yeast to higher organisms such as Drosophila and mouse. However, gene targeting in higher plants, including the most widely used model plant Arabidopsis thaliana, remains challenging. Here we report a sequential transformation method for gene targeting in Arabidopsis. We find that parental lines expressing the bacterial endonuclease Cas9 from the egg cell- and early embryo-specific DD45 gene promoter can improve the frequency of single-guide RNA-targeted gene knock-ins and sequence replacements via homologous recombination at several endogenous sites in the Arabidopsis genome. These heritable gene targeting can be identified by regular PCR. Our approach enables routine and fine manipulation of the Arabidopsis genome.
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Directory of Open Access Journals (Sweden)
Hua-Bing Li
2013-04-01
Full Text Available Polycomb bodies are foci of Polycomb proteins in which different Polycomb target genes are thought to co-localize in the nucleus, looping out from their chromosomal context. We have shown previously that insulators, not Polycomb response elements (PREs, mediate associations among Polycomb Group (PcG targets to form Polycomb bodies. Here we use live imaging and 3C interactions to show that transgenes containing PREs and endogenous PcG-regulated genes are targeted by insulator proteins to different nuclear structures depending on their state of activity. When two genes are repressed, they co-localize in Polycomb bodies. When both are active, they are targeted to transcription factories in a fashion dependent on Trithorax and enhancer specificity as well as the insulator protein CTCF. In the absence of CTCF, assembly of Polycomb bodies is essentially reduced to those representing genomic clusters of Polycomb target genes. The critical role of Trithorax suggests that stable association with a specialized transcription factory underlies the cellular memory of the active state.
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Targeted gene therapy and cell reprogramming in Fanconi anemia
Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A
2014-01-01
Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. PMID:24859981
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Demarcation of local neighborhoods to study relations between contextual factors and health
Directory of Open Access Journals (Sweden)
Chor Dora
2010-06-01
Full Text Available Abstract Background Several studies have highlighted the importance of collective social factors for population health. One of the major challenges is an adequate definition of the spatial units of analysis which present properties potentially related to the target outcomes. Political and administrative divisions of urban areas are the most commonly used definition, although they suffer limitations in their ability to fully express the neighborhoods as social and spatial units. Objective This study presents a proposal for defining the boundaries of local neighborhoods in Rio de Janeiro city. Local neighborhoods are constructed by means of aggregation of contiguous census tracts which are homogeneous regarding socioeconomic indicators. Methodology Local neighborhoods were created using the SKATER method (TerraView software. Criteria used for socioeconomic homogeneity were based on four census tract indicators (income, education, persons per household, and percentage of population in the 0-4-year age bracket considering a minimum population of 5,000 people living in each local neighborhood. The process took into account the geographic boundaries between administrative neighborhoods (a political-administrative division larger than a local neighborhood, but smaller than a borough and natural geographic barriers. Results The original 8,145 census tracts were collapsed into 794 local neighborhoods, distributed along 158 administrative neighborhoods. Local neighborhoods contained a mean of 10 census tracts, and there were an average of five local neighborhoods per administrative neighborhood. The local neighborhood units demarcated in this study are less socioeconomically heterogeneous than the administrative neighborhoods and provide a means for decreasing the well-known statistical variability of indicators based on census tracts. The local neighborhoods were able to distinguish between different areas within administrative neighborhoods
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Demarcation of local neighborhoods to study relations between contextual factors and health.
Santos, Simone M; Chor, Dora; Werneck, Guilherme Loureiro
2010-06-29
Several studies have highlighted the importance of collective social factors for population health. One of the major challenges is an adequate definition of the spatial units of analysis which present properties potentially related to the target outcomes. Political and administrative divisions of urban areas are the most commonly used definition, although they suffer limitations in their ability to fully express the neighborhoods as social and spatial units. This study presents a proposal for defining the boundaries of local neighborhoods in Rio de Janeiro city. Local neighborhoods are constructed by means of aggregation of contiguous census tracts which are homogeneous regarding socioeconomic indicators. Local neighborhoods were created using the SKATER method (TerraView software). Criteria used for socioeconomic homogeneity were based on four census tract indicators (income, education, persons per household, and percentage of population in the 0-4-year age bracket) considering a minimum population of 5,000 people living in each local neighborhood. The process took into account the geographic boundaries between administrative neighborhoods (a political-administrative division larger than a local neighborhood, but smaller than a borough) and natural geographic barriers. The original 8,145 census tracts were collapsed into 794 local neighborhoods, distributed along 158 administrative neighborhoods. Local neighborhoods contained a mean of 10 census tracts, and there were an average of five local neighborhoods per administrative neighborhood.The local neighborhood units demarcated in this study are less socioeconomically heterogeneous than the administrative neighborhoods and provide a means for decreasing the well-known statistical variability of indicators based on census tracts. The local neighborhoods were able to distinguish between different areas within administrative neighborhoods, particularly in relation to squatter settlements. Although the literature on
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Targeting the human lysozyme gene on bovine αs1- casein gene ...
African Journals Online (AJOL)
ajl yemi
2011-11-28
Nov 28, 2011 ... Targeting an exogenous gene into a favorable gene locus and for expression under endogenous regulators is ... case, the expression of human lysozyme could be regulated by the endogenous cis-element of αs1- casein gene in .... Mouse mammary epithelial C127 cells (Cell Bank, Chinese. Academy of ...
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Co-factors necessary for PPAR mediated transactivation of endogenous target genes
DEFF Research Database (Denmark)
Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk
of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...
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PSAT: A web tool to compare genomic neighborhoods of multiple prokaryotic genomes
Directory of Open Access Journals (Sweden)
Wasnick Michael
2008-03-01
Full Text Available Abstract Background The conservation of gene order among prokaryotic genomes can provide valuable insight into gene function, protein interactions, or events by which genomes have evolved. Although some tools are available for visualizing and comparing the order of genes between genomes of study, few support an efficient and organized analysis between large numbers of genomes. The Prokaryotic Sequence homology Analysis Tool (PSAT is a web tool for comparing gene neighborhoods among multiple prokaryotic genomes. Results PSAT utilizes a database that is preloaded with gene annotation, BLAST hit results, and gene-clustering scores designed to help identify regions of conserved gene order. Researchers use the PSAT web interface to find a gene of interest in a reference genome and efficiently retrieve the sequence homologs found in other bacterial genomes. The tool generates a graphic of the genomic neighborhood surrounding the selected gene and the corresponding regions for its homologs in each comparison genome. Homologs in each region are color coded to assist users with analyzing gene order among various genomes. In contrast to common comparative analysis methods that filter sequence homolog data based on alignment score cutoffs, PSAT leverages gene context information for homologs, including those with weak alignment scores, enabling a more sensitive analysis. Features for constraining or ordering results are designed to help researchers browse results from large numbers of comparison genomes in an organized manner. PSAT has been demonstrated to be useful for helping to identify gene orthologs and potential functional gene clusters, and detecting genome modifications that may result in loss of function. Conclusion PSAT allows researchers to investigate the order of genes within local genomic neighborhoods of multiple genomes. A PSAT web server for public use is available for performing analyses on a growing set of reference genomes through any
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Targeted gene therapy and cell reprogramming in Fanconi anemia.
Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A
2014-06-01
Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.
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Durham Neighborhood Compass Neighborhoods
City and County of Durham, North Carolina — The Durham Neighborhood Compass is a quantitative indicators project with qualitative values, integrating data from local government, the Census Bureau and other...
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Specific genetic modifications of domestic animals by gene targeting and animal cloning
Directory of Open Access Journals (Sweden)
Zhou Jiangfeng
2003-11-01
Full Text Available Abstract The technology of gene targeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large livestock species until the successful creation of the first mammalian clone "Dolly" the sheep. The combination of the technologies for gene targeting of somatic cells with those of animal cloning made it possible to introduce specific genetic mutations into domestic animals. In this review, the principles of gene targeting in somatic cells and the challenges of nuclear transfer using gene-targeted cells are discussed. The relevance of gene targeting in domestic animals for applications in bio-medicine and agriculture are also examined.
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Lamé ris, J.G.; Hipp, J.R.; Tolsma, J.
2018-01-01
This study examines the effects of neighborhood racial in-group size, economic deprivation and the prevalence of crime on neighborhood cohesion among U.S. whites. We explore to what extent residents' perceptions of their neighborhood mediate these macro-micro relationships. We use a recent
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Positive-negative-selection-mediated gene targeting in rice
Directory of Open Access Journals (Sweden)
Zenpei eShimatani
2015-01-01
Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.
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Cancer gene therapy with targeted adenoviruses.
Bachtarzi, Houria; Stevenson, Mark; Fisher, Kerry
2008-11-01
Clinical experience with adenovirus vectors has highlighted the need for improved delivery and targeting. This manuscript aims to provide an overview of the techniques currently under development for improving adenovirus delivery to malignant cells in vivo. Primary research articles reporting improvements in adenoviral gene delivery are described. Strategies include genetic modification of viral coat proteins, non-genetic modifications including polymer encapsulation approaches and pharmacological interventions. Reprogramming adenovirus tropism in vitro has been convincingly demonstrated using a range of genetic and physical strategies. These studies have provided new insights into our understanding of virology and the field is progressing. However, there are still some limitations that need special consideration before adenovirus-targeted cancer gene therapy emerges as a routine treatment in the clinical setting.
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China’s Neighborhood Environment and Options for Neighborhood Strategy
Institute of Scientific and Technical Information of China (English)
ZHOU FANGYIN
2016-01-01
Since the 18th CPC National Congress,especially since the Central Conference on Work Relating to Neighborhood Diplomacy held in October 2013,China’s neighborhood diplomacy has been energetic,proactive and promising,achieving important results in several aspects.At the same time,it is also in face of challenges
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DEFF Research Database (Denmark)
Damm, Anna Piil
2012-01-01
of men living in the neighborhood, but positively affected by the employment rate of non-Western immigrant men and co-national men living in the neighborhood. This is strong evidence that immigrants find jobs in part through their employed immigrant and co-ethnic contacts in the neighborhood of residence...... successfully addresses the methodological problem of endogenous neighborhood selection. Taking account of location sorting, living in a socially deprived neighborhood does not affect labor market outcomes of refugee men. Furthermore, their labor market outcomes are not affected by the overall employment rate...
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Targeted gene deletion of miRNAs in mice by TALEN system.
Takada, Shuji; Sato, Tempei; Ito, Yoshiaki; Yamashita, Satoshi; Kato, Tomoko; Kawasumi, Miyuri; Kanai-Azuma, Masami; Igarashi, Arisa; Kato, Tomomi; Tamano, Moe; Asahara, Hiroshi
2013-01-01
Mice are among the most valuable model animal species with an enormous amount of heritage in genetic modification studies. However, targeting genes in mice is sometimes difficult, especially for small genes, such as microRNAs (miRNAs) and targeting genes in repeat sequences. Here we optimized the application of TALEN system for mice and successfully obtained gene targeting technique in mice for intergenic region and series of microRNAs. Microinjection of synthesized RNA of TALEN targeting each gene in one cell stage of embryo was carried out and injected oocytes were transferred into pseudopregnant ICR female mice, producing a high success rate of the targeted deletion of miRNA genes. In our condition, TALEN RNA without poly(A) tail worked better than that of with poly(A) tail. This mutated allele in miRNA was transmitted to the next generation, suggesting the successful germ line transmission of this targeting method. Consistent with our notion of miRNAs maturation mechanism, in homozygous mutant mice of miR-10a, the non- mutated strand of miRNAs expression was completely diminished. This method will lead us to expand and accelerate our genetic research using mice in a high throughput way.
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Promoting Active Urban Aging: A Measurement Approach to Neighborhood Walkability for Older Adults
Directory of Open Access Journals (Sweden)
Rachael L. Weiss
2010-01-01
Full Text Available Understanding the role of the built environment on physical activity behavior among older adults is an important public health goal, but evaluating these relationships remains complicated due to the difficulty of measuring specific attributes of the environment. As a result, there is conflicting evidence regarding the association between perceived and objectively measured walkability and physical activity among urban-dwelling older adults. This suggests that both actual environmental features and perceptions of these attributes influence walking behavior. The purpose of this pilot project is to create an Objective Walkability Index (OWI by census block using a Geographic Information System (GIS and supplement the results with resident perceptions thus more accurately characterizing the context of walkability. Computerized Neighborhood Environment Tracking (ComNET was used to systematically assess environmental risks impacting activity patterns of older adults in two New York City neighborhoods. In addition, the Senior Center Evaluation of the Neighborhood Environment (SCENE survey was administered to older adults attending two senior centers located within the target neighborhoods. The results indicate that there is substantial variation in OWI score both between and within the neighborhoods suggesting that residence in some communities may increase the risk of inactivity among older adults. Also, low walkability census blocks were clustered within each neighborhood providing an opportunity for targeted investigation into localized threats to walkability. A lack of consensus regarding the association between the built environment and physical activity among older adults is a consequence of the problems inherent in measuring these determinants. Further empirical evidence evaluating the complex relationships between the built environment and physical activity is an essential step towards creating active communities.
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Promoting Active Urban Aging: A Measurement Approach to Neighborhood Walkability for Older Adults.
Weiss, Rachael L; Maantay, Juliana A; Fahs, Marianne
2010-01-01
Understanding the role of the built environment on physical activity behavior among older adults is an important public health goal, but evaluating these relationships remains complicated due to the difficulty of measuring specific attributes of the environment. As a result, there is conflicting evidence regarding the association between perceived and objectively measured walkability and physical activity among urban-dwelling older adults. This suggests that both actual environmental features and perceptions of these attributes influence walking behavior. The purpose of this pilot project is to create an Objective Walkability Index (OWI) by census block using a Geographic Information System (GIS) and supplement the results with resident perceptions thus more accurately characterizing the context of walkability. Computerized Neighborhood Environment Tracking (ComNET) was used to systematically assess environmental risks impacting activity patterns of older adults in two New York City neighborhoods. In addition, the Senior Center Evaluation of the Neighborhood Environment (SCENE) survey was administered to older adults attending two senior centers located within the target neighborhoods. The results indicate that there is substantial variation in OWI score both between and within the neighborhoods suggesting that residence in some communities may increase the risk of inactivity among older adults. Also, low walkability census blocks were clustered within each neighborhood providing an opportunity for targeted investigation into localized threats to walkability. A lack of consensus regarding the association between the built environment and physical activity among older adults is a consequence of the problems inherent in measuring these determinants. Further empirical evidence evaluating the complex relationships between the built environment and physical activity is an essential step towards creating active communities.
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Barrington, Wendy E; Stafford, Mai; Hamer, Mark; Beresford, Shirley A A; Koepsell, Thomas; Steptoe, Andrew
2014-05-01
Associations between measures of neighborhood socioeconomic deprivation and health have been identified, yet work is needed to uncover explanatory mechanisms. One hypothesized pathway is through stress, yet the few studies that have evaluated associations between characteristics of deprived neighborhoods and biomarkers of stress are mixed. This study evaluated whether objectively measured neighborhood socioeconomic deprivation and individual perceived neighborhood characteristics (i.e. social control and fear of crime) impacted cortisol responses to an induced stressor among older healthy adults. Data from Heart Scan, a sub-study of the Whitehall II cohort, were used to generate multilevel piecewise growth-curve models of cortisol trajectories after a laboratory stressor accounting for neighborhood and demographic characteristics. Neighborhood socioeconomic deprivation was significantly associated with individual perceptions of social control and fear of crime in the neighborhood while an association with blunted cortisol reactivity was only evidence among women. Social control was significantly associated with greater cortisol reactivity and mediation between neighborhood socioeconomic deprivation and cortisol reactivity was suggested among women. These findings support a gender-dependent role of neighborhood in stress process models of health. Published by Elsevier Ltd.
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Directory of Open Access Journals (Sweden)
Nina Thakkar Rivera
2016-01-01
Full Text Available The American Heart Association reports the annual incidence of out-of-hospital cardiopulmonary arrests (OHCA is greater than 300,000 with a survival rate of 9.5%. Bystander cardiopulmonary resuscitation (CPR saves one life for every 30, with a 10% decrease in survival associated with every minute of delay in CPR initiation. Bystander CPR and training vary widely by region. We conducted a retrospective study of 320 persons who suffered OHCA in South Florida over 25 months. Increased survival, overall and with bystander CPR, was seen with increasing income (p=0.05, with a stronger disparity between low- and high-income neighborhoods (p=0.01 and p=0.03, resp.. Survival with bystander CPR was statistically greater in white- versus black-predominant neighborhoods (p=0.04. Increased survival, overall and with bystander CPR, was seen with high- versus low-education neighborhoods (p=0.03. Neighborhoods with more high school age persons displayed the lowest survival. We discovered a significant disparity in OHCA survival within neighborhoods of low-income, black-predominance, and low-education. Reduced survival was seen in neighborhoods with larger populations of high school students. This group is a potential target for training, and instruction can conceivably change survival outcomes in these neighborhoods, closing the gap, thus improving survival for all.
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Adolescent Physical Activity: Moderation of Individual Factors by Neighborhood Environment.
D'Angelo, Heather; Fowler, Stephanie L; Nebeling, Linda C; Oh, April Y
2017-06-01
Less than a third of U.S. adolescents meet federal physical activity (PA) guidelines. Understanding correlates of PA at multiple levels of the Social Ecological Model could improve PA interventions among youth. This study examines (1) associations between factors across the Social Ecological Model including psychosocial factors, perceived neighborhood physical and social environment characteristics, and adolescent moderate to vigorous PA (MVPA) and (2) whether perceived neighborhood characteristics moderate associations between psychosocial factors and MVPA. A national sample of adolescents (aged 12-17 years) in the 2014 Family Life, Activity, Sun, Health, and Eating Study was used to examine associations between psychosocial characteristics, perceived neighborhood social and physical characteristics, and self-reported weekly minutes of MVPA. Analyses were conducted in 2015. Interaction terms between psychosocial and neighborhood variables were added to multiple linear regression models to examine moderation hypotheses. Significant two-way interactions revealed that neighborhoods with features perceived as supportive of PA strengthened several psychosocial-MVPA associations. The positive associations between MVPA and friend norms, friend support, and attitudes were strengthened for adolescents living in neighborhoods with high versus low PA resource availability (all p<0.05). Furthermore, the association between controlled and autonomous motivation and MVPA was strengthened under conditions of shops/stores near (versus distant from) adolescents' homes (p<0.05). The association between some psychosocial factors and adolescent MVPA may be environment dependent. Neighborhood physical and social environments supportive of PA are important to consider when developing targeted PA interventions and may strengthen the association between psychosocial-level factors and adolescent MVPA. Copyright © 2017 American Journal of Preventive Medicine. All rights reserved.
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Targeting Herpetic Keratitis by Gene Therapy
Directory of Open Access Journals (Sweden)
Hossein Mostafa Elbadawy
2012-01-01
Full Text Available Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1 can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.
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Targeted gene deletion of miRNAs in mice by TALEN system.
Directory of Open Access Journals (Sweden)
Shuji Takada
Full Text Available Mice are among the most valuable model animal species with an enormous amount of heritage in genetic modification studies. However, targeting genes in mice is sometimes difficult, especially for small genes, such as microRNAs (miRNAs and targeting genes in repeat sequences. Here we optimized the application of TALEN system for mice and successfully obtained gene targeting technique in mice for intergenic region and series of microRNAs. Microinjection of synthesized RNA of TALEN targeting each gene in one cell stage of embryo was carried out and injected oocytes were transferred into pseudopregnant ICR female mice, producing a high success rate of the targeted deletion of miRNA genes. In our condition, TALEN RNA without poly(A tail worked better than that of with poly(A tail. This mutated allele in miRNA was transmitted to the next generation, suggesting the successful germ line transmission of this targeting method. Consistent with our notion of miRNAs maturation mechanism, in homozygous mutant mice of miR-10a, the non- mutated strand of miRNAs expression was completely diminished. This method will lead us to expand and accelerate our genetic research using mice in a high throughput way.
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Pesch, Lawrence P.
2014-01-01
This case study focuses on the way a neighborhood association connects schools to broad change in an urban neighborhood of a large Midwestern city. The first section provides a review of the literature on community involvement in school and neighborhood reform. It reviews the historical origins of the current school-community relationship, the…
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Directory of Open Access Journals (Sweden)
Roya Pedram Fatemi
2014-01-01
Full Text Available Non-protein coding RNAs (ncRNAs make up the overwhelming majority of transcripts in the genome and have recently gained attention for their complex regulatory role in cells, including the regulation of protein-coding genes. Furthermore, ncRNAs play an important role in normal development and their expression levels are dysregulated in several diseases. Recently, several long noncoding RNAs (lncRNAs have been shown to alter the epigenetic status of genomic loci and suppress the expression of target genes. This review will present examples of such a mechanism and focus on the potential to target lncRNAs for achieving therapeutic gene upregulation by de-repressing genes that are epigenetically silenced in various diseases. Finally, the potential to target lncRNAs, through their interactions with epigenetic enzymes, using various tools, such as small molecules, viral vectors and antisense oligonucleotides, will be discussed. We suggest that small molecule modulators of a novel class of drug targets, lncRNA-protein interactions, have great potential to treat some cancers, cardiovascular disease, and neurological disorders.
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Measuring physical neighborhood quality related to health.
Rollings, Kimberly A; Wells, Nancy M; Evans, Gary W
2015-04-29
Although sociodemographic factors are one aspect of understanding the effects of neighborhood environments on health, equating neighborhood quality with socioeconomic status ignores the important role of physical neighborhood attributes. Prior work on neighborhood environments and health has relied primarily on level of socioeconomic disadvantage as the indicator of neighborhood quality without attention to physical neighborhood quality. A small but increasing number of studies have assessed neighborhood physical characteristics. Findings generally indicate that there is an association between living in deprived neighborhoods and poor health outcomes, but rigorous evidence linking specific physical neighborhood attributes to particular health outcomes is lacking. This paper discusses the methodological challenges and limitations of measuring physical neighborhood environments relevant to health and concludes with proposed directions for future work.
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Gene targeting approaches to complex genetic diseases: atherosclerosis and essential hypertension.
Smithies, O; Maeda, N
1995-01-01
Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. The resulting "knockout" mice have confirmed some hypotheses, have upset others, but have rarely been uninformative. Models of several human genetic diseases have been produced by targeting--including Gaucher disease, cystic fibrosis, and the fragile X syndrome. These di...
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An ensemble method to predict target genes and pathways in uveal melanoma
Directory of Open Access Journals (Sweden)
Wei Chao
2018-04-01
Full Text Available This work proposes to predict target genes and pathways for uveal melanoma (UM based on an ensemble method and pathway analyses. Methods: The ensemble method integrated a correlation method (Pearson correlation coefficient, PCC, a causal inference method (IDA and a regression method (Lasso utilizing the Borda count election method. Subsequently, to validate the performance of PIL method, comparisons between confirmed database and predicted miRNA targets were performed. Ultimately, pathway enrichment analysis was conducted on target genes in top 1000 miRNA-mRNA interactions to identify target pathways for UM patients. Results: Thirty eight of the predicted interactions were matched with the confirmed interactions, indicating that the ensemble method was a suitable and feasible approach to predict miRNA targets. We obtained 50 seed miRNA-mRNA interactions of UM patients and extracted target genes from these interactions, such as ASPG, BSDC1 and C4BP. The 601 target genes in top 1,000 miRNA-mRNA interactions were enriched in 12 target pathways, of which Phototransduction was the most significant one. Conclusion: The target genes and pathways might provide a new way to reveal the molecular mechanism of UM and give hand for target treatments and preventions of this malignant tumor.
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Mannan-Modified PLGA Nanoparticles for Targeted Gene Delivery
Directory of Open Access Journals (Sweden)
Fansheng Kong
2012-01-01
Full Text Available The studies of targeted gene delivery nanocarriers have gained increasing attention during the past decades. In this study, mannan modified DNA loaded bioadhesive PLGA nanoparticles (MAN-DNA-NPs were investigated for targeted gene delivery to the Kupffer cells (KCs. Bioadhesive PLGA nanoparticles were prepared and subsequently bound with pEGFP. Following the coupling of the mannan-based PE-grafted ligands (MAN-PE with the DNA-NPs, the MAN-DNA-NPs were delivered intravenously to rats. The transfection efficiency was determined from the isolated KCs and flow cytometry was applied for the quantitation of gene expression after 48 h post transfection. The size of the MAN-DNA-NPs was found to be around 190 nm and the Zeta potential was determined to be −15.46mV. The pEGFP binding capacity of MAN-DNA-NPs was (88.9±5.8% and the in vitro release profiles of the MAN-DNA-NPs follow the Higuchi model. When compared with non-modified DNA-NPs and Lipofectamine 2000-DNA, MAN-DNA-NPs produced the highest gene expressions, especially in vivo. The in vivo data from flow cytometry analysis showed that MAN-DNA-NPs displayed a remarkably higher transfection efficiency (39% than non-modified DNA-NPs (25% and Lipofectamine 2000-DNA (23% in KCs. The results illustrate that MAN-DNA-NPs have the ability to target liver KCs and could function as promising active targeting drug delivery vectors.
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Yoon, Tae-Ho; Noh, Maengseok; Han, Junhee; Jung-Choi, Kyunghee; Khang, Young-Ho
2015-12-01
A neighborhood-level analysis of mortality from suicide would be informative in developing targeted approaches to reducing suicide. This study aims to examine the association of community characteristics with suicide in the 424 neighborhoods of Seoul, South Korea. Neighborhood-level mortality and population data (2005-2011) were obtained to calculate age-standardized suicide rates. Eight community characteristics and their associated deprivation index were employed as determinants of suicide rates. The Bayesian hierarchical model with mixed effects for neighborhoods was used to fit age-standardized suicide rates and other covariates with consideration of spatial correlations. Suicide rates for 424 neighborhoods were between 7.32 and 71.09 per 100,000. Ninety-nine percent of 424 neighborhoods recorded greater suicide rates than the Organization for Economic Cooperation and Development member countries' average. A stepwise relationship between area deprivation and suicide was found. Neighborhood-level indicators for lack of social support (residents living alone and the divorced or separated) and socioeconomic disadvantages (low educational attainment) were positively associated with suicide mortality after controlling for other covariates. Finding from this study could be used to identify priority areas and to develop community-based programs for preventing suicide in Seoul, South Korea.
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Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target
2016-06-01
AWARD NUMBER: W81XWH-14-1-0107 TITLE: Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target PRINCIPAL...AND SUBTITLE Tumor Microenvironment Gene Signature as a 5a. CONTRACT NUMBER W81XWH-14-1-0107 Prognostic Classifier and Therapeutic Target 5b...gene signature that correlates with poor survival in ovarian cancer patients. We are refining this gene signature to develop biomarkers for the
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Dwyer, Laura A; Patel, Minal; Nebeling, Linda C; Oh, April Y
2018-05-01
Neighborhood and psychosocial variables are related to physical activity (PA), yet interactions between these factors in predicting PA are infrequently studied. This analysis examines the independent associations and interactions between self-reported neighborhood and psychosocial variables in relation to moderate to vigorous PA (MVPA) among adults from a US panel sample. In adjusted models, neighborhood social capital was positively associated with meeting MVPA guidelines. Fewer barriers, greater self-efficacy, and greater autonomous motivation also corresponded with greater odds of meeting MVPA guidelines. An interaction between social capital and autonomous motivation showed that social capital was only associated with MVPA when autonomous motivation was high. Participants who reported both high autonomous motivation and high social capital were most likely to meet MVPA guidelines. Neighborhood social capital, barriers, self-efficacy, and autonomous motivation may be important correlates in promoting adults' PA. Future directions include using objective neighborhood and PA data in similar analyses and investigating associations of neighborhood and psychosocial variables with multiple PA activities. Intervention research to promote PA should also examine whether effects of interventions targeting psychosocial constructs are moderated by features of an individual's neighborhood or whether perceived social capital can be addressed in interventions in conjunction with psychosocial variables.
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Directory of Open Access Journals (Sweden)
Zhao QQ
2012-06-01
Full Text Available Qing-Qing Zhao,1,2 Yu-Lan Hu,1 Yang Zhou,3 Ni Li,1 Min Han,1 Gu-Ping Tang,4 Feng Qiu,2 Yasuhiko Tabata,5 Jian-Qing Gao,11Institute of Pharmaceutics, Zhejiang University, Hangzhou, China; 2Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 3Institute of Biochemistry, Iowa State University, Ames, IA, USA; 4Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, China; 5Institute for Frontier Medical Sciences, Kyoto University, Kyoto, JapanBackground: The success of gene transfection is largely dependent on the development of a vehicle or vector that can efficiently deliver a gene to cells with minimal toxicity.Methods: A liver cancer-targeted specific peptide (FQHPSF sequence was successfully synthesized and linked with chitosan-linked polyethylenimine (CP to form a new targeted gene delivery vector called CPT (CP/peptide. The structure of CPT was confirmed by 1H nuclear magnetic resonance spectroscopy and ultraviolet spectrophotometry. The particle size of CPT/DNA complexes was measured using laser diffraction spectrometry and the cytotoxicity of the copolymer was evaluated by methylthiazol tetrazolium method. The transfection efficiency evaluation of the CP copolymer was performed using luciferase activity assay. Cellular internalization of the CP/DNA complex was observed under confocal laser scanning microscopy. The targeting specificity of the polymer coupled to peptide was measured by competitive inhibition transfection study. The liver targeting specificity of the CPT copolymer in vivo was demonstrated by combining the copolymer with a therapeutic gene, interleukin-12, and assessed by its abilities in suppressing the growth of ascites tumor in mouse model.Results: The results showed that the liver cancer-targeted specific peptide was successfully synthesized and linked with CP to form a new targeted gene delivery vector called CPT. The composition of CPT
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Chang, Ling-Yin; Foshee, Vangie A; Reyes, Heathe Luz McNaughton; Ennett, Susan T; Halpern, Carolyn T
2015-03-01
Neighborhood context plays a role in the development of adolescent health risk behaviors, but few studies have investigated the influence of neighborhoods on the perpetration of dating violence. This longitudinal study examined the direct effects of risky neighborhood structural and physical characteristics on trajectories of the perpetration of dating violence, tested whether collective efficacy mediated these relationships, and determined if the effects varied by the sex of the adolescent. Adolescent data are from a multi-wave longitudinal study from grades 8 to 12; neighborhood data were collected from parents' interviews and U.S. Census data. Multilevel growth curve models were conducted with 3,218 students; the sample was 50% male, 41% White, 50% Black, and 9% other race/ethnicity. In models examining risky neighborhood variables one at a time, and controlling for potential individual-level confounders, the sex of the adolescent interacted with economic disadvantage, residential instability, and physical disorder; these risky neighborhood characteristics increased risk for girls' but not boys' perpetrating of dating violence. In full models with all of the risky neighborhood variables, the sex of the adolescent continued to interact with neighborhood economic disadvantage; living in economically disadvantaged neighborhoods increased girls' but not boys' risk for dating violence across all ages. No other risky neighborhood effects were found for boys or girls. Collective efficacy did not mediate the relationships between other neighborhood characteristics and the outcome. These findings suggest that dating violence prevention strategies for girls should consider the contexts in which they live rather than only targeting changes in their individual characteristics.
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Identification and Regulation of c-Myb Target Genes in MCF-7 Cells
Directory of Open Access Journals (Sweden)
O'Rourke John P
2011-01-01
Full Text Available Abstract Background The c-Myb transcription factor regulates differentiation and proliferation in hematopoietic cells, stem cells and epithelial cells. Although oncogenic versions of c-Myb were first associated with leukemias, over expression or rearrangement of the c-myb gene is common in several types of solid tumors, including breast cancers. Expression of the c-myb gene in human breast cancer cells is dependent on estrogen stimulation, but little is known about the activities of the c-Myb protein or what genes it regulates in estrogen-stimulated cells. Methods We used chromatin immunoprecipitation coupled with whole genome promoter tiling microarrays to identify endogenous c-Myb target genes in human MCF-7 breast cancer cells and characterized the activity of c-Myb at a panel of target genes during different stages of estrogen deprivation and stimulation. Results By using different antibodies and different growth conditions, the c-Myb protein was found associated with over 10,000 promoters in MCF-7 cells, including many genes that encode cell cycle regulators or transcription factors and more than 60 genes that encode microRNAs. Several previously identified c-Myb target genes were identified, including CCNB1, MYC and CXCR4 and novel targets such as JUN, KLF4, NANOG and SND1. By studying a panel of these targets to validate the results, we found that estradiol stimulation triggered the association of c-Myb with promoters and that association correlated with increased target gene expression. We studied one target gene, CXCR4, in detail, showing that c-Myb associated with the CXCR4 gene promoter and activated a CXCR4 reporter gene in transfection assays. Conclusions Our results show that c-Myb associates with a surprisingly large number of promoters in human cells. The results also suggest that estradiol stimulation leads to large-scale, genome-wide changes in c-Myb activity and subsequent changes in gene expression in human breast cancer
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Identification and Regulation of c-Myb Target Genes in MCF-7 Cells
International Nuclear Information System (INIS)
Quintana, Anita M; Liu, Fan; O'Rourke, John P; Ness, Scott A
2011-01-01
The c-Myb transcription factor regulates differentiation and proliferation in hematopoietic cells, stem cells and epithelial cells. Although oncogenic versions of c-Myb were first associated with leukemias, over expression or rearrangement of the c-myb gene is common in several types of solid tumors, including breast cancers. Expression of the c-myb gene in human breast cancer cells is dependent on estrogen stimulation, but little is known about the activities of the c-Myb protein or what genes it regulates in estrogen-stimulated cells. We used chromatin immunoprecipitation coupled with whole genome promoter tiling microarrays to identify endogenous c-Myb target genes in human MCF-7 breast cancer cells and characterized the activity of c-Myb at a panel of target genes during different stages of estrogen deprivation and stimulation. By using different antibodies and different growth conditions, the c-Myb protein was found associated with over 10,000 promoters in MCF-7 cells, including many genes that encode cell cycle regulators or transcription factors and more than 60 genes that encode microRNAs. Several previously identified c-Myb target genes were identified, including CCNB1, MYC and CXCR4 and novel targets such as JUN, KLF4, NANOG and SND1. By studying a panel of these targets to validate the results, we found that estradiol stimulation triggered the association of c-Myb with promoters and that association correlated with increased target gene expression. We studied one target gene, CXCR4, in detail, showing that c-Myb associated with the CXCR4 gene promoter and activated a CXCR4 reporter gene in transfection assays. Our results show that c-Myb associates with a surprisingly large number of promoters in human cells. The results also suggest that estradiol stimulation leads to large-scale, genome-wide changes in c-Myb activity and subsequent changes in gene expression in human breast cancer cells
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Directory of Open Access Journals (Sweden)
Johanna Meier-Soelch
2018-04-01
Full Text Available The potent proinflammatory cytokine interleukin (IL-1 triggers gene expression through the NF-κB signaling pathway. Here, we investigated the cofactor requirements of strongly regulated IL-1 target genes whose expression is impaired in p65 NF-κB-deficient murine embryonic fibroblasts. By two independent small-hairpin (shRNA screens, we examined 170 genes annotated to encode nuclear cofactors for their role in Cxcl2 mRNA expression and identified 22 factors that modulated basal or IL-1-inducible Cxcl2 levels. The functions of 16 of these factors were validated for Cxcl2 and further analyzed for their role in regulation of 10 additional IL-1 target genes by RT-qPCR. These data reveal that each inducible gene has its own (quantitative requirement of cofactors to maintain basal levels and to respond to IL-1. Twelve factors (Epc1, H2afz, Kdm2b, Kdm6a, Mbd3, Mta2, Phf21a, Ruvbl1, Sin3b, Suv420h1, Taf1, and Ube3a have not been previously implicated in inflammatory cytokine functions. Bioinformatics analysis indicates that they are components of complex nuclear protein networks that regulate chromatin functions and gene transcription. Collectively, these data suggest that downstream from the essential NF-κB signal each cytokine-inducible target gene has further subtle requirements for individual sets of nuclear cofactors that shape its transcriptional activation profile.
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D. C. Kent; Won Keun Min
2002-01-01
Neighborhood spaces, pretopological spaces, and closure spaces are topological space generalizations which can be characterized by means of their associated interior (or closure) operators. The category NBD of neighborhood spaces and continuous maps contains PRTOP as a bicoreflective subcategory and CLS as a bireflective subcategory, whereas TOP is bireflectively embedded in PRTOP and bicoreflectively embedded in CLS. Initial and final structures are described in these categories, and it is s...
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A targeted resequencing gene panel for focal epilepsy.
Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C
2016-04-26
We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.
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Anti-EGFR immunonanoparticles containing IL12 and salmosin genes for targeted cancer gene therapy.
Kim, Jung Seok; Kang, Seong Jae; Jeong, Hwa Yeon; Kim, Min Woo; Park, Sang Il; Lee, Yeon Kyung; Kim, Hong Sung; Kim, Keun Sik; Park, Yong Serk
2016-09-01
Tumor-directed gene delivery is of major interest in the field of cancer gene therapy. Varied functionalizations of non-viral vectors have been suggested to enhance tumor targetability. In the present study, we prepared two different types of anti-EGF receptor (EGFR) immunonanoparticles containing pDNA, neutrally charged liposomes and cationic lipoplexes, for tumor-directed transfection of cancer therapeutic genes. Even though both anti-EGFR immunonanoparticles had a high binding affinity to the EGFR-positive cancer cells, the anti-EGFR immunolipoplex formulation exhibited approximately 100-fold higher transfection to the target cells than anti-EGFR immunoliposomes. The lipoplex formulation also showed a higher transfection to SK-OV-3 tumor xenografts in mice. Thus, IL12 and/or salmosin genes were loaded in the anti-EGFR immunolipoplexes and intravenously administered to mice carrying SK-OV-3 tumors. Co-transfection of IL12 and salmosin genes using anti-EGFR immunolipoplexes significantly reduced tumor growth and pulmonary metastasis. Furthermore, combinatorial treatment with doxorubicin synergistically inhibited tumor growth. These results suggest that anti-EGFR immunolipoplexes containing pDNA encoding therapeutic genes could be utilized as a gene-transfer modality for cancer gene therapy.
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Ovcharenko, Aleksandr; Ibanez, Daniel; Delalondre, Fabien; Sahni, Onkar; Jansen, Kenneth E.; Carothers, Christopher D.; Shephard, Mark S.
2012-01-01
packing to manage message flow control and reduce the number and time of communication calls. The test application demonstrated is parallel unstructured mesh adaptation. Results on IBM Blue Gene/P and Cray XE6 computers show that the use of neighborhood
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Alcohol and Cigarette Advertising on Billboards: Targeting with Social Cues.
Schooler, Caroline; Basil, Michael D.
A study examined whether billboard advertising of tobacco and alcohol products is differentially targeted toward White, Black, Asian, and Hispanic neighborhoods. The study analyzed 901 billboards in neighborhood commercial districts in San Francisco, California, giving particular attention to tobacco and alcohol billboards. Neighborhood census…
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Weß, Ludger; Schnieders, Frank
2017-12-01
Cancer therapy is once again experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing only single targets or pathways. Even the combination of several neo-antigens in cancer vaccines is not sufficient for successful, lasting tumor eradication. The focus has therefore shifted to the immune system's role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells. Immune processes, however, require novel concepts beyond the traditional "single-target-single drug" paradigm and need parallel targeting of diverse cells and mechanisms. This review gives a perspective on the role of gene therapy technologies in the evolving immuno-oncology space and identifies gene therapy as a major driver in the development and regulation of effective cancer immunotherapy. Present challenges and breakthroughs ranging from chimeric antigen receptor T-cell therapy, gene-modified oncolytic viruses, combination cancer vaccines, to RNA therapeutics are spotlighted. Gene therapy is recognized as the most prominent technology enabling effective immuno-oncology strategies.
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How Neighborhood Disadvantage Reduces Birth Weight
Directory of Open Access Journals (Sweden)
Emily Moiduddin
2008-06-01
Full Text Available In this analysis we connect structural neighborhood conditions to birth outcomes through their intermediate effects on mothers’ perceptions of neighborhood danger and their tendency to abuse substances during pregnancy. We hypothesize that neighborhood poverty and racial/ethnic concentration combine to produce environments that mothers perceive as unsafe, thereby increasing the likelihood of negative coping behaviors (substance abuse. We expect these behaviors, in turn, to produce lower birth weights. Using data from the Fragile Families and Child Wellbeing Study, a survey of a cohort of children born between 1998 and 2000 and their mothers in large cities in the United States, we find little evidence to suggest that neighborhood circumstances have strong, direct effects on birth weight. Living in a neighborhood with more foreigners had a positive effect on birth weight. To the extent that neighborhood conditions influence birth weight, the effect mainly occurs through an association with perceived neighborhood danger and subsequent negative coping behaviors. Poverty and racial/ethnic concentration increase a mother’s sense that her neighborhood is unsafe. The perception of an unsafe neighborhood, in turn, associates with a greater likelihood of smoking cigarettes and using illegal drugs, and these behaviors have strong and significant effects in reducing birth weight. However, demographic characteristics, rather than perceived danger or substance abuse, mediate the influence of neighborhood characteristics on birth weight.
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Community, Democracy, and Neighborhood News.
Hindman, Elizabeth Blanks
1998-01-01
Contributes to scholarship on democracy, community, and journalism by examining the interplay between communication, democracy, and community at an inner-city neighborhood newspaper. Concludes that, through its focus on neighborhood culture, acknowledgment of conflict, and attempts to provide a forum for the neighborhood's self-definition, the…
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Inducement of radionuclides targeting therapy by gene transfection
International Nuclear Information System (INIS)
Luo Quanyong
2001-01-01
The author presents an overview of gene transfection methods to genetically induce tumor cells to express enhanced levels of cell surface antigens and receptors to intake radiolabeled antibody and peptide targeting and thus increase their therapeutic effect in radiotherapy. The current research include inducement of radioimmunotherapy through CEA gene transfection, inducement of iodine-131 therapy by sodium iodide symporter gene transfection and inducement of MIBG therapy by noradrenaline transporter gene transfection. These studies raise the prospect that gene-therapy techniques could be used to enable the treatment of a wide range of tumors with radiopharmaceuticals of established clinical acceptability
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AJ, Milam; CDM, Furr-Holden; PJ, Leaf
2010-01-01
Community and school violence continue to be a major public health problem, especially among urban children and adolescents. Little research has focused on the effect of school safety and neighborhood violence on academic performance. This study examines the effect of the school and neighborhood climate on academic achievement among a population of 3rd-5th grade students in an urban public school system. Community and school safety were assessed using the School Climate Survey, an annual city-wide assessment of student’s perception of school and community safety. Community violence was measured using the Neighborhood Inventory for Environmental Typology, an objective observational assessment of neighborhood characteristics. Academic achievement was measured using the Maryland State Assessment (MSA), a standardized exam given to all Maryland 3rd-8th graders. School Climate Data and MSA data were aggregated by school and grade. Objective assessments of neighborhood environment and students’ self-reported school and neighborhood safety were both strongly associated with academic performance. Increasing neighborhood violence was associated with statistically significant decreases from 4.2%-8.7% in math and reading achievement; increasing perceived safety was associated with significant increases in achievement from 16%-22%. These preliminary findings highlight the adverse impact of perceived safety and community violence exposure on primary school children’s academic performance. PMID:21197388
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STAT3 Target Genes Relevant to Human Cancers
International Nuclear Information System (INIS)
Carpenter, Richard L.; Lo, Hui-Wen
2014-01-01
Since its discovery, the STAT3 transcription factor has been extensively studied for its function as a transcriptional regulator and its role as a mediator of development, normal physiology, and pathology of many diseases, including cancers. These efforts have uncovered an array of genes that can be positively and negatively regulated by STAT3, alone and in cooperation with other transcription factors. Through regulating gene expression, STAT3 has been demonstrated to play a pivotal role in many cellular processes including oncogenesis, tumor growth and progression, and stemness. Interestingly, recent studies suggest that STAT3 may behave as a tumor suppressor by activating expression of genes known to inhibit tumorigenesis. Additional evidence suggested that STAT3 may elicit opposing effects depending on cellular context and tumor types. These mixed results signify the need for a deeper understanding of STAT3, including its upstream regulators, parallel transcription co-regulators, and downstream target genes. To help facilitate fulfilling this unmet need, this review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers
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Neighborhood Quality and Labor Market Outcomes
DEFF Research Database (Denmark)
Damm, Anna Piil
of men living in the neighborhood, but positively affected by the employment rate of non-Western immigrant men and co-national men living in the neighborhood. This is strong evidence that immigrants find jobs in part through their employed immigrant and co-ethnic contacts in the neighborhood of residence...... successfully addresses the methodological problem of endogenous neighborhood selection. Taking account of location sorting, living in a socially deprived neighborhood does not affect labor market outcomes of refugee men. Furthermore, their labor market outcomes are not affected by the overall employment rate...
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International Nuclear Information System (INIS)
Yuan, Chenyan; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng; An, Yanli
2014-01-01
Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression. (paper)
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Cloning, characterization and targeting of the mouse HEXA gene
Energy Technology Data Exchange (ETDEWEB)
Wakamatsu, N.; Trasler, J.M.; Gravel, R.A. [McGill Univ., Quebec (Canada)] [and others
1994-09-01
The HEXA gene, encoding the {alpha} subunit of {beta}-hexosaminidase A, is essential for the metabolism of ganglioside G{sub M2}, and defects in this gene cause Tay-Sachs disease in humans. To elucidate the role of the gene in the nervous system of the mouse and to establish a mouse model of Tay-Sachs disease, we have cloned and characterized the HEXA gene and targeted a disruption of the gene in mouse ES cells. The mouse HEXA gene spans {approximately}26 kb and consists of 14 exons, similar to the human gene. A heterogeneous transcription initiation site was identified 21-42 bp 5{prime} of the initiator ATG, with two of the sites fitting the consensus CTCA (A = start) as seen for some weak initiator systems. Promoter analysis showed that the first 150 bp 5{prime} of the ATG contained 85% of promoter activity observed in constructs containing up to 1050 bp of 5{prime} sequence. The active region contained a sequence matching that of the adenovirus major late promoter upstream element factor. A survey of mouse tissues showed that the highest mRNA levels were in (max to min): testis (5.5 x brain cortex), adrenal, epididymis, heart, brain, lung, kidney, and liver (0.3 x brain cortex). A 12 kb BstI/SalI fragment containing nine exons was disrupted with the insertion of the bacterial neo{sup r} gene in exon 11 and was targeted into 129/Sv ES cells by homologous recombination. Nine of 153 G418 resistant clones were correctly targeted as confirmed by Southern blotting. The heterozygous ES cells were microinjected into mouse blastocysts and implanted into pseudo-pregnant mice. Nine male chimeric mice, showing that 40-95% chimerism for the 129/Sv agouti coat color marker, are being bred in an effort to generate germline transmission of the disrupted HEXA gene.
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Gene therapy and radionuclides targeting therapy in mammary carcinoma
International Nuclear Information System (INIS)
Song Jinhua
2003-01-01
Breast carcinoma's gene therapy is a hotspot in study of the tumor's therapy in the recent years. Currently the major therapy methods that in the experimentative and primary clinical application phases include immunological gene therapy, multidrug resistance gene therapy, antisense oligonucleotide therapy and suicide gene therapy. The gene targeting brachytherapy, which is combined with gene therapy and radiotherapy has enhanced the killer effects of the suicide gene and nuclide in tumor cells. That has break a new path in tumor's gene therapy. The further study in this field will step up it's space to the clinical application
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Neighborhood cohesion, neighborhood disorder, and cardiometabolic risk.
Robinette, Jennifer W; Charles, Susan T; Gruenewald, Tara L
2018-02-01
Perceptions of neighborhood disorder (trash, vandalism) and cohesion (neighbors trust one another) are related to residents' health. Affective and behavioral factors have been identified, but often in studies using geographically select samples. We use a nationally representative sample (n = 9032) of United States older adults from the Health and Retirement Study to examine cardiometabolic risk in relation to perceptions of neighborhood cohesion and disorder. Lower cohesion is significantly related to greater cardiometabolic risk in 2006/2008 and predicts greater risk four years later (2010/2012). The longitudinal relation is partially accounted for by anxiety and physical activity. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Who Gentrifies Low-Income Neighborhoods?
McKinnish, Terra; Walsh, Randall; White, T Kirk
2010-03-01
This paper uses confidential Census data, specifically the 1990 and 2000 Census Long Form data, to study demographic processes in neighborhoods that gentrified during the 1990's. In contrast to previous studies, the analysis is conducted at the more refined census-tract level, with a narrower definition of gentrification and more closely matched comparison neighborhoods. Furthermore, our access to individual-level data with census tract identifiers allows us to separately identify recent in-migrants and long-term residents. Our results indicate that, on average, the demographic flows associated with the gentrification of urban neighborhoods during the 1990's are not consistent with displacement and harm to minority households. In fact, taken as a whole, our results suggest that gentrification of predominantly black neighborhoods creates neighborhoods that are attractive to middle-class black households.
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Kim, Joongbaeck; Ross, Catherine E.
2009-01-01
Is neighborhood-specific social support the most effective type of social support for buffering the effect of neighborhood disorder on depression? Matching theory suggests that it is. The authors extend the research on neighborhood disorder and adult depression by showing that individuals who have higher levels of both general and…
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Christian, Hayley; Knuiman, Matthew; Divitini, Mark; Foster, Sarah; Hooper, Paula; Boruff, Bryan; Bull, Fiona; Giles-Corti, Billie
2017-07-12
There is limited longitudinal evidence confirming the role of neighborhood environment attributes in encouraging people to walk more or if active people simply choose to live in activity-friendly neighborhoods. Natural experiments of policy changes to create more walkable communities provide stronger evidence for a causal effect of neighborhood environments on residents' walking. We aimed to investigate longitudinal associations between objective and perceived neighborhood environment measures and neighborhood recreational walking. We analyzed longitudinal data collected over 8 yr (four surveys) from the RESIDential Environments (RESIDE) Study (Perth, Australia, 2003-2012). At each time point, participants reported the frequency and total minutes of recreational walking/week within their neighborhood and neighborhood environment perceptions. Objective measures of the neighborhood environment were generated using a Geographic Information System (GIS). Local recreational walking was influenced by objectively measured access to a medium-/large-size park, beach access, and higher street connectivity, which was reduced when adjusted for neighborhood perceptions. In adjusted models, positive perceptions of access to a park and beach, higher street connectivity, neighborhood esthetics, and safety from crime were independent determinants of increased neighborhood recreational walking. Local recreational walking increased by 9 min/wk (12% increase in frequency) for each additional perceived neighborhood attribute present. Our findings provide urban planners and policy makers with stronger causal evidence of the positive impact of well-connected neighborhoods and access to local parks of varying sizes on local residents' recreational walking and health. https://doi.org/10.1289/EHP823.
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Urbanism, Neighborhood Context, and Social Networks.
Cornwell, Erin York; Behler, Rachel L
2015-09-01
Theories of urbanism suggest that the urban context erodes individuals' strong social ties with friends and family. Recent research has narrowed focus to the neighborhood context, emphasizing how localized structural disadvantage affects community-level cohesion and social capital. In this paper, we argue that neighborhood context also shapes social ties with friends and family- particularly for community-dwelling seniors. We hypothesize that neighborhood disadvantage, residential instability, and disorder restrict residents' abilities to cultivate close relationships with neighbors and non-neighbor friends and family. Using data from the National Social Life, Health, and Aging Project (NSHAP), we find that older adults who live in disadvantaged neighborhoods have smaller social networks. Neighborhood disadvantage is also associated with less close network ties and less frequent interaction - but only among men. Furthermore, residents of disordered neighborhoods have smaller networks and weaker ties. We urge scholars to pay greater attention to how neighborhood context contributes to disparities in network-based access to resources.
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Social Network resources and self-rated health in a deprived Danish neighborhood
DEFF Research Database (Denmark)
Tanggaard Andersen, Pernille; Holst Algren, Maria; Fromsejer Heiberg, Regina
2017-01-01
Research has demonstrated that living in a deprived neighborhood contributes to the occurrence and development of poor health. Furthermore evidence shows that social networks are fundamental resources in preventing poor mental health. Neighborhood relationships and networks are vital for sustaining...... and improving quality of life. However, to determine potentials for public health action, the health impact of various types of network resources need to be explored and the association between socioeconomic position and self-rated health needs to be analysed to determine whether it is partially explained...... by social network resources. This is the main aim of this article. Cross-sectional data from one deprived neighborhood located in Denmark were collected in 2008 and 2013 using a postal health survey. The target group was defined as adults older than 16 years. In 2008, 408 residents participated...
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Leventhal, T; Brooks-Gunn, J
2000-03-01
This article provides a comprehensive review of research on the effects of neighborhood residence on child and adolescent well-being. The first section reviews key methodological issues. The following section considers links between neighborhood characteristics and child outcomes and suggests the importance of high socioeconomic status (SES) for achievement and low SES and residential instability for behavioral/emotional outcomes. The third section identifies 3 pathways (institutional resources, relationships, and norms/collective efficacy) through which neighborhoods might influence development, and which represent an extension of models identified by C. Jencks and S. Mayer (1990) and R. J. Sampson (1992). The models provide a theoretical base for studying neighborhood mechanisms and specify different levels (individual, family, school, peer, community) at which processes may operate. Implications for an emerging developmental framework for research on neighborhoods are discussed.
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Who Gentrifies Low-Income Neighborhoods?*
McKinnish, Terra; Walsh, Randall; White, T. Kirk
2009-01-01
This paper uses confidential Census data, specifically the 1990 and 2000 Census Long Form data, to study demographic processes in neighborhoods that gentrified during the 1990’s. In contrast to previous studies, the analysis is conducted at the more refined census-tract level, with a narrower definition of gentrification and more closely matched comparison neighborhoods. Furthermore, our access to individual-level data with census tract identifiers allows us to separately identify recent in-migrants and long-term residents. Our results indicate that, on average, the demographic flows associated with the gentrification of urban neighborhoods during the 1990’s are not consistent with displacement and harm to minority households. In fact, taken as a whole, our results suggest that gentrification of predominantly black neighborhoods creates neighborhoods that are attractive to middle-class black households. PMID:20161532
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Directory of Open Access Journals (Sweden)
Janne Boone-Heinonen
Full Text Available Recent obesity prevention initiatives focus on healthy neighborhood design, but most research examines neighborhood food retail and physical activity (PA environments in isolation. We estimated joint, interactive, and cumulative impacts of neighborhood food retail and PA environment characteristics on body mass index (BMI throughout early adulthood.We used cohort data from the Coronary Artery Risk Development in Young Adults (CARDIA Study [n=4,092; Year 7 (24-42 years, 1992-1993 followed over 5 exams through Year 25 (2010-2011; 12,921 person-exam observations], with linked time-varying geographic information system-derived neighborhood environment measures. Using regression with fixed effects for individuals, we modeled time-lagged BMI as a function of food and PA resource density (counts per population and neighborhood development intensity (a composite density score. We controlled for neighborhood poverty, individual-level sociodemographics, and BMI in the prior exam; and included significant interactions between neighborhood measures and by sex. Using model coefficients, we simulated BMI reductions in response to single and combined neighborhood improvements. Simulated increase in supermarket density (from 25(th to 75(th percentile predicted inter-exam reduction in BMI of 0.09 kg/m(2 [estimate (95% CI: -0.09 (-0.16, -0.02]. Increasing commercial PA facility density predicted BMI reductions up to 0.22 kg/m(2 in men, with variation across other neighborhood features [estimate (95% CI range: -0.14 (-0.29, 0.01 to -0.22 (-0.37, -0.08]. Simultaneous increases in supermarket and commercial PA facility density predicted inter-exam BMI reductions up to 0.31 kg/m(2 in men [estimate (95% CI range: -0.23 (-0.39, -0.06 to -0.31 (-0.47, -0.15] but not women. Reduced fast food restaurant and convenience store density and increased public PA facility density and neighborhood development intensity did not predict reductions in BMI.Findings suggest that
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Nearest neighbors by neighborhood counting.
Wang, Hui
2006-06-01
Finding nearest neighbors is a general idea that underlies many artificial intelligence tasks, including machine learning, data mining, natural language understanding, and information retrieval. This idea is explicitly used in the k-nearest neighbors algorithm (kNN), a popular classification method. In this paper, this idea is adopted in the development of a general methodology, neighborhood counting, for devising similarity functions. We turn our focus from neighbors to neighborhoods, a region in the data space covering the data point in question. To measure the similarity between two data points, we consider all neighborhoods that cover both data points. We propose to use the number of such neighborhoods as a measure of similarity. Neighborhood can be defined for different types of data in different ways. Here, we consider one definition of neighborhood for multivariate data and derive a formula for such similarity, called neighborhood counting measure or NCM. NCM was tested experimentally in the framework of kNN. Experiments show that NCM is generally comparable to VDM and its variants, the state-of-the-art distance functions for multivariate data, and, at the same time, is consistently better for relatively large k values. Additionally, NCM consistently outperforms HEOM (a mixture of Euclidean and Hamming distances), the "standard" and most widely used distance function for multivariate data. NCM has a computational complexity in the same order as the standard Euclidean distance function and NCM is task independent and works for numerical and categorical data in a conceptually uniform way. The neighborhood counting methodology is proven sound for multivariate data experimentally. We hope it will work for other types of data.
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Neighborhood Context and Immigrant Young Children's Development
Leventhal, Tama; Shuey, Elizabeth A.
2014-01-01
This study explored how neighborhood social processes and resources, relevant to immigrant families and immigrant neighborhoods, contribute to young children's behavioral functioning and achievement across diverse racial/ethnic groups. Data were drawn from the Project on Human Development in Chicago Neighborhoods, a neighborhood-based,…
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Zhang, Weixiong; Ruan, Jianhua; Ho, Tuan-Hua David; You, Youngsook; Yu, Taotao; Quatrano, Ralph S
2005-07-15
A fundamental problem of computational genomics is identifying the genes that respond to certain endogenous cues and environmental stimuli. This problem can be referred to as targeted gene finding. Since gene regulation is mainly determined by the binding of transcription factors and cis-regulatory DNA sequences, most existing gene annotation methods, which exploit the conservation of open reading frames, are not effective in finding target genes. A viable approach to targeted gene finding is to exploit the cis-regulatory elements that are known to be responsible for the transcription of target genes. Given such cis-elements, putative target genes whose promoters contain the elements can be identified. As a case study, we apply the above approach to predict the genes in model plant Arabidopsis thaliana which are inducible by a phytohormone, abscisic acid (ABA), and abiotic stress, such as drought, cold and salinity. We first construct and analyze two ABA specific cis-elements, ABA-responsive element (ABRE) and its coupling element (CE), in A.thaliana, based on their conservation in rice and other cereal plants. We then use the ABRE-CE module to identify putative ABA-responsive genes in A.thaliana. Based on RT-PCR verification and the results from literature, this method has an accuracy rate of 67.5% for the top 40 predictions. The cis-element based targeted gene finding approach is expected to be widely applicable since a large number of cis-elements in many species are available.
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Corominola Ocaña, Víctor
2015-01-01
NeighborHood és una aplicació basada en el núvol, adaptable a qualsevol dispositiu (mòbil, tablet, desktop). L'objectiu d'aquesta aplicació és poder permetre als usuaris introduir a les persones del seu entorn més immediat i que aquestes persones siguin visibles per a la resta d'usuaris. NeighborHood es una aplicación basada en la nube, adaptable a cualquier dispositivo (móvil, tablet, desktop). El objetivo de esta aplicación es poder permitir a los usuarios introducir a las personas de su...
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Knorr, Eileen; Fishilevich, Elane; Tenbusch, Linda; Frey, Meghan L F; Rangasamy, Murugesan; Billion, Andre; Worden, Sarah E; Gandra, Premchand; Arora, Kanika; Lo, Wendy; Schulenberg, Greg; Valverde-Garcia, Pablo; Vilcinskas, Andreas; Narva, Kenneth E
2018-02-01
RNAi shows potential as an agricultural technology for insect control, yet, a relatively low number of robust lethal RNAi targets have been demonstrated to control insects of agricultural interest. In the current study, a selection of lethal RNAi target genes from the iBeetle (Tribolium castaneum) screen were used to demonstrate efficacy of orthologous targets in the economically important coleopteran pests Diabrotica virgifera virgifera and Meligethes aeneus. Transcript orthologs of 50 selected genes were analyzed in D. v. virgifera diet-based RNAi bioassays; 21 of these RNAi targets showed mortality and 36 showed growth inhibition. Low dose injection- and diet-based dsRNA assays in T. castaneum and D. v. virgifera, respectively, enabled the identification of the four highly potent RNAi target genes: Rop, dre4, ncm, and RpII140. Maize was genetically engineered to express dsRNA directed against these prioritized candidate target genes. T 0 plants expressing Rop, dre4, or RpII140 RNA hairpins showed protection from D. v. virgifera larval feeding damage. dsRNA targeting Rop, dre4, ncm, and RpII140 in M. aeneus also caused high levels of mortality both by injection and feeding. In summary, high throughput systems for model organisms can be successfully used to identify potent RNA targets for difficult-to-work with agricultural insect pests.
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Newbury, Joanne; Arseneault, Louise; Caspi, Avshalom; Moffitt, Terrie E; Odgers, Candice L; Fisher, Helen L
2018-02-15
Little is known about the impact of urbanicity, adverse neighborhood conditions and violent crime victimization on the emergence of adolescent psychotic experiences. Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins who were interviewed about adolescent psychotic experiences at age 18. Urbanicity, neighborhood characteristics, and personal victimization by violent crime were measured during childhood and adolescence via geocoded census data, surveys of over 5000 immediate neighbors of the E-Risk participants, and interviews with participants themselves. Adolescents raised in urban vs rural neighborhoods were significantly more likely to have psychotic experiences (OR = 1.67, 95% CI = 1.21-2.30, P = .002). This association remained significant after considering potential confounders including family socioeconomic status, family psychiatric history, and adolescent substance problems (OR = 1.43, 95% CI = 1.01-2.03, P = .042), but became nonsignificant after considering adverse social conditions in urban neighborhoods such as low social cohesion and high neighborhood disorder (OR = 1.35, 95% CI = 0.94-1.92, P = .102). The combined association of adverse neighborhood social conditions and personal crime victimization with adolescent psychotic experiences (adjusted OR = 4.86, 95% CI = 3.28-7.20, P < .001) was substantially greater than for either exposure alone, highlighting a potential interaction between neighborhood conditions and crime victimization (interaction contrast ratio = 1.81, 95% CI = -0.03 to 3.65) that was significant at the P = .054 level. Cumulative effects of adverse neighborhood social conditions and personal victimization by violent crime during upbringing partly explain why adolescents in urban settings are more likely to report psychotic experiences. Early intervention efforts for psychosis could be targeted towards victimized youth living in urban and socially
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Luo, Yan; Wang, Yongsheng; Liu, Jun; Cui, Chenchen; Wu, Yongyan; Lan, Hui; Chen, Qi; Liu, Xu; Quan, Fusheng; Guo, Zekun; Zhang, Yong
2016-02-08
Targeting exogenous genes at milk protein loci via gene-targeting technology is an ideal strategy for producing large quantities of pharmaceutical proteins. Transcription-activator-like effector (TALE) nucleases (TALENs) are an efficient genome-editing tool. However, the off-target effects may lead to unintended gene mutations. In this study, we constructed TALENs and TALE nickases directed against exon 2 of the bovine β-lactoglobulin (BLG) locus. The nickases can induce a site-specific DNA single-strand break, without inducing double-strand break and nonhomologous end joining mediated gene mutation, and lower cell apoptosis rate than TALENs. After co-transfecting the bovine fetal fibroblasts with human serum albumin (HSA) gene-targeting vector and TALE nickase expression vectors, approximately 4.8% (40/835) of the cell clones contained HSA at BLG locus. Unexpectedly, one homozygous gene-targeted cell clone (1/835, 0.1%) was obtained by targeting both alleles of BLG in a single round of transfection. The recombinant protein mimicking the endogenous BLG was highly expressed and correctly folded in the mammary glands of the targeted cows, and the expression level of HSA was significantly increased in the homozygous targeted cows. Results suggested that the combination of TALE nickase-mediated gene targeting and somatic cell nuclear transfer is a feasible and safe approach in producing gene-targeted livestock.
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From genes to milk: genomic organization and epigenetic regulation of the mammary transcriptome.
Lemay, Danielle G; Pollard, Katherine S; Martin, William F; Freeman Zadrowski, Courtneay; Hernandez, Joseph; Korf, Ian; German, J Bruce; Rijnkels, Monique
2013-01-01
Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an organism's survival.
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Garthe, Rachel C; Gorman-Smith, Deborah; Gregory, Joshua; E Schoeny, Michael
2018-03-14
The link between relationship violence and aspects of neighborhood concentrated disadvantage (e.g., percent of unemployed adults, percent of families below poverty level), has been established. However, the literature examining neighborhood social processes, including informal social control and social cohesion, in relation to adolescent dating violence has shown mixed results with a limited theoretical foundation and methodology. Using a social disorganization theoretical framework, this study examined the mediating role of these neighborhood social processes in the relation between concentrated disadvantage and adolescent dating violence within an urban context. Participants included 605 adult residents in 30 census tracts and 203 adolescents from neighborhoods on the West and South sides of Chicago. Neighborhood-level concentrated disadvantage was measured via Census data, adult residents reported on neighborhood social processes, and youth reported on dating violence. Informal social control was negatively associated with dating violence, and social cohesion was positively associated with dating violence. A multilevel mediation model showed that concentrated disadvantage was related to higher levels of dating violence via lower levels of informal social control. These results extend social disorganization theory to dating violence within an urban context, while also highlighting the important role of neighborhood processes on relationship violence. Implications for research and intervention programming are discussed. © Society for Community Research and Action 2018.
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Tolmachov, Oleg E
2015-01-01
Gene delivery in vivo that is tightly focused on the intended target cells is essential to maximize the benefits of gene therapy and to reduce unwanted side-effects. Cell surface markers are immediately available for probing by therapeutic gene vectors and are often used to direct gene transfer with these vectors to specific target cell populations. However, it is not unusual for the choice of available extra-cellular markers to be too scarce to provide a reliable definition of the desired therapeutically relevant set of target cells. Therefore, interrogation of intra-cellular determinants of cell-specificity, such as tissue-specific transcription factors, can be vital in order to provide detailed cell-guiding information to gene vector particles. An important improvement in cell-specific gene delivery can be achieved through auto-buildup in vector homing efficiency using intelligent 'self-focusing' of swarms of vector particles on target cells. Vector self-focusing was previously suggested to rely on the release of diffusible chemo-attractants after a successful target-specific hit by 'scout' vector particles. I hypothesize that intelligent self-focusing behaviour of swarms of cell-targeted therapeutic gene vectors can be accomplished without the employment of difficult-to-use diffusible chemo-attractants, instead relying on the intra-swarm signalling through cells expressing a non-diffusible extra-cellular receptor for the gene vectors. In the proposed model, cell-guiding information is gathered by the 'scout' gene vector particles, which: (1) attach to a variety of cells via a weakly binding (low affinity) receptor; (2) successfully facilitate gene transfer into these cells; (3) query intra-cellular determinants of cell-specificity with their transgene expression control elements and (4) direct the cell-specific biosynthesis of a vector-encoded strongly binding (high affinity) cell-surface receptor. Free members of the vector swarm loaded with therapeutic cargo
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Cancer gene therapy targeting angiogenesis: An updated Review
Liu, Ching-Chiu; Shen, Zan; Kung, Hsiang-Fu; Lin, Marie CM
2006-01-01
Since the relationship between angiogenesis and tumor growth was established by Folkman in 1971, scientists have made efforts exploring the possibilities in treating cancer by targeting angiogenesis. Inhibition of angiogenesis growth factors and administration of angiogenesis inhibitors are the basics of anti-angiogenesis therapy. Transfer of anti-angiogenesis genes has received attention recently not only because of the advancement of recombinant vectors, but also because of the localized and sustained expression of therapeutic gene product inside the tumor after gene transfer. This review provides the up-to-date information about the strategies and the vectors studied in the field of anti-angiogenesis cancer gene therapy. PMID:17109514
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Comprehensive Neighborhood Portraits and Child Asthma Disparities.
Kranjac, Ashley W; Kimbro, Rachel T; Denney, Justin T; Osiecki, Kristin M; Moffett, Brady S; Lopez, Keila N
2017-07-01
Objectives Previous research has established links between child, family, and neighborhood disadvantages and child asthma. We add to this literature by first characterizing neighborhoods in Houston, TX by demographic, economic, and air quality characteristics to establish differences in pediatric asthma diagnoses across neighborhoods. Second, we identify the relative risk of social, economic, and environmental risk factors for child asthma diagnoses. Methods We geocoded and linked electronic pediatric medical records to neighborhood-level social and economic indicators. Using latent profile modeling techniques, we identified Advantaged, Middle-class, and Disadvantaged neighborhoods. We then used a modified version of the Blinder-Oaxaca regression decomposition method to examine differences in asthma diagnoses across children in these different neighborhoods. Results Both compositional (the characteristics of the children and the ambient air quality in the neighborhood) and associational (the relationship between child and air quality characteristics and asthma) differences within the distinctive neighborhood contexts influence asthma outcomes. For example, unequal exposure to PM 2.5 and O 3 among children in Disadvantaged and Middle-class neighborhoods contribute to asthma diagnosis disparities within these contexts. For children in Disadvantaged and Advantaged neighborhoods, associational differences between racial/ethnic and socioeconomic characteristics and asthma diagnoses explain a significant proportion of the gap. Conclusions for Practice Our results provide evidence that differential exposure to pollution and protective factors associated with non-Hispanic White children and children from affluent families contribute to asthma disparities between neighborhoods. Future researchers should consider social and racial inequalities as more proximate drivers, not merely as associated, with asthma disparities in children.
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EBF factors drive expression of multiple classes of target genes governing neuronal development.
Green, Yangsook S; Vetter, Monica L
2011-04-30
Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.
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Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice
Directory of Open Access Journals (Sweden)
Donald R. Love
2013-03-01
Full Text Available The role of gene deletion and duplication in the aetiology of disease has become increasingly evident over the last decade. In addition to the classical deletion/duplication disorders diagnosed using molecular techniques, such as Duchenne Muscular Dystrophy and Charcot-Marie-Tooth Neuropathy Type 1A, the significance of partial or whole gene deletions in the pathogenesis of a large number single-gene disorders is becoming more apparent. A variety of dosage analysis methods are available to the diagnostic laboratory but the widespread application of many of these techniques is limited by the expense of the kits/reagents and restrictive targeting to a particular gene or portion of a gene. These limitations are particularly important in the context of a small diagnostic laboratory with modest sample throughput. We have developed a gene-targeted, custom-designed comparative genomic hybridisation (CGH array that allows twelve clinical samples to be interrogated simultaneously for exonic deletions/duplications within any gene (or panel of genes on the array. We report here on the use of the array in the analysis of a series of clinical samples processed by our laboratory over a twelve-month period. The array has proven itself to be robust, flexible and highly suited to the diagnostic environment.
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Tendulkar, Shalini A.; Koenen, Karestan C.; Dunn, Erin C.; Buka, Stephen; Subramanian, S. V.
2012-01-01
Background Social support is frequently linked to positive parenting behavior. Similarly, studies increasingly show a link between neighborhood residential environment and positive parenting behavior. However, less is known about how the residential environment influences parental social support. To address this gap, we examine the relationship between neighborhood concentrated disadvantage and collective efficacy and the level and change in parental caregiver perceptions of non-familial social support. Methodology/Principal Findings The data for this study came from three data sources, the Project on Human Development in Chicago Neighborhoods (PHDCN) Study's Longitudinal Cohort Survey of caregivers and their offspring, a Community Survey of adult residents in these same neighborhoods and the 1990 Census. Social support is measured at Wave 1 and Wave 3 and neighborhood characteristics are measured at Wave 1. Multilevel linear regression models are fit. The results show that neighborhood collective efficacy is a significant (ß = .04; SE = .02; p = .03), predictor of the positive change in perceived social support over a 7 year period, however, not of the level of social support, adjusting for key compositional variables and neighborhood concentrated disadvantage. In contrast concentrated neighborhood disadvantage is not a significant predictor of either the level or change in social support. Conclusion Our finding suggests that neighborhood collective efficacy may be important for inducing the perception of support from friends in parental caregivers over time. PMID:22493683
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Tendulkar, Shalini A; Koenen, Karestan C; Dunn, Erin C; Buka, Stephen; Subramanian, S V
2012-01-01
Social support is frequently linked to positive parenting behavior. Similarly, studies increasingly show a link between neighborhood residential environment and positive parenting behavior. However, less is known about how the residential environment influences parental social support. To address this gap, we examine the relationship between neighborhood concentrated disadvantage and collective efficacy and the level and change in parental caregiver perceptions of non-familial social support. The data for this study came from three data sources, the Project on Human Development in Chicago Neighborhoods (PHDCN) Study's Longitudinal Cohort Survey of caregivers and their offspring, a Community Survey of adult residents in these same neighborhoods and the 1990 Census. Social support is measured at Wave 1 and Wave 3 and neighborhood characteristics are measured at Wave 1. Multilevel linear regression models are fit. The results show that neighborhood collective efficacy is a significant (ß = .04; SE = .02; p = .03), predictor of the positive change in perceived social support over a 7 year period, however, not of the level of social support, adjusting for key compositional variables and neighborhood concentrated disadvantage. In contrast concentrated neighborhood disadvantage is not a significant predictor of either the level or change in social support. Our finding suggests that neighborhood collective efficacy may be important for inducing the perception of support from friends in parental caregivers over time.
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Schools, Neighborhood Risk Factors, and Crime
Willits, Dale; Broidy, Lisa; Denman, Kristine
2013-01-01
Prior research has identified a link between schools (particularly high schools) and neighborhood crime rates. However, it remains unclear whether the relationship between schools and crime is a reflection of other criminogenic dynamics at the neighborhood level or whether schools influence neighborhood crime patterns independently of other…
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Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells.
Byrne, Susan M; Ortiz, Luis; Mali, Prashant; Aach, John; Church, George M
2015-02-18
Sequence-specific nucleases such as TALEN and the CRISPR/Cas9 system have so far been used to disrupt, correct or insert transgenes at precise locations in mammalian genomes. We demonstrate efficient 'knock-in' targeted replacement of multi-kilobase genes in human induced pluripotent stem cells (iPSC). Using a model system replacing endogenous human genes with their mouse counterpart, we performed a comprehensive study of targeting vector design parameters for homologous recombination. A 2.7 kilobase (kb) homozygous gene replacement was achieved in up to 11% of iPSC without selection. The optimal homology arm length was around 2 kb, with homology length being especially critical on the arm not adjacent to the cut site. Homologous sequence inside the cut sites was detrimental to targeting efficiency, consistent with a synthesis-dependent strand annealing (SDSA) mechanism. Using two nuclease sites, we observed a high degree of gene excisions and inversions, which sometimes occurred more frequently than indel mutations. While homozygous deletions of 86 kb were achieved with up to 8% frequency, deletion frequencies were not solely a function of nuclease activity and deletion size. Our results analyzing the optimal parameters for targeting vector design will inform future gene targeting efforts involving multi-kilobase gene segments, particularly in human iPSC. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
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Novel Hematopoietic Target Genes in the NRF2-Mediated Transcriptional Pathway
Directory of Open Access Journals (Sweden)
Michelle R. Campbell
2013-01-01
Full Text Available Nuclear factor- (erythroid-derived 2 like 2 (NFE2L2, NRF2 is a key transcriptional activator of the antioxidant response pathway and is closely related to erythroid transcription factor NFE2. Under oxidative stress, NRF2 heterodimerizes with small Maf proteins and binds cis-acting enhancer sequences found near oxidative stress response genes. Using the dietary isothiocyanate sulforaphane (SFN to activate NRF2, chromatin immunoprecipitation sequencing (ChIP-seq identified several hundred novel NRF2-mediated targets beyond its role in oxidative stress. Activated NRF2 bound the antioxidant response element (ARE in promoters of several known and novel target genes involved in iron homeostasis and heme metabolism, including known targets FTL and FTH1, as well as novel binding in the globin locus control region. Five novel NRF2 target genes were chosen for followup: AMBP, ABCB6, FECH, HRG-1 (SLC48A1, and TBXAS1. SFN-induced gene expression in erythroid K562 and lymphoid cells were compared for each target gene. NRF2 silencing showed reduced expression in lymphoid, lung, and hepatic cells. Furthermore, stable knockdown of NRF2 negative regulator KEAP1 in K562 cells resulted in increased NQO1, AMBP, and TBXAS1 expression. NFE2 binding sites in K562 cells revealed similar binding profiles as lymphoid NRF2 sites in all potential NRF2 candidates supporting a role for NRF2 in heme metabolism and erythropoiesis.
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Identification of apoptosis-related PLZF target genes
International Nuclear Information System (INIS)
Bernardo, Maria Victoria; Yelo, Estefania; Gimeno, Lourdes; Campillo, Jose Antonio; Parrado, Antonio
2007-01-01
The PLZF gene encodes a BTB/POZ-zinc finger-type transcription factor, involved in physiological development, proliferation, differentiation, and apoptosis. In this paper, we investigate proliferation, survival, and gene expression regulation in stable clones from the human haematopoietic K562, DG75, and Jurkat cell lines with inducible expression of PLZF. In Jurkat cells, but not in K562 and DG75 cells, PLZF induced growth suppression and apoptosis in a cell density-dependent manner. Deletion of the BTB/POZ domain of PLZF abrogated growth suppression and apoptosis. PLZF was expressed with a nuclear speckled pattern distinctively in the full-length PLZF-expressing Jurkat clones, suggesting that the nuclear speckled localization is required for PLZF-induced apoptosis. By microarray analysis, we identified that the apoptosis-inducer TP53INP1, ID1, and ID3 genes were upregulated, and the apoptosis-inhibitor TERT gene was downregulated. The identification of apoptosis-related PLZF target genes may have biological and clinical relevance in cancer typified by altered PLZF expression
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Mapping of HNF4alpha target genes in intestinal epithelial cells
DEFF Research Database (Denmark)
Boyd, Mette; Bressendorff, Simon; Moller, Jette
2009-01-01
ABSTRACT: BACKGROUND: The role of HNF4alpha has been extensively studied in hepatocytes and pancreatic beta-cells, and HNF4alpha is also regarded as key regulator of intestinal epithelial cell differentiation as well. The aim of the present work is to identify novel HNF4alpha target genes....... The HNF4alpha ChIP-chip data was matched with gene expression and histone H3 acetylation status of the promoters in order to identify HNF4alpha binding to actively transcribed genes with an open chromatin structure. RESULTS: 1,541 genes were identified as potential HNF4alpha targets, many of which have...
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Tarokh, Zahra; Naderi-Manesh, Hossein; Nazari, Mahboobeh
2017-03-01
Prostate cancer is the second leading cause of death due to cancer in men. Owing to shortcomings in the current treatments, other therapies are being considered. Toxic gene delivery is one of the most effective methods for cancer therapy. Cationic polymers are able to form stable nanoparticles via interaction with nucleic acids electrostatically. Branched polyethylenimine that contains amine groups has notable buffering capacity and the ability to escape from endosome through the proton sponge effect. However, the cytotoxicity of this polymer is high, and modification is one of the applicable strategies to overcome this problem. In this study, PEI was targeted with chlorotoxin (CTX) via N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) cross-linker. CTX can bind specifically to matrix metalloproteinase-2 that is overexpressed in certain cancers. Melittin as the major component of bee venom has been reported to have anti-cancer activity. This was thus selected to deliver to PC3 cell line. Flow cytometry analysis revealed that transfection efficiency of targeted nanoparticles is significantly higher compared to non-targeted nanoparticles. Targeted nanoparticles carrying the melittin gene also decreased cell viability of PC3 cells significantly while no toxic effects were observed on NIH3T3 cell line. Therefore, CTX-targeted nanoparticles carrying the melittin gene could serve as an appropriate gene delivery system for prostate and other MMP-2 positive cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.
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Impact of Urban Neighborhood Disadvantage on Late Stage Breast Cancer Diagnosis in Virginia.
DeGuzman, Pam Baker; Cohn, Wendy F; Camacho, Fabian; Edwards, Brandy L; Sturz, Vanessa N; Schroen, Anneke T
2017-04-01
Research suggests that residents of inner-city urban neighborhoods have higher rates of late stage cancer diagnosis. Identifying urban neighborhoods with high rates of both concentrated disadvantage and late stage cancer diagnosis may assist health care providers to target screening interventions to reduce disparities. The purposes of this study were to (1) create an index to evaluate concentrated disadvantage (CD) using non-racial measures of poverty, (2) determine the impact of neighborhood CD on late stage breast cancer diagnosis in US cities, and (3) to understand the role of obesity on this relationship. We used census block group- (CBG) level poverty indicators from five Virginia cities to develop the index. Breast cancer cases of women aged 18-65 who lived in the five cities were identified from the 2000-2012 Virginia Cancer Registry. A logistic regression model with random intercept was used to evaluate the impact of disadvantage on late stage breast cancer diagnosis. CBG-level maps were developed to geographically identify neighborhoods with both high rates of CD and late breast cancer staging. Over 900 CBGs and 6000 breast cases were included. Global fit of the concentrated disadvantage model was acceptable. The effect of disadvantage on late stage was significant (OR = 1.0083, p = 0.032). Inner-city poverty impacts risk of late stage breast cancer diagnosis. Area-level obesity is highly correlated with neighborhood poverty (ρ = 0.74, p diagnosis for urban poor and for minorities living in these underserved neighborhoods, but more study is needed to understanding the complex relationship between concentrated neighborhood poverty, obesity, and late stage diagnosis.
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Internet Bad Neighborhoods Aggregation
Moreira Moura, Giovane; Sadre, R.; Sperotto, Anna; Pras, Aiko; Paschoal Gaspary, L.; De Turk, Filip
Internet Bad Neighborhoods have proven to be an innovative approach for fighting spam. They have also helped to understand how spammers are distributed on the Internet. In our previous works, the size of each bad neighborhood was fixed to a /24 subnetwork. In this paper, however, we investigate if
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Directory of Open Access Journals (Sweden)
Katherine King
Full Text Available Researchers have speculated that negative life events are more common in troubled neighborhoods, amplifying adverse effects on health. Using a clustered representative sample of Chicago residents (2001-03; n = 3,105 from the Chicago Community Adult Health Survey, we provide the first documentation that negative life events are highly geographically clustered compared to health outcomes. Associations between neighborhood context and negative life events were also found to vary by event type. We then demonstrate the power of a contextualized approach by testing path models in which life events mediate the relation between neighborhood characteristics and health outcomes, including self-rated health, anxiety, and depression. The indirect paths between neighborhood conditions and health through negative life event exposure are highly significant and large compared to the direct paths from neighborhood conditions to health. Our results indicate that neighborhood conditions can have acute as well as chronic effects on health, and that negative life events are a powerful mechanism by which context may influence health.
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King, Katherine; Ogle, Christin
2014-01-01
Researchers have speculated that negative life events are more common in troubled neighborhoods, amplifying adverse effects on health. Using a clustered representative sample of Chicago residents (2001-03; n = 3,105) from the Chicago Community Adult Health Survey, we provide the first documentation that negative life events are highly geographically clustered compared to health outcomes. Associations between neighborhood context and negative life events were also found to vary by event type. We then demonstrate the power of a contextualized approach by testing path models in which life events mediate the relation between neighborhood characteristics and health outcomes, including self-rated health, anxiety, and depression. The indirect paths between neighborhood conditions and health through negative life event exposure are highly significant and large compared to the direct paths from neighborhood conditions to health. Our results indicate that neighborhood conditions can have acute as well as chronic effects on health, and that negative life events are a powerful mechanism by which context may influence health.
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Neighborhood perceptions and allostatic load
DEFF Research Database (Denmark)
van Deurzen, Ioana; Rod, Naja Hulvej; Christensen, Ulla
2016-01-01
An influential argument explaining why living in certain neighborhoods can become harmful to one's health maintains that individuals can perceive certain characteristics of the neighborhood as threatening and the prolonged exposure to a threatening environment could induce chronic stress. Following...... this line of argumentation, in the present study we test whether subjective perceptions of neighborhood characteristics relate to an objective measure of stress-related physiological functioning, namely allostatic load (AL). We use a large dataset of 5280 respondents living in different regions of Denmark...... and we account for two alternative mechanisms, i.e., the objective characteristics of the living environment and the socio-economic status of individuals. Our results support the chronic stress mechanisms linking neighborhood quality to health. Heightened perceptions of disorder and pollution were found...
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Directory of Open Access Journals (Sweden)
Shalini A Tendulkar
Full Text Available BACKGROUND: Social support is frequently linked to positive parenting behavior. Similarly, studies increasingly show a link between neighborhood residential environment and positive parenting behavior. However, less is known about how the residential environment influences parental social support. To address this gap, we examine the relationship between neighborhood concentrated disadvantage and collective efficacy and the level and change in parental caregiver perceptions of non-familial social support. METHODOLOGY/PRINCIPAL FINDINGS: The data for this study came from three data sources, the Project on Human Development in Chicago Neighborhoods (PHDCN Study's Longitudinal Cohort Survey of caregivers and their offspring, a Community Survey of adult residents in these same neighborhoods and the 1990 Census. Social support is measured at Wave 1 and Wave 3 and neighborhood characteristics are measured at Wave 1. Multilevel linear regression models are fit. The results show that neighborhood collective efficacy is a significant (ß = .04; SE = .02; p = .03, predictor of the positive change in perceived social support over a 7 year period, however, not of the level of social support, adjusting for key compositional variables and neighborhood concentrated disadvantage. In contrast concentrated neighborhood disadvantage is not a significant predictor of either the level or change in social support. CONCLUSION: Our finding suggests that neighborhood collective efficacy may be important for inducing the perception of support from friends in parental caregivers over time.
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EBF factors drive expression of multiple classes of target genes governing neuronal development
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Vetter Monica L
2011-04-01
Full Text Available Abstract Background Early B cell factor (EBF family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. Results We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. Conclusions The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.
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Neighborhoods, US, 2017, Zillow, SEGS
U.S. Environmental Protection Agency — This web service depicts nearly 17,000 neighborhood boundaries in over 650 U.S. cities. Zillow created the neighborhood boundaries and is sharing them with the...
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Chen, Jiang; Ding, Jie; Wang, Ziwei; Zhu, Jian; Wang, Xuejian; Du, Jiyi
2017-03-21
This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profiling in two human colon cancer cell lines. An Affymetrix Human Transcriptome Array 2.0 was used to identify differentially expressed genes (DEGs). We screened out LSD1-target gene associated with proliferation, metastasis, and invasion from DEGs via Gene Ontology and Pathway Studio. Subsequently, four key genes (CABYR, FOXF2, TLE4, and CDH1) were computationally predicted as metastasis-related LSD1-target genes. ChIp-PCR was applied after RT-PCR and Western blot validations to detect the occupancy of LSD1-target gene promoter-bound LSD1. A total of 3633 DEGs were significantly upregulated, and 4642 DEGs were downregulated in LSD1-silenced SW620 cells. A total of 4047 DEGs and 4240 DEGs were upregulated and downregulated in LSD1-overexpressed HT-29 cells, respectively. RT-PCR and Western blot validated the microarray analysis results. ChIP assay results demonstrated that LSD1 might be negative regulators for target genes CABYR and CDH1. The expression level of LSD1 is negatively correlated with mono- and dimethylation of histone H3 lysine4(H3K4) at LSD1- target gene promoter region. No significant mono-methylation and dimethylation of H3 lysine9 methylation was detected at the promoter region of CABYR and CDH1. LSD1- depletion contributed to the upregulation of CABYR and CDH1 through enhancing the dimethylation of H3K4 at the LSD1-target genes promoter. LSD1- overexpression mediated the downregulation of CABYR and CDH1expression through decreasing the mono- and dimethylation of H3K4 at LSD1-target gene promoter in colon cancer cells. CABYR and CDH1 might be potential LSD1-target genes in colon
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Directory of Open Access Journals (Sweden)
Robert eGerlai
2016-04-01
Full Text Available Gene targeting with homologous recombination in embryonic stem cells created a revolution in the analysis of the function of genes in behavioral brain research. The technology allowed unprecedented precision with which one could manipulate genes and study the effect of this manipulation on the central nervous system. With gene targeting, the uncertainty inherent in psychopharmacology regarding whether a particular compound would act only through a specific target was removed. Thus, gene targeting became highly popular. However, with this popularity came the realization that like other methods, gene targeting also suffered from some technical and principal problems. For example, two decades ago, issues about compensatory changes and about genetic linkage were raised. Since then, the technology developed, and its utility has been better delineated. This review will discuss the pros and cons of the technique along with these advancements from the perspective of the neuroscientist user. It will also compare and contrast methods that may represent novel alternatives to the homologous recombination based gene targeting approach, including the TALEN and the CRISPR/Cas9 systems. The goal of the review is not to provide detailed recipes, but to attempt to present a short summary of these approaches a behavioral geneticist or neuroscientist may consider for the analysis of brain function and behavior.
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Loh, Venurs H Y; Rachele, Jerome N; Brown, Wendy J; Ghani, Fatima; Turrell, Gavin
2018-04-20
Residents of more socioeconomically disadvantaged neighborhoods are more likely to report poorer physical function, although the reasons for this remain unknown. It is possible that neighborhood-level perceptions of safety from crime contribute to this relationship through its association with walking for recreation. Data were obtained from the fourth wave (collected in 2013) of the HABITAT (How Areas in Brisbane Influence HealTh and AcTivity) multilevel longitudinal study of middle- to older-aged adults (46-74 y) residing in 200 neighborhoods in Brisbane, Australia. The data were analyzed separately for men (n = 2190) and women (n = 2977) using multilevel models. Residents of the most disadvantaged neighborhoods had poorer physical function, perceived their neighborhoods to be less safe from crime, and do less walking for recreation. These factors accounted for differences in physical function between disadvantaged and advantaged neighborhoods (24% for men and 25% for women). This study highlights the importance of contextual characteristics, through their associations with behaviors, that can have in explaining the relationship between neighborhood disadvantage and physical function. Interventions aimed at improving neighborhood safety integrated with supportive environments for physical activity may have positive impact on physical function among all socioeconomic groups.
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Neighborhood disorder, peer network health, and substance use among young urban adolescents.
Mason, Michael J; Light, John M; Mennis, Jeremy; Rusby, Julie C; Westling, Erika; Crewe, Stephanie; Zaharakis, Nikola; Way, Thomas; Flay, Brian R
2017-09-01
The current study investigated the moderating effect of peer networks on neighborhood disorder's association with substance use in a sample of primarily African American urban adolescents. A convenience sample of 248 adolescents was recruited from urban health care settings and followed for two years, assessing psychological, social, and geographic risk and protective characteristics. A subset of 106 substance using participants were used for the analyses. A moderation model was tested to determine if the influence of neighborhood disorder (percent vacant housing, assault index, percent single parent headed households, percent home owner occupied, percent below poverty line) on substance use was moderated by peer network health (sum of peer risk and protective behaviors). Evidence for hypothesized peer network moderation was supported. A latent growth model found that peer network health is most strongly associated with lower baseline substance use for young adolescents residing in more disordered neighborhoods. Over the course of two years (ages approximately 14-16) this protective effect declines, and the decline is stronger for more disordered neighborhoods. Understanding the longitudinal moderating effects of peer networks within high-risk urban settings is important to the development and testing of contextually sensitive peer-based interventions. suggest that targeting the potential protective qualities of peer networks may be a promising approach for interventions seeking to reduce substance use, particularly among younger urban adolescents living in high-risk neighborhoods. Copyright © 2017 Elsevier B.V. All rights reserved.
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Conduct Disorder and Neighborhood Effects.
Jennings, Wesley G; Perez, Nicholas M; Reingle Gonzalez, Jennifer M
2018-05-07
There has been a considerable amount of scholarly attention to the relationship between neighborhood effects and conduct disorder, particularly in recent years. Having said this, it has been nearly two decades since a comprehensive synthesis of this literature has been conducted. Relying on a detailed and comprehensive search strategy and inclusion criteria, this article offers a systematic and interdisciplinary review of 47 empirical studies that have examined neighborhood effects and conduct disorder. Described results suggest that there are generally robust linkages between adverse neighborhood factors and conduct disorder and externalizing behavior problems, as 67 of the 93 (72.04%) effect sizes derived from these studies yielded statistically significant neighborhood effects. The review also identifies salient mediating and moderating influences. It discusses study limitations and directions for future research as well.
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Jack, Elizabeth; McCormack, Gavin R
2014-06-04
participation, HW x physical barriers and MW x pedestrian infrastructure were positively associated with minutes, and HW x safety from crime was negatively associated with minutes, of transportation walking. Neither neighborhood type nor its interactions with perceived measures of walkability were associated with recreational walking, although perceived aesthetics was associated with participation (OR = 1.18, p < .05). Objectively-determined and self-reported built characteristics are associated with neighborhood-based transportation walking. The objectively-determined built environment might moderate associations between perceptions of walkability and neighborhood-based transportation walking. Interventions that target perceptions in addition to modifications to the neighborhood built environment could result in increases in physical activity among adults.
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Newbury, Joanne; Arseneault, Louise; Caspi, Avshalom; Moffitt, Terrie E; Odgers, Candice L
2018-01-01
Abstract Background: Little is known about the impact of urbanicity, adverse neighborhood conditions and violent crime victimization on the emergence of adolescent psychotic experiences. Methods: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins who were interviewed about adolescent psychotic experiences at age 18. Urbanicity, neighborhood characteristics, and personal victimization by violent crime were measured during childhood and adolescence via geocoded census data, surveys of over 5000 immediate neighbors of the E-Risk participants, and interviews with participants themselves. Results: Adolescents raised in urban vs rural neighborhoods were significantly more likely to have psychotic experiences (OR = 1.67, 95% CI = 1.21–2.30, P = .002). This association remained significant after considering potential confounders including family socioeconomic status, family psychiatric history, and adolescent substance problems (OR = 1.43, 95% CI = 1.01–2.03, P = .042), but became nonsignificant after considering adverse social conditions in urban neighborhoods such as low social cohesion and high neighborhood disorder (OR = 1.35, 95% CI = 0.94–1.92, P = .102). The combined association of adverse neighborhood social conditions and personal crime victimization with adolescent psychotic experiences (adjusted OR = 4.86, 95% CI = 3.28–7.20, P crime victimization (interaction contrast ratio = 1.81, 95% CI = −0.03 to 3.65) that was significant at the P = .054 level. Conclusions: Cumulative effects of adverse neighborhood social conditions and personal victimization by violent crime during upbringing partly explain why adolescents in urban settings are more likely to report psychotic experiences. Early intervention efforts for psychosis could be targeted towards victimized youth living in urban and socially adverse neighborhoods. PMID:28535284
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Madyun, Na'im; Lee, Moosung
2010-01-01
The underachievement of ethnic minority youth from disadvantaged neighborhoods is a pervasive educational issue this nation is facing. Based on an ecological perspective, we examined the contextual effects of neighborhood ethnic density and neighborhood disadvantage on the academic achievement of Hmong immigrant youths. Utilizing hierarchical…
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Chai, Hui; Yan, Zhaoyuan; Huang, Ke; Jiang, Yuanqing; Zhang, Lin
2018-02-01
This study aimed to systematically investigate the relationship between miRNA expression and the occurrence of ventricular septal defect (VSD), and characterize the miRNA target genes and pathways that can lead to VSD. The miRNAs that were differentially expressed in blood samples from VSD and normal infants were screened and validated by implementing miRNA microarrays and qRT-PCR. The target genes regulated by differentially expressed miRNAs were predicted using three target gene databases. The functions and signaling pathways of the target genes were enriched using the GO database and KEGG database, respectively. The transcription and protein expression of specific target genes in critical pathways were compared in the VSD and normal control groups using qRT-PCR and western blotting, respectively. Compared with the normal control group, the VSD group had 22 differentially expressed miRNAs; 19 were downregulated and three were upregulated. The 10,677 predicted target genes participated in many biological functions related to cardiac development and morphogenesis. Four target genes (mGLUR, Gq, PLC, and PKC) were involved in the PKC pathway and four (ECM, FAK, PI3 K, and PDK1) were involved in the PI3 K-Akt pathway. The transcription and protein expression of these eight target genes were significantly upregulated in the VSD group. The 22 miRNAs that were dysregulated in the VSD group were mainly downregulated, which may result in the dysregulation of several key genes and biological functions related to cardiac development. These effects could also be exerted via the upregulation of eight specific target genes, the subsequent over-activation of the PKC and PI3 K-Akt pathways, and the eventual abnormal cardiac development and VSD.
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Paired hormone response elements predict caveolin-1 as a glucocorticoid target gene.
Directory of Open Access Journals (Sweden)
Marinus F van Batenburg
2010-01-01
Full Text Available Glucocorticoids act in part via glucocorticoid receptor binding to hormone response elements (HREs, but their direct target genes in vivo are still largely unknown. We developed the criterion that genomic occurrence of paired HREs at an inter-HRE distance less than 200 bp predicts hormone responsiveness, based on synergy of multiple HREs, and HRE information from known target genes. This criterion predicts a substantial number of novel responsive genes, when applied to genomic regions 10 kb upstream of genes. Multiple-tissue in situ hybridization showed that mRNA expression of 6 out of 10 selected genes was induced in a tissue-specific manner in mice treated with a single dose of corticosterone, with the spleen being the most responsive organ. Caveolin-1 was strongly responsive in several organs, and the HRE pair in its upstream region showed increased occupancy by glucocorticoid receptor in response to corticosterone. Our approach allowed for discovery of novel tissue specific glucocorticoid target genes, which may exemplify responses underlying the permissive actions of glucocorticoids.
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Geometrical tile design for complex neighborhoods.
Czeizler, Eugen; Kari, Lila
2009-01-01
Recent research has showed that tile systems are one of the most suitable theoretical frameworks for the spatial study and modeling of self-assembly processes, such as the formation of DNA and protein oligomeric structures. A Wang tile is a unit square, with glues on its edges, attaching to other tiles and forming larger and larger structures. Although quite intuitive, the idea of glues placed on the edges of a tile is not always natural for simulating the interactions occurring in some real systems. For example, when considering protein self-assembly, the shape of a protein is the main determinant of its functions and its interactions with other proteins. Our goal is to use geometric tiles, i.e., square tiles with geometrical protrusions on their edges, for simulating tiled paths (zippers) with complex neighborhoods, by ribbons of geometric tiles with simple, local neighborhoods. This paper is a step toward solving the general case of an arbitrary neighborhood, by proposing geometric tile designs that solve the case of a "tall" von Neumann neighborhood, the case of the f-shaped neighborhood, and the case of a 3 x 5 "filled" rectangular neighborhood. The techniques can be combined and generalized to solve the problem in the case of any neighborhood, centered at the tile of reference, and included in a 3 x (2k + 1) rectangle.
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Neighborhood and Network Disadvantage among Urban Renters
Directory of Open Access Journals (Sweden)
Matthew Desmond
2015-06-01
Full Text Available Drawing on novel survey data, this study maps the distribution of neighborhood and network disadvantage in a population of Milwaukee renters and evaluates the relationship between each disadvantage and multiple social and health outcomes. We find that many families live in neighborhoods with above average disadvantage but are embedded in networks with below average disadvantage, and vice versa. Neighborhood (but not network disadvantage is associated with lower levels of neighborly trust but also with higher levels of community support (e.g., providing neighbors with food. Network (but not neighborhood disadvantage is associated with lower levels of civic engagement. Asthma and diabetes are associated exclusively with neighborhood disadvantage, but depression is associated exclusively with network disadvantage. These findings imply that some social problems may be better addressed by neighborhood interventions and others by network interventions.
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Functional Interpretation of Neighborhood Public Spaces in Terms of Identity
Directory of Open Access Journals (Sweden)
Hamid Majedi
2015-03-01
Full Text Available The aim of this article is to evaluate the effect of neighborhood public space transformation due to rapid urbanization in Tehran since 1960s, on the formation of neighborhood identity. In order to find the role of public spaces in enhancing neighborhood identities, two middle class neighborhoods with different spatial organizations are compared with each other: Nazi Abad a planned neighborhood and Mehran a typical unplanned neighborhood which developed through rapid urbanization. Next, the effect of neighborhood public spaces on neighborhood inhabitants is evaluated from two perspectives: Perceptual dimension and social dimension. The findings indicate that planned spatial organization and various neighborhood public spaces result in stronger neighborhood identity. It enhances both perceptual dimension of neighborhood identity(place attachment and its social dimension (sense of community. In contrast unplanned spatial organization which is the typical feature of Tehran neighborhoods leads to weak neighborhood identity.
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Reproducible gene targeting in recalcitrant Escherichia coli isolates
Directory of Open Access Journals (Sweden)
De Greve Henri
2011-06-01
Full Text Available Abstract Background A number of allele replacement methods can be used to mutate bacterial genes. For instance, the Red recombinase system of phage Lambda has been used very efficiently to inactivate chromosomal genes in E. coli K-12, through recombination between regions of homology. However, this method does not work reproducibly in some clinical E. coli isolates. Findings The procedure was modified by using longer homologous regions (85 bp and 500-600 bp, to inactivate genes in the uropathogenic E. coli strain UTI89. An lrhA regulator mutant, and deletions of the lac operon as well as the complete type 1 fimbrial gene cluster, were obtained reproducibly. The modified method is also functional in other recalcitrant E. coli, like the avian pathogenic E. coli strain APEC1. The lrhA regulator and lac operon deletion mutants of APEC1 were successfully constructed in the same way as the UTI89 mutants. In other avian pathogenic E. coli strains (APEC3E, APEC11A and APEC16A it was very difficult or impossible to construct these mutants, with the original Red recombinase-based method, with a Red recombinase-based method using longer (85 bp homologous regions or with our modified protocol, using 500 - 600 bp homologous regions. Conclusions The method using 500-600 bp homologous regions can be used reliably in some clinical isolates, to delete single genes or entire operons by homologous recombination. However, it does not invariably show a greater efficiency in obtaining mutants, when compared to the original Red-mediated gene targeting method or to the gene targeting method with 85 bp homologous regions. Therefore the length of the homology regions is not the only limiting factor for the construction of mutants in these recalcitrant strains.
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Villanueva, Karen; Knuiman, Matthew; Nathan, Andrea; Giles-Corti, Billie; Christian, Hayley; Foster, Sarah; Bull, Fiona
2014-01-01
We explored the impact of neighborhood walkability on young adults, early-middle adults, middle-aged adults, and older adults' walking across different neighborhood buffers. Participants completed the Western Australian Health and Wellbeing Surveillance System Survey (2003-2009) and were allocated a neighborhood walkability score at 200m, 400m, 800m, and 1600m around their home. We found little difference in strength of associations across neighborhood size buffers for all life stages. We conclude that neighborhood walkability supports more walking regardless of adult life stage and is relevant for small (e.g., 200m) and larger (e.g., 1600m) neighborhood buffers. © 2013 The Authors. Published by Elsevier Ltd All rights reserved.
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Dodson, Jennifer L; Hsiao, Ya-Chun; Kasat-Shors, Madhuri; Murray, Laura; Nguyen, Nga Kim; Richards, Adam K; Gittelsohn, Joel
2009-01-01
To understand influences on diet among low-income African-American adolescents in East Baltimore. Formative research was conducted for a food store-centered healthy diet intervention targeted to inner-city youth. Family, school and neighborhood influences on eating habits and health concepts were explored. Family structure, economic resources and past experiences influence what food means to adolescents. Healthy food in school and local stores is limited. Terminology to categorize foods was identified, including the term "home foods". Suggested adolescent nutritional interventions include promotion of home-based eating, improving availability of healthy foods in school and neighborhood stores, and targeted educational materials.
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Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines
Energy Technology Data Exchange (ETDEWEB)
Gulec, Cagri, E-mail: cagri.gulec@gmail.com; Coban, Neslihan, E-mail: neslic@istanbul.edu.tr; Ozsait-Selcuk, Bilge, E-mail: ozsaitb@istanbul.edu.tr; Sirma-Ekmekci, Sema, E-mail: semasirma@gmail.com; Yildirim, Ozlem, E-mail: ozlm-yildirim@hotmail.com; Erginel-Unaltuna, Nihan, E-mail: nihanerginel@yahoo.com
2017-04-01
ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. Due to its possible involvement in, and potential therapeutic target for atherosclerosis, we aimed to identify ROR-alpha target genes in monocytic and endothelial cell lines. We performed chromatin immunoprecipitation (ChIP) followed by tiling array (ChIP-on-chip) for ROR-alpha in monocytic cell line THP1 and endothelial cell line HUVEC. Following bioinformatic analysis of the array data, we tested four candidate genes in terms of dependence of their expression level on ligand-mediated ROR-alpha activity, and two of them in terms of promoter occupancy by ROR-alpha. Bioinformatic analyses of ChIP-on-chip data suggested that ROR-alpha binds to genomic regions near the transcription start site (TSS) of more than 3000 genes in THP1 and HUVEC. Potential ROR-alpha target genes in both cell types seem to be involved mainly in membrane receptor activity, signal transduction and ion transport. While SPP1 and IKBKA were shown to be direct target genes of ROR-alpha in THP1 monocytes, inflammation related gene HMOX1 and heat shock protein gene HSPA8 were shown to be potential target genes of ROR-alpha. Our results suggest that ROR-alpha may regulate signaling receptor activity, and transmembrane transport activity through its potential target genes. ROR-alpha seems also to play role in cellular sensitivity to environmental substances like arsenite and chloroprene. Although, the expression analyses have shown that synthetic ROR-alpha ligands can modulate some of potential ROR-alpha target genes, functional significance of ligand-dependent modulation of gene expression needs to be confirmed with further analyses.
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Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia
2009-06-16
microRNAs (miRNAs) are single-stranded RNA molecules of about 20-23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA.
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Mining predicted essential genes of Brugia malayi for nematode drug targets.
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Sanjay Kumar
Full Text Available We report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets. However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression.
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Normal Collagen and Bone Production by Gene-targeted Human Osteogenesis Imperfecta iPSCs
Deyle, David R; Khan, Iram F; Ren, Gaoying; Wang, Pei-Rong; Kho, Jordan; Schwarze, Ulrike; Russell, David W
2012-01-01
Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease. PMID:22031238
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Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems
Energy Technology Data Exchange (ETDEWEB)
Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)
2011-01-18
The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.
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Analysis of Deregulated microRNAs and Their Target Genes in Gastric Cancer.
Directory of Open Access Journals (Sweden)
Simonas Juzėnas
Full Text Available MicroRNAs (miRNAs are widely studied non-coding RNAs that modulate gene expression. MiRNAs are deregulated in different tumors including gastric cancer (GC and have potential diagnostic and prognostic implications. The aim of our study was to determine miRNA profile in GC tissues, followed by evaluation of deregulated miRNAs in plasma of GC patients. Using available databases and bioinformatics methods we also aimed to evaluate potential target genes of confirmed differentially expressed miRNA and validate these findings in GC tissues.The study included 51 GC patients and 51 controls. Initially, we screened miRNA expression profile in 13 tissue samples of GC and 12 normal gastric tissues with TaqMan low density array (TLDA. In the second stage, differentially expressed miRNAs were validated in a replication cohort using qRT-PCR in tissue and plasma samples. Subsequently, we analyzed potential target genes of deregulated miRNAs using bioinformatics approach, determined their expression in GC tissues and performed correlation analysis with targeting miRNAs.Profiling with TLDA revealed 15 deregulated miRNAs in GC tissues compared to normal gastric mucosa. Replication analysis confirmed that miR-148a-3p, miR-204-5p, miR-223-3p and miR-375 were consistently deregulated in GC tissues. Analysis of GC patients' plasma samples showed significant down-regulation of miR-148a-3p, miR-375 and up-regulation of miR-223-3p compared to healthy subjects. Further, using bioinformatic tools we identified targets of replicated miRNAs and performed disease-associated gene enrichment analysis. Ultimately, we evaluated potential target gene BCL2 and DNMT3B expression by qRT-PCR in GC tissue, which correlated with targeting miRNA expression.Our study revealed miRNA profile in GC tissues and showed that miR-148a-3p, miR-223-3p and miR-375 are deregulated in GC plasma samples, but these circulating miRNAs showed relatively weak diagnostic performance as sole biomarkers
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Identification of gene targets against dormant phase Mycobacterium tuberculosis infections
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Murphy Dennis J
2007-07-01
Full Text Available Abstract Background Mycobacterium tuberculosis, the causative agent of tuberculosis (TB, infects approximately 2 billion people worldwide and is the leading cause of mortality due to infectious disease. Current TB therapy involves a regimen of four antibiotics taken over a six month period. Patient compliance, cost of drugs and increasing incidence of drug resistant M. tuberculosis strains have added urgency to the development of novel TB therapies. Eradication of TB is affected by the ability of the bacterium to survive up to decades in a dormant state primarily in hypoxic granulomas in the lung and to cause recurrent infections. Methods The availability of M. tuberculosis genome-wide DNA microarrays has lead to the publication of several gene expression studies under simulated dormancy conditions. However, no single model best replicates the conditions of human pathogenicity. In order to identify novel TB drug targets, we performed a meta-analysis of multiple published datasets from gene expression DNA microarray experiments that modeled infection leading to and including the dormant state, along with data from genome-wide insertional mutagenesis that examined gene essentiality. Results Based on the analysis of these data sets following normalization, several genome wide trends were identified and used to guide the selection of targets for therapeutic development. The trends included the significant up-regulation of genes controlled by devR, down-regulation of protein and ATP synthesis, and the adaptation of two-carbon metabolism to the hypoxic and nutrient limited environment of the granuloma. Promising targets for drug discovery were several regulatory elements (devR/devS, relA, mprAB, enzymes involved in redox balance and respiration, sulfur transport and fixation, pantothenate, isoprene, and NAD biosynthesis. The advantages and liabilities of each target are discussed in the context of enzymology, bacterial pathways, target tractability
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Friedman, Esther M; Shih, Regina A; Slaughter, Mary E; Weden, Margaret M; Cagney, Kathleen A
2017-02-01
Recent evidence suggests that living in a neighborhood with a greater percentage of older adults is associated with better individual health, including lower depression, better self-rated health, and a decreased risk of overall mortality. However, much of the work to date suffers from four limitations. First, none of the U.S.-based studies examine the association at the national level. Second, no studies have examined three important hypothesized mechanisms - neighborhood socioeconomic status and neighborhood social and physical characteristics - which are significantly correlated with both neighborhood age structure and health. Third, no U.S. study has longitudinally examined cognitive health trajectories. We build on this literature by examining nine years of nationally-representative data from the Health and Retirement Study (2002-2010) on men and women aged 51 and over linked with Census data to examine the relationship between the percentage of adults 65 and older in a neighborhood and individual cognitive health trajectories. Our results indicate that living in a neighborhood with a greater percentage of older adults is related to better individual cognition at baseline but we did not find any significant association with cognitive decline. We also explored potential mediators including neighborhood socioeconomic status, perceived neighborhood cohesion and perceived neighborhood physical disorder. We did not find evidence that neighborhood socioeconomic status explains this relationship; however, there is suggestive evidence that perceived cohesion and disorder may explain some of the association between age structure and cognition. Although more work is needed to identify the precise mechanisms, this work may suggest a potential contextual target for public health interventions to prevent cognitive impairment. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Preparation and characterization of magnetic gene vectors for targeting gene delivery
Energy Technology Data Exchange (ETDEWEB)
Zheng, S.W.; Liu, G. [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); Hong, R.Y., E-mail: rhong@suda.edu.cn [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); State Key Laboratory of Multi-phase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080 (China); Li, H.Z. [State Key Laboratory of Multi-phase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080 (China); Li, Y.G., E-mail: ilguoliang@sohu.com [Department of radiology, the First Affiliated Hospital of Soochow University, Suzhou 215007 (China); Wei, D.G., E-mail: dougwei@deas.harvard.edu [Center for Nanoscale Systems, School of Engineering and Applied Science, Harvard University, 11 Oxford Street, Cambridge, MA 02139 (United States)
2012-10-15
Highlights: Black-Right-Pointing-Pointer PEI is ideal candidate polymer for the design of gene delivery systems. Black-Right-Pointing-Pointer PEI-CMD-MNPs exhibited a typical superparamagnetic behavior. Black-Right-Pointing-Pointer PEI-CMD-MNPs were well stable over the entire range of pH and NaCl concentration. Black-Right-Pointing-Pointer DNA-PEI-CMD-MNPs transfected cells by a magnet have higher transfection efficiency and gene expression efficiency. - Abstract: The PEI-CMD-MNPs were successfully prepared by the surface modification of magnetic Fe{sub 3}O{sub 4} nanoparticles with carboxymethyl dextran (CMD) and polyethyleneimine (PEI). The PEI-CMD-MNPs polyplexes exhibited a typical superparamagnetic behavior and were well stable over the entire range of pH and NaCl concentration. These PEI-CMD-MNPs were used as magnetic gene vectors for targeting gene delivery. The prepared MNPs at different surface modification stages were characterized using Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), field emissions canning electron microscopy (FE-SEM), powder X-ray diffraction (XRD) and dynamic laser light scattering (DLS) analysis. The magnetic properties were studied by vibrating sample magnetometer (VSM). To evaluate the performance of the magnetic nanoparticles as gene transfer vector, the PEI-CMD-MNPs were used to delivery green fluorescent protein (GFP) gene into BHK21 cells. The expression of GFP gene was detected by fluorescence microscope. DNA-PEI-CMD-MNPs polyplexes absorbed by the cells were also monitored by Magnetic resonance imaging (MRI). The transfection efficiency and gene expression efficiency of that transfected with a magnet were much higher than that of standard transfection.
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Chutuape, Kate S; Ziff, Mauri; Auerswald, Colette; Castillo, Marné; McFadden, Antionette; Ellen, Jonathan
2009-01-01
Finding and accessing members of youth subpopulations, such as young men who have sex with men (YMSM) of color or young females of color, for behavioral or disease surveillance or study recruitment, pose particular challenges. Venue-based sampling strategies--which hinge on where individuals congregate or "hang out" rather than where they live--appear to be effective alternatives. Methods used to identify venues focus on engaging members of social networks to learn where targeted populations congregate. However, it is not always clear if and how these methods differ according to gender, whether the youth accessed at a venue are actually from neighborhoods in which the venues are found, and whether the location of venues relative to neighborhoods of residence is different for young men and young women. This study illustrates the gender differences in venue type and venue location where eligible youth study participants from high-risk neighborhoods could be accessed for HIV research across 15 research sites (sites). The findings indicate that the study's method led to identifying venues where one quarter or more of the youth were eligible study participants and from the high-risk neighborhoods. Sites targeting young women of color had a higher proportion of eligible study participants who were also from the high-risk neighborhoods than sites targeting YMSM. Clubs were most commonly identified by sites targeting YMSM as recruitment venues, whereas neighborhood-based service or commercial centers were more common venues for young women of color. This study reveals how venue-based recruitment strategies can be tailored and resources maximized by understanding the key differences in the types of venues preferred by males and females and by recognizing that female-preferred venues are more likely to be closer to home.
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New developments in demographic targeting--the implications of 1991.
Humby, C R
1989-01-01
This paper examines benefits that systems such as ACORN, a demographic marketing system that classifies neighborhoods, offer today and monitors some of the trends. It then considers the impact of the 1992 UK census and gives a view of what marketeers can expect in the next 5 years. Neighborhood classifications represent a summary of the consumption patterns of a set of neighbors. If we could reach individuals based on the current life stage the gains to be had would be as great again as that offered by the neighborhood classifications themselves. The greatest weakness of all the neighborhood-based systems is their inability to target at life stage or age.
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Neighborhood properties are important determinants of temperature sensitive mutations.
Directory of Open Access Journals (Sweden)
Svetlana Lockwood
Full Text Available Temperature-sensitive (TS mutants are powerful tools to study gene function in vivo. These mutants exhibit wild-type activity at permissive temperatures and reduced activity at restrictive temperatures. Although random mutagenesis can be used to generate TS mutants, the procedure is laborious and unfeasible in multicellular organisms. Further, the underlying molecular mechanisms of the TS phenotype are poorly understood. To elucidate TS mechanisms, we used a machine learning method-logistic regression-to investigate a large number of sequence and structure features. We developed and tested 133 features, describing properties of either the mutation site or the mutation site neighborhood. We defined three types of neighborhood using sequence distance, Euclidean distance, and topological distance. We discovered that neighborhood features outperformed mutation site features in predicting TS mutations. The most predictive features suggest that TS mutations tend to occur at buried and rigid residues, and are located at conserved protein domains. The environment of a buried residue often determines the overall structural stability of a protein, thus may lead to reversible activity change upon temperature switch. We developed TS prediction models based on logistic regression and the Lasso regularized procedure. Through a ten-fold cross-validation, we obtained the area under the curve of 0.91 for the model using both sequence and structure features. Testing on independent datasets suggested that the model predicted TS mutations with a 50% precision. In summary, our study elucidated the molecular basis of TS mutants and suggested the importance of neighborhood properties in determining TS mutations. We further developed models to predict TS mutations derived from single amino acid substitutions. In this way, TS mutants can be efficiently obtained through experimentally introducing the predicted mutations.
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Kenney, Mary Kay
2012-04-01
To examine national patterns of peer and parent interactive play opportunities that enhance early learning/socialization. Bivariate and multivariable analyses of cross-sectional data on 22,797 children aged 1-5 years from the National Survey of Children's Health 2007 were performed to determine the child, family, and neighborhood factors associated with four parent-initiated activities. Outcomes measures included time (days/week) children spent: participating in peer play; being read to; sung to/told stories; and taken on family outings. Covariates included race/ethnicity, poverty, TV watching, childcare, child and maternal physical and mental health, family factors (structure, size, language, stress, education), and neighborhood factors (amenities, support, physical condition, safety). According to adjusted regression models, minority children from lower income, non-English-speaking households with limited education, poorer maternal health and greater parenting stress were read to/told stories less than children without these characteristics, while neighborhood factors exerted less influence. In contrast, significant reductions in days/week of peer play were associated with unsupportive neighborhoods and those with the poorest physical conditions and limited amenities. Likewise, reductions in outings were associated with fewer neighborhood amenities. The findings of this study indicate that a variety of child, family, and neighborhood factors are associated with parent-initiated behaviors such as reading, storytelling, peer interactive play, and family outings. Appropriate evidence-based home visiting interventions targeting child health, parenting skills, early childhood education, and social services in at-risk communities would appear to be appropriate vehicles for addressing such parent-initiated play activities that have the potential to enhance development.
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Energy Technology Data Exchange (ETDEWEB)
Hayakawa, Kazuo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Ikeya, Makoto [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Fukuta, Makoto [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Woltjen, Knut [Department of Reprogramming Sciences, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Tamaki, Sakura; Takahara, Naoko; Kato, Tomohisa; Sato, Shingo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Otsuka, Takanobu [Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Toguchida, Junya, E-mail: togjun@frontier.kyoto-u.ac.jp [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto (Japan)
2013-03-22
Highlights: ► We tried to identify targets of synovial sarcoma (SS)-associated SYT–SSX fusion gene. ► We established pluripotent stem cell (PSC) lines with inducible SYT–SSX gene. ► SYT–SSX responsive genes were identified by the induction of SYT–SSX in PSC. ► SS-related genes were selected from database by in silico analyses. ► 51 genes were finally identified among SS-related genes as targets of SYT–SSX in PSC. -- Abstract: Synovial sarcoma (SS) is a malignant soft tissue tumor harboring chromosomal translocation t(X; 18)(p11.2; q11.2), which produces SS-specific fusion gene, SYT–SSX. Although precise function of SYT–SSX remains to be investigated, accumulating evidences suggest its role in gene regulation via epigenetic mechanisms, and the product of SYT–SSX target genes may serve as biomarkers of SS. Lack of knowledge about the cell-of-origin of SS, however, has placed obstacle in the way of target identification. Here we report a novel approach to identify SYT–SSX2 target genes using human pluripotent stem cells (hPSCs) containing a doxycycline-inducible SYT–SSX2 gene. SYT–SSX2 was efficiently induced both at mRNA and protein levels within three hours after doxycycline administration, while no morphological change of hPSCs was observed until 24 h. Serial microarray analyses identified genes of which the expression level changed more than twofold within 24 h. Surprisingly, the majority (297/312, 95.2%) were up-regulated genes and a result inconsistent with the current concept of SYT–SSX as a transcriptional repressor. Comparing these genes with SS-related genes which were selected by a series of in silico analyses, 49 and 2 genes were finally identified as candidates of up- and down-regulated target of SYT–SSX, respectively. Association of these genes with SYT–SSX in SS cells was confirmed by knockdown experiments. Expression profiles of SS-related genes in hPSCs and human mesenchymal stem cells (hMSCs) were strikingly
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Saito, Shinta; Ura, Kiyoe; Kodama, Miho; Adachi, Noritaka
2015-06-30
Targeted gene modification by homologous recombination provides a powerful tool for studying gene function in cells and animals. In higher eukaryotes, non-homologous integration of targeting vectors occurs several orders of magnitude more frequently than does targeted integration, making the gene-targeting technology highly inefficient. For this reason, negative-selection strategies have been employed to reduce the number of drug-resistant clones associated with non-homologous vector integration, particularly when artificial nucleases to introduce a DNA break at the target site are unavailable or undesirable. As such, an exon-trap strategy using a promoterless drug-resistance marker gene provides an effective way to counterselect non-homologous integrants. However, constructing exon-trapping targeting vectors has been a time-consuming and complicated process. By virtue of highly efficient att-mediated recombination, we successfully developed a simple and rapid method to construct plasmid-based vectors that allow for exon-trapping gene targeting. These exon-trap vectors were useful in obtaining correctly targeted clones in mouse embryonic stem cells and human HT1080 cells. Most importantly, with the use of a conditionally cytotoxic gene, we further developed a novel strategy for negative selection, thereby enhancing the efficiency of counterselection for non-homologous integration of exon-trap vectors. Our methods will greatly facilitate exon-trapping gene-targeting technologies in mammalian cells, particularly when combined with the novel negative selection strategy.
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Microarray-Based Identification of Transcription Factor Target Genes
Gorte, M.; Horstman, A.; Page, R.B.; Heidstra, R.; Stromberg, A.; Boutilier, K.A.
2011-01-01
Microarray analysis is widely used to identify transcriptional changes associated with genetic perturbation or signaling events. Here we describe its application in the identification of plant transcription factor target genes with emphasis on the design of suitable DNA constructs for controlling TF
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Protein targeting in the analysis of learning and memory: a potential alternative to gene targeting.
Gerlai, R; Williams, S P; Cairns, B; Van Bruggen, N; Moran, P; Shih, A; Caras, I; Sauer, H; Phillips, H S; Winslow, J W
1998-11-01
Gene targeting using homologous recombination in embryonic stem (ES) cells offers unprecedented precision with which one may manipulate single genes and investigate the in vivo effects of defined mutations in the mouse. Geneticists argue that this technique abrogates the lack of highly specific pharmacological tools in the study of brain function and behavior. However, by now it has become clear that gene targeting has some limitations too. One problem is spatial and temporal specificity of the generated mutation, which may appear in multiple brain regions or even in other organs and may also be present throughout development, giving rise to complex, secondary phenotypical alterations. This may be a disadvantage in the functional analysis of a number of genes associated with learning and memory processes. For example, several proteins, including neurotrophins--cell-adhesion molecules--and protein kinases, that play a significant developmental role have recently been suggested to be also involved in neural and behavioral plasticity. Knocking out genes of such proteins may lead to developmental alterations or even embryonic lethality in the mouse, making it difficult to study their function in neural plasticity, learning, and memory. Therefore, alternative strategies to gene targeting may be needed. Here, we suggest a potentially useful in vivo strategy based on systemic application of immunoadhesins, genetically engineered fusion proteins possessing the Fc portion of the human IgG molecule and, for example, a binding domain of a receptor of interest. These proteins are stable in vivo and exhibit high binding specificity and affinity for the endogenous ligand of the receptor, but lack the ability to signal. Thus, if delivered to the brain, immunoadhesins may specifically block signalling of the receptor of interest. Using osmotic minipumps, the protein can be infused in a localized region of the brain for a specified period of time (days or weeks). Thus, the location
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de Groote, M.L.; Verschure, P.J.; Rots, M.G.
2012-01-01
Despite significant advances made in epigenetic research in recent decades, many questions remain unresolved, especially concerning cause and consequence of epigenetic marks with respect to gene expression modulation (GEM). Technologies allowing the targeting of epigenetic enzymes to predetermined
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de Groote, Marloes L.; Verschure, Pernette J.; Rots, Marianne G.
2012-01-01
Despite significant advances made in epigenetic research in recent decades, many questions remain unresolved, especially concerning cause and consequence of epigenetic marks with respect to gene expression modulation (GEM). Technologies allowing the targeting of epigenetic enzymes to predetermined
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Retinoschisislike alterations in the mouse eye caused by gene targeting of the Norrie disease gene.
Ruether, K; van de Pol, D; Jaissle, G; Berger, W; Tornow, R P; Zrenner, E
1997-03-01
To investigate the retinal function and morphology of mice carrying a replacement mutation in exon 2 of the Norrie disease gene. Recently, Norrie disease mutant mice have been generated using gene targeting technology. The mutation removes the 56 N-terminal amino acids of the Norrie gene product. Ganzfeld electroretinograms (ERGs) were obtained in five animals hemizygous or homozygous for the mutant gene and in three female animals heterozygous for the mutant gene. As controls, three males carrying the wild-type gene were examined. Electroretinogram testing included rod a- and b-wave V-log I functions, oscillatory potentials, and cone responses. The fundus morphology has been visualized by scanning laser ophthalmoscopy. Rod and cone ERG responses and fundus morphology were not significantly different among female heterozygotes and wild-type mice. In contrast, the hemizygous mice displayed a severe loss of ERG b-wave, leading to a negatively shaped scotopic ERG and a marked reduction of oscillatory potentials. The a-wave was normal at low intensities, and only with brighter flashes was there a moderate amplitude loss. Cone amplitudes were barely recordable in the gene-targeted males. Ophthalmoscopy revealed snowflakelike vitreal changes, retinoschisis, and pigment epithelium irregularities in hemizygotes and homozygotes, but no changes in female heterozygotes. The negatively shaped scotopic ERG in male mice with a Norrie disease gene mutation probably was caused by retinoschisis. Pigment epithelial changes and degenerations of the outer retina are relatively mild. These findings may be a clue to the embryonal retinoschisislike pathogenesis of Norrie disease in humans or it may indicate a different expression of the Norrie disease gene defect in mice compared to that in humans.
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Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.
Directory of Open Access Journals (Sweden)
Carolyn Glass
Full Text Available The ecotropic virus integration site 1 (EVI1 transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia.
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Osypuk, Theresa L
2015-02-01
The impact of housing and neighborhood context on children's mental health, as addressed by Flouri et al. (Soc Psychiatry Psychiatr Epidemiol, 2014), is an important, understudied topic in social epidemiology. Although the vast majority of this body of research has been descriptive, generating translational research is essential. This article offers guidance on interpreting evidence from observational studies for translation into policy, related to three policy-relevant elements of housing: receipt of affordable housing subsidies, the target population to which results generalize, and operationalization and modeling of neighborhood context. Policy translation is imperative for understanding which levers outside the health sector can be manipulated to change fundamental causes of mental health related to housing and neighborhood. Shifting from policy relevance to policy translation may be challenging, especially for understanding social causation in observational studies, but it is a necessary shift for improving population health.
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Neighborhood Poverty and Adolescent Development
McBride Murry, Velma; Berkel, Cady; Gaylord-Harden, Noni K.; Copeland-Linder, Nikeea; Nation, Maury
2011-01-01
This article provides a comprehensive review of studies conducted over the past decade on the effects of neighborhood and poverty on adolescent normative and nonnormative development. Our review includes a summary of studies examining the associations between neighborhood poverty and adolescent identity development followed by a review of studies…
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Meurer, William J; Levine, Deborah A; Kerber, Kevin A; Zahuranec, Darin B; Burke, James; Baek, Jonggyu; Sánchez, Brisa; Smith, Melinda A; Morgenstern, Lewis B; Lisabeth, Lynda D
2016-03-01
Delay to hospital arrival limits acute stroke treatment. Use of emergency medical services (EMS) is key in ensuring timely stroke care. We aim to identify neighborhoods with low EMS use and to evaluate whether neighborhood-level factors are associated with EMS use. We conducted a secondary analysis of data from the Brain Attack Surveillance in Corpus Christi project, a population-based stroke surveillance study of ischemic stroke and intracerebral hemorrhage cases presenting to emergency departments in Nueces County, TX. The primary outcome was arrival by EMS. The primary exposures were neighborhood resident age, poverty, and violent crime. We estimated the association of neighborhood-level factors with EMS use, using hierarchic logistic regression, controlling for individual factors (stroke severity, ethnicity, and age). During 2000 to 2009 there were 4,004 identified strokes, with EMS use data available for 3,474. Nearly half (49%) of stroke cases arrived by EMS. Adjusted stroke EMS use was lower in neighborhoods with higher family income (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.75 to 0.97) and a larger percentage of older adults (OR 0.70; 95% CI 0.56 to 0.89). Individual factors associated with stroke EMS use included white race (OR 1.41; 95% CI 1.13 to 1.76) and older age (OR 1.36 per 10-year age increment; 95% CI 1.27 to 1.46). The proportion of neighborhood stroke cases arriving by EMS ranged from 17% to 71%. The fully adjusted model explained only 0.3% (95% CI 0% to 1.1%) of neighborhood EMS stroke use variance, indicating that individual factors are more strongly associated with stroke EMS use than neighborhood factors. Although some neighborhood-level factors were associated with EMS use, patient-level factors explained nearly all variability in stroke EMS use. In this community, strategies to increase EMS use should target individuals rather than specific neighborhoods. Copyright © 2015 American College of Emergency Physicians. Published by
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Functional characterization of endogenous siRNA target genes in Caenorhabditis elegans
Directory of Open Access Journals (Sweden)
Heikkinen Liisa
2008-06-01
Full Text Available Abstract Background Small interfering RNA (siRNA molecules mediate sequence specific silencing in RNA interference (RNAi, a gene regulatory phenomenon observed in almost all organisms. Large scale sequencing of small RNA libraries obtained from C. elegans has revealed that a broad spectrum of siRNAs is endogenously transcribed from genomic sequences. The biological role and molecular diversity of C. elegans endogenous siRNA (endo-siRNA molecules, nonetheless, remain poorly understood. In order to gain insight into their biological function, we annotated two large libraries of endo-siRNA sequences, identified their cognate targets, and performed gene ontology analysis to identify enriched functional categories. Results Systematic trends in categorization of target genes according to the specific length of siRNA sequences were observed: 18- to 22-mer siRNAs were associated with genes required for embryonic development; 23-mers were associated uniquely with post-embryonic development; 24–26-mers were associated with phosphorus metabolism or protein modification. Moreover, we observe that some argonaute related genes associate with siRNAs with multiple reads. Sequence frequency graphs suggest that different lengths of siRNAs share similarities in overall sequence structure: the 5' end begins with G, while the body predominates with U and C. Conclusion These results suggest that the lengths of endogenous siRNA molecules are consequential to their biological functions since the gene ontology categories for their cognate mRNA targets vary depending upon their lengths.
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E2F target genes: unraveling the biology
DEFF Research Database (Denmark)
Bracken, Adrian P; Ciro, Marco; Cocito, Andrea
2004-01-01
The E2F transcription factors are downstream effectors of the retinoblastoma protein (pRB) pathway and are required for the timely regulation of numerous genes essential for DNA replication and cell cycle progression. Several laboratories have used genome-wide approaches to discover novel target...
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Directory of Open Access Journals (Sweden)
Te-I Albert Tsai
2014-05-01
Full Text Available New Urbanist development in the U.S. aims at enhancing a sense of community and seeks to return to the design of early transitional neighborhoods which have pedestrian-oriented environments with retail shops and services within walking distances of housing. Meanwhile, 6000 of Taiwan’s community associations have been running community empowerment programs supported by the Council for Cultural Affairs that have helped many neighborhoods to rebuild so-called community cohesion. This research attempts to evaluate whether neighborhoods with facilities near housing and shorter travel distances within a neighborhood would promote stronger social interactions and form a better community attachment than neighborhoods that have various opportunities for residents to participate in either formal or informal social gatherings. After interviewing and surveying residents from 19 neighborhoods in Taipei’s Beitou District, and correlating the psychological sense of community with inner neighborhood’s daily travel distances and numbers of participatory activities held by community organizations under empowerment programs together with frequencies of regular individual visits and casual meetings, statistical evidence yielded that placing public facilities near residential locations is more effective than providing various programs for elevating a sense of community.
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The Neighborhood Environment: Perceived Fall Risk, Resources, and Strategies for Fall Prevention.
Chippendale, Tracy; Boltz, Marie
2015-08-01
To explore the experience of older adults in their neighborhood in relation to perceived fall risk, fear of falling (FOF), and resources/strategies for fall prevention. Fourteen older adults, 65 years of age and older from 3 urban senior centers, participated in this qualitative study. The semistructured interview guidelines and background questionnaire were developed by the researchers based on the literature and an existing measure of walkability. Both tools were refined based on pilot interviews with seniors. Collaizzi's phenomenological method was used for data analysis. Five themes emerged from the data: (a) The built environment contributes to perceived fall risk and FOF, (b) personal strategies used to adapt to perceived neighborhood fall risks-behavioral approaches, (c) resources for physical activity and safety, (d) barriers to physical activity and exercise, and (e) neighborhood features as a motivator. Urban-dwelling seniors perceive that neighborhood features contribute to or mitigate fall risk and FOF. Behavioral strategies are used by seniors to prevent outdoor falls. The findings can help clinicians develop targeted fall prevention interventions for well elders and help urban planners to design and retrofit urban environments to reduce fall risk. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Crispr-mediated Gene Targeting of Human Induced Pluripotent Stem Cells.
Byrne, Susan M; Church, George M
2015-01-01
CRISPR/Cas9 nuclease systems can create double-stranded DNA breaks at specific sequences to efficiently and precisely disrupt, excise, mutate, insert, or replace genes. However, human embryonic stem or induced pluripotent stem cells (iPSCs) are more difficult to transfect and less resilient to DNA damage than immortalized tumor cell lines. Here, we describe an optimized protocol for genome engineering of human iPSCs using a simple transient transfection of plasmids and/or single-stranded oligonucleotides. With this protocol, we achieve transfection efficiencies greater than 60%, with gene disruption efficiencies from 1-25% and gene insertion/replacement efficiencies from 0.5-10% without any further selection or enrichment steps. We also describe how to design and assess optimal sgRNA target sites and donor targeting vectors; cloning individual iPSC by single cell FACS sorting, and genotyping successfully edited cells.
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Construction of a mouse model of factor VIII deficiency by gene targeting
Energy Technology Data Exchange (ETDEWEB)
Bi, L.; Lawler, A.; Gearhart, J. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others
1994-09-01
To develop a small animal model of hemophilia A for gene therapy experiments, we set out to construct a mouse model for factor VIII deficiency by gene targeting. First, we screened a mouse liver cDNA library using a human FVIII cDNA probe. We cloned a 2.6 Kb partial mouse factor VIII cDNA which extends from 800 base pairs of the 3{prime} end of exon 14 to the 5{prime} end of exon 26. A mouse genomic library made from strain 129 was then screened to obtain genomic fragments covering the exons desired for homologous recombination. Two genomic clones were obtained, and one covering exon 15 through 22 was used for gene targeting. To make gene targeting constructs, a 5.8 Kb genomic DNA fragment covering exons 15 to 19 of the mouse FVIII gene was subcloned, and the neo expression cassette was inserted into exons 16 and 17 separately by different strategies. These two constructs were named MFVIIIC-16 and MFVIIIC-17. The constructs were linearized and transfected into strain 129 mouse ES cells by electroporation. Factor VIII gene-knockout ES cell lines were selected by G-418 and screened by genomic Southern blots. Eight exon 16 targeted cell lines and five exon 17 targeted cell lines were obtained. Three cell lines from each construct were injected into blastocysts and surgically transferred into foster mothers. Multiple chimeric mice with 70-90% hair color derived from the ES-cell genotype were seen with both constructs. Germ line transmission of the ES-cell genotype has been obtained for the MFVIIIC-16 construct, and multiple hemophilia A carrier females have been identified. Factor VIII-deficient males will be conceived soon.
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Context dependent regulatory patterns of the androgen receptor and androgen receptor target genes
International Nuclear Information System (INIS)
Olsen, Jan Roger; Azeem, Waqas; Hellem, Margrete Reime; Marvyin, Kristo; Hua, Yaping; Qu, Yi; Li, Lisha; Lin, Biaoyang; Ke, XI- Song; Øyan, Anne Margrete; Kalland, Karl- Henning
2016-01-01
Expression of the androgen receptor (AR) is associated with androgen-dependent proliferation arrest and terminal differentiation of normal prostate epithelial cells. Additionally, activation of the AR is required for survival of benign luminal epithelial cells and primary cancer cells, thus androgen deprivation therapy (ADT) leads to apoptosis in both benign and cancerous tissue. Escape from ADT is known as castration-resistant prostate cancer (CRPC). In the course of CRPC development the AR typically switches from being a cell-intrinsic inhibitor of normal prostate epithelial cell proliferation to becoming an oncogene that is critical for prostate cancer cell proliferation. A clearer understanding of the context dependent activation of the AR and its target genes is therefore desirable. Immortalized human prostate basal epithelial EP156T cells and progeny cells that underwent epithelial to mesenchymal transition (EMT), primary prostate epithelial cells (PrECs) and prostate cancer cell lines LNCaP, VCaP and 22Rv1 were used to examine context dependent restriction and activation of the AR and classical target genes, such as KLK3. Genome-wide gene expression analyses and single cell protein analyses were applied to study the effect of different contexts. A variety of growth conditions were tested and found unable to activate AR expression and transcription of classical androgen-dependent AR target genes, such as KLK3, in prostate epithelial cells with basal cell features or in mesenchymal type prostate cells. The restriction of androgen- and AR-dependent transcription of classical target genes in prostate basal epithelial cells was at the level of AR expression. Exogenous AR expression was sufficient for androgen-dependent transcription of AR target genes in prostate basal epithelial cells, but did not exert a positive feedback on endogenous AR expression. Treatment of basal prostate epithelial cells with inhibitors of epigenetic gene silencing was not efficient in
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2015-08-01
This report provides the findings from the third phase of a three-part study about the influences of neighborhood crimes on travel : mode choice. While previous phases found evidence that high levels of neighborhood crime discourage people from choos...
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Active transportation in adult survivors of childhood cancer and neighborhood controls.
Slater, Megan E; Kelly, Aaron S; Sadak, Karim T; Ross, Julie A
2016-02-01
Childhood cancer survivors (CCS) are at high risk of treatment-related late effects, including cardiovascular disease and diabetes, which can be exacerbated by inadequate physical activity (PA). Previous PA interventions targeting CCS have focused on the domain of leisure-time/recreational PA. Active transportation, another domain of PA, has not been described in CCS. Therefore, this study aimed to identify active transportation behaviors, barriers, and correlates in adult CCS. We recruited 158 adult CCS and 153 controls matched on age, sex, and neighborhood for a survey regarding active transportation behaviors and perceptions. Linear and logistic regression models accounting for correlation among matched participants were used. Adult CCS engaged in similar levels of active transportation as controls (2.72 vs. 2.32 h/week, P = 0.40) despite perceiving greater health-related barriers (1.88 vs. 1.65 (measured on four-point Likert scale), P = 0.01). Marital/relationship status (odds ratio (OR) = 0.30, 95 % confidence interval (CI) = 0.11-0.81), planning/psychosocial barriers (OR = 0.15, 95 % CI = 0.04-0.53), and perceived neighborhood walkability (OR = 2.55, 95 % CI = 1.14-5.66) were correlates of active transportation among adult CCS, while objective neighborhood walkability (OR = 1.03, 95 % CI = 1.01-1.05) was a correlate among controls. Results suggest adult CCS and controls utilize active transportation at approximately equal levels. Factors other than health, including perceived neighborhood walkability, are related to active transportation behaviors to a greater degree in adult CCS. Interventions might consider promoting active transportation as a way to incorporate more PA into the daily lives of adult CCS. Such interventions will not be likely successful, however, without existing or improved neighborhood walkability/bikeability.
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Active Transportation in Adult Survivors of Childhood Cancer and Neighborhood Controls
Slater, Megan E.; Kelly, Aaron S.; Sadak, Karim T.; Ross, Julie A.
2015-01-01
Purpose Childhood cancer survivors (CCS) are at high risk of treatment-related late effects, including cardiovascular disease and diabetes, which can be exacerbated by inadequate physical activity (PA). Previous PA interventions targeting CCS have focused on the domain of leisure-time/recreational PA. Active transportation, another domain of PA, has not been described in CCS. Therefore, this study aimed to identify active transportation behaviors, barriers, and correlates in adult CCS. Methods We recruited 158 adult CCS and 153 controls matched on age, sex, and neighborhood for a survey regarding active transportation behaviors and perceptions. Linear and logistic regression models accounting for correlation among matched participants were used. Results Adult CCS engaged in similar levels of active transportation as controls (2.72 vs. 2.32 hours/week, P=0.40) despite perceiving greater health-related barriers (1.88 vs. 1.65 (measured on four-point Likert scale), P=0.01). Marital/relationship status (odds ratio (OR)=0.30, 95% confidence interval (CI)=0.11–0.81), planning/psychosocial barriers (OR=0.15, 95% CI=0.04–0.53), and perceived neighborhood walkability (OR=2.55, 95% CI=1.14–5.66) were correlates of active transportation among adult CCS, while objective neighborhood walkability (OR=1.03, 95% CI=1.01–1.05) was a correlate among controls. Conclusions Results suggest adult CCS and controls utilize active transportation at approximately equal levels. Factors other than health, including perceived neighborhood walkability, appear to influence active transportation behaviors to a greater degree in adult CCS. Implications for Cancer Survivors Interventions might consider promoting active transportation as a way to incorporate more PA into the daily lives of adult CCS. Such interventions will not be widely successful, however, without existing or improved neighborhood walkability/bikeability. PMID:25809159
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Defensible Spaces in Philadelphia: Exploring Neighborhood Boundaries Through Spatial Analysis
Directory of Open Access Journals (Sweden)
Rory Kramer
2017-02-01
Full Text Available Few spatial scales are as important to individual outcomes as the neighborhood. However, it is nearly impossible to define neighborhoods in a generalizable way. This article proposes that by shifting the focus to measuring neighborhood boundaries rather than neighborhoods, scholars can avoid the problem of the indefinable neighborhood and better approach questions of what predicts racial segregation across areas. By quantifying an externality space theory of neighborhood boundaries, this article introduces a novel form of spatial analysis to test where potential physical markers of neighborhood boundaries (major roads, rivers, railroads, and the like are associated with persistent racial boundaries between 1990 and 2010. Using Philadelphia as a case study, the paper identifies neighborhoods with persistent racial boundaries. It theorizes that local histories of white reactions to black in-migration explain which boundaries persistently resisted racial turnover, unlike the majority of Philadelphia’s neighborhoods, and that those racial boundaries shape the location, progress, and reaction to new residential development in those neighborhoods.
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Notthoff, Nanna; Carstensen, Laura L
2017-06-01
Positively framed messages seem to promote walking in older adults better than negatively framed messages. This study targeted elderly people in communities unfavorable to walking. Walking was measured with pedometers during baseline (1 week) and intervention (4 weeks). Participants ( n = 74) were informed about either the benefits of walking or the negative consequences of not walking. Perceived neighborhood walkability was assessed with a modified version of the Neighborhood Walkability Scale. When perceived walkability was high, positively framed messages were more effective than negatively framed messages in promoting walking; when perceived walkability was low, negatively framed messages were comparably effective to positively framed messages.
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Kotler, Neil G.
This pamphlet provides information on the history of and current trends toward neighborhood economic enterprises and provides guidance for setting up such enterprises. A bibliography of books, articles, and newsletters that have information on how to start and sustain neighborhood businesses and cooperatives is provided. Also included is a list of…
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Engineering liposomal nanoparticles for targeted gene therapy.
Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S
2017-08-01
Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.
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Dual CRISPR-Cas9 Cleavage Mediated Gene Excision and Targeted Integration in Yarrowia lipolytica.
Gao, Difeng; Smith, Spencer; Spagnuolo, Michael; Rodriguez, Gabriel; Blenner, Mark
2018-05-29
CRISPR-Cas9 technology has been successfully applied in Yarrowia lipolytica for targeted genomic editing including gene disruption and integration; however, disruptions by existing methods typically result from small frameshift mutations caused by indels within the coding region, which usually resulted in unnatural protein. In this study, a dual cleavage strategy directed by paired sgRNAs is developed for gene knockout. This method allows fast and robust gene excision, demonstrated on six genes of interest. The targeted regions for excision vary in length from 0.3 kb up to 3.5 kb and contain both non-coding and coding regions. The majority of the gene excisions are repaired by perfect nonhomologous end-joining without indel. Based on this dual cleavage system, two targeted markerless integration methods are developed by providing repair templates. While both strategies are effective, homology mediated end joining (HMEJ) based method are twice as efficient as homology recombination (HR) based method. In both cases, dual cleavage leads to similar or improved gene integration efficiencies compared to gene excision without integration. This dual cleavage strategy will be useful for not only generating more predictable and robust gene knockout, but also for efficient targeted markerless integration, and simultaneous knockout and integration in Y. lipolytica. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Putrik, Polina; de Vries, Nanne K; Mujakovic, Suhreta; van Amelsvoort, Ludovic; Kant, Ijmert; Kunst, Anton E; van Oers, Hans; Jansen, Maria
2015-02-01
Characteristics of an individual alone cannot exhaustively explain all the causes of poor health, and neighborhood of residence have been suggested to be one of the factors that contribute to health. However, knowledge about aspects of the neighborhood that are most important to health is limited. The main objective of this study was to explore associations between certain features of neighborhood environment and self-rated health and depressive symptoms in Maastricht (The Netherlands). A large amount of routinely collected neighborhood data were aggregated by means of factor analysis to 18 characteristics of neighborhood social and physical environment. Associations between these characteristics and self-rated health and presence of depressive symptoms were further explored in multilevel logistic regression models adjusted for individual demographic and socio-economic factors. The study sample consisted of 9,879 residents (mean age 55 years, 48 % male). Residents of unsafe communities were less likely to report good health (OR 0.88 95 % CI 0.80-0.97) and depressive symptoms (OR 0.81 95 % CI 0.69-0.97), and less cohesive environment was related to worse self-rated health (OR 0.81 95 % CI 0.72-0.92). Residents of neighborhoods with more car traffic nuisance and more disturbance from railway noise reported worse mental health (OR 0.79 95 % CI 0.68-0.92 and 0.85 95 % CI 0.73-0.99, respectively). We did not observe any association between health and quality of parking and shopping facilities, facilities for public or private transport, neighborhood aesthetics, green space, industrial nuisance, sewerage, neighbor nuisance or satisfaction with police performance. Our findings can be used to support development of integrated health policies targeting broader determinants of health. Improving safety, social cohesion and decreasing traffic nuisance in disadvantaged neighborhoods might be a promising way to improve the health of residents and reduce health inequalities.
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Space, race, and poverty: Spatial inequalities in walkable neighborhood amenities?
Directory of Open Access Journals (Sweden)
John Whalen
2012-05-01
Full Text Available BACKGROUND Multiple and varied benefits have been suggested for increased neighborhood walkability. However, spatial inequalities in neighborhood walkability likely exist and may be attributable, in part, to residential segregation. OBJECTIVE Utilizing a spatial demographic perspective, we evaluated potential spatial inequalities in walkable neighborhood amenities across census tracts in Boston, MA (US. METHODS The independent variables included minority racial/ethnic population percentages and percent of families in poverty. Walkable neighborhood amenities were assessed with a composite measure. Spatial autocorrelation in key study variables were first calculated with the Global Moran's I statistic. Then, Spearman correlations between neighborhood socio-demographic characteristics and walkable neighborhood amenities were calculated as well as Spearman correlations accounting for spatial autocorrelation. We fit ordinary least squares (OLS regression and spatial autoregressive models when appropriate as a final step. RESULTS Significant positive spatial autocorrelation was found in neighborhood socio-demographic characteristics (e.g. census tract percent Black, but not walkable neighborhood amenities or in the OLS regression residuals. Spearman correlations between neighborhood socio-demographic characteristics and walkable neighborhood amenities were not statistically significant, nor were neighborhood socio-demographic characteristics significantly associated with walkable neighborhood amenities in OLS regression models. CONCLUSIONS Our results suggest that there is residential segregation in Boston and that spatial inequalities do not necessarily show up using a composite measure. COMMENTS Future research in other geographic areas (including international contexts and using different definitions of neighborhoods (including small-area definitions should evaluate if spatial inequalities are found using composite measures, but also should
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Construction of RNAi lentiviral vector targeting mouse Islet-1 gene
Directory of Open Access Journals (Sweden)
Shen-shen ZHI
2011-02-01
Full Text Available Objective To construct and select RNAi lentiviral vectors that can silence mouse Islet-1 gene effectively.Methods Three groups of RNAi-target of mouse Islet-1 gene were designed,and corresponding shRNA oligo(sh1,sh2 and sh3 were synthesized,and then they were respectively inserted to the PLVTHM vector that had been digested by endonuclease.Agarose gel electrophoresis and sequencing were used to select and indentify the positive clones.The positive clones were extracted and then mixed with E.coli to amplify positive clones.The amplified clones were then infected into 293T along with the other 3 helper plasmids to produce lentiviral vector.After the construction of the lentiviral vector,plaque formation test was performed to determine the titer of lentiviral vector.The lentiviral vectors were then infected into C3H10T1/2 cells.The transfect efficiency of the lentiviral vectors was determined with flow cytometry with detection of green fluorescent protein(GFP.Q-PCR was employed to detect the RNAi efficiency of the lentiviral vectors.Results Agarose gel electrophoresis analysis showed that the clones with right gene at the target size were successfully established;gene sequencing showed that the right DNA fragments had been inserted;plaque formation test showed that the titer of the virus solution was 3.87×108TU/ml;the transfect efficiency of the lentiviral vector infected into C3H10T1/2 cells was 90.36%.All the 3 groups of shRNA targets(sh1,sh2 and sh3 showed an inhibitory effect on Islet-1 gene,and the sh1 showed the highest inhibitory effect(76.8%,as compared with that of normal cells(P < 0.05.Conclusion The RNAi lentiviral vector that can effectively silence the mouse Islet-1 gene has been constructed successfully,which may lay a foundation for further investigation of Islet-1 gene.
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Minh, Anita; Muhajarine, Nazeem; Janus, Magdalena; Brownell, Marni; Guhn, Martin
2017-07-01
This paper describes a scoping review of 42 studies of neighborhood effects on developmental health for children ages 0-6, published between 2009 and 2014. It focuses on three themes: (1) theoretical mechanisms that drive early childhood development, i.e. how neighborhoods matter for early childhood development; (2) dependence of such mechanisms on place-based characteristics i.e. where neighborhood effects occur; (3) dependence of such mechanisms on child characteristics, i.e. for whom is development most affected. Given that ecological systems theories postulate diverse mechanisms via which neighborhood characteristics affect early child development, we specifically examine evidence on mediation and/or moderation effects. We conclude by discussing future challenges, and proposing recommendations for analyses that utilize ecological longitudinal population-based databases. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Nonviral Gene Targeting at rDNA Locus of Human Mesenchymal Stem Cells
Directory of Open Access Journals (Sweden)
Youjin Hu
2013-01-01
Full Text Available Background. Genetic modification, such as the addition of exogenous genes to the MSC genome, is crucial to their use as cellular vehicles. Due to the risks associated with viral vectors such as insertional mutagenesis, the safer nonviral vectors have drawn a great deal of attention. Methods. VEGF, bFGF, vitamin C, and insulin-transferrin-selenium-X were supplemented in the MSC culture medium. The cells’ proliferation and survival capacity was measured by MTT, determination of the cumulative number of cells, and a colony-forming efficiency assay. The plasmid pHr2-NL was constructed and nucleofected into MSCs. The recombinants were selected using G418 and characterized using PCR and Southern blotting. Results. BFGF is critical to MSC growth and it acted synergistically with vitamin C, VEGF, and ITS-X, causing the cells to expand significantly. The neomycin gene was targeted to the rDNA locus of human MSCs using a nonviral human ribosomal targeting vector. The recombinant MSCs retained multipotential differentiation capacity, typical levels of hMSC surface marker expression, and a normal karyotype, and none were tumorigenic in nude mice. Conclusions. Exogenous genes can be targeted to the rDNA locus of human MSCs while maintaining the characteristics of MSCs. This is the first nonviral gene targeting of hMSCs.
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Neighborhood-level LGBT hate crimes and current illicit drug use among sexual minority youth.
Duncan, Dustin T; Hatzenbuehler, Mark L; Johnson, Renee M
2014-02-01
To investigate whether past-30 day illicit drug use among sexual minority youth was more common in neighborhoods with a greater prevalence of hate crimes targeting lesbian, gay, bisexual, and transgender (LGBT, or sexual minority) individuals. We used a population-based survey of public school youth in Boston, Massachusetts, consisting of 1292 9th-12th grade students from the 2008 Boston Youth Survey Geospatial Dataset (sexual minority n=108). Data on LGBT hate crimes involving assaults or assaults and battery between 2005 and 2008 were obtained from the Boston Police Department and linked to youths' residential address. Youth reported past-30 day use of marijuana and other illicit drugs. Wilcoxon-Mann-Whitney tests and corresponding p-values were computed to assess differences in substance use by neighborhood-level LGBT assault hate crime rate among sexual minority youth (n=103). The LGBT assault hate crime rate in the neighborhoods of sexual minority youth who reported current marijuana use was 23.7 per 100,000, compared to 12.9 per 100,000 for sexual minority youth who reported no marijuana use (p=0.04). No associations between LGBT assault hate crimes and marijuana use among heterosexual youth (p>0.05) or between sexual minority marijuana use and overall neighborhood-level violent and property crimes (p>0.05) were detected, providing evidence for result specificity. We found a significantly greater prevalence of marijuana use among sexual minority youth in neighborhoods with a higher prevalence of LGBT assault hate crimes. These results suggest that neighborhood context (i.e., LGBT hate crimes) may contribute to sexual orientation disparities in marijuana use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Wallace Helen M
2006-10-01
Full Text Available Abstract Background The potential public health benefits of targeting environmental interventions by genotype depend on the environmental and genetic contributions to the variance of common diseases, and the magnitude of any gene-environment interaction. In the absence of prior knowledge of all risk factors, twin, family and environmental data may help to define the potential limits of these benefits in a given population. However, a general methodology to analyze twin data is required because of the potential importance of gene-gene interactions (epistasis, gene-environment interactions, and conditions that break the 'equal environments' assumption for monozygotic and dizygotic twins. Method A new model for gene-gene and gene-environment interactions is developed that abandons the assumptions of the classical twin study, including Fisher's (1918 assumption that genes act as risk factors for common traits in a manner necessarily dominated by an additive polygenic term. Provided there are no confounders, the model can be used to implement a top-down approach to quantifying the potential utility of genetic prediction and prevention, using twin, family and environmental data. The results describe a solution space for each disease or trait, which may or may not include the classical twin study result. Each point in the solution space corresponds to a different model of genotypic risk and gene-environment interaction. Conclusion The results show that the potential for reducing the incidence of common diseases using environmental interventions targeted by genotype may be limited, except in special cases. The model also confirms that the importance of an individual's genotype in determining their risk of complex diseases tends to be exaggerated by the classical twin studies method, owing to the 'equal environments' assumption and the assumption of no gene-environment interaction. In addition, if phenotypes are genetically robust, because of epistasis
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Identification of hookworm DAF-16/FOXO response elements and direct gene targets.
Directory of Open Access Journals (Sweden)
Xin Gao
2010-08-01
Full Text Available The infective stage of the parasitic nematode hookworm is developmentally arrested in the environment and needs to infect a specific host to complete its life cycle. The canine hookworm (Ancylostoma caninum is an excellent model for investigating human hookworm infections. The transcription factor of A. caninum, Ac-DAF-16, which has a characteristic fork head or "winged helix" DNA binding domain (DBD, has been implicated in the resumption of hookworm development in the host. However, the precise roles of Ac-DAF-16 in hookworm parasitism and its downstream targets are unknown. In the present study, we combined molecular techniques and bioinformatics to identify a group of Ac-DAF-16 binding sites and target genes.The DNA binding domain of Ac-DAF-16 was used to select genomic fragments by in vitro genomic selection. Twenty four bound genomic fragments were analyzed for the presence of the DAF-16 family binding element (DBE and possible alternative Ac-DAF-16 bind motifs. The 22 genes linked to these genomic fragments were identified using bioinformatics tools and defined as candidate direct gene targets of Ac-DAF-16. Their developmental stage-specific expression patterns were examined. Also, a new putative DAF-16 binding element was identified.Our results show that Ac-DAF-16 is involved in diverse biological processes throughout hookworm development. Further investigation of these target genes will provide insights into the molecular basis by which Ac-DAF-16 regulates its downstream gene network in hookworm infection.
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Schaake, K.; Burgers, J.; Mulder, C.H.
2010-01-01
We address the influence of both the ethnic composition of the neighborhood and the ethnicity of individual residents on moving out of neighborhoods in the Netherlands. Using the Housing Research Netherlands survey and multinomial logistic regression analyses of moving out versus not moving or
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Rapid Development, Build-Out Ratio and Subsequent Neighborhood Turnover
Directory of Open Access Journals (Sweden)
George O. Rogers
2018-04-01
Full Text Available Neighborhood development is primarily comprised of structural elements that include design elements, nearby amenities and ecological attributes. This paper assumes that the process of development itself also influences the character of the neighborhood—specifically, that the rate of development and build-out ratio influences neighborhood turnover. While the structural components clearly set a framework for development, the process of development expresses the character of the neighborhood in subtle messages conveyed through the market. Neighborhoods in the rapidly growing university town of College Station, Texas are analyzed in terms of neighborhood design, nearby amenities and landscape ecology components. Residential property records are used to characterize each neighborhood in terms of the rate of development and current build-out ratio. The multivariate analysis indicates that the development rate increases subsequent neighborhood turnover rates while the build-out ratio decreases it.
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Genome-wide identification of structural variants in genes encoding drug targets
DEFF Research Database (Denmark)
Rasmussen, Henrik Berg; Dahmcke, Christina Mackeprang
2012-01-01
The objective of the present study was to identify structural variants of drug target-encoding genes on a genome-wide scale. We also aimed at identifying drugs that are potentially amenable for individualization of treatments based on knowledge about structural variation in the genes encoding...
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Neighborhood decline and the economic crisis : an introduction
van Kempen, Ronald; Bolt, Gideon; van Ham, Maarten
2016-01-01
Urban neighborhoods are still important in the lives of its residents. Therefore, it is important to find out how the recent global financial and economic crisis affects these neighborhoods. Which types of neighborhoods and which residents suffer more than others? This introduction provides an
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Osypuk, Theresa L.
2016-01-01
The impact of housing and neighborhood context on children’s mental health, as addressed by Flouri and colleagues [1], is an important, understudied topic in social epidemiology. Although the vast majority of this body of research has been descriptive, generating translational research is essential. This article offers guidance on interpreting evidence from observational studies for translation into policy, related to three policy-relevant elements of housing: receipt of affordable housing subsidies, the target population to which results generalize, and operationalization and modeling of neighborhood context. Policy translation is imperative for understanding which levers outside the health sector can be manipulated to change fundamental causes of mental health related to housing and neighborhood. Shifting from policy relevance to policy translation may be challenging, especially for understanding social causation in observational studies, but it’s a necessary shift for improving population health. PMID:25527210
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Desprez, Pierre-Yves; Campisi, Judith
2014-08-19
A method for treatment of breast cancer and other types of cancer. The method comprises targeting and modulating Id-1 gene expression, if any, for the Id-1 gene, or gene products in breast or other epithelial cancers in a patient by delivering products that modulate Id-1 gene expression. When expressed, Id-1 gene is a prognostic indicator that cancer cells are invasive and metastatic.
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Neighborhood Energy/Economic Development project
Energy Technology Data Exchange (ETDEWEB)
1991-12-31
Energy costs impact low income communities more than anyone else. Low income residents pay a larger percentage of their incomes for energy costs. In addition, they generally have far less discretionary energy use to eliminate in response to increasing energy prices. Furthermore, with less discretionary income, home energy efficiency improvements are often too expensive. Small neighborhood businesses are in the same situation. Improved efficiency in the use of energy can improve this situation by reducing energy costs for residents and local businesses. More importantly, energy management programs can increase the demand for local goods and services and lead to the creation of new job training and employment opportunities. In this way, neighborhood based energy efficiency programs can support community economic development. The present project, undertaken with the support of the Urban Consortium Energy Task Force, was intended to serve as a demonstration of energy/economic programming at the neighborhood level. The San Francisco Neighborhood Energy/Economic Development (NEED) project was designed to be a visible demonstration of bringing the economic development benefits of energy management home to low-income community members who need it most. To begin, a Community Advisory Committee was established to guide the design of the programs to best meet needs of the community. Subsequently three neighborhood energy/economic development programs were developed: The small business energy assistance program; The youth training and weatherization program; and, The energy review of proposed housing development projects.
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Neighborhood Effects on Health: Concentrated Advantage and Disadvantage
Finch, Brian K.; Do, D. Phuong; Heron, Melonie; Bird, Chloe; Seeman, Teresa; Lurie, Nicole
2010-01-01
We investigate an alternative conceptualization of neighborhood context and its association with health. Using an index that measures a continuum of concentrated advantage and disadvantage, we examine whether the relationship between neighborhood conditions and health varies by socio-economic status. Using NHANES III data geo-coded to census tracts, we find that while largely uneducated neighborhoods are universally deleterious, individuals with more education benefit from living in highly educated neighborhoods to a greater degree than individuals with lower levels of education. PMID:20627796
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Neighborhood Integration and Connectivity Predict Cognitive Performance and Decline
Directory of Open Access Journals (Sweden)
Amber Watts PhD
2015-08-01
Full Text Available Objective: Neighborhood characteristics may be important for promoting walking, but little research has focused on older adults, especially those with cognitive impairment. We evaluated the role of neighborhood characteristics on cognitive function and decline over a 2-year period adjusting for measures of walking. Method: In a study of 64 older adults with and without mild Alzheimer’s disease (AD, we evaluated neighborhood integration and connectivity using geographical information systems data and space syntax analysis. In multiple regression analyses, we used these characteristics to predict 2-year declines in factor analytically derived cognitive scores (attention, verbal memory, mental status adjusting for age, sex, education, and self-reported walking. Results : Neighborhood integration and connectivity predicted cognitive performance at baseline, and changes in cognitive performance over 2 years. The relationships between neighborhood characteristics and cognitive performance were not fully explained by self-reported walking. Discussion : Clearer definitions of specific neighborhood characteristics associated with walkability are needed to better understand the mechanisms by which neighborhoods may impact cognitive outcomes. These results have implications for measuring neighborhood characteristics, design and maintenance of living spaces, and interventions to increase walking among older adults. We offer suggestions for future research measuring neighborhood characteristics and cognitive function.
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Girls' self-efficacy in the context of neighborhood gender stratification.
Soller, Brian; Jackson, Aubrey L
2018-05-01
Scholars have linked neighborhood characteristics to self-efficacy, but few have considered how gender factors into this association. We integrate literature on neighborhoods, gender stratification, and self-efficacy to examine the association between women's relative resources among neighborhood residents and adolescents' self-efficacy. We hypothesize that girls report more self-efficacy when they reside in neighborhoods where women have more socioeconomic resources relative to men. We test this hypothesis using data from the Project on Human Development in Chicago Neighborhoods and the 1990 Census. Results from multilevel regression models with gender-interacted effects indicate the neighborhood level of women's relative resources was not associated with boys' self-efficacy. However, girls reported higher self-efficacy when women's relative resources in their neighborhoods were greater. This association persisted after including potential individual- and neighborhood-level confounding variables. Our study underscores the importance of attending to gendered processes when understanding how neighborhoods impact youth. Copyright © 2018. Published by Elsevier Inc.
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Examining public open spaces by neighborhood-level walkability and deprivation.
Badland, Hannah M; Keam, Rosanna; Witten, Karen; Kearns, Robin
2010-11-01
Public open spaces (POS) are recognized as important to promote physical activity engagement. However, it is unclear how POS attributes, such as activities available, environmental quality, amenities present, and safety, are associated with neighborhood-level walkability and deprivation. Twelve neighborhoods were selected within 1 constituent city of Auckland, New Zealand based on higher (n = 6) or lower (n = 6) walkability characteristics. Neighborhoods were dichotomized as more (n = 7) or less (n = 5) socioeconomically deprived. POS (n = 69) were identified within these neighborhoods and audited using the New Zealand-Public Open Space Tool. Unpaired 1-way analysis of variance tests were applied to compare differences in attributes and overall score of POS by neighborhood walkability and deprivation. POS located in more walkable neighborhoods have significantly higher overall scores when compared with less walkable neighborhoods. Deprivation comparisons identified POS located in less deprived communities have better quality environments, but fewer activities and safety features present when compared with more deprived neighborhoods. A positive relationship existed between presence of POS attributes and neighborhood walkability, but the relationship between POS and neighborhood-level deprivation was less clear. Variation in neighborhood POS quality alone is unlikely to explain poorer health outcomes for residents in more deprived areas.
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Christian, Hayley; Knuiman, Matthew; Divitini, Mark; Foster, Sarah; Hooper, Paula; Boruff, Bryan; Bull, Fiona; Giles-Corti, Billie
2017-01-01
Background: There is limited longitudinal evidence confirming the role of neighborhood environment attributes in encouraging people to walk more or if active people simply choose to live in activity-friendly neighborhoods. Natural experiments of policy changes to create more walkable communities provide stronger evidence for a causal effect of neighborhood environments on residents’ walking. Objectives: We aimed to investigate longitudinal associations between objective and perceived neighbor...
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Ryvicker, Miriam; Sridharan, Sridevi
2018-01-01
Older adults' health is sensitive to variations in neighborhood environment, yet few studies have examined how neighborhood factors influence their health care access. This study examined whether neighborhood environmental factors help to explain racial and socioeconomic disparities in health care access and outcomes among urban older adults with diabetes. Data from 123 233 diabetic Medicare beneficiaries aged 65 years and older in New York City were geocoded to measures of neighborhood walkability, public transit access, and primary care supply. In 2008, 6.4% had no office-based "evaluation and management" (E&M) visits. Multilevel logistic regression indicated that this group had greater odds of preventable hospitalization in 2009 (odds ratio = 1.31; 95% confidence interval: 1.22-1.40). Nonwhites and low-income individuals had greater odds of a lapse in E&M visits and of preventable hospitalization. Neighborhood factors did not help to explain these disparities. Further research is needed on the mechanisms underlying these disparities and older adults' ability to navigate health care. Even in an insured population living in a provider-dense city, targeted interventions may be needed to overcome barriers to chronic illness care for older adults in the community.
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Li, Fangwei; Shi, Wenhua; Wan, Yixin; Wang, Qingting; Feng, Wei; Yan, Xin; Wang, Jian; Chai, Limin; Zhang, Qianqian; Li, Manxiang
2017-12-01
The expression of microRNA (miR)-140-5p is known to be reduced in both pulmonary arterial hypertension (PAH) patients and monocrotaline-induced PAH models in rat. Identification of target genes for miR-140-5p with bioinformatics analysis may reveal new pathways and connections in PAH. This study aimed to explore downstream target genes and relevant signaling pathways regulated by miR-140-5p to provide theoretical evidences for further researches on role of miR-140-5p in PAH. Multiple downstream target genes and upstream transcription factors (TFs) of miR-140-5p were predicted in the analysis. Gene ontology (GO) enrichment analysis indicated that downstream target genes of miR-140-5p were enriched in many biological processes, such as biological regulation, signal transduction, response to chemical stimulus, stem cell proliferation, cell surface receptor signaling pathways. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis found that downstream target genes were mainly located in Notch, TGF-beta, PI3K/Akt, and Hippo signaling pathway. According to TF-miRNA-mRNA network, the important downstream target genes of miR-140-5p were PPI, TGF-betaR1, smad4, JAG1, ADAM10, FGF9, PDGFRA, VEGFA, LAMC1, TLR4, and CREB. After thoroughly reviewing published literature, we found that 23 target genes and seven signaling pathways were truly inhibited by miR-140-5p in various tissues or cells; most of these verified targets were in accordance with our present prediction. Other predicted targets still need further verification in vivo and in vitro .
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Tian, Zhiqiang; Wang, Huaizhi; Jia, Zhengcai; Shi, Jinglei; Tang, Jun; Mao, Liwei; Liu, Hongli; Deng, Yijing; He, Yangdong; Ruan, Zhihua; Li, Jintao; Wu, Yuzhang; Ni, Bing
2010-12-01
Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K(18)) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the 'mimoretrovirus'. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin α(v)β(3) interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K(18)/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.
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Better Buildings Neighborhood Program Progress Stories
Energy Technology Data Exchange (ETDEWEB)
None
2012-04-19
n neighborhoods across the country, stories are emerging constantly of individuals, businesses, and organizations that are benefiting from energy efficiency. Included are the stories of real people making their homes, businesses, and communities better with the help of the Better Buildings Neighborhood Program.
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Neighborhood social capital and individual health.
Mohnen, S.M.; Groenewegen, P.P.; Völker, B.; Flap, H.
2011-01-01
Neighborhood social capital is increasingly considered to be an important determinant of an individual's health. Using data from the Netherlands we investigate the influence of neighborhood social capital on an individual's self-reported health, while accounting for other conditions of health on
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Identification of novel androgen receptor target genes in prostate cancer
Directory of Open Access Journals (Sweden)
Gerald William L
2007-06-01
Full Text Available Abstract Background The androgen receptor (AR plays critical roles in both androgen-dependent and castrate-resistant prostate cancer (PCa. However, little is known about AR target genes that mediate the receptor's roles in disease progression. Results Using Chromatin Immunoprecipitation (ChIP Display, we discovered 19 novel loci occupied by the AR in castrate resistant C4-2B PCa cells. Only four of the 19 AR-occupied regions were within 10-kb 5'-flanking regulatory sequences. Three were located up to 4-kb 3' of the nearest gene, eight were intragenic and four were in gene deserts. Whereas the AR occupied the same loci in C4-2B (castrate resistant and LNCaP (androgen-dependent PCa cells, differences between the two cell lines were observed in the response of nearby genes to androgens. Among the genes strongly stimulated by DHT in C4-2B cells – D-dopachrome tautomerase (DDT, Protein kinase C delta (PRKCD, Glutathione S- transferase theta 2 (GSTT2, Transient receptor potential cation channel subfamily V member 3 (TRPV3, and Pyrroline-5-carboxylate reductase 1 (PYCR1 – most were less strongly or hardly stimulated in LNCaP cells. Another AR target gene, ornithine aminotransferase (OAT, was AR-stimulated in a ligand-independent manner, since it was repressed by AR siRNA knockdown, but not stimulated by DHT. We also present evidence for in vivo AR-mediated regulation of several genes identified by ChIP Display. For example, PRKCD and PYCR1, which may contribute to PCa cell growth and survival, are expressed in PCa biopsies from primary tumors before and after ablation and in metastatic lesions in a manner consistent with AR-mediated stimulation. Conclusion AR genomic occupancy is similar between LNCaP and C4-2B cells and is not biased towards 5' gene flanking sequences. The AR transcriptionally regulates less than half the genes nearby AR-occupied regions, usually but not always, in a ligand-dependent manner. Most are stimulated and a few are
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Directory of Open Access Journals (Sweden)
Goffeau André
2009-10-01
Full Text Available Abstract Background Pleiotropic Drug Resistant transporters (PDR are members of the ATP-Binding Cassette (ABC subfamily which export antifungals and other xenobiotics in fungi and plants. This subfamily of transmembrane transporters has nine known members in Saccharomyces cerevisiae. We have analyzed the complex evolution of the pleiotropic drug resistance proteins (Pdrp subfamily where gene duplications and deletions occur independently in individual genomes. This study was carried out on 62 Pdrp from nine hemiascomycetous species, seven of which span 6 of the 14 clades of the Saccharomyces complex while the two others species, Debaryomyces hansenii and Yarrowia lipolytica, are further apart from an evolutive point of view. Results Combined phylogenetic and neighborhood analyses enabled us to identify five Pdrp clusters in the Saccharomyces complex. Three of them comprise orthologs of the Pdrp sensu stricto, Pdr5p, Pdr10p, Pdr12p, Pdr15p, Snq2p and YNR070wp. The evolutive pathway of the orthologs of Snq2 and YNR070w is particularly complex due to a tandem gene array in Eremothecium gossypii, Kluyveromyces lactis and Saccharomyces (Lachancea kluyveri. This pathway and different cases of duplications and deletions were clarified by using a neighborhood analysis based on synteny. For the two distant species, Yarrowia lipolytica and Debaryomyces hansenii, no neighborhood evidence is available for these clusters and many homologs of Pdr5 and Pdr15 are phylogenetically assigned to species-based clusters. Two other clusters comprise the orthologs of the sensu lato Pdrp, Aus1p/Pdr11p and YOL075cp respectively. The evolutionary pathway of these clusters is simpler. Nevertheless, orthologs of these genes are missing in some species. Conclusion Numerous duplications were traced among the Hemiascomycetous Pdrp studied. The role of the Whole Genome Duplication (WGD is sorted out and our analyses confirm the common ancestrality of Pdr5p and Pdr15p. A tandem
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Seret, Marie-Line; Diffels, Julie F; Goffeau, André; Baret, Philippe V
2009-10-01
Pleiotropic Drug Resistant transporters (PDR) are members of the ATP-Binding Cassette (ABC) subfamily which export antifungals and other xenobiotics in fungi and plants. This subfamily of transmembrane transporters has nine known members in Saccharomyces cerevisiae. We have analyzed the complex evolution of the pleiotropic drug resistance proteins (Pdrp) subfamily where gene duplications and deletions occur independently in individual genomes. This study was carried out on 62 Pdrp from nine hemiascomycetous species, seven of which span 6 of the 14 clades of the Saccharomyces complex while the two others species, Debaryomyces hansenii and Yarrowia lipolytica, are further apart from an evolutive point of view. Combined phylogenetic and neighborhood analyses enabled us to identify five Pdrp clusters in the Saccharomyces complex. Three of them comprise orthologs of the Pdrp sensu stricto, Pdr5p, Pdr10p, Pdr12p, Pdr15p, Snq2p and YNR070wp. The evolutive pathway of the orthologs of Snq2 and YNR070w is particularly complex due to a tandem gene array in Eremothecium gossypii, Kluyveromyces lactis and Saccharomyces (Lachancea) kluyveri. This pathway and different cases of duplications and deletions were clarified by using a neighborhood analysis based on synteny. For the two distant species, Yarrowia lipolytica and Debaryomyces hansenii, no neighborhood evidence is available for these clusters and many homologs of Pdr5 and Pdr15 are phylogenetically assigned to species-based clusters. Two other clusters comprise the orthologs of the sensu lato Pdrp, Aus1p/Pdr11p and YOL075cp respectively. The evolutionary pathway of these clusters is simpler. Nevertheless, orthologs of these genes are missing in some species. Numerous duplications were traced among the Hemiascomycetous Pdrp studied. The role of the Whole Genome Duplication (WGD) is sorted out and our analyses confirm the common ancestrality of Pdr5p and Pdr15p. A tandem gene array is observed in Eremothecium gossypii. One
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Obesogenic and youth oriented restaurant marketing in public housing neighborhoods.
Lee, Rebecca E; Heinrich, Katie M; Reese-Smith, Jacqueline Y; Regan, Gail R; Adamus-Leach, Heather J
2014-03-01
To compare restaurant marketing by restaurant and neighborhood type. All restaurants (61=fast food, FF; 72=table service, TS) within an 800-meter radius of 13 public housing developments (HD) and 4 comparison neighborhoods were audited using the Restaurant Assessment Tool©2010. HD neighborhoods were lower income and higher minority than comparison neighborhoods with similar density and street connectivity. Restaurants in HD neighborhoods had fewer healthy entrées than comparison neighborhoods. FF restaurants had cheaper beverages and more children's meals, supersize drinks, free prize with purchase, super-size items, special characters, and more items geared to driving than TS restaurants. Residents of lower socioeconomic neighborhoods may be differentially exposed to unhealthy food options.
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Identification of Spt5 target genes in zebrafish development reveals its dual activity in vivo.
Directory of Open Access Journals (Sweden)
Keerthi Krishnan
Full Text Available Spt5 is a conserved essential protein that represses or stimulates transcription elongation in vitro. Immunolocalization studies on Drosophila polytene chromosomes suggest that Spt5 is associated with many loci throughout the genome. However, little is known about the prevalence and identity of Spt5 target genes in vivo during development. Here, we identify direct target genes of Spt5 using fog(sk8 zebrafish mutant, which disrupts the foggy/spt5 gene. We identified that fog(sk8 and their wildtype siblings differentially express less than 5% of genes examined. These genes participate in diverse biological processes from stress response to cell fate specification. Up-regulated genes exhibit shorter overall gene length compared to all genes examined. Through chromatin immunoprecipitation in zebrafish embryos, we identified a subset of developmentally critical genes that are bound by both Spt5 and RNA polymerase II. The protein occupancy patterns on these genes are characteristic of both repressive and stimulatory elongation regulation. Together our findings establish Spt5 as a dual regulator of transcription elongation in vivo and identify a small but diverse set of target genes critically dependent on Spt5 during development.
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Xie, Aris; Belcik, Todd; Qi, Yue; Morgan, Terry K; Champaneri, Shivam A; Taylor, Sarah; Davidson, Brian P; Zhao, Yan; Klibanov, Alexander L; Kuliszewski, Michael A; Leong-Poi, Howard; Ammi, Azzdine; Lindner, Jonathan R
2012-12-01
Ultrasound-mediated gene delivery can be amplified by acoustic disruption of microbubble carriers that undergo cavitation. We hypothesized that endothelial targeting of microbubbles bearing cDNA is feasible and, through optimizing proximity to the vessel wall, increases the efficacy of gene transfection. Contrast ultrasound-mediated gene delivery is a promising approach for site-specific gene therapy, although there are concerns with the reproducibility of this technique and the safety when using high-power ultrasound. Cationic lipid-shelled decafluorobutane microbubbles bearing a targeting moiety were prepared and compared with nontargeted microbubbles. Microbubble targeting efficiency to endothelial adhesion molecules (P-selectin or intercellular adhesion molecule [ICAM]-1) was tested using in vitro flow chamber studies, intravital microscopy of tumor necrosis factor-alpha (TNF-α)-stimulated murine cremaster muscle, and targeted contrast ultrasound imaging of P-selectin in a model of murine limb ischemia. Ultrasound-mediated transfection of luciferase reporter plasmid charge coupled to microbubbles in the post-ischemic hindlimb muscle was assessed by in vivo optical imaging. Charge coupling of cDNA to the microbubble surface was not influenced by the presence of targeting ligand, and did not alter the cavitation properties of cationic microbubbles. In flow chamber studies, surface conjugation of cDNA did not affect attachment of targeted microbubbles at microvascular shear stresses (0.6 and 1.5 dyne/cm(2)). Attachment in vivo was also not affected by cDNA according to intravital microscopy observations of venular adhesion of ICAM-1-targeted microbubbles and by ultrasound molecular imaging of P-selectin-targeted microbubbles in the post-ischemic hindlimb in mice. Transfection at the site of high acoustic pressures (1.0 and 1.8 MPa) was similar for control and P-selectin-targeted microbubbles but was associated with vascular rupture and hemorrhage. At 0.6 MPa
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Effects of semantic neighborhood density in abstract and concrete words.
Reilly, Megan; Desai, Rutvik H
2017-12-01
Concrete and abstract words are thought to differ along several psycholinguistic variables, such as frequency and emotional content. Here, we consider another variable, semantic neighborhood density, which has received much less attention, likely because semantic neighborhoods of abstract words are difficult to measure. Using a corpus-based method that creates representations of words that emphasize featural information, the current investigation explores the relationship between neighborhood density and concreteness in a large set of English nouns. Two important observations emerge. First, semantic neighborhood density is higher for concrete than for abstract words, even when other variables are accounted for, especially for smaller neighborhood sizes. Second, the effects of semantic neighborhood density on behavior are different for concrete and abstract words. Lexical decision reaction times are fastest for words with sparse neighborhoods; however, this effect is stronger for concrete words than for abstract words. These results suggest that semantic neighborhood density plays a role in the cognitive and psycholinguistic differences between concrete and abstract words, and should be taken into account in studies involving lexical semantics. Furthermore, the pattern of results with the current feature-based neighborhood measure is very different from that with associatively defined neighborhoods, suggesting that these two methods should be treated as separate measures rather than two interchangeable measures of semantic neighborhoods. Copyright © 2017 Elsevier B.V. All rights reserved.
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Felicidade, Ingrid; Marcarini, Juliana Cristina; Carreira, Clísia Mara; Amarante, Marla Karine; Afman, Lydia A; Mantovani, Mário Sérgio; Ribeiro, Lúcia Regina
2015-01-01
The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. Q-PCR was utilized to assess the mRNA expression levels of target genes. In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors. © 2014 S. Karger AG, Basel.
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Neighborhood social capital and individual health
Mohnen, S.M.; Groenewegen, P.P.; Völker, B.G.M.; Flap, H.D.
2010-01-01
Neighborhood social capital is increasingly considered to be an important determinant of an individual’s health. Using data from the Netherlands we investigate the influence of neighborhood social capital on an individual’s self-reported health, while accounting for other conditions of health on
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Target genes discovery through copy number alteration analysis in human hepatocellular carcinoma.
Gu, De-Leung; Chen, Yen-Hsieh; Shih, Jou-Ho; Lin, Chi-Hung; Jou, Yuh-Shan; Chen, Chian-Feng
2013-12-21
High-throughput short-read sequencing of exomes and whole cancer genomes in multiple human hepatocellular carcinoma (HCC) cohorts confirmed previously identified frequently mutated somatic genes, such as TP53, CTNNB1 and AXIN1, and identified several novel genes with moderate mutation frequencies, including ARID1A, ARID2, MLL, MLL2, MLL3, MLL4, IRF2, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3, JAK1, KEAP1, NFE2L2, C16orf62, LEPR, RAC2, and IL6ST. Functional classification of these mutated genes suggested that alterations in pathways participating in chromatin remodeling, Wnt/β-catenin signaling, JAK/STAT signaling, and oxidative stress play critical roles in HCC tumorigenesis. Nevertheless, because there are few druggable genes used in HCC therapy, the identification of new therapeutic targets through integrated genomic approaches remains an important task. Because a large amount of HCC genomic data genotyped by high density single nucleotide polymorphism arrays is deposited in the public domain, copy number alteration (CNA) analyses of these arrays is a cost-effective way to reveal target genes through profiling of recurrent and overlapping amplicons, homozygous deletions and potentially unbalanced chromosomal translocations accumulated during HCC progression. Moreover, integration of CNAs with other high-throughput genomic data, such as aberrantly coding transcriptomes and non-coding gene expression in human HCC tissues and rodent HCC models, provides lines of evidence that can be used to facilitate the identification of novel HCC target genes with the potential of improving the survival of HCC patients.
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Rodrigues, Thais B; Duan, Jian J; Palli, Subba R; Rieske, Lynne K
2018-03-22
Recent study has shown that RNA interference (RNAi) is efficient in emerald ash borer (EAB), Agrilus planipennis, and that ingestion of double-stranded RNA (dsRNA) targeting specific genes causes gene silencing and mortality in neonates. Here, we report on the identification of highly effective target genes for RNAi-mediated control of EAB. We screened 13 candidate genes in neonate larvae and selected the most effective target genes for further investigation, including their effect on EAB adults and on a non-target organism, Tribolium castaneum. The two most efficient target genes selected, hsp (heat shock 70-kDa protein cognate 3) and shi (shibire), caused up to 90% mortality of larvae and adults. In EAB eggs, larvae, and adults, the hsp is expressed at higher levels when compared to that of shi. Ingestion of dsHSP and dsSHI caused mortality in both neonate larvae and adults. Administration of a mixture of both dsRNAs worked better than either dsRNA by itself. In contrast, injection of EAB.dsHSP and EAB.dsSHI did not cause mortality in T. castaneum. Thus, the two genes identified cause high mortality in the EAB with no apparent phenotype effects in a non-target organism, the red flour beetle, and could be used in RNAi-mediated control of this invasive pest.
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Advances in plant gene-targeted and functional markers: a review
Directory of Open Access Journals (Sweden)
Poczai Péter
2013-02-01
Full Text Available Abstract Public genomic databases have provided new directions for molecular marker development and initiated a shift in the types of PCR-based techniques commonly used in plant science. Alongside commonly used arbitrarily amplified DNA markers, other methods have been developed. Targeted fingerprinting marker techniques are based on the well-established practices of arbitrarily amplified DNA methods, but employ novel methodological innovations such as the incorporation of gene or promoter elements in the primers. These markers provide good reproducibility and increased resolution by the concurrent incidence of dominant and co-dominant bands. Despite their promising features, these semi-random markers suffer from possible problems of collision and non-homology analogous to those found with randomly generated fingerprints. Transposable elements, present in abundance in plant genomes, may also be used to generate fingerprints. These markers provide increased genomic coverage by utilizing specific targeted sites and produce bands that mostly seem to be homologous. The biggest drawback with most of these techniques is that prior genomic information about retrotransposons is needed for primer design, prohibiting universal applications. Another class of recently developed methods exploits length polymorphism present in arrays of multi-copy gene families such as cytochrome P450 and β-tubulin genes to provide cross-species amplification and transferability. A specific class of marker makes use of common features of plant resistance genes to generate bands linked to a given phenotype, or to reveal genetic diversity. Conserved DNA-based strategies have limited genome coverage and may fail to reveal genetic diversity, while resistance genes may be under specific evolutionary selection. Markers may also be generated from functional and/or transcribed regions of the genome using different gene-targeting approaches coupled with the use of RNA information
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Advances in plant gene-targeted and functional markers: a review
2013-01-01
Public genomic databases have provided new directions for molecular marker development and initiated a shift in the types of PCR-based techniques commonly used in plant science. Alongside commonly used arbitrarily amplified DNA markers, other methods have been developed. Targeted fingerprinting marker techniques are based on the well-established practices of arbitrarily amplified DNA methods, but employ novel methodological innovations such as the incorporation of gene or promoter elements in the primers. These markers provide good reproducibility and increased resolution by the concurrent incidence of dominant and co-dominant bands. Despite their promising features, these semi-random markers suffer from possible problems of collision and non-homology analogous to those found with randomly generated fingerprints. Transposable elements, present in abundance in plant genomes, may also be used to generate fingerprints. These markers provide increased genomic coverage by utilizing specific targeted sites and produce bands that mostly seem to be homologous. The biggest drawback with most of these techniques is that prior genomic information about retrotransposons is needed for primer design, prohibiting universal applications. Another class of recently developed methods exploits length polymorphism present in arrays of multi-copy gene families such as cytochrome P450 and β-tubulin genes to provide cross-species amplification and transferability. A specific class of marker makes use of common features of plant resistance genes to generate bands linked to a given phenotype, or to reveal genetic diversity. Conserved DNA-based strategies have limited genome coverage and may fail to reveal genetic diversity, while resistance genes may be under specific evolutionary selection. Markers may also be generated from functional and/or transcribed regions of the genome using different gene-targeting approaches coupled with the use of RNA information. Such techniques have the
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Lopes, CDF; Gonçalves, NP; Gomes, CP; Saraiva, MJ; Pêgo, AP
2017-01-01
Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the br...
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Using GPS Data to Study Neighborhood Walkability and Physical Activity.
Rundle, Andrew G; Sheehan, Daniel M; Quinn, James W; Bartley, Katherine; Eisenhower, Donna; Bader, Michael M D; Lovasi, Gina S; Neckerman, Kathryn M
2016-03-01
Urban form characteristics intended to support pedestrian activity, collectively referred to as neighborhood walkability, are thought to increase total physical activity. However, little is known about how neighborhood walkability influences utilization of neighborhood space by residents and their overall physical activity. Sociodemographic information and data on mobility and physical activity over 1-week periods measured by GPS loggers and accelerometers were collected from 803 residents of New York City between November 2010 and November 2011. Potentially accessible neighborhood areas were defined as land area within a 1-kilometer distance of the subject's home (radial buffer) and within a 1-kilometer journey on the street network from the home (network buffer). To define actual areas utilized by subjects, a minimum convex polygon was plotted around GPS waypoints falling within 1 kilometer of the home. A neighborhood walkability scale was calculated for each neighborhood area. Data were analyzed in 2014. Total residential neighborhood space utilized by subjects was significantly associated with street intersection density and was significantly negatively associated with residential density and subway stop density within 1 kilometer of the home. Walkability scale scores were significantly higher within utilized as compared with non-utilized neighborhood areas. Neighborhood walkability in the utilized neighborhood area was positively associated with total weekly physical activity (32% [95% CI=17%, 49%] more minutes of moderate-equivalent physical activity across the interquartile range of walkability). Neighborhood walkability is associated with neighborhood spaces utilized by residents and total weekly physical activity. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Paula Paulo
2012-07-01
Full Text Available This work aimed to evaluate whether ETS transcription factors frequently involved in rearrangements in prostate carcinomas (PCa, namely ERG and ETV1, regulate specific or shared target genes. We performed differential expression analysis on nine normal prostate tissues and 50 PCa enriched for different ETS rearrangements using exon-level expression microarrays, followed by in vitro validation using cell line models. We found specific deregulation of 57 genes in ERG-positive PCa and 15 genes in ETV1-positive PCa, whereas deregulation of 27 genes was shared in both tumor subtypes. We further showed that the expression of seven tumor-associated ERG target genes (PLA1A, CACNA1D, ATP8A2, HLA-DMB, PDE3B, TDRD1, and TMBIM1 and two tumor-associated ETV1 target genes (FKBP10 and GLYATL2 was significantly affected by specific ETS silencing in VCaP and LNCaP cell line models, respectively, whereas the expression of three candidate ERG and ETV1 shared targets (GRPR, KCNH8, and TMEM45B was significantly affected by silencing of either ETS. Interestingly, we demonstrate that the expression of TDRD1, the topmost overexpressed gene of our list of ERG-specific candidate targets, is inversely correlated with the methylation levels of a CpG island found at -66 bp of the transcription start site in PCa and that TDRD1 expression is regulated by direct binding of ERG to the CpG island in VCaP cells. We conclude that ETS transcription factors regulate specific and shared target genes and that TDRD1, FKBP10, and GRPR are promising therapeutic targets and can serve as diagnostic markers for molecular subtypes of PCa harboring specific fusion gene rearrangements.
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Neighborhood quality and labor market outcomes
DEFF Research Database (Denmark)
Damm, Anna Piil
2014-01-01
of refugee men. Their labor market outcomes are also not affected by the overall employment rate and the overall average skill level in the neighborhood. However, an increase in the average skill level of non-Western immigrant men living in the neighborhood raises their employment probability, while...
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Engineering nucleases for gene targeting: safety and regulatory considerations.
Pauwels, Katia; Podevin, Nancy; Breyer, Didier; Carroll, Dana; Herman, Philippe
2014-01-25
Nuclease-based gene targeting (NBGT) represents a significant breakthrough in targeted genome editing since it is applicable from single-celled protozoa to human, including several species of economic importance. Along with the fast progress in NBGT and the increasing availability of customized nucleases, more data are available about off-target effects associated with the use of this approach. We discuss how NBGT may offer a new perspective for genetic modification, we address some aspects crucial for a safety improvement of the corresponding techniques and we also briefly relate the use of NBGT applications and products to the regulatory oversight. Copyright © 2013 Elsevier B.V. All rights reserved.
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NEIGHBORHOOD NORMS AND SUBSTANCE USE AMONG TEENS
Musick, Kelly; Seltzer, Judith A.; Schwartz, Christine R.
2008-01-01
This paper uses new data from the Los Angeles Family and Neighborhood Survey (L.A. FANS) to examine how neighborhood norms shape teenagers’ substance use. Specifically, it takes advantage of clustered data at the neighborhood level to relate adult neighbors’ attitudes and behavior with respect to smoking, drinking, and drugs, which we treat as norms, to teenagers’ own smoking, drinking, and drug use. We use hierarchical linear models to account for parents’ attitudes and behavior and other characteristics of individuals and families. We also investigate how the association between neighborhood norms and teen behavior depends on: (1) the strength of norms, as measured by consensus in neighbors’ attitudes and conformity in their behavior; (2) the willingness and ability of neighbors to enforce norms, for instance, by monitoring teens’ activities; and (3) the degree to which teens are exposed to their neighbors. We find little association between neighborhood norms and teen substance use, regardless of how we condition the relationship. We discuss possible theoretical and methodological explanations for this finding. PMID:18496598
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[Discovery of the target genes inhibited by formic acid in Candida shehatae].
Cai, Peng; Xiong, Xujie; Xu, Yong; Yong, Qiang; Zhu, Junjun; Shiyuan, Yu
2014-01-04
At transcriptional level, the inhibitory effects of formic acid was investigated on Candida shehatae, a model yeast strain capable of fermenting xylose to ethanol. Thereby, the target genes were regulated by formic acid and the transcript profiles were discovered. On the basis of the transcriptome data of C. shehatae metabolizing glucose and xylose, the genes responsible for ethanol fermentation were chosen as candidates by the combined method of yeast metabolic pathway analysis and manual gene BLAST search. These candidates were then quantitatively detected by RQ-PCR technique to find the regulating genes under gradient doses of formic acid. By quantitative analysis of 42 candidate genes, we finally identified 10 and 5 genes as markedly down-regulated and up-regulated targets by formic acid, respectively. With regard to gene transcripts regulated by formic acid in C. shehatae, the markedly down-regulated genes ranking declines as follows: xylitol dehydrogenase (XYL2), acetyl-CoA synthetase (ACS), ribose-5-phosphate isomerase (RKI), transaldolase (TAL), phosphogluconate dehydrogenase (GND1), transketolase (TKL), glucose-6-phosphate dehydrogenase (ZWF1), xylose reductase (XYL1), pyruvate dehydrogenase (PDH) and pyruvate decarboxylase (PDC); and a declining rank for up-regulated gens as follows: fructose-bisphosphate aldolase (ALD), glucokinase (GLK), malate dehydrogenase (MDH), 6-phosphofructokinase (PFK) and alcohol dehydrogenase (ADH).
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Neighborhood differences in social capital in Ghent (Belgium): a multilevel approach.
Neutens, Tijs; Vyncke, Veerle; De Winter, Dieter; Willems, Sara
2013-11-13
Little research has focused on the spatial distribution of social capital, despite social capital's rising popularity in health research and policy. This study examines the neighborhood differences in social capital and the determinants that explain these differences. Five components of neighborhood social capital are identified by means of factor and reliability analyses using data collected in the cross-sectional SWING study from 762 inhabitants in 42 neighbourhoods in the city of Ghent (Belgium). Neighborhood differences in social capital are explored using hierarchical linear models with cross-level interactions. Significant neighborhood differences are found for social cohesion, informal social control and social support, but not for social leverage and generalized trust. Our findings suggest that neighborhood social capital depends on both characteristics of individuals living in the neighborhood (attachment to neighborhood) and characteristics of the neighborhood itself (deprivation and residential turnover). Our analysis further shows that neighborhood deprivation reinforces the negative effect of declining neighborhood attachment on social cohesion and informal social control. This study foregrounds the importance of contextual effects in encouraging neighborhood social capital. Given the importance of neighborhood-level characteristics, it can be anticipated social capital promoting initiatives are likely to be more effective when tailored to specific areas. Second, our analyses show that not all forms of social capital are influenced by contextual factors to the same extent, implying that changes in neighborhood characteristics are conducive to, say, trust while leaving social support unaffected. Finally, our analysis has demonstrated that complex interrelationships between individual- and neighborhood-level variables exist, which are often overlooked in current work.
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Healthy neighborhoods: walkability and air pollution.
Marshall, Julian D; Brauer, Michael; Frank, Lawrence D
2009-11-01
The built environment may influence health in part through the promotion of physical activity and exposure to pollution. To date, no studies have explored interactions between neighborhood walkability and air pollution exposure. We estimated concentrations of nitric oxide (NO), a marker for direct vehicle emissions), and ozone (O(3)) and a neighborhood walkability score, for 49,702 (89% of total) postal codes in Vancouver, British Columbia, Canada. NO concentrations were estimated from a land-use regression model, O(3) was estimated from ambient monitoring data; walkability was calculated based on geographic attributes such as land-use mix, street connectivity, and residential density. All three attributes exhibit an urban-rural gradient, with high walkability and NO concentrations, and low O(3) concentrations, near the city center. Lower-income areas tend to have higher NO concentrations and walkability and lower O(3) concentrations. Higher-income areas tend to have lower pollution (NO and O(3)). "Sweet-spot" neighborhoods (low pollution, high walkability) are generally located near but not at the city center and are almost exclusively higher income. Increased concentration of activities in urban settings yields both health costs and benefits. Our research identifies neighborhoods that do especially well (and especially poorly) for walkability and air pollution exposure. Work is needed to ensure that the poor do not bear an undue burden of urban air pollution and that neighborhoods designed for walking, bicycling, or mass transit do not adversely affect resident's exposure to air pollution. Analyses presented here could be replicated in other cities and tracked over time to better understand interactions among neighborhood walkability, air pollution exposure, and income level.
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Cultural mechanisms and the persistence of neighborhood violence.
Kirk, David S; Papachristos, Andrew V
2011-01-01
Sociologists have given considerable attention to identifying the neighborhood-level social-interactional mechanisms that influence outcomes such as crime, educational attainment, and health. Yet, cultural mechanisms are often overlooked in quantitative studies of neighborhood effects. This paper adds a cultural dimension to neighborhood effects research by exploring the consequences of legal cynicism. Legal cynicism refers to a cultural frame in which people perceive the law as illegitimate, unresponsive, and ill equipped to ensure public safety. The authors find that legal cynicism explains why homicide persisted in certain Chicago neighborhoods during the 1990s despite declines in poverty and declines in violence city-wide.
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Dunn, Erin C; Richmond, Tracy K; Milliren, Carly E; Subramanian, S V
2015-01-01
Despite much interest in understanding the influence of contexts on health, most research has focused on one context at a time, ignoring the reality that individuals have simultaneous memberships in multiple settings. Using the example of smoking behavior among adolescents in the National Longitudinal Study of Adolescent Health, we applied cross-classified multilevel modeling (CCMM) to examine fixed and random effects for schools and neighborhoods. We compared the CCMM results with those obtained from a traditional multilevel model (MLM) focused on either the school and neighborhood separately. In the MLMs, 5.2% of the variation in smoking was due to differences between neighborhoods (when schools were ignored) and 6.3% of the variation in smoking was due to differences between schools (when neighborhoods were ignored). However in the CCMM examining neighborhood and school variation simultaneously, the neighborhood-level variation was reduced to 0.4%. Results suggest that using MLM, instead of CCMM, could lead to overestimating the importance of certain contexts and could ultimately lead to targeting interventions or policies to the wrong settings. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Evi Berchtold
Full Text Available Several methods predict activity changes of transcription factors (TFs from a given regulatory network and measured expression data. But available gene regulatory networks are incomplete and contain many condition-dependent regulations that are not relevant for the specific expression measurement. It is not known which combination of active TFs is needed to cause a change in the expression of a target gene. A method to systematically evaluate the inferred activity changes is missing. We present such an evaluation strategy that indicates for how many target genes the observed expression changes can be explained by a given set of active TFs. To overcome the problem that the exact combination of active TFs needed to activate a gene is typically not known, we assume a gene to be explained if there exists any combination for which the predicted active TFs can possibly explain the observed change of the gene. We introduce the i-score (inconsistency score, which quantifies how many genes could not be explained by the set of activity changes of TFs. We observe that, even for these minimal requirements, published methods yield many unexplained target genes, i.e. large i-scores. This holds for all methods and all expression datasets we evaluated. We provide new optimization methods to calculate the best possible (minimal i-score given the network and measured expression data. The evaluation of this optimized i-score on a large data compendium yields many unexplained target genes for almost every case. This indicates that currently available regulatory networks are still far from being complete. Both the presented Act-SAT and Act-A* methods produce optimal sets of TF activity changes, which can be used to investigate the difficult interplay of expression and network data. A web server and a command line tool to calculate our i-score and to find the active TFs associated with the minimal i-score is available from https://services.bio.ifi.lmu.de/i-score.
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Horizontal transfer of a eukaryotic plastid-targeted protein gene to cyanobacteria
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Keeling Patrick J
2007-06-01
Full Text Available Abstract Background Horizontal or lateral transfer of genetic material between distantly related prokaryotes has been shown to play a major role in the evolution of bacterial and archaeal genomes, but exchange of genes between prokaryotes and eukaryotes is not as well understood. In particular, gene flow from eukaryotes to prokaryotes is rarely documented with strong support, which is unusual since prokaryotic genomes appear to readily accept foreign genes. Results Here, we show that abundant marine cyanobacteria in the related genera Synechococcus and Prochlorococcus acquired a key Calvin cycle/glycolytic enzyme from a eukaryote. Two non-homologous forms of fructose bisphosphate aldolase (FBA are characteristic of eukaryotes and prokaryotes respectively. However, a eukaryotic gene has been inserted immediately upstream of the ancestral prokaryotic gene in several strains (ecotypes of Synechococcus and Prochlorococcus. In one lineage this new gene has replaced the ancestral gene altogether. The eukaryotic gene is most closely related to the plastid-targeted FBA from red algae. This eukaryotic-type FBA once replaced the plastid/cyanobacterial type in photosynthetic eukaryotes, hinting at a possible functional advantage in Calvin cycle reactions. The strains that now possess this eukaryotic FBA are scattered across the tree of Synechococcus and Prochlorococcus, perhaps because the gene has been transferred multiple times among cyanobacteria, or more likely because it has been selectively retained only in certain lineages. Conclusion A gene for plastid-targeted FBA has been transferred from red algae to cyanobacteria, where it has inserted itself beside its non-homologous, functional analogue. Its current distribution in Prochlorococcus and Synechococcus is punctate, suggesting a complex history since its introduction to this group.
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Chen, Jiang; Du, Yinan; He, Xueyan; Huang, Xingxu; Shi, Yun S
2017-03-31
The most powerful way to probe protein function is to characterize the consequence of its deletion. Compared to conventional gene knockout (KO), conditional knockout (cKO) provides an advanced gene targeting strategy with which gene deletion can be performed in a spatially and temporally restricted manner. However, for most species that are amphiploid, the widely used Cre-flox conditional KO (cKO) system would need targeting loci in both alleles to be loxP flanked, which in practice, requires time and labor consuming breeding. This is considerably significant when one is dealing with multiple genes. CRISPR/Cas9 genome modulation system is advantaged in its capability in targeting multiple sites simultaneously. Here we propose a strategy that could achieve conditional KO of multiple genes in mouse with Cre recombinase dependent Cas9 expression. By transgenic construction of loxP-stop-loxP (LSL) controlled Cas9 (LSL-Cas9) together with sgRNAs targeting EGFP, we showed that the fluorescence molecule could be eliminated in a Cre-dependent manner. We further verified the efficacy of this novel strategy to target multiple sites by deleting c-Maf and MafB simultaneously in macrophages specifically. Compared to the traditional Cre-flox cKO strategy, this sgRNAs-LSL-Cas9 cKO system is simpler and faster, and would make conditional manipulation of multiple genes feasible.
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Directory of Open Access Journals (Sweden)
Zhang Kang-Jian
2012-02-01
Full Text Available Abstract Background Gene therapy and viral therapy are used for cancer therapy for many years, but the results are less than satisfactory. Our aim was to construct a new recombinant adenovirus which is more efficient to kill hepatocarcinoma cells but more safe to normal cells. Methods By using the Cancer Targeting Gene-Viro-Therapy strategy, Apoptin, a promising cancer therapeutic gene was inserted into the double-regulated oncolytic adenovirus AD55 in which E1A gene was driven by alpha fetoprotein promoter along with a 55 kDa deletion in E1B gene to form AD55-Apoptin. The anti-tumor effects and safety were examined by western blotting, virus yield assay, real time polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide assay, Hoechst33342 staining, Fluorescence-activated cell sorting, xenograft tumor model, Immunohistochemical assay, liver function analysis and Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay. Results The recombinant virus AD55-Apoptin has more significant antitumor effect for hepatocelluar carcinoma cell lines (in vitro than that of AD55 and even ONYX-015 but no or little impair on normal cell lines. Furthermore, it also shows an obvious in vivo antitumor effect on the Huh-7 liver carcinoma xenograft in nude mice with bigger beginning tumor volume till about 425 mm3 but has no any damage on the function of liver. The induction of apoptosis is involved in AD55-Apoptin induced antitumor effects. Conclusion The AD55-Apoptin can be a potential anti-hepatoma agent with remarkable antitumor efficacy as well as higher safety in cancer targeting gene-viro-therapy system.
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Directory of Open Access Journals (Sweden)
Tatiana Flisikowska
Full Text Available Rabbits are widely used in biomedical research, yet techniques for their precise genetic modification are lacking. We demonstrate that zinc finger nucleases (ZFNs introduced into fertilized oocytes can inactivate a chosen gene by mutagenesis and also mediate precise homologous recombination with a DNA gene-targeting vector to achieve the first gene knockout and targeted sequence replacement in rabbits. Two ZFN pairs were designed that target the rabbit immunoglobulin M (IgM locus within exons 1 and 2. ZFN mRNAs were microinjected into pronuclear stage fertilized oocytes. Founder animals carrying distinct mutated IgM alleles were identified and bred to produce offspring. Functional knockout of the immunoglobulin heavy chain locus was confirmed by serum IgM and IgG deficiency and lack of IgM(+ and IgG(+ B lymphocytes. We then tested whether ZFN expression would enable efficient targeted sequence replacement in rabbit oocytes. ZFN mRNA was co-injected with a linear DNA vector designed to replace exon 1 of the IgM locus with ∼1.9 kb of novel sequence. Double strand break induced targeted replacement occurred in up to 17% of embryos and in 18% of fetuses analyzed. Two major goals have been achieved. First, inactivation of the endogenous IgM locus, which is an essential step for the production of therapeutic human polyclonal antibodies in the rabbit. Second, establishing efficient targeted gene manipulation and homologous recombination in a refractory animal species. ZFN mediated genetic engineering in the rabbit and other mammals opens new avenues of experimentation in immunology and many other research fields.
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Bödeker, Malte; Bucksch, Jens; Wallmann-Sperlich, Birgit
2018-01-01
The Neighborhood Physical Activity Questionnaire allows to assess physical activity within and outside the neighborhood. Study objectives were to examine the criterion-related validity and health/functioning associations of Neighborhood Physical Activity Questionnaire-derived physical activity in German older adults. A total of 107 adults aged…
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In silico prediction of novel therapeutic targets using gene-disease association data.
Ferrero, Enrico; Dunham, Ian; Sanseau, Philippe
2017-08-29
Target identification and validation is a pressing challenge in the pharmaceutical industry, with many of the programmes that fail for efficacy reasons showing poor association between the drug target and the disease. Computational prediction of successful targets could have a considerable impact on attrition rates in the drug discovery pipeline by significantly reducing the initial search space. Here, we explore whether gene-disease association data from the Open Targets platform is sufficient to predict therapeutic targets that are actively being pursued by pharmaceutical companies or are already on the market. To test our hypothesis, we train four different classifiers (a random forest, a support vector machine, a neural network and a gradient boosting machine) on partially labelled data and evaluate their performance using nested cross-validation and testing on an independent set. We then select the best performing model and use it to make predictions on more than 15,000 genes. Finally, we validate our predictions by mining the scientific literature for proposed therapeutic targets. We observe that the data types with the best predictive power are animal models showing a disease-relevant phenotype, differential expression in diseased tissue and genetic association with the disease under investigation. On a test set, the neural network classifier achieves over 71% accuracy with an AUC of 0.76 when predicting therapeutic targets in a semi-supervised learning setting. We use this model to gain insights into current and failed programmes and to predict 1431 novel targets, of which a highly significant proportion has been independently proposed in the literature. Our in silico approach shows that data linking genes and diseases is sufficient to predict novel therapeutic targets effectively and confirms that this type of evidence is essential for formulating or strengthening hypotheses in the target discovery process. Ultimately, more rapid and automated target
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Varrault, Annie; Dantec, Christelle; Le Digarcher, Anne; Chotard, Laëtitia; Bilanges, Benoit; Parrinello, Hugues; Dubois, Emeric; Rialle, Stéphanie; Severac, Dany; Bouschet, Tristan; Journot, Laurent
2017-10-13
PLAGL1/ZAC1 undergoes parental genomic imprinting, is paternally expressed, and is a member of the imprinted gene network (IGN). It encodes a zinc finger transcription factor with anti-proliferative activity and is a candidate tumor suppressor gene on 6q24 whose expression is frequently lost in various neoplasms. Conversely, gain of PLAGL1 function is responsible for transient neonatal diabetes mellitus, a rare genetic disease that results from defective pancreas development. In the present work, we showed that Plagl1 up-regulation was not associated with DNA damage-induced cell cycle arrest. It was rather associated with physiological cell cycle exit that occurred with contact inhibition, growth factor withdrawal, or cell differentiation. To gain insights into Plagl1 mechanism of action, we identified Plagl1 target genes by combining chromatin immunoprecipitation and genome-wide transcriptomics in transfected cell lines. Plagl1-elicited gene regulation correlated with multiple binding to the proximal promoter region through a GC-rich motif. Plagl1 target genes included numerous genes involved in signaling, cell adhesion, and extracellular matrix composition, including collagens. Plagl1 targets also included 22% of the 409 genes that make up the IGN. Altogether, this work identified Plagl1 as a transcription factor that coordinated the regulation of a subset of IGN genes and controlled extracellular matrix composition. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
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The global financial crisis and neighborhood decline
Zwiers, Merle; Bolt, Gideon; Van Ham, Maarten; Van Kempen, Ronald
2016-01-01
Neighborhood decline is a complex and multidimensional process. National and regional variations in economic and political structures (including varieties in national welfare state arrangements), combined with differences in neighborhood history, development, and population composition, make it
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Oligopeptide complex for targeted non-viral gene delivery to adipocytes
Won, Young-Wook; Adhikary, Partho Protim; Lim, Kwang Suk; Kim, Hyung Jin; Kim, Jang Kyoung; Kim, Yong-Hee
2014-12-01
Commercial anti-obesity drugs acting in the gastrointestinal tract or the central nervous system have been shown to have limited efficacy and severe side effects. Anti-obesity drug development is thus focusing on targeting adipocytes that store excess fat. Here, we show that an adipocyte-targeting fusion-oligopeptide gene carrier consisting of an adipocyte-targeting sequence and 9-arginine (ATS-9R) selectively transfects mature adipocytes by binding to prohibitin. Injection of ATS-9R into obese mice confirmed specific binding of ATS-9R to fat vasculature, internalization and gene expression in adipocytes. We also constructed a short-hairpin RNA (shRNA) for silencing fatty-acid-binding protein 4 (shFABP4), a key lipid chaperone in fatty-acid uptake and lipid storage in adipocytes. Treatment of obese mice with ATS-9R/shFABP4 led to metabolic recovery and body-weight reduction (>20%). The ATS-9R/shFABP4 oligopeptide complex could prove to be a safe therapeutic approach to regress and treat obesity as well as obesity-induced metabolic syndromes.
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Neighborhood Influences on Late Life Cognition in the ACTIVE Study
Directory of Open Access Journals (Sweden)
Shannon M. Sisco
2012-01-01
Full Text Available Low neighborhood-level socioeconomic status has been associated with poorer health, reduced physical activity, increased psychological stress, and less neighborhood-based social support. These outcomes are correlates of late life cognition, but few studies have specifically investigated the neighborhood as a unique source of explanatory variance in cognitive aging. This study supplemented baseline cognitive data from the ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly study with neighborhood-level data to investigate (1 whether neighborhood socioeconomic position (SEP predicts cognitive level, and if so, whether it differentially predicts performance in general and specific domains of cognition and (2 whether neighborhood SEP predicts differences in response to short-term cognitive intervention for memory, reasoning, or processing speed. Neighborhood SEP positively predicted vocabulary, but did not predict other general or specific measures of cognitive level, and did not predict individual differences in response to cognitive intervention.
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Khang, Chang Hyun; Park, Sook-Young; Lee, Yong-Hwan; Kang, Seogchan
2005-06-01
Rapid progress in fungal genome sequencing presents many new opportunities for functional genomic analysis of fungal biology through the systematic mutagenesis of the genes identified through sequencing. However, the lack of efficient tools for targeted gene replacement is a limiting factor for fungal functional genomics, as it often necessitates the screening of a large number of transformants to identify the desired mutant. We developed an efficient method of gene replacement and evaluated factors affecting the efficiency of this method using two plant pathogenic fungi, Magnaporthe grisea and Fusarium oxysporum. This method is based on Agrobacterium tumefaciens-mediated transformation with a mutant allele of the target gene flanked by the herpes simplex virus thymidine kinase (HSVtk) gene as a conditional negative selection marker against ectopic transformants. The HSVtk gene product converts 5-fluoro-2'-deoxyuridine to a compound toxic to diverse fungi. Because ectopic transformants express HSVtk, while gene replacement mutants lack HSVtk, growing transformants on a medium amended with 5-fluoro-2'-deoxyuridine facilitates the identification of targeted mutants by counter-selecting against ectopic transformants. In addition to M. grisea and F. oxysporum, the method and associated vectors are likely to be applicable to manipulating genes in a broad spectrum of fungi, thus potentially serving as an efficient, universal functional genomic tool for harnessing the growing body of fungal genome sequence data to study fungal biology.
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Integrative analysis of RUNX1 downstream pathways and target genes
Directory of Open Access Journals (Sweden)
Liu Marjorie
2008-07-01
Full Text Available Abstract Background The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML. The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1 cell lines with RUNX1 mutations from FPD-AML patients, 2 over-expression of RUNX1 and CBFβ, and 3 Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBFβ. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease
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Department of Housing and Urban Development — This tool assists the public and Choice Neighborhoods applicants to prepare data to submit with their grant application by allowing applicants to draw the exact...
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Neighborhood Risk, Parental Socialization Styles, and Adolescent Conduct Problems
Directory of Open Access Journals (Sweden)
Enrique Gracia
2010-12-01
Full Text Available This article aims to analyze the influence of parental socialization styles (authoritarian, authoritative, indulgent and neglectful, and perceived neighborhood risk on three indicators of conduct problems in adolescence (school misconduct, delinquency, and drug use. The sample consists of 1,017 adolescents, aged between 12 and 17. Results from four multivariate factorial designs yielded only main effects of parenting styles and neighborhood risk. Adolescents from authoritative and indulgent families showed lower conduct problems than those with authoritarian and neglectful parents. Also, higher levels of perceived neighborhood risk were significantly associated with more conduct problems. There were no significant interaction effects between parenting styles and perceived neighborhood risk, but results yielded a significant interaction effect between neighborhood risk and sex. Overall, results do not support the idea that parenting styles are more effective under certain neighborhood risk conditions, and suggest that neighbourhood risk influences adolescents’ psychosocial adjustment beyond the influence of parental socialization styles.
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International Nuclear Information System (INIS)
Ailan, He; Shuanglin, Xiang; Xiangwen, Xiao; Daolong, Ren; Lu, Gan; Xiaofeng, Ding; Xi, Qiao; Xingwang, Hu; Rushi, Liu; Jian, Zhang
2009-01-01
Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis. To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2γ binding sites on genomic DNA from human breast cancer cell line MDA-MB-453. 20 novel DNA fragments proximal to potential AP-2γ targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2γ target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2γ. Decreased expression and overexpression of AP-2γ in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2γ directly regulates them. This suggested that AP-2γ can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future
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Directory of Open Access Journals (Sweden)
Miaomiao Fan
Full Text Available Small interfering RNAs (siRNAs are widely used to repress gene expression by targeting mRNAs. Some reports reveal that siRNAs can also activate or inhibit gene expression through targeting the gene promoters. Our group has found that microRNAs (miRNAs could activate gene transcription via interaction with the TATA-box motif in gene promoters. To investigate whether siRNA targeting the same region could upregulate the promoter activity, we test the activating efficiency of siRNAs targeting the TATA-box motif of 16 genes and perform a systematic analysis to identify the common features of the functional siRNAs for effective activation of gene promoters. Further, we try various modifications to improve the activating efficiency of siRNAs and find that it is quite useful to design the promoter-targeting activating siRNA by following several rules such as (a complementary to the TATA-box-centered region; (b UA usage at the first two bases of the antisense strand; (c twenty-three nucleotides (nts in length; (d 2'-O-Methyl (2'-OMe modification at the 3' terminus of the antisense strand; (e avoiding mismatches at the 3' end of the antisense strand. The optimized activating siRNAs potently enhance the expression of interleukin-2 (IL-2 gene in human and mouse primary CD4+ T cells with a long-time effect. Taken together, our study provides a guideline for rational design the promoter-targeting siRNA to sequence-specifically enhance gene expression.
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Efficient in planta gene targeting in tomato using geminiviral replicons and the CRISPR/Cas9 system.
Dahan-Meir, Tal; Filler-Hayut, Shdema; Melamed-Bessudo, Cathy; Bocobza, Samuel; Czosnek, Henryk; Aharoni, Asaph; Levy, Avraham A
2018-04-18
Current breeding relies mostly on random mutagenesis and recombination to generate novel genetic variation. However, targeted genome editing is becoming an increasingly important tool for precise plant breeding. Using the CRISPR-Cas system combined with the bean yellow dwarf virus rolling circle replicon we optimized a method for targeted mutagenesis and gene replacement in tomato. The carotenoid isomerase (CRTISO) and phytoene synthase 1 (PSY1) genes from the carotenoid biosynthesis pathway were chosen as targets due to their easily detectable change of phenotype. We took advantage of the geminiviral replicon amplification as a mean to provide a large amount of donor template for the repair of a CRISPR-Cas-induced DNA double strand break (DSB) in the target gene, via homologous recombination. Mutagenesis experiments, performed in the Micro-Tom variety achieved precise modification of the CRTISO and PSY1 loci at an efficiency of up to 90%. In the gene targeting experiments, our target was a fast-neutron-induced crtiso allele that contained a 281bp deletion. This deletion was repaired with the wildtype sequence through homologous recombination between the CRISPR-Cas-induced DSB in the crtiso target and the amplified donor in 25% of the plants transformed. This shows that efficient gene targeting can be achieved in the absence of selection markers or reporters using a single and modular construct that is adaptable to other tomato targets and other crops. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A
2016-07-27
Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
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Quantification of differential gene expression by multiplexed targeted resequencing of cDNA
Arts, Peer; van der Raadt, Jori; van Gestel, Sebastianus H.C.; Steehouwer, Marloes; Shendure, Jay; Hoischen, Alexander; Albers, Cornelis A.
2017-01-01
Whole-transcriptome or RNA sequencing (RNA-Seq) is a powerful and versatile tool for functional analysis of different types of RNA molecules, but sample reagent and sequencing cost can be prohibitive for hypothesis-driven studies where the aim is to quantify differential expression of a limited number of genes. Here we present an approach for quantification of differential mRNA expression by targeted resequencing of complementary DNA using single-molecule molecular inversion probes (cDNA-smMIPs) that enable highly multiplexed resequencing of cDNA target regions of ∼100 nucleotides and counting of individual molecules. We show that accurate estimates of differential expression can be obtained from molecule counts for hundreds of smMIPs per reaction and that smMIPs are also suitable for quantification of relative gene expression and allele-specific expression. Compared with low-coverage RNA-Seq and a hybridization-based targeted RNA-Seq method, cDNA-smMIPs are a cost-effective high-throughput tool for hypothesis-driven expression analysis in large numbers of genes (10 to 500) and samples (hundreds to thousands). PMID:28474677
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Association Between Neighborhood Violence and Biological Stress in Children.
Theall, Katherine P; Shirtcliff, Elizabeth A; Dismukes, Andrew R; Wallace, Maeve; Drury, Stacy S
2017-01-01
.002 [0.001]; P = .04), as did children exposed to more violent crime within 500 m of their home (β [SE] -0.032 [0.014]; P = .02). Neighborhoods are important targets for interventions to reduce the effect of exposure to violence in the lives of children. These findings provide the first evidence that objective exposures to neighborhood-level violence influence both physiological and cellular markers of stress, even in children.
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Phonotactics, Neighborhood Activation, and Lexical Access for Spoken Words
Vitevitch, Michael S.; Luce, Paul A.; Pisoni, David B.; Auer, Edward T.
2012-01-01
Probabilistic phonotactics refers to the relative frequencies of segments and sequences of segments in spoken words. Neighborhood density refers to the number of words that are phonologically similar to a given word. Despite a positive correlation between phonotactic probability and neighborhood density, nonsense words with high probability segments and sequences are responded to more quickly than nonsense words with low probability segments and sequences, whereas real words occurring in dense similarity neighborhoods are responded to more slowly than real words occurring in sparse similarity neighborhoods. This contradiction may be resolved by hypothesizing that effects of probabilistic phonotactics have a sublexical focus and that effects of similarity neighborhood density have a lexical focus. The implications of this hypothesis for models of spoken word recognition are discussed. PMID:10433774
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Identification of miRNAs and their target genes in developing soybean seeds by deep sequencing
Directory of Open Access Journals (Sweden)
Chen Shou-Yi
2011-01-01
Full Text Available Abstract Background MicroRNAs (miRNAs regulate gene expression by mediating gene silencing at transcriptional and post-transcriptional levels in higher plants. miRNAs and related target genes have been widely studied in model plants such as Arabidopsis and rice; however, the number of identified miRNAs in soybean (Glycine max is limited, and global identification of the related miRNA targets has not been reported in previous research. Results In our study, a small RNA library and a degradome library were constructed from developing soybean seeds for deep sequencing. We identified 26 new miRNAs in soybean by bioinformatic analysis and further confirmed their expression by stem-loop RT-PCR. The miRNA star sequences of 38 known miRNAs and 8 new miRNAs were also discovered, providing additional evidence for the existence of miRNAs. Through degradome sequencing, 145 and 25 genes were identified as targets of annotated miRNAs and new miRNAs, respectively. GO analysis indicated that many of the identified miRNA targets may function in soybean seed development. Additionally, a soybean homolog of Arabidopsis SUPPRESSOR OF GENE SLIENCING 3 (AtSGS3 was detected as a target of the newly identified miRNA Soy_25, suggesting the presence of feedback control of miRNA biogenesis. Conclusions We have identified large numbers of miRNAs and their related target genes through deep sequencing of a small RNA library and a degradome library. Our study provides more information about the regulatory network of miRNAs in soybean and advances our understanding of miRNA functions during seed development.
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Yang, Qing-Li; Shen, Ji-Qing; Jiang, Zhi-Hua; Yang, Yi-Chao; Li, Hong-Mei; Chen, Ying-Dan; Zhou, Xiao-Nong
2014-06-01
To identify Clonorchis sinensis metacercariae using PCR targeting ribosomal DNA ITS region and COX1 gene. Pseudorasbora parva were collected from Hengxian County of Guangxi at the end of May 2013. Single metacercaria of C. sinensis and other trematodes were separated from muscle tissue of P. parva by digestion method. Primers targeting ribosomal DNA ITS region and COX1 gene of C. sinensis were designed for PCR and the universal primers were used as control. The sensitivity and specificity of the PCR detection were analyzed. C. sinensis metacercariae at different stages were identified by PCR. DNA from single C. sinensis metacercaria was detected by PCR targeting ribosomal DNA ITS region and COX1 gene. The specific amplicans have sizes of 437/549, 156/249 and 195/166 bp, respectively. The ratio of the two positive numbers in PCR with universal primers and specific primers targeting C. sinensis ribosomal DNA ITS1 and ITS2 regions was 0.905 and 0.952, respectively. The target gene fragments were amplified by PCR using COX1 gene-specific primers. The PCR with specific primers did not show any non-specific amplification. However, the PCR with universal primers targeting ribosomal DNA ITS regions performed serious non-specific amplification. C. sinensis metacercariae at different stages are identified by morphological observation and PCR method. Species-specific primers targeting ribosomal DNA ITS region show higher sensitivity and specificity than the universal primers. PCR targeting COX1 gene shows similar sensitivity and specificity to PCR with specific primers targeting ribosomal DNA ITS regions.
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Demarcation of local neighborhoods to study relations between contextual factors and health
Chor Dora; Santos Simone M; Werneck Guilherme
2010-01-01
Abstract Background Several studies have highlighted the importance of collective social factors for population health. One of the major challenges is an adequate definition of the spatial units of analysis which present properties potentially related to the target outcomes. Political and administrative divisions of urban areas are the most commonly used definition, although they suffer limitations in their ability to fully express the neighborhoods as social and spatial units. Objective This...
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Nicksic, Nicole E; Salahuddin, Meliha; Butte, Nancy F; Hoelscher, Deanna M
2018-05-01
A growing body of research has examined the relationship between perceived neighborhood safety and parental encouragement for child physical activity (PA), yet these potential predictors have not been studied together to predict child outdoor PA. The purpose of this study is to examine these predictors and parent- and child-reported child outdoor PA. The Texas Childhood Obesity Research Demonstration study collected data from fifth-grade students attending 31 elementary schools across Austin and Houston and their parents (N = 748 parent-child dyads). Mixed-effects linear and logistic regressions stratified by gender and adjusted for sociodemographic covariates assessed associations among parental-perceived neighborhood safety, parental encouragement for child's outdoor PA, and parent- and child-reported child's outdoor PA. Parental-perceived neighborhood safety was significantly associated with encouraging outdoor PA (P = .01) and child-reported child's outdoor PA in boys, but not in girls. Significant associations were found between parental encouragement and child-reported outdoor PA for girls (P < .05) and parent-reported outdoor PA (P < .01) for boys and girls. Parent encouragement of PA and neighborhood safety are potential predictors of child outdoor PA and could be targeted in youth PA interventions.
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Lu, Sha; Yin, Xiaoyan; Spollen, William; Zhang, Ning; Xu, Dong; Schoelz, James; Bilyeu, Kristin; Zhang, Zhanyuan J
2015-01-01
In the past decade, RNA silencing has gained significant attention because of its success in genomic scale research and also in the genetic improvement of crop plants. However, little is known about the molecular basis of siRNA processing in association with its target transcript. To reveal this process for improving hpRNA-mediated gene silencing in crop plants, the soybean GmFAD3 gene family was chosen as a test model. We analyzed RNAi mutant soybean lines in which three members of the GmFAD3 gene family were silenced. The silencing levels of FAD3A, FAD3B and FAD3C were correlated with the degrees of sequence homology between the inverted repeat of hpRNA and the GmFAD3 transcripts in the RNAi lines. Strikingly, transgenes in two of the three RNAi lines were heavily methylated, leading to a dramatic reduction of hpRNA-derived siRNAs. Small RNAs corresponding to the loop portion of the hairpin transcript were detected while much lower levels of siRNAs were found outside of the target region. siRNAs generated from the 318-bp inverted repeat were found to be diced much more frequently at stem sequences close to the loop and associated with the inferred cleavage sites on the target transcripts, manifesting "hot spots". The top candidate hpRNA-derived siRNA share certain sequence features with mature miRNA. This is the first comprehensive and detailed study revealing the siRNA-mediated gene silencing mechanism in crop plants using gene family GmFAD3 as a test model.
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Ancient Origin of the U2 Small Nuclear RNA Gene-Targeting Non-LTR Retrotransposons Utopia.
Kojima, Kenji K; Jurka, Jerzy
2015-01-01
Most non-long terminal repeat (non-LTR) retrotransposons encoding a restriction-like endonuclease show target-specific integration into repetitive sequences such as ribosomal RNA genes and microsatellites. However, only a few target-specific lineages of non-LTR retrotransposons are distributed widely and no lineage is found across the eukaryotic kingdoms. Here we report the most widely distributed lineage of target sequence-specific non-LTR retrotransposons, designated Utopia. Utopia is found in three supergroups of eukaryotes: Amoebozoa, SAR, and Opisthokonta. Utopia is inserted into a specific site of U2 small nuclear RNA genes with different strength of specificity for each family. Utopia families from oomycetes and wasps show strong target specificity while only a small number of Utopia copies from reptiles are flanked with U2 snRNA genes. Oomycete Utopia families contain an "archaeal" RNase H domain upstream of reverse transcriptase (RT), which likely originated from a plant RNase H gene. Analysis of Utopia from oomycetes indicates that multiple lineages of Utopia have been maintained inside of U2 genes with few copy numbers. Phylogenetic analysis of RT suggests the monophyly of Utopia, and it likely dates back to the early evolution of eukaryotes.
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2011-01-01
Background DNA transposons have emerged as indispensible tools for manipulating vertebrate genomes with applications ranging from insertional mutagenesis and transgenesis to gene therapy. To fully explore the potential of two highly active DNA transposons, piggyBac and Tol2, as mammalian genetic tools, we have conducted a side-by-side comparison of the two transposon systems in the same setting to evaluate their advantages and disadvantages for use in gene therapy and gene discovery. Results We have observed that (1) the Tol2 transposase (but not piggyBac) is highly sensitive to molecular engineering; (2) the piggyBac donor with only the 40 bp 3'-and 67 bp 5'-terminal repeat domain is sufficient for effective transposition; and (3) a small amount of piggyBac transposases results in robust transposition suggesting the piggyBac transpospase is highly active. Performing genome-wide target profiling on data sets obtained by retrieving chromosomal targeting sequences from individual clones, we have identified several piggyBac and Tol2 hotspots and observed that (4) piggyBac and Tol2 display a clear difference in targeting preferences in the human genome. Finally, we have observed that (5) only sites with a particular sequence context can be targeted by either piggyBac or Tol2. Conclusions The non-overlapping targeting preference of piggyBac and Tol2 makes them complementary research tools for manipulating mammalian genomes. PiggyBac is the most promising transposon-based vector system for achieving site-specific targeting of therapeutic genes due to the flexibility of its transposase for being molecularly engineered. Insights from this study will provide a basis for engineering piggyBac transposases to achieve site-specific therapeutic gene targeting. PMID:21447194
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MicroRNA-target gene responses to lead-induced stress in cotton (Gossypium hirsutum L.).
He, Qiuling; Zhu, Shuijin; Zhang, Baohong
2014-09-01
MicroRNAs (miRNAs) play key roles in plant responses to various metal stresses. To investigate the miRNA-mediated plant response to heavy metals, cotton (Gossypium hirsutum L.), the most important fiber crop in the world, was exposed to different concentrations (0, 25, 50, 100, and 200 µM) of lead (Pb) and then the toxicological effects were investigated. The expression patterns of 16 stress-responsive miRNAs and 10 target genes were monitored in cotton leaves and roots by quantitative real-time PCR (qRT-PCR); of these selected genes, several miRNAs and their target genes are involved in root development. The results show a reciprocal regulation of cotton response to lead stress by miRNAs. The characterization of the miRNAs and the associated target genes in response to lead exposure would help in defining the potential roles of miRNAs in plant adaptation to heavy metal stress and further understanding miRNA regulation in response to abiotic stress.
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Neighborhood Poverty and Nonmarital Fertility: Spatial and Temporal Dimensions
South, Scott J.; Crowder, Kyle
2010-01-01
Data from 4,855 respondents to the Panel Study of Income Dynamics were used to examine spatial and temporal dimensions of the effect of neighborhood poverty on teenage premarital childbearing. Although high poverty in the immediate neighborhood increased the risk of becoming an unmarried parent, high poverty in surrounding neighborhoods reduced…
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Gene Therapy Targeting HIV Entry
Directory of Open Access Journals (Sweden)
Chuka Didigu
2014-03-01
Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.
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Banks and the Racial Patterning of Homicide: A Study of Chicago Neighborhoods
Directory of Open Access Journals (Sweden)
María B. Veléz
2009-12-01
Full Text Available While bank investment is a driving force behind neighborhood viability, few studies have directly examined the effects of bank loan practices on neighborhood crime rates. This paper proposes that variation in residential bank loans helps explain the higher rates of homicide in minority neighborhoods in Chicago compared to white neighborhoods. It finds that black and Latino neighborhoods would experience fewer homicides if more financial capital were infused into these neighborhoods. These findings suggest that neighborhoods are shaped profoundly by the decisions of external economic actors.
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The sound of enemies and friends in the neighborhood.
Pecher, Diane; Boot, Inge; van Dantzig, Saskia; Madden, Carol J; Huber, David E; Zeelenberg, René
2011-01-01
Previous studies (e.g., Pecher, Zeelenberg, & Wagenmakers, 2005) found that semantic classification performance is better for target words with orthographic neighbors that are mostly from the same semantic class (e.g., living) compared to target words with orthographic neighbors that are mostly from the opposite semantic class (e.g., nonliving). In the present study we investigated the contribution of phonology to orthographic neighborhood effects by comparing effects of phonologically congruent orthographic neighbors (book-hook) to phonologically incongruent orthographic neighbors (sand-wand). The prior presentation of a semantically congruent word produced larger effects on subsequent animacy decisions when the previously presented word was a phonologically congruent neighbor than when it was a phonologically incongruent neighbor. In a second experiment, performance differences between target words with versus without semantically congruent orthographic neighbors were larger if the orthographic neighbors were also phonologically congruent. These results support models of visual word recognition that assume an important role for phonology in cascaded access to meaning.
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Gene targeting and cloning in pigs using fetal liver derived cells.
Waghmare, Sanjeev K; Estrada, Jose; Reyes, Luz; Li, Ping; Ivary, Bess; Sidner, Richard A; Burlak, Chris; Tector, A Joseph
2011-12-01
Since there are no pig embryonic stem cells, pig genetic engineering is done in fetal fibroblasts that remain totipotent for only 3 to 5 wk. Nuclear donor cells that remain totipotent for longer periods of time would facilitate complicated genetic engineering in pigs. The goal of this study was to test the feasibility of using fetal liver-derived cells (FLDC) to perform gene targeting, and create a genetic knockout pig. FLDC were isolated and processed using a human liver stem cell protocol. Single copy α-1,3-galactosyl transferase knockout (GTKO) FLDCs were created using electroporation and neomycin resistant colonies were screened using PCR. Homozygous GTKO cells were created through loss of heterozygosity mutations in single GTKO FLDCs. Double GTKO FLDCs were used in somatic cell nuclear transfer (SCNT) to create GTKO pigs. FLDCs grew for more than 80 population doublings, maintaining normal karyotype. Gene targeting and loss of heterozygosity mutations produced homozygous GTKO FLDCs. FLDCs used in SCNT gave rise to homozygous GTKO pigs. FDLCs can be used in gene targeting and SCNT to produce genetically modified pigs. The increased life span in culture compared to fetal fibroblasts may facilitate genetic engineering in the pig. Copyright © 2011 Elsevier Inc. All rights reserved.
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Honda, Arata; Hirose, Michiko; Sankai, Tadashi; Yasmin, Lubna; Yuzawa, Kazuaki; Honsho, Kimiko; Izu, Haruna; Iguchi, Atsushi; Ikawa, Masahito; Ogura, Atsuo
2015-01-01
Targeted genome editing of nonrodent mammalian species has provided the potential for highly accurate interventions into gene function in humans and the generation of useful animal models of human diseases. Here we show successful clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated (Cas)-mediated gene targeting via circular plasmid injection in rabbits. The rabbit tyrosinase gene (TYR) was effectively disrupted, and we confirmed germline transmission by pronuclear injection of a circular plasmid expressing humanized Cas9 (hCas9) and single-guide RNA. Direct injection into pronuclear stage zygotes was possible following an in vitro validation assay. Neither off-target mutagenesis nor hCas9 transgenesis was detected in any of the genetically targeted pups and embryos examined. Gene targeting with this rapid and simplified strategy will help accelerate the development of translational research using other nonrodent mammalian species.
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Ovcharenko, Aleksandr
2012-03-01
This paper introduces a general-purpose communication package built on top of MPI which is aimed at improving inter-processor communications independently of the supercomputer architecture being considered. The package is developed to support parallel applications that rely on computation characterized by large number of messages of various sizes, often small, that are focused within processor neighborhoods. In some cases, such as solvers having static mesh partitions, the number and size of messages are known a priori. However, in other cases such as mesh adaptation, the messages evolve and vary in number and size and include the dynamic movement of partition objects. The current package provides a utility for dynamic applications based on two key attributes that are: (i) explicit consideration of the neighborhood communication pattern to avoid many-to-many calls and also to reduce the number of collective calls to a minimum, and (ii) use of non-blocking MPI functions along with message packing to manage message flow control and reduce the number and time of communication calls. The test application demonstrated is parallel unstructured mesh adaptation. Results on IBM Blue Gene/P and Cray XE6 computers show that the use of neighborhood-based communication control leads to scalable results when executing generally imbalanced mesh adaptation runs. © 2011 Elsevier B.V. All rights reserved.
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Vitamin D Pathway Status and the Identification of Target Genes in the Mouse Mammary Gland
2014-11-01
breast cancer stem cells with oncolytic herpes simplex virus. Cancer Gene Therapy 2012;19(10):707-14. June 21, 2012 – Poster Presentation – Presented...AD_________________ Award Number: W81XWH-11-1-0152 TITLE: Vitamin D Pathway Status and the Identification of Target Genes in the Mouse Mammary... Identification of Target Genes in the 5b. GRANT NUMBER W81XWH-11-1-0152 Mouse Mammary Gland 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT
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Ma, Julie; Grogan-Kaylor, Andrew; Lee, Shawna J
2018-02-01
This study employed fixed effects regression that controls for selection bias, omitted variables bias, and all time-invariant aspects of parent and child characteristics to examine the simultaneous associations between neighborhood disorganization, maternal spanking, and aggressive behavior in early childhood using data from the Fragile Families and Child Wellbeing Study (FFCWS). Analysis was based on 2,472 children and their mothers who participated in Wave 3 (2001-2003; child age 3) and Wave 4 (2003-2006; child age 5) of the FFCWS. Results indicated that higher rates of neighborhood crime and violence predicted higher levels of child aggression. Maternal spanking in the past year, whether frequent or infrequent, was also associated with increases in aggressive behavior. This study contributes statistically rigorous evidence that exposure to violence in the neighborhood as well as the family context are predictors of child aggression. We conclude with a discussion for the need for multilevel prevention and intervention approaches that target both community and parenting factors. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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The MSX1 homeoprotein recruits G9a methyltransferase to repressed target genes in myoblast cells.
Directory of Open Access Journals (Sweden)
Jingqiang Wang
Full Text Available Although the significance of lysine modifications of core histones for regulating gene expression is widely appreciated, the mechanisms by which these modifications are incorporated at specific regulatory elements during cellular differentiation remains largely unknown. In our previous studies, we have shown that in developing myoblasts the Msx1 homeoprotein represses gene expression by influencing the modification status of chromatin at its target genes. We now show that genomic binding by Msx1 promotes enrichment of the H3K9me2 mark on repressed target genes via recruitment of G9a histone methyltransferase, the enzyme responsible for catalyzing this histone mark. Interaction of Msx1 with G9a is mediated via the homeodomain and is required for transcriptional repression and regulation of cellular differentiation, as well as enrichment of the H3K9me2 mark in proximity to Msx1 binding sites on repressed target genes in myoblast cells as well as the developing limb. We propose that regulation of chromatin status by Msx1 recruitment of G9a and other histone modifying enzymes to regulatory regions of target genes represents an important means of regulating the gene expression during development.
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Identification of the human ApoAV gene as a novel RORα target gene
International Nuclear Information System (INIS)
Lind, Ulrika; Nilsson, Tina; McPheat, Jane; Stroemstedt, Per-Erik; Bamberg, Krister; Balendran, Clare; Kang, Daiwu
2005-01-01
Retinoic acid receptor-related orphan receptor-α (RORα) (NR1F1) is an orphan nuclear receptor with a potential role in metabolism. Previous studies have shown that RORα regulates transcription of the murine Apolipoprotein AI gene and human Apolipoprotein CIII genes. In the present study, we present evidence that RORα also induces transcription of the human Apolipoprotein AV gene, a recently identified apolipoprotein associated with triglyceride levels. Adenovirus-mediated overexpression of RORα increased the endogenous expression of ApoAV in HepG2 cells and RORα also enhanced the activity of an ApoAV promoter construct in transiently transfected HepG2 cells. Deletion and mutation studies identified three AGGTCA motifs in the ApoAV promoter that mediate RORα transactivation, one of which overlaps with a previously identified binding site for PPARα. Together, these results suggest a novel mechanism whereby RORα modulates lipid metabolism and implies RORα as a potential target for the treatment of dyslipidemia and atherosclerosis
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HisB as novel selection marker for gene targeting approaches in Aspergillus niger.
Fiedler, Markus R M; Gensheimer, Tarek; Kubisch, Christin; Meyer, Vera
2017-03-08
For Aspergillus niger, a broad set of auxotrophic and dominant resistance markers is available. However, only few offer targeted modification of a gene of interest into or at a genomic locus of choice, which hampers functional genomics studies. We thus aimed to extend the available set by generating a histidine auxotrophic strain with a characterized hisB locus for targeted gene integration and deletion in A. niger. A histidine-auxotrophic strain was established via disruption of the A. niger hisB gene by using the counterselectable pyrG marker. After curing, a hisB - , pyrG - strain was obtained, which served as recipient strain for further studies. We show here that both hisB orthologs from A. nidulans and A. niger can be used to reestablish histidine prototrophy in this recipient strain. Whereas the hisB gene from A. nidulans was suitable for efficient gene targeting at different loci in A. niger, the hisB gene from A. niger allowed efficient integration of a Tet-on driven luciferase reporter construct at the endogenous non-functional hisB locus. Subsequent analysis of the luciferase activity revealed that the hisB locus is tight under non-inducing conditions and allows even higher luciferase expression levels compared to the pyrG integration locus. Taken together, we provide here an alternative selection marker for A. niger, hisB, which allows efficient homologous integration rates as well as high expression levels which compare favorably to the well-established pyrG selection marker.
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Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci
DEFF Research Database (Denmark)
Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan
2017-01-01
BACKGROUND: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors...... (TFs) critical to somatic tumorigenesis. METHODS: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery...... to interact with PAX8 in the literature to the PAX8-target set and applying an alternative to GSEA, interval enrichment, further confirmed this association (P=0.006). Fifteen of the 157 genes from this expanded PAX8 pathway were near eight loci associated with SOC risk at P
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Community Gardening, Neighborhood Meetings, and Social Capital
Alaimo, Katherine; Reischl, Thomas M.; Allen, Julie Ober
2010-01-01
This study examined associations between participation in community gardening/beautification projects and neighborhood meetings with perceptions of social capital at both the individual and neighborhood levels. Data were analyzed from a cross-sectional stratified random telephone survey conducted in Flint, Michigan (N=1916). Hierarchical linear…
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Lee, Joseph G L; Baker, Hannah M; Ranney, Leah M; Goldstein, Adam O
2015-10-08
Retailer noncompliance with limited US tobacco regulations on advertising and labeling was historically patterned by neighborhood in ways that promote health disparities. In 2010, the US Food and Drug Administration (FDA) began enforcing stronger tobacco retailer regulations under the Family Smoking Prevention and Tobacco Control Act of 2009. However, recent research has found no differences in compliance by neighborhood characteristics for FDA advertising and labeling inspections. We sought to investigate the neighborhood characteristics associated with retailer noncompliance with specific FDA advertising and labeling inspections (ie, violations of bans on self-service displays, selling single cigarettes, false or mislabeled products, vending machines, flavored cigarettes, and free samples). We coded FDA advertising and labeling warning letters (n = 718) for type of violations and geocoded advertising and labeling inspections from January 1 through July 31, 2014 (N = 33,543). Using multilevel models, we examined cross-sectional associations between types of violations and neighborhood characteristics previously associated with disparities (ie, percentage black, Latino, under the poverty line, and younger than 18 years). Retailer advertising and labeling violations are patterned by who lives in the neighborhood; regulated tobacco products are more likely to be stored behind the counter as the percentage of black or Latino residents increases, and single cigarettes are more often available for purchase in neighborhoods as the percentage of black, poor, or young residents increases. Contrary to previous null findings, noncompliance with FDA advertising and labeling regulations is patterned by neighborhood characteristics, sometimes in opposite directions. Given the low likelihood of self-service violations in the same neighborhoods that have high likelihood of single cigarette sales, we suggest targeted approaches to FDA retailer inspections and education campaigns.
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Caceres, Alan Joseph J; Castillo, Juan; Lee, Jinnie; St John, Katherine
2013-01-01
A nearest-neighbor-interchange (NNI)-walk is a sequence of unrooted phylogenetic trees, T1, T2, . . . , T(k) where each consecutive pair of trees differs by a single NNI move. We give tight bounds on the length of the shortest NNI-walks that visit all trees in a subtree-prune-and-regraft (SPR) neighborhood of a given tree. For any unrooted, binary tree, T, on n leaves, the shortest walk takes Θ(n²) additional steps more than the number of trees in the SPR neighborhood. This answers Bryant’s Second Combinatorial Challenge from the Phylogenetics Challenges List, the Isaac Newton Institute, 2011, and the Penny Ante Problem List, 2009.
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Can neighborhoods explain racial/ethnic differences in adolescent inactivity?
Richmond, Tracy K; Field, Alison E; Rich, Michael
2007-01-01
To determine if neighborhoods and their attributes contribute to racial/ethnic disparities in adolescent inactivity. We undertook a cross-sectional analysis of the National Longitudinal Study of Adolescent Health (n = 17,007), a nationally representative school-based study in the United States. Stratifying by gender, we used multivariate linear regression and multi-level modeling to determine whether neighborhood of residence may partially explain racial/ethnic disparities in adolescent physical inactivity, defined as hours viewing television or videos/DVDs and/or playing computer/video games each week. Participants lived in largely segregated communities. Black and Hispanic adolescent girls reported higher levels of inactivity than White adolescent girls (21 vs. 15 vs. 13 hours/week, respectively, p violent crime in the neighborhood was associated with inactivity, despite the individual's perception of his/her neighborhood as safe not being predictive. Although inactivity varies by race/ethnicity and gender, only in Hispanic adolescent girls does neighborhood fully explain the differential use. Our findings suggest that approaches other than changing neighborhood characteristics are needed to eliminate racial/ethnic disparities in adolescent inactivity.
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SVMRFE based approach for prediction of most discriminatory gene target for type II diabetes
Directory of Open Access Journals (Sweden)
Atul Kumar
2017-06-01
Full Text Available Type II diabetes is a chronic condition that affects the way our body metabolizes sugar. The body's important source of fuel is now becoming a chronic disease all over the world. It is now very necessary to identify the new potential targets for the drugs which not only control the disease but also can treat it. Support vector machines are the classifier which has a potential to make a classification of the discriminatory genes and non-discriminatory genes. SVMRFE a modification of SVM ranks the genes based on their discriminatory power and eliminate the genes which are not involved in causing the disease. A gene regulatory network has been formed with the top ranked coding genes to identify their role in causing diabetes. To further validate the results pathway study was performed to identify the involvement of the coding genes in type II diabetes. The genes obtained from this study showed a significant involvement in causing the disease, which may be used as a potential drug target.
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Fast and sensitive detection of indels induced by precise gene targeting
DEFF Research Database (Denmark)
Yang, Zhang; Steentoft, Catharina; Hauge, Camilla
2015-01-01
The nuclease-based gene editing tools are rapidly transforming capabilities for altering the genome of cells and organisms with great precision and in high throughput studies. A major limitation in application of precise gene editing lies in lack of sensitive and fast methods to detect...... and characterize the induced DNA changes. Precise gene editing induces double-stranded DNA breaks that are repaired by error-prone non-homologous end joining leading to introduction of insertions and deletions (indels) at the target site. These indels are often small and difficult and laborious to detect...
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Energy Technology Data Exchange (ETDEWEB)
Ueda, Kohei [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Fujiki, Katsunori; Shirahige, Katsuhiko [Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo (Japan); Gomez-Sanchez, Celso E. [Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, MS (United States); Endocrinology, University of Mississippi Medical Center, MS (United States); Fujita, Toshiro [Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo (Japan); Nangaku, Masaomi [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Nagase, Miki, E-mail: mnagase-tky@umin.ac.jp [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Department of Anatomy and Life Structure, School of Medicine Juntendo University, Tokyo (Japan)
2014-02-28
Highlights: • We define a target gene of MR as that with MR-binding to the adjacent region of DNA. • We use ChIP-seq analysis in combination with microarray. • We, for the first time, explore the genome-wide binding profile of MR. • We reveal 5 genes as the direct target genes of MR in the renal epithelial cell-line. - Abstract: Background and objective: Mineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). Methods: We analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10{sup −7} M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10{sup −7} M aldosterone for 3 h by microarray. Results: 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10{sup −9} M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. Conclusions: We, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases.
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The neighborhood environment and obesity: Understanding variation by race/ethnicity.
Wong, Michelle S; Chan, Kitty S; Jones-Smith, Jessica C; Colantuoni, Elizabeth; Thorpe, Roland J; Bleich, Sara N
2018-06-01
Neighborhood characteristics have been associated with obesity, but less is known whether relationships vary by race/ethnicity. This study examined the relationship between soda consumption - a behavior strongly associated with obesity - and weight status with neighborhood sociodemographic, social, and built environments by race/ethnicity. We merged data on adults from the 2011-2013 California Health Interview Survey, U.S. Census data, and InfoUSA (n=62,396). Dependent variables were soda consumption and weight status outcomes (body mass index and obesity status). Main independent variables were measures of three neighborhood environments: social (social cohesion and safety), sociodemographic (neighborhood socioeconomic status, educational attainment, percent Asian, percent Hispanic, and percent black), and built environments (number of grocery stores, convenience stores, fast food restaurants, and gyms in neighborhood). We fit multi-level linear and logistic regression models, stratified by individual race/ethnicity (NH (non-Hispanic) Whites, NH African Americans, Hispanics, and NH Asians) controlling for individual-level characteristics, to estimate neighborhood contextual effects on study outcomes. Lower neighborhood educational attainment was associated with higher odds of obesity and soda consumption in all racial/ethnic groups. We found fewer associations between study outcomes and the neighborhood, especially the built environment, among NH African Americans and NH Asians. While improvements to neighborhood environment may be promising to reduce obesity, null associations among minority subgroups suggest that changes, particularly to the built environment, may alone be insufficient to address obesity in these groups. Published by Elsevier Inc.
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Neighborhood-level social processes and substantiated cases of child maltreatment.
Molnar, Beth E; Goerge, Robert M; Gilsanz, Paola; Hill, Andrea; Subramanian, S V; Holton, John K; Duncan, Dustin T; Beatriz, Elizabeth D; Beardslee, William R
2016-01-01
Child maltreatment is a preventable public health problem. Research has demonstrated that neighborhood structural factors (e.g. poverty, crime) can influence the proportion of a neighborhood's children who are victims of maltreatment. A newer strategy is the identification of potentially modifiable social processes at the neighborhood level that can also influence maltreatment. Toward this end, this study examines neighborhood-level data (maltreatment cases substantiated by Illinois' child protection agency, 1995-2005, social processes measured by the Project on Human Development in Chicago Neighborhoods, U.S. Census data, proportions of neighborhoods on public assistance, and crime data) that were linked across clusters of contiguous, relatively homogenous Chicago, IL census tracts with respect to racial/ethnic and socioeconomic composition. Our analysis-an ecological-level, repeated cross-sectional design utilizing random-intercept logit models-with a sensitivity analysis using spatial models to control for spatial autocorrelation-revealed consistent associations between neighborhood social processes and maltreatment. Neighborhoods higher in collective efficacy, intergenerational closure, and social networks, and lower in disorder had lower proportions of neglect, physical abuse, and sexual abuse substantiated cases, controlling for differences in structural factors. Higher collective efficacy and social network size also predicted a lower proportion of substance-exposed infants. This research indicates that strategies to mobilize neighborhood-level protective factors may decrease child maltreatment more effectively than individual and family-focused efforts alone. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Spatial dimensions of the effect of neighborhood disadvantage on delinquency
Vogel, M.S.; South, S.J.
2016-01-01
esearch examining the relationship between neighborhood socioeconomic disadvantage and adolescent offending typically examines only the influence of residential neighborhoods. This strategy may be problematic as 1) neighborhoods are rarely spatially independent of each other and 2) adolescents spend
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Effect of Chemical Prevention Drugs-based MicroRNAs and Their Target Genes on Tumor Inhibition
Directory of Open Access Journals (Sweden)
Yanhui JIANG
2015-04-01
Full Text Available Chemopreventive drugs including natural chemopreventive drugs and synthetic chemopreventive drugs, it not only can prevent cancer, can also play a role in tumor treatment. MicroRNAs (miRNAs is a kind of short chains of non-coding RNA, regulating the expression of many genes through the way of degradation of mRNA or inhibitting mRNA translation. In recent years, more and more studies have shown that chemopreventive drugs through influence the expression of miRNAs and their target genes play a role in the prevention and treatment in a variety of tumors, and chemopreventive drugs on the experimental study of miRNAs and their target genes in tumor have demonstrated a good safety and efficacy. Effect on chemopreventive drugs-based microRNAs and their target genes into cancer cells will be expected as a new starting point for cancer research. The thesis expounds and analyzes between the natural chemopreventive drugs and synthetic chemopreventive drugs and miRNAs and their target genes in tumor research progress.
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Efficient and Heritable Gene Targeting in Tilapia by CRISPR/Cas9
Li, Minghui; Yang, Huihui; Zhao, Jiue; Fang, Lingling; Shi, Hongjuan; Li, Mengru; Sun, Yunlv; Zhang, Xianbo; Jiang, Dongneng; Zhou, Linyan; Wang, Deshou
2014-01-01
Studies of gene function in non-model animals have been limited by the approaches available for eliminating gene function. The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated) system has recently become a powerful tool for targeted genome editing. Here, we report the use of the CRISPR/Cas9 system to disrupt selected genes, including nanos2, nanos3, dmrt1, and foxl2, with efficiencies as high as 95%. In addition, mutations in dmrt1 and foxl2 induced by CRISPR/Cas9 were efficiently transmitted through the germline to F1. Obvious phenotypes were observed in the G0 generation after mutation of germ cell or somatic cell-specific genes. For example, loss of Nanos2 and Nanos3 in XY and XX fish resulted in germ cell-deficient gonads as demonstrated by GFP labeling and Vasa staining, respectively, while masculinization of somatic cells in both XY and XX gonads was demonstrated by Dmrt1 and Cyp11b2 immunohistochemistry and by up-regulation of serum androgen levels. Our data demonstrate that targeted, heritable gene editing can be achieved in tilapia, providing a convenient and effective approach for generating loss-of-function mutants. Furthermore, our study shows the utility of the CRISPR/Cas9 system for genetic engineering in non-model species like tilapia and potentially in many other teleost species. PMID:24709635
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International Nuclear Information System (INIS)
Tian Ju; Wang Zhigang; Ren Jianli; Zhang Qingfeng; Liu Li
2012-01-01
Objective: To prepare an anti-P-selectin targeted ultrasound contrast agent carrying genes and cell-penetrating peptides (CPP) and to investigate its feasibility of delivery to hypoxic human umbilical vein endothelial cells (HUVEC). Methods: Anti-P-selectin targeted ultrasound contrast agent carrying a green fluorescent protein gene (pEGFP-N1) and CPP was prepared by mechanical vibration and carbodiimide techniques. The appearance, distribution, concentration and diameter of the ultrasound contrast agent were measured. The gene and CPP distribution on the agent was investigated using confocal laser scanning microscopy (CLSM). The efficiency of the ultrasound contrast agent to carry the gene and CPP was investigated by fluorospectrophotometry. HUVEC were cultured in vitro and hypoxic HUVEC were prepared using hydrogen peroxide (H 2 O 2 ). Hypoxic HUVEC were randomly assigned targeted ultrasound contrast agents and non-targeted ultrasound contrast agents for transfection. The transfection effect of green fluorescent protein in the two groups was observed using fluorescence microscopy and flow cytometry. T-test and linear correlation analysis were used for statistical analysis. Results: The average diameter of anti-P-selectin targeted ultrasound contrast agents carrying gene and CPP was (2.15 ±0.36) μm and the concentration was (1.58 ± 0.23) × 10 7 /ml.The results of CLSM showed that gene and CPP were distributed on the shell of the agent. The gene encapsulation efficiency was 28% (y=0.932x-0.09, r=0.993, P<0.05), and the CPP encapsulation efficiency was 25% (y=5.875x-0.81, r=0.987, P<0.05). EGFP expression was observed using fluorescence microscopy in targeted ultrasound contrast agents and non-targeted ultrasound contrast agents. The average transfection efficiencies of targeted ultrasound contrast agents and non-targeted ultrasound contrast agents were (18.74 ± 0.47) % and (15.34 ± 0.22) % after 24 h (t=10.923, P<0.001). Conclusions: The in vitro studies
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Directory of Open Access Journals (Sweden)
Jonathan A Scolnick
Full Text Available Fusion genes are known to be key drivers of tumor growth in several types of cancer. Traditionally, detecting fusion genes has been a difficult task based on fluorescent in situ hybridization to detect chromosomal abnormalities. More recently, RNA sequencing has enabled an increased pace of fusion gene identification. However, RNA-Seq is inefficient for the identification of fusion genes due to the high number of sequencing reads needed to detect the small number of fusion transcripts present in cells of interest. Here we describe a method, Single Primer Enrichment Technology (SPET, for targeted RNA sequencing that is customizable to any target genes, is simple to use, and efficiently detects gene fusions. Using SPET to target 5701 exons of 401 known cancer fusion genes for sequencing, we were able to identify known and previously unreported gene fusions from both fresh-frozen and formalin-fixed paraffin-embedded (FFPE tissue RNA in both normal tissue and cancer cells.
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Research Progresses of Halo Streams in the Solar Neighborhood
Xi-long, Liang; Jing-kun, Zhao; Yu-qin, Chen; Gang, Zhao
2018-01-01
The stellar streams originated from the Galactic halo may be detected when they pass by the solar neighborhood, and they still keep some information at their birth times. Thus, the investigation of halo streams in the solar neighborhood is very important for understanding the formation and evolution of our Galaxy. In this paper, the researches of halo streams in the solar neighborhood are briefly reviewed. We have introduced the methods how to detect the halo streams and identify their member stars, summarized the progresses in the observation of member stars of halo streams and in the study of their origins, introduced in detail how to analyze the origins of halo streams in the solar neighborhood by means of numerical simulation and chemical abundance, and finally discussed the prospects of the LAMOST and GAIA in the research of halo streams in the solar neighborhood.
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Directory of Open Access Journals (Sweden)
Sha Lu
Full Text Available In the past decade, RNA silencing has gained significant attention because of its success in genomic scale research and also in the genetic improvement of crop plants. However, little is known about the molecular basis of siRNA processing in association with its target transcript. To reveal this process for improving hpRNA-mediated gene silencing in crop plants, the soybean GmFAD3 gene family was chosen as a test model. We analyzed RNAi mutant soybean lines in which three members of the GmFAD3 gene family were silenced. The silencing levels of FAD3A, FAD3B and FAD3C were correlated with the degrees of sequence homology between the inverted repeat of hpRNA and the GmFAD3 transcripts in the RNAi lines. Strikingly, transgenes in two of the three RNAi lines were heavily methylated, leading to a dramatic reduction of hpRNA-derived siRNAs. Small RNAs corresponding to the loop portion of the hairpin transcript were detected while much lower levels of siRNAs were found outside of the target region. siRNAs generated from the 318-bp inverted repeat were found to be diced much more frequently at stem sequences close to the loop and associated with the inferred cleavage sites on the target transcripts, manifesting "hot spots". The top candidate hpRNA-derived siRNA share certain sequence features with mature miRNA. This is the first comprehensive and detailed study revealing the siRNA-mediated gene silencing mechanism in crop plants using gene family GmFAD3 as a test model.
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Xu, Huo; Jiang, Yifan; Liu, Dengyou; Liu, Kai; Zhang, Yafeng; Yu, Suhong; Shen, Zhifa; Wu, Zai-Sheng
2018-06-29
The sensitive detection of cancer-related genes is of great significance for early diagnosis and treatment of human cancers, and previous isothermal amplification sensing systems were often based on the reuse of target DNA, the amplification of enzymatic products and the accumulation of reporting probes. However, no reporting probes are able to be transformed into target species and in turn initiate the signal of other probes. Herein we reported a simple, isothermal and highly sensitive homogeneous assay system for tumor suppressor p53 gene detection based on a new autonomous DNA machine, where the signaling probe, molecular beacon (MB), was able to execute the function similar to target DNA besides providing the common signal. In the presence of target p53 gene, the operation of DNA machine can be initiated, and cyclical nucleic acid strand-displacement polymerization (CNDP) and nicking/polymerization cyclical amplification (NPCA) occur, during which the MB was opened by target species and cleaved by restriction endonuclease. In turn, the cleaved fragments could activate the next signaling process as target DNA did. According to the functional similarity, the cleaved fragment was called twin target, and the corresponding fashion to amplify the signal was named twin target self-amplification. Utilizing this newly-proposed DNA machine, the target DNA could be detected down to 0.1 pM with a wide dynamic range (6 orders of magnitude) and single-base mismatched targets were discriminated, indicating a very high assay sensitivity and good specificity. In addition, the DNA machine was not only used to screen the p53 gene in complex biological matrix but also was capable of practically detecting genomic DNA p53 extracted from A549 cell line. This indicates that the proposed DNA machine holds the potential application in biomedical research and early clinical diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.
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Byck, Gayle R; Bolland, John; Dick, Danielle; Swann, Gregory; Henry, David; Mustanski, Brian
2015-11-01
This study examined whether relocating from a high-poverty neighborhood to a lower poverty neighborhood as part of a federal housing relocation program (HOPE VI; Housing Opportunities for People Everywhere) had effects on adolescent mental and behavioral health compared to adolescents consistently living in lower poverty neighborhoods. Sociodemographic, risk behavior, and neighborhood data were collected from 592 low-income, primarily African-American adolescents and their primary caregivers. Structured psychiatric interviews were conducted with adolescents. Prerelocation neighborhood, demographic, and risk behavior data were also included. Hierarchical Linear Modeling (HLM) was used to test associations between neighborhood variables and risk outcomes. HLM was used to test whether the effect of neighborhood relocation and neighborhood characteristics might explain differences in sexual risk taking, substance use, and mental health outcomes. Adolescents who relocated of HOPE VI neighborhoods (n = 158) fared worse than control group participants (n = 429) on most self-reported mental health outcomes. The addition of subjective neighborhood measures generally did not substantively change these results. Our findings suggest that moving from a high-poverty neighborhood to a somewhat lower poverty neighborhood is not associated with better mental health and risk behavior outcomes in adolescents. The continued effects of having grown up in a high-poverty neighborhood, the small improvements in their new neighborhoods, the comparatively short length of time they lived in their new neighborhood, and/or the stress of moving appears to worsen most of the mental health outcomes of HOPE VI compared to control group participants who consistently lived in the lower poverty neighborhoods. © 2015 Association for Child and Adolescent Mental Health.
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Yang, Yong; Jiang, Yu; Xu, Yanqing; Mzayek, Fawaz; Levy, Marian
2018-03-01
To examine the influence of neighborhood environment on childhood overweight and obesity in Shelby County Schools, Tennessee, and whether and to what extent that influence varies by age, gender, and the specific environment characteristics. 41,283 students were surveyed covering both individual-level covariates and several objective measures of neighborhood environment. Multilevel logistic regressions were used to examine the influence of neighborhood-level variables on overweight+obesity and obesity with adjustment of individual-level covariates. Further, a stratified analysis for each of the six groups by school level and gender. For both overweight+obesity and obesity, younger children were less sensitive to neighborhood characteristics than older children, and boys are less sensitive than girls. For girls in middle and high schools, the risk of overweight+obesity and obesity were positively associated with population density, and negatively associated with percent of poverty and percent of unhealthy food. Boys' risk of overweight+obesity and obesity were positively associated with distance to park. Neighborhood environment plays an important role in childhood overweight and obesity, and the effects vary by age, gender, and the specific neighborhood characteristic. Intervention programs tailored to specific groups may be more effective than ones targeted to children as a whole. Copyright © 2018 Elsevier Inc. All rights reserved.
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Association between neighborhood safety and overweight status among urban adolescents
Directory of Open Access Journals (Sweden)
Johnson Renee M
2009-08-01
Full Text Available Abstract Background Neighborhood safety may be an important social environmental determinant of overweight. We examined the relationship between perceived neighborhood safety and overweight status, and assessed the validity of reported neighborhood safety among a representative community sample of urban adolescents (who were racially and ethnically diverse. Methods Data come from the 2006 Boston Youth Survey, a cross-sectional study in which public high school students in Boston, MA completed a pencil-and-paper survey. The study used a two-stage, stratified sampling design whereby schools and then 9th–12th grade classrooms within schools were selected (the analytic sample included 1,140 students. Students reported their perceptions of neighborhood safety and several associated dimensions. With self-reported height and weight data, we computed body mass index (BMI, kg/m2 for the adolescents based on CDC growth charts. Chi-square statistics and corresponding p-values were computed to compare perceived neighborhood safety by the several associated dimensions. Prevalence ratios (PRs and 95% confidence intervals (CI were calculated to examine the association between perceived neighborhood safety and the prevalence of overweight status controlling for relevant covariates and school site. Results More than one-third (35.6% of students said they always felt safe in their neighborhood, 43.9% said they sometimes felt safe, 11.6% rarely felt safe, and 8.9% never felt safe. Those students who reported that they rarely or never feel safe in their neighborhoods were more likely than those who said they always or sometimes feel safe to believe that gang violence was a serious problem in their neighborhood or school (68.0% vs. 44.1%, p p = 0.025. In the fully adjusted model (including grade and school stratified by race/ethnicity, we found a statistically significant association between feeling unsafe in one's own neighborhood and overweight status among
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Race, Neighborhood Economic Status, Income Inequality and Mortality.
Directory of Open Access Journals (Sweden)
Nicolle A Mode
Full Text Available Mortality rates in the United States vary based on race, individual economic status and neighborhood. Correlations among these variables in most urban areas have limited what conclusions can be drawn from existing research. Our study employs a unique factorial design of race, sex, age and individual poverty status, measuring time to death as an objective measure of health, and including both neighborhood economic status and income inequality for a sample of middle-aged urban-dwelling adults (N = 3675. At enrollment, African American and White participants lived in 46 unique census tracts in Baltimore, Maryland, which varied in neighborhood economic status and degree of income inequality. A Cox regression model for 9-year mortality identified a three-way interaction among sex, race and individual poverty status (p = 0.03, with African American men living below poverty having the highest mortality. Neighborhood economic status, whether measured by a composite index or simply median household income, was negatively associated with overall mortality (p<0.001. Neighborhood income inequality was associated with mortality through an interaction with individual poverty status (p = 0.04. While racial and economic disparities in mortality are well known, this study suggests that several social conditions associated with health may unequally affect African American men in poverty in the United States. Beyond these individual factors are the influences of neighborhood economic status and income inequality, which may be affected by a history of residential segregation. The significant association of neighborhood economic status and income inequality with mortality beyond the synergistic combination of sex, race and individual poverty status suggests the long-term importance of small area influence on overall mortality.
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Walking to Work: The Roles of Neighborhood Walkability and Socioeconomic Deprivation.
Kelly, Cheryl M; Lian, Min; Struthers, Jim; Kammrath, Anna
2015-06-16
There are few studies that aimed to find a relationship between transportation-related physical activity and neighborhood socioeconomic condition using a composite deprivation index. The purpose of this study is to assess the relationship of neighborhood walkability and socioeconomic deprivation with percentage of adults walking to work. A walkability index and a socioeconomic deprivation index were created at block group-level. The outcome variable, percentage of adults who walk to work was dichotomized as walkability and socioeconomic deprivation with walking to work. Individuals in the most walkable neighborhoods are almost 5 times more likely to walk to work than individuals in the least walkable neighborhoods (OR = 4.90, 95% CI = 2.80-8.59). After adjusting for neighborhood socioeconomic deprivation, individuals in the most walkable neighborhoods are almost 3 times more likely to walk to work than individuals in the least walkable neighborhoods (OR = 2.98, 95% CI = 1.62-5.49). Walkability (as measured by the walkability index) is a very strong indicator of walking to work even after controlling for neighborhood socioeconomic disadvantage.
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CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy.
Chen, Shuliang; Yu, Xiao; Guo, Deyin
2018-01-16
Currently, a new gene editing tool-the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system-is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy.
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Barvkar, Vitthal T; Pardeshi, Varsha C; Kale, Sandip M; Qiu, Shuqing; Rollins, Meaghen; Datla, Raju; Gupta, Vidya S; Kadoo, Narendra Y
2013-04-01
MicroRNAs (miRNAs) are small (20-24 nucleotide long) endogenous regulatory RNAs that play important roles in plant growth and development. They regulate gene expression at the post-transcriptional level by translational repression or target degradation and gene silencing. In this study, we identified 116 conserved miRNAs belonging to 23 families from the flax (Linum usitatissimum L.) genome using a computational approach. The precursor miRNAs varied in length; while most of the mature miRNAs were 21 nucleotide long, intergenic and showed conserved signatures of RNA polymerase II transcripts in their upstream regions. Promoter region analysis of the flax miRNA genes indicated prevalence of MYB transcription factor binding sites. Four miRNA gene clusters containing members of three phylogenetic groups were identified. Further, 142 target genes were predicted for these miRNAs and most of these represent transcriptional regulators. The miRNA encoding genes were expressed in diverse tissues as determined by digital expression analysis as well as real-time PCR. The expression of fourteen miRNAs and nine target genes was independently validated using the quantitative reverse transcription PCR (qRT-PCR). This study suggests that a large number of conserved plant miRNAs are also found in flax and these may play important roles in growth and development of flax.
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Does Race Matter in Neighborhood Preferences? Results from a Video Experiment
Krysan, Maria; Couper, Mick P.; Farley, Reynolds; Forman, Tyrone
2013-01-01
Persistent racial residential segregation is often seen as the result of the preferences of whites and blacks: whites prefer to live with whites while blacks wish to live near many other blacks. The origin of these preferences and their social psychological underpinnings are hotly debated. Are neighborhood preferences colorblind or race-conscious? Does neighborhood racial composition have a net influence upon preferences or is race a proxy for social class? If preferences are race-conscious, is this more a matter of a desire to be in a neighborhood with one’s “own kind” or to avoid being in a neighborhood with another racial group? We tested the racial proxy hypothesis using an innovative experiment that isolated the net effects of race and social class and followed it with an analysis of the social psychological factors associated with residential preferences. Face-to-face surveys using computer assisted interviewing were conducted with random samples of Detroit and Chicago residents. Respondents were asked how desirable they would rate neighborhoods shown in videos in which racial composition and social class characteristics were manipulated and they also completed—via computer assisted self-interviews—questions tapping into perceptions of discrimination, racial and neighborhood stereotypes, and in-group identity. We find that net of social class, the race of a neighborhood's residents significantly influenced how it was rated. Whites said the all-white neighborhoods were most desirable. The independent effect of racial composition was smaller among blacks and blacks identified the racially mixed neighborhood as most desirable. Hypotheses about how racial group identity, stereotypes, and experiences of discrimination influenced the effect of race of residents upon neighborhood preferences were tested and show that for whites, those who hold negative stereotypes about African Americans and the neighborhoods where they live are significantly influenced by
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A Novel PCR Assay for Listeria welshimeri Targeting Transcriptional Regulator Gene lwe1801
Transcriptional regulator genes encode a group of specialized molecules that play essential roles in microbial responses to changing external conditions. These genes have been shown to possess species or group specificity and are useful as detection targets for diagnostic application. The present st...
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Directory of Open Access Journals (Sweden)
Feixiong Cheng
2016-09-01
Full Text Available Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase. Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline that may be potential for antiviral indication (e.g. anti-Ebola. In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.
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Directory of Open Access Journals (Sweden)
Anne E Bygrave
2004-08-01
Full Text Available Systemic lupus erythematosus (SLE is a multisystem autoimmune disorder in which complex genetic factors play an important role. Several strains of gene-targeted mice have been reported to develop SLE, implicating the null genes in the causation of disease. However, hybrid strains between 129 and C57BL/6 mice, widely used in the generation of gene-targeted mice, develop spontaneous autoimmunity. Furthermore, the genetic background markedly influences the autoimmune phenotype of SLE in gene-targeted mice. This suggests an important role in the expression of autoimmunity of as-yet-uncharacterised background genes originating from these parental mouse strains. Using genome-wide linkage analysis, we identified several susceptibility loci, derived from 129 and C57BL/6 mice, mapped in the lupus-prone hybrid (129 x C57BL/6 model. By creating a C57BL/6 congenic strain carrying a 129-derived Chromosome 1 segment, we found that this 129 interval was sufficient to mediate the loss of tolerance to nuclear antigens, which had previously been attributed to a disrupted gene. These results demonstrate important epistatic modifiers of autoimmunity in 129 and C57BL/6 mouse strains, widely used in gene targeting. These background gene influences may account for some, or even all, of the autoimmune traits described in some gene-targeted models of SLE.
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Neighborhood Factors and Dating Violence Among Youth: A Systematic Review.
Johnson, Renee M; Parker, Elizabeth M; Rinehart, Jenny; Nail, Jennifer; Rothman, Emily F
2015-09-01
The purpose of this review is to summarize the empirical research on neighborhood-level factors and dating violence among adolescents and emerging adults to guide future research and practice. In 2015, a total of 20 articles were identified through a search of the literature using PubMed. Eligible articles included those that (1) had been published in a peer-reviewed journal since 2005; (2) reported a measure of association between at least one neighborhood-level factor and dating violence; and (3) had a study population of youth aged dating violence and neighborhood factors, and measures of effect. Results were summarized into three categories based on the aspect of neighborhood that was the focus of the work: demographic and structural characteristics (n=11); neighborhood disorder (n=12); and social disorganization (n=8). There was some evidence to suggest that neighborhood disadvantage is associated with dating violence, but very little evidence to suggest that residence characteristics (e.g., racial heterogeneity) are associated with dating violence. Results do suggest that perceived neighborhood disorder is associated with physical dating violence perpetration, but do not suggest that it is associated with physical dating violence victimization. Social control and community connectedness are both associated with dating violence, but findings on collective efficacy are mixed. Existing research suggests that neighborhood factors may be associated with dating violence. However, there is a limited body of research on the neighborhood context of dating violence, and more rigorous research is needed. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
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Lopes, Cátia D F; Gonçalves, Nádia P; Gomes, Carla P; Saraiva, Maria J; Pêgo, Ana P
2017-03-01
Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies. Copyright © 2016 Elsevier Ltd. All rights reserved.
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ADOLESCENTS’ EXPOSURE TO COMMUNITY VIOLENCE: ARE NEIGHBORHOOD YOUTH ORGANIZATIONS PROTECTIVE?
Gardner, Margo; Brooks-Gunn, Jeanne
2011-01-01
Using data from the Project on Human Development in Chicago Neighborhoods (PHDCN), we identified a significant inverse association between the variety of youth organizations available at the neighborhood level and adolescents’ exposure to community violence. We examined two non-competing explanations for this finding. First, at the individual level, we tested the hypothesis that access to a greater variety of neighborhood youth organizations predicts adolescents’ participation in organized community-based activities, which, in turn, protects against community violence exposure. Second, at the neighborhood level, we tested the hypothesis that lower violent crime rates explain the inverse relation between neighborhood youth organization variety and community violence exposure. Our findings supported the latter of these two mechanisms. PMID:21666761
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Differences by Sexual Orientation in Perceptions of Neighborhood Cohesion: Implications for Health.
Henning-Smith, Carrie; Gonzales, Gilbert
2018-06-01
A large body of research documents the relationship between health and place, including the positive association between neighborhood cohesion and health. However, very little research has examined neighborhood cohesion by sexual orientation. This paper addresses that gap by examining differences in perceived neighborhood cohesion by sexual orientation. We use data from the 2016 National Health Interview Survey (n = 28,164 respondents aged 18 years and older) to examine bivariate differences by sexual orientation in four measures of neighborhood cohesion. We then use ordered logistic regression models to assess the relationship between sexual orientation and a scaled measure of neighborhood cohesion, adjusting for socio-demographic characteristics, living arrangements, health status, region, and neighborhood tenure. We find that lesbian, gay, and bisexual (LGB) adults are less likely to say that they live in a close-knit neighborhood (54.6 vs. 65.6%, p < 0.001), they can count on their neighbors (74.7 vs. 83.1%, p < 0.001), they trust their neighbors (75.5 vs. 83.7%, p < 0.001), or people in their neighborhood help each other out (72.9 vs. 83.1%, p < 0.001), compared to heterosexual adults. Even after controlling for socio-demographic factors, neighborhood cohesion scores are lower for LGB adults compared to heterosexual adults (odds ratio of better perceived neighborhood cohesion for sexual minorities: 0.70, p < 0.001). Overall, LGB adults report worse neighborhood cohesion across multiple measures, even after adjusting for individual characteristics and neighborhood tenure. Because living in a cohesive neighborhood is associated with better health outcomes, future research, community-level initiatives, and public policy efforts should focus on creating welcoming neighborhood environments for sexual minorities.
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Independent Effects of Neighborhood Poverty and Psychosocial Stress on Obesity Over Time.
Kwarteng, Jamila L; Schulz, Amy J; Mentz, Graciela B; Israel, Barbara A; Perkins, Denise White
2017-12-01
The objective of the study was to examine the independent effects of neighborhood poverty and psychosocial stress on increases in central adiposity over time. Data are from a community sample of 157 Non-Hispanic Black, Non-Hispanic White, and Hispanic adults collected in 2002-2003 and 2007-2008, and from the 2000 Decennial Census. The dependent variable was waist circumference. Independent variables included neighborhood poverty, perceived neighborhood physical environment, family stress, safety stress, everyday unfair treatment, and a cumulative stress index. Weighted 3-level hierarchical linear regression models for a continuous outcome were used to assess the effects of neighborhood poverty and psychosocial stress on central adiposity over time. We also assessed whether psychosocial stress mediated the association between neighborhood poverty and central adiposity. Neighborhood poverty and everyday unfair treatment at baseline were independently associated with increases in central adiposity over time, accounting for the other indicators of stress. Perceptions of the neighborhood physical environment and cumulative stress mediated associations between neighborhood poverty and central adiposity. Results suggest that residing in neighborhoods with higher concentrations of poverty and exposure to everyday unfair treatment independently heighten risk of increased central adiposity over time. Associations between neighborhood poverty and central adiposity were mediated by perceptions of the neighborhood physical environment and by the cumulative stress index. Public health strategies to reduce obesity should consider neighborhood poverty and exposure to multiple sources of psychosocial stress, including everyday unfair treatment.
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Directory of Open Access Journals (Sweden)
Mathieu Dalvai
Full Text Available Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gene expression has not been tested directly. We show that in ERalpha-positive breast cancer cells (MCF-7 the estrogen receptor gene and downstream target genes are cell cycle regulated with expression levels varying as much as three-fold between phases of the cell cycle. Steroid free culture conditions commonly used to assess the effect of hormones or antiestrogens on gene expression also block MCF-7 cells in G1-phase when several ERalpha target genes are overexpressed. Thus, cell cycle effects have to be taken into account when analyzing the impact of hormonal treatments on gene transcription. We found that antiestrogens repress transcription of several ERalpha target genes specifically in S phase. This observation corroborates the more rapid and strong impact of antiestrogen treatments on cell proliferation in thymidine, hydroxyurea or aphidicolin arrested cells and correlates with an increase of apoptosis compared to similar treatments in lovastatin or nocodazol treated cells. Hence, cell cycle effects synergize with the action of antiestrogens. An interesting therapeutic perspective could be to enhance the action of anti-estrogens by associating hormone-therapy with specific cell cycle drugs.
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Gene Targeting and Expression Modulation by Peptide Nucleic Acids (PNA)
DEFF Research Database (Denmark)
Nielsen, Peter E
2010-01-01
Peptide nucleic acids (PNA) are artificial structural mimics of nucleic acids capable of sequence specific hybridization to both RNA and DNA. Thus they have obvious potential as gene targeting agents for drug discovery approaches. An overview with emphasis on recent progress on RNA "interference...
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Neighborhood and Friendship Composition in Adolescence
Edling, Christofer; Rydgren, Jens
2010-01-01
The social surroundings in which an individual grows up and spends his or her everyday life have an effect on his or her life chances. Much of the research into this phenomenon focuses on so-called neighborhood effects and has put particular emphasis on the negative effects of growing up in a poor neighborhood. Originating from the sociological study of inner-city problems in the United States, the research has recentl...
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Reed, Elizabeth; Silverman, Jay G; Raj, Anita; Decker, Michele R; Miller, Elizabeth
2011-04-01
This study aims to examine the link between male perpetration of teen dating violence (TDV) and neighborhood violence, as well as associations with gender attitudes and perceived peer and neighborhood norms related to violence among a sample of urban adolescent boys. Participants of this cross-sectional study (N = 275) were between the ages of 14 and 20 years and recruited from urban community health centers. Crude and adjusted logistic and linear regression models were used to examine TDV perpetration in relation to (a) neighborhood violence involvement, (b) perceptions of peer violence, (c) perceptions of neighborhood violence, and (d) gender attitudes. Slightly more than one in four (28%) boys reported at least one form of TDV perpetration; among boys who have ever had sex, almost half (45%) reported at least one form of TDV perpetration. In logistic and linear regression models adjusted for demographics, boys who reported TDV perpetration were more likely to report involvement in neighborhood violence (odds ratio (OR) = 3.1; 95% confidence interval (CI) = 1.7-5.5), beliefs that their friends have perpetrated TDV (OR = 2.7; 95%CI = 1.4-5.1), perceptions of violent activity within their neighborhood (OR = 3.0; 95%CI = 1.4-6.3), and greater support of traditional gender norms (β = 3.2, p = 0.002). The findings suggest that efforts are needed to address boys' behaviors related to the perpetration of multiple forms of violence and require explicit efforts to reduce perceived norms of violence perpetration as well as problematic gender attitudes (e.g., increasing support for gender equity) across boys' life contexts.
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Planning According to New Urbanism: the Ostadsara Neighborhood Case Study
Directory of Open Access Journals (Sweden)
Nader Zali
2016-12-01
Full Text Available The modern urbanism activities have led to rupture of previous spatial structure of neighborhoods and destruction of their identity. The New Urbanism Movement, as one of the successful models in urbanization field attempts to revive this lost national-social identity through the project of returning to traditional structure of neighborhoods by applying modern urbanization models and methods. The current paper aims at evaluation and analysis of “the Ostadsara neighborhood's organization based on new urbanism principles” and representation of solutions for planning a successful neighborhood center considering these principles. In this regard, various methods including library method, observation, photography, questionnaire and interview with users of the environment were utilized. The results from identification and assessment of weaknesses and strengths and specification and analysis of potential threats and opportunities shows the possibility of applying walkability, connectivity and integration, improvement of public transportation, improvement of architecture quality and urban design, maintenance and improvement of public and green open spaces, maintenance and strengthening the structure of traditional neighborhood units and using cooperation of Ostadsara neighborhood's inhabitants. Finally, the current study will represent appropriate strategies for changing the mentioned neighborhood into a desirable and prosperous one.
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Neighborhood Decline and the Economic Crisis (discussion paper)
Zwiers, M.D.; Bolt, G.; Van Ham, M.; Van Kempen, R.
2014-01-01
Neighborhood decline is a complex and multidimensional process. National and regional variation in economic and political structures (including variety in national welfare state arrangements), combined with differences in neighborhood history, development and population composition, makes it
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Targeted, homology-driven gene insertion in stem cells by ZFN-loaded 'all-in-one' lentiviral vectors
DEFF Research Database (Denmark)
Cai, Yujia; Laustsen, Anders; Zhou, Yan
2016-01-01
-driven mechanism into safe loci. This insertion mechanism is driven by time-restricted exposure of treated cells to ZFNs. We show targeted gene integration in human stem cells, including CD34+ hematopoietic progenitors and induced pluripotent stem cells (iPSCs). Notably, targeted insertions are identified in 89......% of transduced iPSCs. Our findings demonstrate the applicability of nuclease-loaded 'all-in-one' IDLVs for site-directed gene insertion in stem cell based gene therapies....
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Neighborhood Design for Walking and Biking
Brown, Barbara B.; Smith, Ken R.; Hanson, Heidi; Fan, Jessie X.; Kowaleski-Jones, Lori; Zick, Cathleen D.
2013-01-01
Background Neighborhood designs often relate to physical activity and to BMI. Purpose Does neighborhood walkability/bikeability relate to BMI and obesity risk and does moderate-to-vigorous physical activity (MVPA) account for some of the relationship? Methods Census 2000 provided walkability/bikeability measures—block group proportions of workers who walk or bike to work, housing age, and population density—and National Health and Nutrition Examination Study (NHANES 2003–2006) provided MVPA accelerometer measures. Regression analyses (2011–2012) adjusted for geographic clustering and multiple control variables. Results Greater density and older housing were associated with lower male BMI in bivariate analyses, but there were no density and housing age effects in multivariate models. For women, greater proportions of neighborhood workers who walk to work (M=0.02) and more MVPA was associated with lower BMI and lower obesity risk. For men, greater proportions of workers who bike to work (M=0.004) and more MVPA was associated with lower BMI and obesity risk. For both effects, MVPA partially mediated the relationships between walkability/bikeability and BMI. If such associations are causal, doubling walk and bike-to-work proportions (to 0.04 and 0.008) would have –0.3 and –0.33 effects on the average BMIs of adult women and men living in the neighborhood. This equates to 1.5 lbs for a 64” woman and 2.3 lbs for a 69” man. Conclusions Although walking/biking to work is rare in the U.S., greater proportions of such workers in neighborhoods relate to lower weight and higher MVPA. Bikeability merits greater attention as a modifiable activity-friendliness factor, particularly for men. PMID:23415119
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Directory of Open Access Journals (Sweden)
Bin Tang
Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.
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International Nuclear Information System (INIS)
Kang, Joo Hyun
2006-01-01
Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner
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Jackson, Belinda M; Abete-Luzi, Patricia; Krause, Michael W; Eisenmann, David M
2014-04-16
The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.
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Abdelaziz, Mohamed; Sherif, Lotfy; ElKhiary, Mostafa; Nair, Sanjeeta; Shalaby, Shahinaz; Mohamed, Sara; Eziba, Noura; El-Lakany, Mohamed; Curiel, David; Ismail, Nahed; Diamond, Michael P; Al-Hendy, Ayman
2016-04-01
Gene therapy is a potentially effective non-surgical approach for the treatment of uterine leiomyoma. We demonstrated that targeted adenovirus vector, Ad-SSTR-RGD-TK/GCV, was highly effective in selectively inducing apoptosis and inhibiting proliferation of human leiomyoma cells in vitro while sparing normal myometrial cells. An in-vivo study, to compare efficacy and safety of modified adenovirus vector Ad-SSTR-RGD-TK/GCV versus untargeted vector for treatment of leiomyoma. Female nude mice were implanted with rat leiomyoma cells subcutaneously. Then mice were randomized into three groups. Group 1 received Ad-LacZ (marker gene), Group 2 received untargeted Ad-TK, and Group 3 received the targeted Ad-SSTR-RGD-TK. Tumors were measured weekly for 4 weeks. Then mice were sacrificed and tissue samples were collected. Evaluation of markers of apoptosis, proliferation, extracellular matrix, and angiogenesis was performed using Western Blot & Immunohistochemistry. Statistical analysis was done using ANOVA. Dissemination of adenovirus was assessed by PCR. In comparison with the untargeted vector, the targeted adenoviral vector significantly shrank leiomyoma size (P leiomyoma lesions with both targeted and untargeted adenovirus. Targeted adenovirus, effectively reduces tumor size in leiomyoma without dissemination to other organs. Further evaluation of this localized targeted strategy for gene therapy is needed in appropriate preclinical humanoid animal models in preparation for a future pilot human trial. © The Author(s) 2016.
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Neighborhood Environment and Cognition in Older Adults: A Systematic Review.
Besser, Lilah M; McDonald, Noreen C; Song, Yan; Kukull, Walter A; Rodriguez, Daniel A
2017-08-01
Some evidence suggests that treating vascular risk factors and performing mentally stimulating activities may delay cognitive impairment onset in older adults. Exposure to a complex neighborhood environment may be one mechanism to help delay cognitive decline. PubMed, Web of Science, and ProQuest Dissertation and Theses Global database were systematically reviewed, identifying 25 studies published from February 1, 1989 to March 5, 2016 (data synthesized, May 3, 2015 to October 7, 2016). The review was restricted to quantitative studies focused on: (1) neighborhood social and built environment and cognition; and (2) community-dwelling adults aged ≥45 years. The majority of studies were cross-sectional, U.S.-based, and found at least one significant association. The diversity of measures and neighborhood definitions limited the synthesis of findings in many instances. Evidence was moderately strong for an association between neighborhood SES and cognition, and modest for associations between neighborhood demographics, design, and destination accessibility and cognition. Most studies examining effect modification found significant associations, with some evidence for effect modification of the neighborhood SES-cognition association by individual-level SES. No studies had low risk of bias and many tested multiple associations that increased the chance of a statistically significant finding. Considering the studies to date, the evidence for an association between neighborhood characteristics and cognition is modest. Future studies should include longitudinal measures of neighborhood characteristics and cognition; examine potential effect modifiers, such as sex and disability; and study mediators that may help elucidate the biological mechanisms linking neighborhood environment and cognition. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
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Prediction of novel target genes and pathways involved in irinotecan-resistant colorectal cancer.
Directory of Open Access Journals (Sweden)
Precious Takondwa Makondi
Full Text Available Acquired drug resistance to the chemotherapeutic drug irinotecan (the active metabolite of which is SN-38 is one of the significant obstacles in the treatment of advanced colorectal cancer (CRC. The molecular mechanism or targets mediating irinotecan resistance are still unclear. It is urgent to find the irinotecan response biomarkers to improve CRC patients' therapy.Genetic Omnibus Database GSE42387 which contained the gene expression profiles of parental and irinotecan-resistant HCT-116 cell lines was used. Differentially expressed genes (DEGs between parental and irinotecan-resistant cells, protein-protein interactions (PPIs, gene ontologies (GOs and pathway analysis were performed to identify the overall biological changes. The most common DEGs in the PPIs, GOs and pathways were identified and were validated clinically by their ability to predict overall survival and disease free survival. The gene-gene expression correlation and gene-resistance correlation was also evaluated in CRC patients using The Cancer Genomic Atlas data (TCGA.The 135 DEGs were identified of which 36 were upregulated and 99 were down regulated. After mapping the PPI networks, the GOs and the pathways, nine genes (GNAS, PRKACB, MECOM, PLA2G4C, BMP6, BDNF, DLG4, FGF2 and FGF9 were found to be commonly enriched. Signal transduction was the most significant GO and MAPK pathway was the most significant pathway. The five genes (FGF2, FGF9, PRKACB, MECOM and PLA2G4C in the MAPK pathway were all contained in the signal transduction and the levels of those genes were upregulated. The FGF2, FGF9 and MECOM expression were highly associated with CRC patients' survival rate but not PRKACB and PLA2G4C. In addition, FGF9 was also associated with irinotecan resistance and poor disease free survival. FGF2, FGF9 and PRKACB were positively correlated with each other while MECOM correlated positively with FGF9 and PLA2G4C, and correlated negatively with FGF2 and PRKACB after doing gene-gene
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Directory of Open Access Journals (Sweden)
Yong Huang
Full Text Available BACKGROUND: Even though the genomes of many model species have already been sequenced, our knowledge of gene regulation in evolution is still very limited. One big obstacle is that it is hard to predict the target genes of transcriptional factors accurately from sequences. In this respect, microRNAs (miRNAs are different from transcriptional factors, as target genes of miRNAs can be readily predicted from sequences. This feature of miRNAs offers an unprecedented vantage point for evolutionary analysis of gene regulation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we analyzed a particular aspect of miRNA evolution, the differences in the "apparent repression effectiveness (ARE" between human miRNAs of different conservational levels. ARE is a measure we designed to evaluate the repression effect of miRNAs on target genes based on publicly available gene expression data in normal tissues and miRNA targeting and expression data. We found that ARE values of more conserved miRNAs are significantly higher than those of less conserved miRNAs in general. We also found the gain in expression abundance and broadness of miRNAs in evolution contributed to the gain in ARE. CONCLUSIONS/SIGNIFICANCE: The ARE measure quantifies the repressive effects of miRNAs and enables us to study the influences of many factors on miRNA-mediated repression, such as conservational levels and expression levels of miRNAs. The gain in ARE can be explained by the existence of a trend of miRNAs in evolution to effectively control more target genes, which is beneficial to the miRNAs but not necessarily to the organism at all times. Our results from miRNAs gave us an insight of the complex interplay between regulators and target genes in evolution.
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Perceived Neighborhood Safety and Adolescent School Functioning
Martin-Storey, Alexa; Crosnoe, Robert
2014-01-01
This study examined the association between adolescents' perceptions of their neighborhoods' safety and multiple elements of their functioning in school with data on 15 year olds from the NICHD Study of Early Child Care and Youth Development (n = 924). In general, perceived neighborhood safety was more strongly associated with aspects of schooling…
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Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu
2014-12-05
Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways.
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Intergenerational Education Transmission: Neighborhood Quality and
Patacchini, Eleonora; Zenou, Yves
2004-01-01
Using cultural transmission, we develop a model that gives some microfoundation to the impact of residential neighborhood on children's educational attainment and then test it using the UK National Child Development Study. We find that, for high-educated parents, the better the quality of the neighborhood in terms of human capital, the higher the parent's involvement in children's education, indicating cultural complementarity. For high-educated parents, we also find that both parents' involv...
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Insights into the regulation of human CNV-miRNAs from the view of their target genes
Directory of Open Access Journals (Sweden)
Wu Xudong
2012-12-01
Full Text Available Abstract Background microRNAs (miRNAs represent a class of small (typically 22 nucleotides in length non-coding RNAs that can degrade their target mRNAs or block their translation. Recent research showed that copy number alterations of miRNAs and their target genes are highly prevalent in cancers; however, the evolutionary and biological functions of naturally existing copy number variable miRNAs (CNV-miRNAs among individuals have not been studied extensively throughout the genome. Results In this study, we comprehensively analyzed the properties of genes regulated by CNV-miRNAs, and found that CNV-miRNAs tend to target a higher average number of genes and prefer to synergistically regulate the same genes; further, the targets of CNV-miRNAs tend to have higher variability of expression within and between populations. Finally, we found the targets of CNV-miRNAs are more likely to be differentially expressed among tissues and developmental stages, and participate in a wide range of cellular responses. Conclusions Our analyses of CNV-miRNAs provide new insights into the impact of copy number variations on miRNA-mediated post-transcriptional networks. The deeper interpretation of patterns of gene expression variation and the functional characterization of CNV-miRNAs will help to broaden the current understanding of the molecular basis of human phenotypic diversity.
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Neighborhood disadvantage and ischemic stroke: the Cardiovascular Health Study (CHS).
Brown, Arleen F; Liang, Li-Jung; Vassar, Stefanie D; Stein-Merkin, Sharon; Longstreth, W T; Ovbiagele, Bruce; Yan, Tingjian; Escarce, José J
2011-12-01
Neighborhood characteristics may influence the risk of stroke and contribute to socioeconomic disparities in stroke incidence. The objectives of this study were to examine the relationship between neighborhood socioeconomic status and incident ischemic stroke and examine potential mediators of these associations. We analyzed data from 3834 whites and 785 blacks enrolled in the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ages≥65 years from 4 US counties. The primary outcome was adjudicated incident ischemic stroke. Neighborhood socioeconomic status was measured using a composite of 6 census tract variables. Race-stratified multilevel Cox proportional hazard models were constructed adjusted for sociodemographic, behavioral, and biological risk factors. Among whites, in models adjusted for sociodemographic characteristics, stroke hazard was significantly higher among residents of neighborhoods in the lowest compared with the highest neighborhood socioeconomic status quartile (hazard ratio, 1.32; 95% CI, 1.01-1.72) with greater attenuation of the hazard ratio after adjustment for biological risk factors (hazard ratio, 1.16; 0.88-1.52) than for behavioral risk factors (hazard ratio, 1.30; 0.99-1.70). Among blacks, we found no significant associations between neighborhood socioeconomic status and ischemic stroke. Higher risk of incident ischemic stroke was observed in the most disadvantaged neighborhoods among whites, but not among blacks. The relationship between neighborhood socioeconomic status and stroke among whites appears to be mediated more strongly by biological than behavioral risk factors.
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A New Neighborhood Every Fall: Aging in Place in a College Town.
Powell, Kathleen H
Older adults who live in residential neighborhoods adjacent to college and university campuses have a unique experience that makes them vulnerable to marginalization and displacement. As these neighborhoods become increasingly dominated by college students living in rental properties, older adults find themselves in the minority in a neighborhood where they have lived for many years. In addition, these neighborhoods are attractive to universities, city governments, and private companies for their development potential, which can result in gentrification. A year-long ethnographic study of a campus-adjacent neighborhood in a small US college town that is home to a medium-sized public university sheds light on the relationships between members of 5 stakeholder groups that have a vested interest in the neighborhood. The study highlights the need for additional research on different types of neighborhoods and their effects on aging in place in addition to outlining social work interventions in campus-adjacent neighborhoods that are designed to enhance these intergenerational spaces.
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Paulk, Nicole K.; Loza, Laura Marquez; Finegold, Milton J.
2012-01-01
Abstract Recombinant adeno-associated virus (rAAV) vectors have clear potential for use in gene targeting but low correction efficiencies remain the primary drawback. One approach to enhancing efficiency is a block of undesired repair pathways like nonhomologous end joining (NHEJ) to promote the use of homologous recombination. The natural product vanillin acts as a potent inhibitor of NHEJ by inhibiting DNA-dependent protein kinase (DNA-PK). Using a homology containing rAAV vector, we previously demonstrated in vivo gene repair frequencies of up to 0.1% in a model of liver disease hereditary tyrosinemia type I. To increase targeting frequencies, we administered vanillin in combination with rAAV. Gene targeting frequencies increased up to 10-fold over AAV alone, approaching 1%. Fah−/−Ku70−/− double knockout mice also had increased gene repair frequencies, genetically confirming the beneficial effects of blocking NHEJ. A second strategy, transient proteasomal inhibition, also increased gene-targeting frequencies but was not additive to NHEJ inhibition. This study establishes the benefit of transient NHEJ inhibition with vanillin, or proteasome blockage with bortezomib, for increasing hepatic gene targeting with rAAV. Functional metabolic correction of a clinically relevant disease model was demonstrated and provided evidence for the feasibility of gene targeting as a therapeutic strategy. PMID:22486314
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Neighborhood perceptions and allostatic load : Evidence from Denmark
van Deurzen, I.A.; Hulvej Rod, Naja; Christensen, Ulla; Hansen, Åse Marie; Lund, Rikke; Dich, Nadya
2016-01-01
An influential argument explaining why living in certain neighborhoods can become harmful to one's health maintains that individuals can perceive certain characteristics of the neighborhood as threatening and the prolonged exposure to a threatening environment could induce chronic stress. Following
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Directory of Open Access Journals (Sweden)
Annette Taugbøl
Full Text Available Salinity is one of the key factors that affects metabolism, survival and distribution of fish species, as all fish osmoregulate and euryhaline fish maintain osmotic differences between their extracellular fluid and either freshwater or seawater. The threespine stickleback (Gasterosteus aculeatus is a euryhaline species with populations in both marine and freshwater environments, where the physiological and genomic basis for salinity tolerance adaptation is not fully understood. Therefore, our main objective in this study was to investigate gene expression of three targeted osmoregulatory genes (Na+/K+-ATPase (ATPA13, cystic fibrosis transmembrane regulator (CFTR and a voltage gated potassium channel gene (KCNH4 and one stress related heat shock protein gene (HSP70 in gill tissue from marine and freshwater populations when exposed to non-native salinity for periods ranging from five minutes to three weeks. Overall, the targeted genes showed highly plastic expression profiles, in addition the expression of ATP1A3 was slightly higher in saltwater adapted fish and KCNH4 and HSP70 had slightly higher expression in freshwater. As no pronounced changes were observed in the expression profiles of the targeted genes, this indicates that the osmoregulatory apparatuses of both the marine and landlocked freshwater stickleback population have not been environmentally canalized, but are able to respond plastically to abrupt salinity challenges.
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Taugbøl, Annette; Arntsen, Tina; Ostbye, Kjartan; Vøllestad, Leif Asbjørn
2014-01-01
Salinity is one of the key factors that affects metabolism, survival and distribution of fish species, as all fish osmoregulate and euryhaline fish maintain osmotic differences between their extracellular fluid and either freshwater or seawater. The threespine stickleback (Gasterosteus aculeatus) is a euryhaline species with populations in both marine and freshwater environments, where the physiological and genomic basis for salinity tolerance adaptation is not fully understood. Therefore, our main objective in this study was to investigate gene expression of three targeted osmoregulatory genes (Na+/K+-ATPase (ATPA13), cystic fibrosis transmembrane regulator (CFTR) and a voltage gated potassium channel gene (KCNH4) and one stress related heat shock protein gene (HSP70)) in gill tissue from marine and freshwater populations when exposed to non-native salinity for periods ranging from five minutes to three weeks. Overall, the targeted genes showed highly plastic expression profiles, in addition the expression of ATP1A3 was slightly higher in saltwater adapted fish and KCNH4 and HSP70 had slightly higher expression in freshwater. As no pronounced changes were observed in the expression profiles of the targeted genes, this indicates that the osmoregulatory apparatuses of both the marine and landlocked freshwater stickleback population have not been environmentally canalized, but are able to respond plastically to abrupt salinity challenges.
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Lenka, Sangram K; Lohia, Bikash; Kumar, Abhay; Chinnusamy, Viswanathan; Bansal, Kailash C
2009-02-01
Abscisic acid (ABA), the popular plant stress hormone, plays a key role in regulation of sub-set of stress responsive genes. These genes respond to ABA through specific transcription factors which bind to cis-regulatory elements present in their promoters. We discovered the ABA Responsive Element (ABRE) core (ACGT) containing CGMCACGTGB motif as over-represented motif among the promoters of ABA responsive co-expressed genes in rice. Targeted gene prediction strategy using this motif led to the identification of 402 protein coding genes potentially regulated by ABA-dependent molecular genetic network. RT-PCR analysis of arbitrarily chosen 45 genes from the predicted 402 genes confirmed 80% accuracy of our prediction. Plant Gene Ontology (GO) analysis of ABA responsive genes showed enrichment of signal transduction and stress related genes among diverse functional categories.
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Sun, Wenyi; Yang, Xiaobing; Wang, Xueying; Lin, Xinping; Wang, Yanan; Zhang, Sufang; Luan, Yushi; Zhao, Zongbao K
2017-07-01
To target a carotenoid biosynthetic gene in the oleaginous yeast Rhodosporidium toruloides by using the Agrobacterium-mediated transformation (AMT) method. The RHTO_04602 locus of R. toruloides NP11, previously assigned to code the carotenoid biosynthetic gene CRTI, was amplified from genomic DNA and cloned into the binary plasmid pZPK-mcs, resulting in pZPK-CRT. A HYG-expression cassette was inserted into the CRTI sequence of pZPK-CRT by utilizing the restriction-free clone strategy. The resulted plasmid was used to transform R. toruloides cells according to the AMT method, leading to a few white transformants. Sequencing analysis of those transformants confirmed homologous recombination and insertional inactivation of CRTI. When the white variants were transformed with a CRTI-expression cassette, cells became red and produced carotenoids as did the wild-type strain NP11. Successful homologous targeting of the CrtI locus confirmed the function of RHTO_04602 in carotenoids biosynthesis in R. toruloides. It provided valuable information for metabolic engineering of this non-model yeast species.
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Energy Technology Data Exchange (ETDEWEB)
Kim, Young June; Ahn, Kwang Sung; Kim, Minjeong; Kim, Min Ju; Park, Sang-Min; Ryu, Junghyun; Ahn, Jin Seop; Heo, Soon Young; Kang, Jee Hyun; Choi, You Jung [Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan (Korea, Republic of); Choi, Seong-Jun [Institute of Tissue Regeneration Engineering, Dankook University, Cheonan (Korea, Republic of); Shim, Hosup, E-mail: shim@dku.edu [Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan (Korea, Republic of); Institute of Tissue Regeneration Engineering, Dankook University, Cheonan (Korea, Republic of); Department of Physiology, Dankook University School of Medicine, Cheonan (Korea, Republic of)
2014-10-03
Highlights: • ATM gene-targeted pigs were produced by somatic cell nuclear transfer. • A novel large animal model for ataxia telangiectasia was developed. • The new model may provide an alternative to the mouse model. - Abstract: Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies.
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International Nuclear Information System (INIS)
Kim, Young June; Ahn, Kwang Sung; Kim, Minjeong; Kim, Min Ju; Park, Sang-Min; Ryu, Junghyun; Ahn, Jin Seop; Heo, Soon Young; Kang, Jee Hyun; Choi, You Jung; Choi, Seong-Jun; Shim, Hosup
2014-01-01
Highlights: • ATM gene-targeted pigs were produced by somatic cell nuclear transfer. • A novel large animal model for ataxia telangiectasia was developed. • The new model may provide an alternative to the mouse model. - Abstract: Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies
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Barriers to Liposomal Gene Delivery: from Application Site to the Target.
Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R
2016-01-01
Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.
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Timperio, Anna; Veitch, Jenny; Carver, Alison
2015-05-01
The aim of this study is to examine associations between the neighborhood social environment and leisure-time physical activity (LTPA)(1) and walking among women, and whether these associations are mediated by perceived personal safety. Women (n = 3784) living in disadvantaged urban and rural neighborhoods within Victoria, Australia completed a self-administered survey on five social environment variables (neighborhood crime, neighborhood violence, seeing others walking and exercising in the neighborhood, social trust/cohesion), perceived personal safety, and their physical activity in 2007/8. Linear regression analyses examined associations between social environment variables and LTPA and walking. Potential mediating pathways were assessed using the product-of-coefficients test. Moderated mediation by urban/rural residence was examined. Each social environment variable was positively associated with engaging in at least 150 min/week of LTPA (OR = 1.16 to 1.56). Only two social environment variables, seeing others walking (OR = 1.45) and exercising (OR = 1.31), were associated with ≥ 150 min/week of walking. Perceived personal safety mediated all associations. Stronger mediation was found in urban areas for crime, violence and social trust/cohesion. The neighborhood social environment is an important influence on physical activity among women living in disadvantaged areas. Feelings of personal safety should not be included in composite or aggregate scores relating to the social environment. Copyright © 2015 Elsevier Inc. All rights reserved.
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Mahajan, Ameya S.; Kondhare, Kirtikumar R.; Rajabhoj, Mohit P.; Kumar, Amit; Ghate, Tejashree; Ravindran, Nevedha; Habib, Farhat; Siddappa, Sundaresha; Banerjee, Anjan K.
2016-01-01
Potato Homeobox 15 (POTH15) is a KNOX-I (Knotted1-like homeobox) family gene in potato that is orthologous to Shoot Meristemless (STM) in Arabidopsis. Despite numerous reports on KNOX genes from different species, studies in potato are limited. Here, we describe photoperiodic regulation of POTH15, its overexpression phenotype, and identification of its potential targets in potato (Solanum tuberosum ssp. andigena). qRT-PCR analysis showed a higher abundance of POTH15 mRNA in shoot tips and stolons under tuber-inducing short-day conditions. POTH15 promoter activity was detected in apical and axillary meristems, stolon tips, tuber eyes, and meristems of tuber sprouts, indicating its role in meristem maintenance and leaf development. POTH15 overexpression altered multiple morphological traits including leaf and stem development, leaflet number, and number of nodes and branches. In particular, the rachis of the leaf was completely reduced and leaves appeared as a bouquet of leaflets. Comparative transcriptomic analysis of 35S::GUS and two POTH15 overexpression lines identified more than 6000 differentially expressed genes, including 2014 common genes between the two overexpression lines. Functional analysis of these genes revealed their involvement in responses to hormones, biotic/abiotic stresses, transcription regulation, and signal transduction. qRT-PCR of selected candidate target genes validated their differential expression in both overexpression lines. Out of 200 randomly chosen POTH15 targets, 173 were found to have at least one tandem TGAC core motif, characteristic of KNOX interaction, within 3.0kb in the upstream sequence of the transcription start site. Overall, this study provides insights to the role of POTH15 in controlling diverse developmental processes in potato. PMID:27217546
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Zadro, J R; Shirley, D; Pinheiro, M B; Bauman, A; Duncan, G E; Ferreira, P H
2017-06-01
The aim of this study was to investigate whether neighborhood walkability moderates the association between low back pain (LBP) and physical activity (PA), using a co-twin design to control for genetics and shared environmental factors. A cross-sectional analysis was performed on 10,228 twins from the Washington State Twin Registry with available data on LBP from recruitment surveys between 2009 and 2013. LBP within the past 3months was our exposure variable. Our outcome variables were sufficient moderate or vigorous-intensity PA (MVPA, defined as at least 75min of vigorous-intensity PA, or 150min of moderate-intensity PA per week), and walking (≥150min per week). Neighborhood walkability, estimated using the commercially available Walk Score®, was our moderator variable. After controlling for the influence of genetics and shared environment, individuals reporting LBP were significantly less likely to engage in sufficient MVPA if they lived in a neighborhood with high walkability (OR=0.59, 95%CI: 0.36-0.96). There was no association between LBP and sufficient MVPA for individuals living in a neighborhood with low walkability (OR=1.27, 95%CI: 0.93-1.72), demonstrating that walkability is a significant moderator of the association between LBP and PA (interaction p=0.013). These findings were similar for the association between LBP and walking (high walkability OR=0.42, 95%CI: 0.22-0.78; low walkability OR=0.71, 95%CI: 0.46-1.12), although the interaction was not significant (p=0.700). Neighborhood walkability moderates the association between LBP and PA. Our results highlight the importance of targeting interventions promoting PA towards individuals with LBP living in a neighborhood with good walkable access to amenities. Copyright © 2017 Elsevier Inc. All rights reserved.
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Kern, David M; Auchincloss, Amy H; Robinson, Lucy F; Stehr, Mark F; Pham-Kanter, Genevieve
2017-08-01
This paper evaluates variation in food prices within and between neighborhoods to improve our understanding of access to healthy foods in urbanized areas and potential economic incentives and barriers to consuming a higher-quality diet. Prices of a selection of healthier foods (dairy, fruit juice, and frozen vegetables) and unhealthy foods (soda, sweets, and salty snacks) were obtained from 1953 supermarkets across the USA during 2009-2012 and were linked to census block group socio-demographics. Analyses evaluated associations between neighborhood SES and proportion Black/Hispanic and the prices of healthier and unhealthy foods, and the relative price of healthier foods compared with unhealthy foods (healthy-to-unhealthy price ratio). Linear hierarchical regression models were used to explore geospatial variation and adjust for confounders. Overall, the price of healthier foods was nearly twice as high as the price of unhealthy foods ($0.590 vs $0.298 per serving; healthy-to-unhealthy price ratio of 1.99). This trend was consistent across all neighborhood characteristics. After adjusting for covariates, no association was found between food prices (healthy, unhealthy, or the healthy-to-unhealthy ratio) and neighborhood SES. Similarly, there was no association between the proportion Black/Hispanic and healthier food price, a very small positive association with unhealthy price, and a modest negative association with the healthy-to-unhealthy ratio. No major differences were seen in food prices across levels of neighborhood SES and proportion Black/Hispanic; however, the price of healthier food was twice as expensive as unhealthy food per serving on average.
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Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery
Kesharwani, Prashant; Iyer, Arun K.
2015-01-01
Advances in the application of nanotechnology in medicine have given rise to multifunctional smart nanocarriers that can be engineered with tunable physicochemical characteristics to deliver one or more therapeutic agent(s) safely and selectively to cancer cells, including intracellular organelle-specific targeting. Dendrimers having properties resembling biomolecules, with well-defined 3D nanopolymeric architectures, are emerging as a highly attractive class of drug and gene delivery vector. The presence of numerous peripheral functional groups on hyperbranched dendrimers affords efficient conjugation of targeting ligands and biomarkers that can recognize and bind to receptors overexpressed on cancer cells for tumor-cell-specific delivery. The present review compiles the recent advances in dendrimer-mediated drug and gene delivery to tumors by passive and active targeting principles with illustrative examples. PMID:25555748
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A systematic review of relations between neighborhoods and mental health.
Truong, Khoa D; Ma, Sai
2006-09-01
The relationship between neighborhood characteristics and resident mental health has been widely investigated in individual studies in recent years, but this literature is not adequately reviewed. To systematically review relevant individual research of the relation between neighborhoods and adult mental health by identifying and synthesizing all relevant studies in this literature. We conducted an electronic search with PubMed and PsycINFO, and manual reference-checking, resulting in 8,562 screened studies of which 29 were selected. Studies were included in the main synthesis if they (i) were published in English in peer reviewed journals; (ii) had relevant definitions and measures of neighborhood characteristics; (iii) utilized standardized measures of adult mental health; (iv) controlled for individual characteristics; (v) reported quantitative results; and, (vi) studied a population in a developed country. We focused on two key areas within this literature: the methodologies utilized to study neighborhood effects and quantitative results. With regard to the former, we examined five major issues: (i) definitions and measures of neighborhoods; (ii) definitions and measures of mental health; (iii) controls for individual level characteristics; (iv) conceptual models; and (v) analytical models. As for quantitative results, the relation was reviewed by types of neighborhood characteristics. We summarized general quantitative findings and drew common conclusions across groups of studies. 27/29 studies found statistically significant association between mental health and at least one measure of neighborhood characteristics, after adjusting for individual factors. This association was evident for all types of neighborhood features, varying from sociodemographic characteristics to physical environment, and from objective to subjective measures. Neighborhood effects were weakened when adding individual-level characteristics into the regression models, and were generally
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Directory of Open Access Journals (Sweden)
Ruixin Hao
Full Text Available Estrogen signaling is important for vertebrate embryonic development. Here we have used zebrafish (Danio rerio as a vertebrate model to analyze estrogen signaling during development. Zebrafish embryos were exposed to 1 µM 17β-estradiol (E2 or vehicle from 3 hours to 4 days post fertilization (dpf, harvested at 1, 2, 3 and 4 dpf, and subjected to RNA extraction for transcriptome analysis using microarrays. Differentially expressed genes by E2-treatment were analyzed with hierarchical clustering followed by biological process and tissue enrichment analysis. Markedly distinct sets of genes were up and down-regulated by E2 at the four different time points. Among these genes, only the well-known estrogenic marker vtg1 was co-regulated at all time points. Despite this, the biological functional categories targeted by E2 were relatively similar throughout zebrafish development. According to knowledge-based tissue enrichment, estrogen responsive genes were clustered mainly in the liver, pancreas and brain. This was in line with the developmental dynamics of estrogen-target tissues that were visualized using transgenic zebrafish containing estrogen responsive elements driving the expression of GFP (Tg(5xERE:GFP. Finally, the identified embryonic estrogen-responsive genes were compared to already published estrogen-responsive genes identified in male adult zebrafish (Gene Expression Omnibus database. The expressions of a few genes were co-regulated by E2 in both embryonic and adult zebrafish. These could potentially be used as estrogenic biomarkers for exposure to estrogens or estrogenic endocrine disruptors in zebrafish. In conclusion, our data suggests that estrogen effects on early embryonic zebrafish development are stage- and tissue- specific.
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Neighborhood crime and access to health-enabling resources in Chicago
Directory of Open Access Journals (Sweden)
Elizabeth L. Tung
2018-03-01
Full Text Available Neighborhood crime may be an important social determinant of health in many high-poverty, urban communities, yet little is known about its relationship with access to health-enabling resources. We recruited an address-based probability sample of 267 participants (ages ≥35 years on Chicago's South Side between 2012 and 2013. Participants were queried about their perceptions of neighborhood safety and prior experiences of neighborhood crime. Survey data were paired to a comprehensive, directly-observed census of the built environment on the South Side of Chicago. Multivariable logistic regression models were used to examine access to health-enabling resources (potential and realized access as a function of neighborhood crime (self-reported neighborhood safety and prior experience of theft or property crime, adjusting for sociodemographic characteristics and self-reported health status. Low potential access was defined as a resident having nearest resources >1 mile from home; poor realized access was defined as bypassing nearby potential resources to use resources >1 mile from home. Poor neighborhood safety was associated with low potential access to large grocery stores (AOR = 1.73, 95% CI = 1.04, 2.87, pharmacies (AOR = 2.24, 95% CI = 1.33, 3.77, and fitness resources (AOR = 1.93, 95% CI = 1.15, 3.24, but not small grocery stores. Any prior experience of neighborhood crime was associated with higher adjusted odds of bypassing nearby pharmacies (AOR = 3.78, 95% CI = 1.11, 12.87. Neighborhood crime may be associated with important barriers to accessing health-enabling resources in urban communities with high rates of crime. Keywords: Built environment, Neighborhood crime, Access to resources, Social determinants of health, Obesity, Hypertension
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Resurgent Ethnicity among Asian Americans: Ethnic Neighborhood Context and Health
Walton, Emily
2012-01-01
In this study I investigate the associations of neighborhood socioeconomic and social environments with the health of Asian Americans living in both Asian ethnic neighborhoods and non-Asian neighborhoods. I use a sample of 1962 Asian Americans from the National Latino and Asian American Study (NLAAS, 2003-04). Three key findings emerge. First,…
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Neighborhood Environmental Health and Premature Death From Cardiovascular Disease.
Gaglioti, Anne H; Xu, Junjun; Rollins, Latrice; Baltrus, Peter; O'Connell, Laura Kathryn; Cooper, Dexter L; Hopkins, Jammie; Botchwey, Nisha D; Akintobi, Tabia Henry
2018-02-01
Cardiovascular disease (CVD) is the leading cause of death in the United States and disproportionately affects racial/ethnic minority groups. Healthy neighborhood conditions are associated with increased uptake of health behaviors that reduce CVD risk, but minority neighborhoods often have poor food access and poor walkability. This study tested the community-driven hypothesis that poor access to food at the neighborhood level and poor neighborhood walkability are associated with racial disparities in premature deaths from CVD. We examined the relationship between neighborhood-level food access and walkability on premature CVD mortality rates at the census tract level for the city of Atlanta using multivariable logistic regression models. We produced maps to illustrate premature CVD mortality, food access, and walkability by census tract for the city. We found significant racial differences in premature CVD mortality rates and geographic disparities in food access and walkability among census tracts in Atlanta. Improved food access and walkability were associated with reduced overall premature CVD mortality in unadjusted models, but this association did not persist in models adjusted for census tract population composition and poverty. Census tracts with high concentrations of minority populations had higher levels of poor food access, poor walkability, and premature CVD mortality. This study highlights disparities in premature CVD mortality and neighborhood food access and walkability at the census tract level in the city of Atlanta. Improving food access may have differential effects for subpopulations living in the same area. These results can be used to calibrate neighborhood-level interventions, and they highlight the need to examine race-specific health outcomes.
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Neighborhood perceptions and allostatic load: Evidence from Denmark.
van Deurzen, Ioana; Rod, Naja Hulvej; Christensen, Ulla; Hansen, Åse Marie; Lund, Rikke; Dich, Nadya
2016-07-01
An influential argument explaining why living in certain neighborhoods can become harmful to one's health maintains that individuals can perceive certain characteristics of the neighborhood as threatening and the prolonged exposure to a threatening environment could induce chronic stress. Following this line of argumentation, in the present study we test whether subjective perceptions of neighborhood characteristics relate to an objective measure of stress-related physiological functioning, namely allostatic load (AL). We use a large dataset of 5280 respondents living in different regions of Denmark and we account for two alternative mechanisms, i.e., the objective characteristics of the living environment and the socio-economic status of individuals. Our results support the chronic stress mechanisms linking neighborhood quality to health. Heightened perceptions of disorder and pollution were found related to AL and this relationship was particularly robust for women. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Shin, J; Cho, K H; Choi, Y; Lee, S G; Park, E-C; Jang, S-I
2016-03-01
The study aims to determine whether dyslipidemia patients living in less affluent neighborhood are at a higher risk of mortality compared to those living in more affluent neighborhoods. A population-based cohort study was conducted using a stratified representative sampling from the National Health Insurance claim data from 2002 to 2013. The target subjects comprise patients newly diagnosed with dyslipidemia receiving medication. We performed a survival analysis using the Cox proportional hazard model. Of 11,946 patients with dyslipidemia, 1053 (8.8%) subjects died during the follow-up period. Of the dyslipidemia patients earning a middle-class income, the adjusted HR in less affluent neighborhoods was higher than that in the more affluent neighborhoods compared to the reference category of high individual SES in more affluent neighborhoods (less affluent; hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.35-1.99 vs. more affluent; HR = 1.48, 95% CI: 1.20-1.81, respectively). We obtained consistent results in patients with lower income, wherein the adjusted HR in less affluent neighborhoods was higher than that in more affluent neighborhoods (less affluent; HR = 1.52, 95% CI: 1.16-1.97 vs. more affluent; HR = 1.41, 95% CI: 1.04-1.92, respectively). Living in a less affluent neighborhood contributes to higher mortality among dyslipidemia patients. The individual- and neighborhood-level variables cumulatively affect individuals such that the most at-risk individuals include those having both individual- and neighborhood-level risk factors. These findings raise important clinical and public health concerns and indicate that neighborhood SES approaches should be essentially considered in health-care policies similar to individual SES. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University
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Sharkey, Joseph R; Horel, Scott; Han, Daikwon; Huber, John C
2009-02-16
To determine the extent to which neighborhood needs (socioeconomic deprivation and vehicle availability) are associated with two criteria of food environment access: 1) distance to the nearest food store and fast food restaurant and 2) coverage (number) of food stores and fast food restaurants within a specified network distance of neighborhood areas of colonias, using ground-truthed methods. Data included locational points for 315 food stores and 204 fast food restaurants, and neighborhood characteristics from the 2000 U.S. Census for the 197 census block group (CBG) study area. Neighborhood deprivation and vehicle availability were calculated for each CBG. Minimum distance was determined by calculating network distance from the population-weighted center of each CBG to the nearest supercenter, supermarket, grocery, convenience store, dollar store, mass merchandiser, and fast food restaurant. Coverage was determined by calculating the number of each type of food store and fast food restaurant within a network distance of 1, 3, and 5 miles of each population-weighted CBG center. Neighborhood need and access were examined using Spearman ranked correlations, spatial autocorrelation, and multivariate regression models that adjusted for population density. Overall, neighborhoods had best access to convenience stores, fast food restaurants, and dollar stores. After adjusting for population density, residents in neighborhoods with increased deprivation had to travel a significantly greater distance to the nearest supercenter or supermarket, grocery store, mass merchandiser, dollar store, and pharmacy for food items. The results were quite different for association of need with the number of stores within 1 mile. Deprivation was only associated with fast food restaurants; greater deprivation was associated with fewer fast food restaurants within 1 mile. CBG with greater lack of vehicle availability had slightly better access to more supercenters or supermarkets, grocery
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Directory of Open Access Journals (Sweden)
Han Daikwon
2009-02-01
Full Text Available Abstract Objective To determine the extent to which neighborhood needs (socioeconomic deprivation and vehicle availability are associated with two criteria of food environment access: 1 distance to the nearest food store and fast food restaurant and 2 coverage (number of food stores and fast food restaurants within a specified network distance of neighborhood areas of colonias, using ground-truthed methods. Methods Data included locational points for 315 food stores and 204 fast food restaurants, and neighborhood characteristics from the 2000 U.S. Census for the 197 census block group (CBG study area. Neighborhood deprivation and vehicle availability were calculated for each CBG. Minimum distance was determined by calculating network distance from the population-weighted center of each CBG to the nearest supercenter, supermarket, grocery, convenience store, dollar store, mass merchandiser, and fast food restaurant. Coverage was determined by calculating the number of each type of food store and fast food restaurant within a network distance of 1, 3, and 5 miles of each population-weighted CBG center. Neighborhood need and access were examined using Spearman ranked correlations, spatial autocorrelation, and multivariate regression models that adjusted for population density. Results Overall, neighborhoods had best access to convenience stores, fast food restaurants, and dollar stores. After adjusting for population density, residents in neighborhoods with increased deprivation had to travel a significantly greater distance to the nearest supercenter or supermarket, grocery store, mass merchandiser, dollar store, and pharmacy for food items. The results were quite different for association of need with the number of stores within 1 mile. Deprivation was only associated with fast food restaurants; greater deprivation was associated with fewer fast food restaurants within 1 mile. CBG with greater lack of vehicle availability had slightly better
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The Digital Hood: Social Media Use among Youth in Disadvantaged Neighborhoods.
Stevens, Robin; Gilliard-Matthews, Stacia; Dunaev, Jamie; Woods, Marcus; Brawner, Bridgette M
2017-06-01
This study examines the role of social media in the lives of youth living in disadvantaged neighborhoods. Feminist Standpoint theory, which privileges the voices of marginalized communities in understanding social phenomena, suggests that youth at the margins have specific knowledge that helps us understand social media more broadly. We conducted semi-structured interviews with 30 females and 30 males aged 13 to 24 about their social worlds and neighborhoods, both on- and offline. The findings reveal a dynamic and somewhat concerning interplay between the geographic neighborhood and the digital neighborhood, whereby negative social interactions in the geographic neighborhood are reproduced and amplified on social media.
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Glycoengineering of Human Cell Lines Using Zinc Finger Nuclease Gene Targeting
DEFF Research Database (Denmark)
Steentoft, Catharina; Bennett, Eric Paul; Clausen, Henrik
2013-01-01
Lectin affinity chromatography is a powerful technique for isolation of glycoproteins carrying a specific glycan structure of interest. However, the enormous diversity of glycans present on the cell surface, as well as on individual proteins, makes it difficult to isolate an entire glycoproteome...... with one or even a series of lectins. Here we present a technique to generate cell lines with homogenous truncated O-glycans using zinc finger nuclease gene targeting. Because of their simplified O-glycoproteome, the cells have been named SimpleCells. Glycoproteins from SimpleCells can be isolated...... in a single purification step by lectin chromatography performed on a long lectin column. This protocol describes Zinc finger nuclease gene targeting of human cells to simplify the glycoproteome, as well as lectin chromatography and isolation of glycopeptides from total cell lysates of SimpleCells....
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Baker, Hannah M.; Ranney, Leah M.; Goldstein, Adam O.
2015-01-01
Introduction Retailer noncompliance with limited US tobacco regulations on advertising and labeling was historically patterned by neighborhood in ways that promote health disparities. In 2010, the US Food and Drug Administration (FDA) began enforcing stronger tobacco retailer regulations under the Family Smoking Prevention and Tobacco Control Act of 2009. However, recent research has found no differences in compliance by neighborhood characteristics for FDA advertising and labeling inspections. We sought to investigate the neighborhood characteristics associated with retailer noncompliance with specific FDA advertising and labeling inspections (ie, violations of bans on self-service displays, selling single cigarettes, false or mislabeled products, vending machines, flavored cigarettes, and free samples). Methods We coded FDA advertising and labeling warning letters (n = 718) for type of violations and geocoded advertising and labeling inspections from January 1 through July 31, 2014 (N = 33,543). Using multilevel models, we examined cross-sectional associations between types of violations and neighborhood characteristics previously associated with disparities (ie, percentage black, Latino, under the poverty line, and younger than 18 years). Results Retailer advertising and labeling violations are patterned by who lives in the neighborhood; regulated tobacco products are more likely to be stored behind the counter as the percentage of black or Latino residents increases, and single cigarettes are more often available for purchase in neighborhoods as the percentage of black, poor, or young residents increases. Conclusion Contrary to previous null findings, noncompliance with FDA advertising and labeling regulations is patterned by neighborhood characteristics, sometimes in opposite directions. Given the low likelihood of self-service violations in the same neighborhoods that have high likelihood of single cigarette sales, we suggest targeted approaches to FDA
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Thewes, Verena; Simon, Ronald; Schroeter, Petra; Schlotter, Magdalena; Anzeneder, Tobias; Büttner, Reinhard; Benes, Vladimir; Sauter, Guido; Burwinkel, Barbara; Nicholson, Robert I; Sinn, Hans-Peter; Schneeweiss, Andreas; Deuschle, Ulrich; Zapatka, Marc; Heck, Stefanie; Lichter, Peter
2015-02-15
Endocrine treatment regimens for breast cancer that target the estrogen receptor-α (ERα) are effective, but acquired resistance remains a limiting drawback. One mechanism of acquired resistance that has been hypothesized is functional substitution of the orphan receptor estrogen-related receptor-α (ERRα) for ERα. To examine this hypothesis, we analyzed ERRα and ERα in recurrent tamoxifen-resistant breast tumors and conducted a genome-wide target gene profiling analysis of MCF-7 breast cancer cell populations that were sensitive or resistant to tamoxifen treatment. This analysis uncovered a global redirection in the target genes controlled by ERα, ERRα, and their coactivator AIB1, defining a novel set of target genes in tamoxifen-resistant cells. Beyond differences in the ERα and ERRα target gene repertoires, both factors were engaged in similar pathobiologic processes relevant to acquired resistance. Functional analyses confirmed a requirement for ERRα in tamoxifen- and fulvestrant-resistant MCF-7 cells, with pharmacologic inhibition of ERRα sufficient to partly restore sensitivity to antiestrogens. In clinical specimens (n = 1041), increased expression of ERRα was associated with enhanced proliferation and aggressive disease parameters, including increased levels of p53 in ERα-positive cases. In addition, increased ERRα expression was linked to reduced overall survival in independent tamoxifen-treated patient cohorts. Taken together, our results suggest that ERα and ERRα cooperate to promote endocrine resistance, and they provide a rationale for the exploration of ERRα as a candidate drug target to treat endocrine-resistant breast cancer. ©2015 American Association for Cancer Research.
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Pien, Li-Chung; Chen, Duan-Rung; Chen, Chiou-Jong; Liang, Kuei-Min; Cheng, Yawen
2015-01-01
Workplace violence is known to pose mental health risks. However, whether or not workplace violence in a surrounding area might further increase the risk of mental distress in workers has rarely been examined. The study subjects were 9,393 male and 7,716 female employees who participated in a nationwide survey in 2010. Their personal experiences of workplace violence over the past 1 year were ascertained by a standardized questionnaire. Also assessed were their psychosocial work characteristics and mental distress problems. Neighborhood-level workplace violence was computed based on aggregated data at the county level and was categorized into low-, medium-, and high-level categories. Multilevel logistic regression models were constructed to examine the associations between neighborhood-level workplace violence and individual-level mental distress problems, with adjustment of individual-level experience of workplace violence. The neighborhood-level prevalence of workplace violence ranged from 4.7 to 14.7% in men and from 6.4 to 14.8% in women across 22 counties. As compared with those who live in counties of the lowest tertile of workplace violence, female workers who lived in counties of the highest tertile of workplace violence had a 1.72-fold increased risk for mental distress problems after controlling for individual experience of workplace violence and other psychosocial work characteristics. Neighborhood-level workplace violence was associated with poor mental health in female workers. Preventative strategies targeting workplace violence should pay attention to neighborhood factors and gender-specific effects that might influence societal tolerance of abusive work practices and workers' vulnerability to mental health impacts of workplace violence.
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Cankorur-Cetinkaya, Ayca; Dikicioglu, Duygu; Oliver, Stephen G
2017-11-01
Genome-scale metabolic models are valuable tools for the design of novel strains of industrial microorganisms, such as Komagataella phaffii (syn. Pichia pastoris). However, as is the case for many industrial microbes, there is no executable metabolic model for K. phaffiii that confirms to current standards by providing the metabolite and reactions IDs, to facilitate model extension and reuse, and gene-reaction associations to enable identification of targets for genetic manipulation. In order to remedy this deficiency, we decided to reconstruct the genome-scale metabolic model of K. phaffii by reconciling the extant models and performing extensive manual curation in order to construct an executable model (Kp.1.0) that conforms to current standards. We then used this model to study the effect of biomass composition on the predictive success of the model. Twelve different biomass compositions obtained from published empirical data obtained under a range of growth conditions were employed in this investigation. We found that the success of Kp1.0 in predicting both gene essentiality and growth characteristics was relatively unaffected by biomass composition. However, we found that biomass composition had a profound effect on the distribution of the fluxes involved in lipid, DNA, and steroid biosynthetic processes, cellular alcohol metabolic process, and oxidation-reduction process. Furthermore, we investigated the effect of biomass composition on the identification of suitable target genes for strain development. The analyses revealed that around 40% of the predictions of the effect of gene overexpression or deletion changed depending on the representation of biomass composition in the model. Considering the robustness of the in silico flux distributions to the changing biomass representations enables better interpretation of experimental results, reduces the risk of wrong target identification, and so both speeds and improves the process of directed strain development
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Building Community: The Neighborhood Context of Social Organization
Swaroop, Sapna; Morenoff, Jeffrey D.
2006-01-01
This study explores how neighborhood context influences participation in local social organization through a multilevel-spatial analysis of residents in Chicago neighborhoods. We construct a typology of community participation based on two dimensions: instrumental vs. expressive motivations for participation and formal vs. informal modes of…
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Neighborhood Processes, Self-Efficacy, and Adolescent Mental Health
Dupere, Veronique; Leventhal, Tama; Vitaro, Frank
2012-01-01
Self-efficacy beliefs are central to mental health. Because adolescents' neighborhoods shape opportunities for experiences of control, predictability, and safety, we propose that neighborhood conditions are associated with adolescents' self-efficacy and, in turn, their internalizing problems (i.e., depression/anxiety symptoms). We tested these…
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Contemporary Neighborhood Theories: Integration versus Romance and Reaction.
Stever, James A.
1978-01-01
This paper discusses the integrative, romantic, and reactive theories of neighborhood government within the context of the urban reform movement and argues that the integrative theory is the one best suited for an effective political relationship between the neighborhood and the greater metropolis. (EB)
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Targeted repression of AXIN2 and MYC gene expression using designer TALEs
International Nuclear Information System (INIS)
Rennoll, Sherri A.; Scott, Samantha A.; Yochum, Gregory S.
2014-01-01
Highlights: • We designed TALE–SID fusion proteins to target AXIN2 and MYC. • TALE–SIDs bound the chromosomal AXIN2 and MYC genes and repressed their expression. • TALE–SIDs repress β-catenin S45F -dependent AXIN2 and MYC transcription. - Abstract: Designer TALEs (dTALEs) are chimeric transcription factors that can be engineered to regulate gene expression in mammalian cells. Whether dTALEs can block gene transcription downstream of signal transduction cascades, however, has yet to be fully explored. Here we tested whether dTALEs can be used to target genes whose expression is controlled by Wnt/β-catenin signaling. TALE DNA binding domains were engineered to recognize sequences adjacent to Wnt responsive enhancer elements (WREs) that control expression of axis inhibition protein 2 (AXIN2) and c-MYC (MYC). These custom DNA binding domains were linked to the mSin3A interaction domain (SID) to generate TALE–SID chimeric repressors. The TALE–SIDs repressed luciferase reporter activity, bound their genomic target sites, and repressed AXIN2 and MYC expression in HEK293 cells. We generated a novel HEK293 cell line to determine whether the TALE–SIDs could function downstream of oncogenic Wnt/β-catenin signaling. Treating these cells with doxycycline and tamoxifen stimulates nuclear accumulation of a stabilized form of β-catenin found in a subset of colorectal cancers. The TALE–SIDs repressed AXIN2 and MYC expression in these cells, which suggests that dTALEs could offer an effective therapeutic strategy for the treatment of colorectal cancer
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Targeted repression of AXIN2 and MYC gene expression using designer TALEs
Energy Technology Data Exchange (ETDEWEB)
Rennoll, Sherri A.; Scott, Samantha A.; Yochum, Gregory S., E-mail: gsy3@psu.edu
2014-04-18
Highlights: • We designed TALE–SID fusion proteins to target AXIN2 and MYC. • TALE–SIDs bound the chromosomal AXIN2 and MYC genes and repressed their expression. • TALE–SIDs repress β-catenin{sup S45F}-dependent AXIN2 and MYC transcription. - Abstract: Designer TALEs (dTALEs) are chimeric transcription factors that can be engineered to regulate gene expression in mammalian cells. Whether dTALEs can block gene transcription downstream of signal transduction cascades, however, has yet to be fully explored. Here we tested whether dTALEs can be used to target genes whose expression is controlled by Wnt/β-catenin signaling. TALE DNA binding domains were engineered to recognize sequences adjacent to Wnt responsive enhancer elements (WREs) that control expression of axis inhibition protein 2 (AXIN2) and c-MYC (MYC). These custom DNA binding domains were linked to the mSin3A interaction domain (SID) to generate TALE–SID chimeric repressors. The TALE–SIDs repressed luciferase reporter activity, bound their genomic target sites, and repressed AXIN2 and MYC expression in HEK293 cells. We generated a novel HEK293 cell line to determine whether the TALE–SIDs could function downstream of oncogenic Wnt/β-catenin signaling. Treating these cells with doxycycline and tamoxifen stimulates nuclear accumulation of a stabilized form of β-catenin found in a subset of colorectal cancers. The TALE–SIDs repressed AXIN2 and MYC expression in these cells, which suggests that dTALEs could offer an effective therapeutic strategy for the treatment of colorectal cancer.
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Simple and Efficient Targeting of Multiple Genes Through CRISPR-Cas9 in Physcomitrella patens
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Mauricio Lopez-Obando
2016-11-01
Full Text Available Powerful genome editing technologies are needed for efficient gene function analysis. The CRISPR-Cas9 system has been adapted as an efficient gene-knock-out technology in a variety of species. However, in a number of situations, knocking out or modifying a single gene is not sufficient; this is particularly true for genes belonging to a common family, or for genes showing redundant functions. Like many plants, the model organism Physcomitrella patens has experienced multiple events of polyploidization during evolution that has resulted in a number of families of duplicated genes. Here, we report a robust CRISPR-Cas9 system, based on the codelivery of a CAS9 expressing cassette, multiple sgRNA vectors, and a cassette for transient transformation selection, for gene knock-out in multiple gene families. We demonstrate that CRISPR-Cas9-mediated targeting of five different genes allows the selection of a quintuple mutant, and all possible subcombinations of mutants, in one experiment, with no mutations detected in potential off-target sequences. Furthermore, we confirmed the observation that the presence of repeats in the vicinity of the cutting region favors deletion due to the alternative end joining pathway, for which induced frameshift mutations can be potentially predicted. Because the number of multiple gene families in Physcomitrella is substantial, this tool opens new perspectives to study the role of expanded gene families in the colonization of land by plants.
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Do Neighborhood Characteristics in Amsterdam Influence Adiposity at Preschool Age?
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E. Jessica Hrudey
2015-05-01
Full Text Available Background: Neighborhood characteristics may contribute to adiposity in young children, but results in the current literature are inconsistent. This study aimed to investigate whether objective (socioeconomic status (SES and subjective (perceived safety, satisfaction with green spaces and perceived physical disorder neighborhood characteristics directly influence child adiposity (as measured by BMI, percent body fat (%BF and waist-to-height ratio (WHtR. Methods: Data on child BMI, %BF and WHtR were obtained from the Amsterdam Born Children and their Development cohort at 5–6 years of age. Three thousand four hundred and sixty nine (3469 children were included in the analyses. Mixed models, using random intercepts for postal code area to account for neighborhood clustering effects, were used to analyze the relationships of interest. Results: Associations were observed for both perceived safety and neighborhood SES with %BF after adjustment for maternal education and ethnicity. All relationships were eliminated with the inclusion of individual covariates and parental BMI into the models. Conclusions: In general, child adiposity at age 5–6 years was not independently associated with neighborhood characteristics, although a small relationship between child %BF and both neighborhood SES and perceived safety cannot be ruled out. At this young age, familial and individual factors probably play a more important role in influencing child adiposity than neighborhood characteristics.
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Cognitive Aspects of Regularity Exhibit When Neighborhood Disappears
Chen, Sau-Chin; Hu, Jon-Fan
2015-01-01
Although regularity refers to the compatibility between pronunciation of character and sound of phonetic component, it has been suggested as being part of consistency, which is defined by neighborhood characteristics. Two experiments demonstrate how regularity effect is amplified or reduced by neighborhood characteristics and reveals the…
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Neighborhood size and local geographic variation of health and social determinants
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Emch Michael
2005-06-01
Full Text Available Abstract Background Spatial filtering using a geographic information system (GIS is often used to smooth health and ecological data. Smoothing disease data can help us understand local (neighborhood geographic variation and ecological risk of diseases. Analyses that use small neighborhood sizes yield individualistic patterns and large sizes reveal the global structure of data where local variation is obscured. Therefore, choosing an optimal neighborhood size is important for understanding ecological associations with diseases. This paper uses Hartley's test of homogeneity of variance (Fmax as a methodological solution for selecting optimal neighborhood sizes. The data from a study area in Vietnam are used to test the suitability of this method. Results The Hartley's Fmax test was applied to spatial variables for two enteric diseases and two socioeconomic determinants. Various neighbourhood sizes were tested by using a two step process to implement the Fmaxtest. First the variance of each neighborhood was compared to the highest neighborhood variance (upper, Fmax1 and then they were compared with the lowest neighborhood variance (lower, Fmax2. A significant value of Fmax1 indicates that the neighborhood does not reveal the global structure of data, and in contrast, a significant value in Fmax2 implies that the neighborhood data are not individualistic. The neighborhoods that are between the lower and the upper limits are the optimal neighbourhood sizes. Conclusion The results of tests provide different neighbourhood sizes for different variables suggesting that optimal neighbourhood size is data dependent. In ecology, it is well known that observation scales may influence ecological inference. Therefore, selecting optimal neigborhood size is essential for understanding disease ecologies. The optimal neighbourhood selection method that is tested in this paper can be useful in health and ecological studies.
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Directory of Open Access Journals (Sweden)
Amy R Krystosik
Full Text Available Cali, Colombia has experienced chikungunya and Zika outbreaks and hypoendemic dengue. Studies have explained Cali's dengue patterns but lack the sub-neighborhood-scale detail investigated here.Spatial-video geonarratives (SVG with Ministry of Health officials and Community Health Workers were collected in hotspots, providing perspective on perceptions of why dengue, chikungunya and Zika hotspots exist, impediments to control, and social outcomes. Using spatial video and Google Street View, sub-neighborhood features possibly contributing to incidence were mapped to create risk surfaces, later compared with dengue, chikungunya and Zika case data.SVG captured insights in 24 neighborhoods. Trash and water risks in Calipso were mapped using SVG results. Perceived risk factors included proximity to standing water, canals, poverty, invasions, localized violence and military migration. These risks overlapped case density maps and identified areas that are suitable for transmission but are possibly underreporting to the surveillance system.Resulting risk maps with local context could be leveraged to increase vector-control efficiency- targeting key areas of environmental risk.
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Curtis, Andrew; Buritica, Paola; Ajayakumar, Jayakrishnan; Squires, Robert; Dávalos, Diana; Pacheco, Robinson; Bhatta, Madhav P.; James, Mark A.
2017-01-01
Background Cali, Colombia has experienced chikungunya and Zika outbreaks and hypoendemic dengue. Studies have explained Cali’s dengue patterns but lack the sub-neighborhood-scale detail investigated here. Methods Spatial-video geonarratives (SVG) with Ministry of Health officials and Community Health Workers were collected in hotspots, providing perspective on perceptions of why dengue, chikungunya and Zika hotspots exist, impediments to control, and social outcomes. Using spatial video and Google Street View, sub-neighborhood features possibly contributing to incidence were mapped to create risk surfaces, later compared with dengue, chikungunya and Zika case data. Results SVG captured insights in 24 neighborhoods. Trash and water risks in Calipso were mapped using SVG results. Perceived risk factors included proximity to standing water, canals, poverty, invasions, localized violence and military migration. These risks overlapped case density maps and identified areas that are suitable for transmission but are possibly underreporting to the surveillance system. Conclusion Resulting risk maps with local context could be leveraged to increase vector-control efficiency- targeting key areas of environmental risk. PMID:28767730
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DEFF Research Database (Denmark)
Frandsen, Rasmus John Normand; Andersson, Jens A.; Kristensen, Matilde Bylov
2008-01-01
Background: The rapid increase in whole genome fungal sequence information allows large scale functional analyses of target genes. Efficient transformation methods to obtain site-directed gene replacement, targeted over-expression by promoter replacement, in-frame epitope tagging or fusion...... of coding sequences with fluorescent markers such as GFP are essential for this process. Construction of vectors for these experiments depends on the directional cloning of two homologous recombination sequences on each side of a selection marker gene. Results: Here, we present a USER Friendly cloning based...
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Social Capital and Economic Development: A Neighborhood Perspective
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Matthew J. Hanka
2017-12-01
Full Text Available Sean Safford’s 2009 book Why the Garden Club Couldn’t Save Youngstown introduces a revolutionary idea that much of a community’s economic resilience is tied to the social capital that exists within it. Recent research suggests that social capital not only benefits those who develop it, but it can serve as a source of economic development in the communities in which it arises. Past quantitative research on the economic benefit of social capital has only examined the city or higher levels of aggregation. This study measures social capital in three diverse socioeconomic neighborhoods to better understand how social capital can serve as a tool for economic development. An ordered probit regression model was developed to examine how individual and neighborhood levels of social capital benefit households within these communities. Moreover, this study addresses how differences in social capital across neighborhoods are explained by both individual and neighborhood characteristics.
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NEIGHBORHOOD TEST DESIGN BASED ON HISTORIC PRECEDENTS
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Besim S. Hakim
2012-07-01
Full Text Available There have been various attempts to emulate traditional architecture and to experiment with the form and aesthetics of building design. However, learning from precedents of urban morphology is rare. This design study is a test at the neighborhood level using the pattern of traditional courtyard housing that is prevalent in the majority of historic towns and cities of North Africa and the Middle East. The study is undertaken at five levels of design enquiry: dwelling types, dwelling groups, neighborhood segment and community center. All of which are synthesized into a full prototype neighborhood comprising of 428 dwelling units covering an area that includes circulation and the community center, of 17.6 hectares. The test demonstrates that the traditional pattern of neighborhoods that are based on the typology of the courtyard dwelling as the initial generator of urban form may be used to develop a contemporary settlement pattern that is compatible with current necessities of lifestyle, vehicular circulation, including parking and infrastructure achieving an attractive livable environment with an overall gross density, that includes a community center, of about 24 dwelling units per hectare.
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Schoemaker, Marieke H.; Rots, Marianne G.; Beljaars, Leonie; Ypma, Arjen Y.; Jansen, Peter L. M.; Poelstra, Klaas; Moshage, Albert; Haisma, Hidde J.
2008-01-01
Chronic liver damage may lead to liver fibrosis. In this process, hepatic activated stellate cells are the key players. Thus, activated stellate cells are attractive targets for antifibrotic gene therapy. Recombinant, adenovirus is a promising vehicle for delivering therapeutic genes to liver cells.
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De Meester, Femke; Van Dyck, Delfien; De Bourdeaudhuij, Ilse; Deforche, Benedicte; Cardon, Greet
2013-03-01
Ecological models emphasize the interaction between individuals and their environment. Furthermore, they posit that environmental variables influence physical activity (PA) not only directly but also indirectly through their interaction with other factors. This study explored if the association between neighborhood walkability and adolescents' PA is moderated by psychosocial factors using data from the Belgian Environmental PA Study in Youth (BEPAS-Y). BEPAS-Y recruited adolescents from 32 neighborhoods differing in objectively determined neighborhood walkability and income. Between 2008 and 2009, 637 adolescents (13-15 years; 49.4% boys) completed a survey measuring socio-demographic and psychosocial factors and wore an accelerometer for seven days. Multilevel-regression analyses revealed that for adolescents living in low-income neighborhoods, the association between neighborhood walkability and PA is moderated by perceived barriers and perceived benefits toward PA. Neighborhood walkability was positively associated with PA among adolescents, living in low-income neighborhoods, who perceived many barriers and few benefits, while for adolescents who perceived few barriers and many benefits, the PA level was high, irrespective of neighborhood walkability. For adolescents, living in high-income neighborhoods, none of the psychosocial attributes moderated the association between neighborhood walkability and PA. These findings provide some support for the predicted interactions posited by ecological models. Improving neighborhood walkability might increase PA-levels of adolescents living in low-income neighborhoods, with less positive psychosocial profiles, or in other words; those who are most difficult to reach through PA interventions. However, in order to increase PA in large populations, interventions focusing solely on improving neighborhood walkability may not have the desired effect. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Neighborhood Child Opportunity and Individual-Level Pediatric Acute Care Use and Diagnoses.
Kersten, Ellen E; Adler, Nancy E; Gottlieb, Laura; Jutte, Douglas P; Robinson, Sarah; Roundfield, Katrina; LeWinn, Kaja Z
2018-05-01
: media-1vid110.1542/5751513300001PEDS-VA_2017-2309 Video Abstract OBJECTIVES: Although health care providers and systems are increasingly interested in patients' nonmedical needs as a means to improve health, little is known about neighborhood conditions that contribute to child health problems. We sought to determine if a novel, publicly available measure of neighborhood context, the Child Opportunity Index, was associated with pediatric acute care visit frequency and diagnoses. This cross-sectional study included San Francisco residents <18 years of age with an emergency department and/or urgent care visit to any of 3 medical systems ( N = 47 175) between 2007 and 2011. Hot-spot analysis was used to compare the spatial distribution of neighborhood child opportunity and income. Generalized estimating equation logistic regression models were used to examine independent associations between neighborhood child opportunity and frequent acute care use (≥4 visits per year) and diagnosis group after adjusting for neighborhood income and patient age, sex, race and/or ethnicity, payer, and health system. Neighborhood child opportunity and income had distinct spatial distributions, and we identified different clusters of high- and low-risk neighborhoods. Children living in the lowest opportunity neighborhoods had significantly greater odds of ≥4 acute care visits per year (odds ratio 1.33; 95% confidence interval 1.03-1.73) compared with those in the highest opportunity neighborhoods. Neighborhood child opportunity was negatively associated with visits for respiratory conditions, asthma, assault, and ambulatory care-sensitive conditions but positively associated with injury-related visits. The Child Opportunity Index could be an effective tool for identifying neighborhood factors beyond income related to child health. Copyright © 2018 by the American Academy of Pediatrics.
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Neighborhood Environmental Health and Premature Death From Cardiovascular Disease
Xu, Junjun; Rollins, Latrice; Baltrus, Peter; O’Connell, Laura Kathryn; Cooper, Dexter L.; Hopkins, Jammie; Botchwey, Nisha D.; Akintobi, Tabia Henry
2018-01-01
Introduction Cardiovascular disease (CVD) is the leading cause of death in the United States and disproportionately affects racial/ethnic minority groups. Healthy neighborhood conditions are associated with increased uptake of health behaviors that reduce CVD risk, but minority neighborhoods often have poor food access and poor walkability. This study tested the community-driven hypothesis that poor access to food at the neighborhood level and poor neighborhood walkability are associated with racial disparities in premature deaths from CVD. Methods We examined the relationship between neighborhood-level food access and walkability on premature CVD mortality rates at the census tract level for the city of Atlanta using multivariable logistic regression models. We produced maps to illustrate premature CVD mortality, food access, and walkability by census tract for the city. Results We found significant racial differences in premature CVD mortality rates and geographic disparities in food access and walkability among census tracts in Atlanta. Improved food access and walkability were associated with reduced overall premature CVD mortality in unadjusted models, but this association did not persist in models adjusted for census tract population composition and poverty. Census tracts with high concentrations of minority populations had higher levels of poor food access, poor walkability, and premature CVD mortality. Conclusion This study highlights disparities in premature CVD mortality and neighborhood food access and walkability at the census tract level in the city of Atlanta. Improving food access may have differential effects for subpopulations living in the same area. These results can be used to calibrate neighborhood-level interventions, and they highlight the need to examine race-specific health outcomes. PMID:29389312
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Working with neighborhood organizations to promote wildfire preparedness
Holly Johnson Shiralipour; Martha C. Monroe; Michelle Payton
2006-01-01
Several government agencies and other natural resource managers have instituted outreach programs to promote wildfire preparedness in wildland-urban interface (WUI) neighborhoods that complement community-wide efforts. To help these programs become more effective, research was undertaken to gain a better understanding of the role that neighbors and neighborhood...
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Production of cloned pigs with targeted attenuation of gene expression.
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Vilceu Bordignon
Full Text Available The objective of this study was to demonstrate that RNA interference (RNAi and somatic cell nuclear transfer (SCNT technologies can be used to attenuate the expression of specific genes in tissues of swine, a large animal species. Apolipoprotein E (apoE, a secreted glycoprotein known for its major role in lipid and lipoprotein metabolism and transport, was selected as the target gene for this study. Three synthetic small interfering RNAs (siRNA targeting the porcine apoE mRNA were tested in porcine granulosa cells in primary culture and reduced apoE mRNA abundance ranging from 45-82% compared to control cells. The most effective sequence was selected for cloning into a short hairpin RNA (shRNA expression vector under the control of RNA polymerase III (U6 promoter. Stably transfected fetal porcine fibroblast cells were generated and used to produce embryos with in vitro matured porcine oocytes, which were then transferred into the uterus of surrogate gilts. Seven live and one stillborn piglet were born from three gilts that became pregnant. Integration of the shRNA expression vector into the genome of clone piglets was confirmed by PCR and expression of the GFP transgene linked to the expression vector. Analysis showed that apoE protein levels in the liver and plasma of the clone pigs bearing the shRNA expression vector targeting the apoE mRNA was significantly reduced compared to control pigs cloned from non-transfected fibroblasts of the same cell line. These results demonstrate the feasibility of applying RNAi and SCNT technologies for introducing stable genetic modifications in somatic cells for eventual attenuation of gene expression in vivo in large animal species.
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Beyond the Cross-Sectional: Neighborhood Poverty Histories and Preterm Birth
Margerison-Zilko, Claire; Jun, Jina; Marchi, Kristen; Fingar, Kathryn; Braveman, Paula
2015-01-01
Objectives. We examined associations between longitudinal neighborhood poverty trajectories and preterm birth (PTB). Methods. Using data from the Neighborhood Change Database (1970–2000) and the American Community Survey (2005–2009), we categorized longitudinal trajectories of poverty for California neighborhoods (i.e., census tracts). Birth data included 23 291 singleton California births from the Maternal and Infant Health Assessment (2003–2009). We estimated associations (adjusted for individual-level covariates) between PTB and longitudinal poverty trajectories and compared these to associations using traditional, cross-sectional measures of poverty. Results. Compared to neighborhoods with long-term low poverty, those with long-term high poverty and those that experienced increasing poverty early in the study period had 41% and 37% increased odds of PTB (95% confidence interval [CI] = 1.18, 1.69 and 1.09, 1.72, respectively). High (compared with low) cross-sectional neighborhood poverty was not associated with PTB (odds ratio = 1.08; 95% CI = 0.91, 1.28). Conclusions. Neighborhood poverty histories may contribute to an understanding of perinatal health and should be considered in future research. PMID:25880941
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A Streaming Distance Transform Algorithm for Neighborhood-Sequence Distances
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Nicolas Normand
2014-09-01
Full Text Available We describe an algorithm that computes a “translated” 2D Neighborhood-Sequence Distance Transform (DT using a look up table approach. It requires a single raster scan of the input image and produces one line of output for every line of input. The neighborhood sequence is specified either by providing one period of some integer periodic sequence or by providing the rate of appearance of neighborhoods. The full algorithm optionally derives the regular (centered DT from the “translated” DT, providing the result image on-the-fly, with a minimal delay, before the input image is fully processed. Its efficiency can benefit all applications that use neighborhood- sequence distances, particularly when pipelined processing architectures are involved, or when the size of objects in the source image is limited.
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Race, Neighborhood Economic Status, Income Inequality and Mortality.
Mode, Nicolle A; Evans, Michele K; Zonderman, Alan B
2016-01-01
Mortality rates in the United States vary based on race, individual economic status and neighborhood. Correlations among these variables in most urban areas have limited what conclusions can be drawn from existing research. Our study employs a unique factorial design of race, sex, age and individual poverty status, measuring time to death as an objective measure of health, and including both neighborhood economic status and income inequality for a sample of middle-aged urban-dwelling adults (N = 3675). At enrollment, African American and White participants lived in 46 unique census tracts in Baltimore, Maryland, which varied in neighborhood economic status and degree of income inequality. A Cox regression model for 9-year mortality identified a three-way interaction among sex, race and individual poverty status (p = 0.03), with African American men living below poverty having the highest mortality. Neighborhood economic status, whether measured by a composite index or simply median household income, was negatively associated with overall mortality (pinequality was associated with mortality through an interaction with individual poverty status (p = 0.04). While racial and economic disparities in mortality are well known, this study suggests that several social conditions associated with health may unequally affect African American men in poverty in the United States. Beyond these individual factors are the influences of neighborhood economic status and income inequality, which may be affected by a history of residential segregation. The significant association of neighborhood economic status and income inequality with mortality beyond the synergistic combination of sex, race and individual poverty status suggests the long-term importance of small area influence on overall mortality.
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Directory of Open Access Journals (Sweden)
Pooja Ghatalia
Full Text Available Kinases are therapeutically actionable targets. Kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR and mammalian target of rapamycin (mTOR improve outcomes in metastatic clear cell renal cell carcinoma (ccRCC, but are not curative. Metastatic tumor tissue has not been comprehensively studied for kinase gene expression. Paired intra-patient kinase gene expression analysis in primary tumor (T, matched normal kidney (N and metastatic tumor tissue (M may assist in identifying drivers of metastasis and prioritizing therapeutic targets. We compared the expression of 519 kinase genes using NanoString in T, N and M in 35 patients to discover genes over-expressed in M compared to T and N tissue. RNA-seq data derived from ccRCC tumors in The Cancer Genome Atlas (TCGA were used to demonstrate differential expression of genes in primary tumor tissue from patients that had metastasis at baseline (n = 79 compared to those that did not develop metastasis for at least 2 years (n = 187. Functional analysis was conducted to identify key signaling pathways by using Ingenuity Pathway Analysis. Of 10 kinase genes overexpressed in metastases compared to primary tumor in the discovery cohort, 9 genes were also differentially expressed in TCGA primary tumors with metastasis at baseline compared to primary tumors without metastasis for at least 2 years: EPHB2, AURKA, GSG2, IKBKE, MELK, CSK, CHEK2, CDC7 and MAP3K8; p<0.001. The top pathways overexpressed in M tissue were pyridoxal 5'-phosphate salvage, salvage pathways of pyrimidine ribonucleotides, NF-kB signaling, NGF signaling and cell cycle control of chromosomal replication. The 9 kinase genes validated to be over-expressed in metastatic ccRCC may represent currently unrecognized but potentially actionable therapeutic targets that warrant functional validation.
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The influence of neighborhood socioeconomic status and walkability on TV viewing time.
Coogan, Patricia F; White, Laura F; Evans, Stephen R; Palmer, Julie R; Rosenberg, Lynn
2012-11-01
Influences on TV viewing time, which is associated with adverse health outcomes such as obesity and diabetes, need clarification. We assessed the relation of neighborhood socioeconomic status (SES) and walkability with TV viewing time in the Black Women's Health Study, a prospective study of African American women. We created neighborhood SES and walkability scores using data from the U.S. census and other sources. We estimated odds ratios for TV viewing 5+ hours/day compared with 0-1 hours/day for quintiles of neighborhood SES and walkability scores. Neighborhood SES was inversely associated with TV viewing time. The odds ratio for watching 5+ hours/day in the highest compared with the lowest quintile of neighborhood SES was 0.66 (95% CI 0.54-0.81). Neighborhood walkability was not associated with TV viewing time. Neighborhood SES should be considered in devising strategies to combat the high levels of sedentariness prevalent in African American women.
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The influencing factors on place attachment in neighborhood of Kampung Melayu
Lestari, W. M.; Sumabrata, J.
2018-03-01
Place attachment on neighborhood differs according to place characteristics and person characteristics. By dividing the research area of Kelurahan Kampung Melayu into flood area and non-flood area, this research aims at analyzing place attachment on neighborhood and analyzing factors influencing the place attachment. This research using quantitative approach using Structural Equation Modeling (SEM). Self-administered questionnaires using likert scale were distributed randomly to 400 residents. Result of the research shows that residents tend to have place attachment to their neighborhood. Factors influencing place attachment on residents born in the neighborhood with length of stay 10 years or longer and having house are family factor for residents living in non-flood area and physical factor as well as social factor for residents in flood area. This research concludes that place attachment on neighborhood is formed because dimension of place is interpreted not merely physically but also socially, namely the existence of family ties and social relationship with people in the neighborhood.
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Isolation and expression analysis of four HD-ZIP III family genes targeted by microRNA166 in peach.
Zhang, C H; Zhang, B B; Ma, R J; Yu, M L; Guo, S L; Guo, L
2015-10-30
MicroRNA166 (miR166) is known to have highly conserved targets that encode proteins of the class III homeodomain-leucine zipper (HD-ZIP III) family, in a broad range of plant species. To further understand the relationship between HD-ZIP III genes and miR166, four HD-ZIP III family genes (PpHB14, PpHB15, PpHB8, and PpREV) were isolated from peach (Prunus persica) tissue and characterized. Spatio-temporal expression profiles of the genes were analyzed. Genes of the peach HD-ZIP III family were predicted to encode five conserved domains. Deduced amino acid sequences and tertiary structures of the four peach HD-ZIP III genes were highly conserved, with corresponding genes in Arabidopsis thaliana. The expression level of four targets displayed the opposite trend to that of miR166 throughout fruit development, with the exception of PpHB14 from 35 to 55 days after full bloom (DAFB). This finding indicates that miR166 may negatively regulate its four targets throughout fruit development. As for leaf and phloem, the same trend in expression level was observed between four targets and miR166 from 75 to 105 DAFB. However, the opposite trend was observed for the transcript level between four targets and miR166 from 35 to 55 DAFB. miRNA166 may negatively regulate four targets in some but not all developmental stages for a given tissue. The four genes studied were observed to have, exactly or generally, the same change tendency as individual tissue development, a finding that suggests genes of the HD-ZIP III family in peach may have complementary or cooperative functions in various tissues.
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Côté-Lussier, Carolyn; Barnett, Tracie A; Kestens, Yan; Tu, Mai Thanh; Séguin, Louise
2015-06-01
Although disadvantaged youth are more likely to be victimized at school, victimization only partly explains their decreased feelings of safety at school. We applied a socioecological approach to test the hypotheses that the experience of poverty is associated with decreased feelings of safety at school, and that residential neighborhood features partly mediate the relationship between poverty and feeling less safe at school. This study draws on the Québec Longitudinal Study of Child Development (QLSCD) which began in 1998 with a representative population-based cohort of 2,120 5-month old infants (49.1% female) and their primary caregiver. The study also includes measures of ego-centred residential neighborhood exposures (based on a 500 m circular buffer zone surrounding the family's residential postal code) derived from a spatial data infrastructure. We used latent growth modeling to estimate youth's family poverty trajectory from age 5 months to 13 years, and structural equation modeling to test our hypotheses. The results suggest that youth experiencing chronic and later-childhood poverty felt less safe at school in part because they lived in neighborhoods that their parents described as being disorderly (e.g., demarked by the presence of garbage, drug use and groups of trouble-makers). These neighborhoods also tended to have less greenery (e.g., trees, parks) and more lone-parent households. Neighborhood features did not help explain the relationship between early-childhood poverty and feeling less safe at school. The findings suggest that targeting residential neighborhood features such as greenery and disorder could improve youth's felt safety at school, particularly for those experiencing chronic and later-childhood poverty.
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Sharkey, Joseph R; Horel, Scott; Han, Daikwon; Huber, John C
2009-01-01
Abstract Objective To determine the extent to which neighborhood needs (socioeconomic deprivation and vehicle availability) are associated with two criteria of food environment access: 1) distance to the nearest food store and fast food restaurant and 2) coverage (number) of food stores and fast food restaurants within a specified network distance of neighborhood areas of colonias, using ground-truthed methods. Methods Data included locational points for 315 food stores and 204 fast food rest...
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Parental Perceptions of Neighborhood Effects in Latino Comunas
Horner, Pilar; Sanchez, Ninive; Castillo, Marcela; Delva, Jorge
2011-01-01
Objectives To obtain rich information about how adult Latinos living in high-poverty/high-drug use neighborhoods perceive and negotiate their environment. Methods In 2008, thirteen adult caregivers in Santiago, Chile were interviewed with open-ended questions to ascertain beliefs about neighborhood effects and drug use. Analysis Inductive analysis was used to develop the codebook/identify trends. Discussion Residents externalized their understanding of drug use and misuse by invoking the concept of delinquent youth. A typology of their perceptions is offered. Learning more about residents’ circumstances may help focus on needs-based interventions. More research with Latino neighborhoods is needed for culturally-competent models of interventions. PMID:22497879
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From Neurons to Neighborhoods: An Update--Workshop Summary
Olson, Steve
2012-01-01
"From Neurons to Neighborhoods: An Update: Workshop Summary" is based on the original study "From Neurons to Neighborhoods: Early Childhood Development," which was released in October of 2000. From the time of the original publication's release, much has occurred to cause a fundamental reexamination of the nation's…
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Interaction between parenting and neighborhood quality on the risk of adolescent regular smoking.
Wen, Xiaozhong; Shenassa, Edmond D
2012-03-01
To conduct the first study to examine potential interaction between parenting style and neighborhood quality on the risk of adolescent regular smoking. We analyzed data from a nationally representative sample of U.S. adolescents (n = 1,213 pairs of adolescents and their parents) who participated in the Panel Study of Income Dynamics during 2002-2003. Regular smoking behavior and parental monitoring level were reported by adolescents. Parenting style (i.e., authoritative, authoritarian, permissive, and uninvolved) was defined by cross-classifying self-reported parental warmth and control. Based on parents' perceived neighborhood quality regarding raising children, neighborhoods were identified as either higher quality or lower quality. Adolescents in lower-quality neighborhoods were more likely to be regular smokers (13.7% vs. 8.5%; adjusted odds ratio [AOR] = 1.93, 95% CI = 1.02-3.65) than those in higher-quality neighborhoods. In lower-quality neighborhoods, adolescents of authoritarian parents (16.9%; AOR = 10.97, 95% CI = 3.36-35.84) were more likely and those of uninvolved parents (20.3%; AOR = 3.47, 95% CI = 0.91-13.17) were marginally more likely to be regular smokers than those of authoritative parents (4.3%). However, among adolescents in higher-quality neighborhoods, parenting style was independent of the risk of regular smoking. There was marginally significant interaction between authoritarian parenting style and neighborhood quality. Parental monitoring was associated with reduced risk of adolescent smoking, regardless of neighborhood quality. There was no interaction between parental monitoring and neighborhood quality. Authoritative parenting is associated with reduced risk of adolescent regular smoking in lower-quality neighborhoods but not in higher-quality neighborhoods. Authoritative parenting style and parental monitoring may buffer adverse influences of low-quality neighborhood.
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Good and Bad Neighborhood Approximations for Outlier Detection Ensembles
DEFF Research Database (Denmark)
Kirner, Evelyn; Schubert, Erich; Zimek, Arthur
2017-01-01
Outlier detection methods have used approximate neighborhoods in filter-refinement approaches. Outlier detection ensembles have used artificially obfuscated neighborhoods to achieve diverse ensemble members. Here we argue that outlier detection models could be based on approximate neighborhoods...... in the first place, thus gaining in both efficiency and effectiveness. It depends, however, on the type of approximation, as only some seem beneficial for the task of outlier detection, while no (large) benefit can be seen for others. In particular, we argue that space-filling curves are beneficial...
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Walk Score(TM), Perceived Neighborhood Walkability, and walking in the US.
Tuckel, Peter; Milczarski, William
2015-03-01
To investigate both the Walk Score(TM) and a self-reported measure of neighborhood walkability ("Perceived Neighborhood Walkability") as estimators of transport and recreational walking among Americans. The study is based upon a survey of a nationally-representative sample of 1224 American adults. The survey gauged walking for both transport and recreation and included a self-reported measure of neighborhood walkability and each respondent's Walk Score(TM). Binary logistic and linear regression analyses were performed on the data. The Walk Score(TM) is associated with walking for transport, but not recreational walking nor total walking. Perceived Neighborhood Walkability is associated with transport, recreational and total walking. Perceived Neighborhood Walkability captures the experiential nature of walking more than the Walk Score(TM).
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Examining the social porosity of environmental features on neighborhood sociability and attachment.
Directory of Open Access Journals (Sweden)
John R Hipp
Full Text Available The local neighborhood forms an integral part of our lives. It provides the context through which social networks are nurtured and the foundation from which a sense of attachment and cohesion with fellow residents can be established. Whereas much of the previous research has examined the role of social and demographic characteristic in relation to the level of neighboring and cohesion, this paper explores whether particular environmental features in the neighborhood affect social porosity. We define social porosity as the degree to which social ties flow over the surface of a neighborhood. The focus of our paper is to examine the extent to which a neighborhood's environmental features impede the level of social porosity present among residents. To do this, we integrate data from the census, topographic databases and a 2010 survey of 4,351 residents from 146 neighborhoods in Australia. The study introduces the concepts of wedges and social holes. The presence of two sources of wedges is measured: rivers and highways. The presence of two sources of social holes is measured: parks and industrial areas. Borrowing from the geography literature, several measures are constructed to capture how these features collectively carve up the physical environment of neighborhoods. We then consider how this influences residents' neighboring behavior, their level of attachment to the neighborhood and their sense of neighborhood cohesion. We find that the distance of a neighborhood to one form of social hole-industrial areas-has a particularly strong negative effect on all three dependent variables. The presence of the other form of social hole-parks-has a weaker negative effect. Neighborhood wedges also impact social interaction. Both the length of a river and the number of highway fragments in a neighborhood has a consistent negative effect on neighboring, attachment and cohesion.
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Directory of Open Access Journals (Sweden)
David A. Brown
2017-09-01
Full Text Available Chromatin modifications and the promoter-associated epigenome are important for the regulation of gene expression. However, the mechanisms by which chromatin-modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live-cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed gene promoters through CFP1, which engages in a form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3. CFP1 defines SET1 complex occupancy on chromatin, and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed, suggesting that normal targeting and function of the SET1 complex are central to creating an appropriately functioning vertebrate promoter-associated epigenome.
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Suen, Colin M; Mei, Shirley H J; Kugathasan, Lakshmi; Stewart, Duncan J
2013-10-01
Pulmonary arterial hypertension (PAH) is a devastating disease that, despite significant advances in medical therapies over the last several decades, continues to have an extremely poor prognosis. Gene therapy is a method to deliver therapeutic genes to replace defective or mutant genes or supplement existing cellular processes to modify disease. Over the last few decades, several viral and nonviral methods of gene therapy have been developed for preclinical PAH studies with varying degrees of efficacy. However, these gene delivery methods face challenges of immunogenicity, low transduction rates, and nonspecific targeting which have limited their translation to clinical studies. More recently, the emergence of regenerative approaches using stem and progenitor cells such as endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have offered a new approach to gene therapy. Cell-based gene therapy is an approach that augments the therapeutic potential of EPCs and MSCs and may deliver on the promise of reversal of established PAH. These new regenerative approaches have shown tremendous potential in preclinical studies; however, large, rigorously designed clinical studies will be necessary to evaluate clinical efficacy and safety. © 2013 American Physiological Society. Compr Physiol 3:1749-1779, 2013.
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The role of neighborhood income inequality in adolescent aggression and violence.
Pabayo, Roman; Molnar, Beth E; Kawachi, Ichiro
2014-10-01
Being a perpetrator or victim of assaults can have detrimental effects on the development and health of adolescents. Area-level income inequality has been suggested to be associated with crime and aggressive behavior. However, most prior research on this association has been ecological. Therefore, the purpose of this investigation was to describe the association between neighborhood-level income inequality and aggression and violence outcomes. Data were collected from a sample of 1,878 adolescents living in 38 neighborhoods participating in the 2008 Boston Youth Survey. We used multilevel logistic regression models to estimate the association between neighborhood income inequality and attacking someone with a weapon, being attacked by someone with a weapon, being physically assaulted, being shown a gun by someone in the neighborhood, shot at by someone in the neighborhood, witnessing someone getting murdered in the past year, and having a close family member or friend murdered. Race and income inequality cross-level interactions were tested. Analyses were stratified by sex. Among nonblack boys, after adjusting for nativity, age, neighborhood-level income, crime, disorder, and proportion of the neighborhood that is black, income inequality was associated with an increased risk for committing acts of aggression and being a victim of violence. Among nonblack girls, those living in neighborhoods with high-income inequality were more likely to witness someone die a violent death in the previous year, in comparison to those in more equal neighborhoods. Income inequality appears to be related to aggression and victimization outcomes among nonblack adolescents living in Boston. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
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McDonald's restaurants and neighborhood deprivation in Scotland and England.
Cummins, Steven C J; McKay, Laura; MacIntyre, Sally
2005-11-01
Features of the local fast food environment have been hypothesized to contribute to the greater prevalence of obesity in deprived neighborhoods. However, few studies have investigated whether fast food outlets are more likely to be found in poorer areas, and those that have are local case studies. In this paper, using national-level data, we examine the association between neighborhood deprivation and the density of McDonald's restaurants in small census areas (neighborhoods) in Scotland and England. Data on population, deprivation, and the location of McDonald's Restaurants were obtained for 38,987 small areas in Scotland and England (6505 "data zones" in Scotland, and 32,482 "super output areas" in England) in January 2005. Measures of McDonald's restaurants per 1000 people for each area were calculated, and areas were divided into quintiles of deprivation. Associations between neighborhood deprivation and outlet density were examined during February 2005, using one-way analysis of variance in Scotland, England, and both countries combined. Statistically significant positive associations were found between neighborhood deprivation and the mean number of McDonald's outlets per 1000 people for Scotland (p<0.001), England (p<0.001), and both countries combined (p<0.001). These associations were broadly linear with greater mean numbers of outlets per 1000 people occurring as deprivation levels increased. Observed associations between presence or absence of fast food outlets and neighborhood deprivation may provide support for environmental explanations for the higher prevalence of obesity in poor neighborhoods.
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Cancer mortality disparities among New York City's Upper Manhattan neighborhoods.
Hashim, Dana; Manczuk, Marta; Holcombe, Randall; Lucchini, Roberto; Boffetta, Paolo
2017-11-01
The East Harlem (EH), Central Harlem (CH), and Upper East Side (UES) neighborhoods of New York City are geographically contiguous to tertiary medical care, but are characterized by cancer mortality rate disparities. This ecological study aims to disentangle the effects of race and neighborhood on cancer deaths. Mortality-to-incidence ratios were determined using neighborhood-specific data from the New York State Cancer Registry and Vital Records Office (2007-2011). Ecological data on modifiable cancer risk factors from the New York City Community Health Survey (2002-2006) were stratified by sex, age group, race/ethnicity, and neighborhood and modeled against stratified mortality rates to disentangle race/ethnicity and neighborhood using logistic regression. Significant gaps in mortality rates were observed between the UES and both CH and EH across all cancers, favoring UES. Mortality-to-incidence ratios of both CH and EH were similarly elevated in the range of 0.41-0.44 compared with UES (0.26-0.30). After covariate and multivariable adjustment, black race (odds ratio=1.68; 95% confidence interval: 1.46-1.93) and EH residence (odds ratio=1.20; 95% confidence interval: 1.07-1.35) remained significant risk factors in all cancers' combined mortality. Mortality disparities remain among EH, CH, and UES neighborhoods. Both neighborhood and race are significantly associated with cancer mortality, independent of each other. Multivariable adjusted models that include Community Health Survey risk factors show that this mortality gap may be avoidable through community-based public health interventions.
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Neighborhood Economic Deprivation and Social Fragmentation: Associations With Children's Sleep.
Bagley, Erika J; Fuller-Rowell, Thomas E; Saini, Ekjyot K; Philbrook, Lauren E; El-Sheikh, Mona
2016-12-09
A growing body of work indicates that experiences of neighborhood disadvantage place children at risk for poor sleep. This study aimed to examine how both neighborhood economic deprivation (a measure of poverty) and social fragmentation (an index of instability) are associated with objective measures of the length and quality of children's sleep. Participants were 210 children (54.3% boys) living predominantly in small towns and semirural communities in Alabama. On average children were 11.3 years old (SD = .63); 66.7% of the children were European American and 33.3% were African American. The sample was socioeconomically diverse with 67.9% of the participants living at or below the poverty line and 32.1% from lower-middle-class or middle-class families. Indicators of neighborhood characteristics were derived from the 2012 American Community Survey and composited to create two variables representing neighborhood economic deprivation and social fragmentation. Child sleep period, actual sleep minutes, and efficiency were examined using actigraphy. Higher levels of neighborhood economic deprivation were associated with fewer sleep minutes and poorer sleep efficiency. More neighborhood social fragmentation was also linked with poorer sleep efficiency. Analyses controlled for demographic characteristics, child health, and family socioeconomic status. Findings indicate that living in economically and socially disadvantaged neighborhoods predicts risk for shorter and lower-quality sleep in children. Examination of community context in addition to family and individual characteristics may provide a more comprehensive understanding of the factors shaping child sleep.
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Lelieveldt, H.T.
2004-01-01
This article analyzes the relationship between social capital and neighborhood-oriented forms of participation within the context of an innovative Dutch neighborhood improvement program. On the basis of a survey among 307 residents, the author studies the link between three dimensions of social
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Neighborhood Frequency Effect in Chinese Word Recognition: Evidence from Naming and Lexical Decision
Li, Meng-Feng; Gao, Xin-Yu; Chou, Tai-Li; Wu, Jei-Tun
2017-01-01
Neighborhood frequency is a crucial variable to know the nature of word recognition. Different from alphabetic scripts, neighborhood frequency in Chinese is usually confounded by component character frequency and neighborhood size. Three experiments were designed to explore the role of the neighborhood frequency effect in Chinese and the stimuli…
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An animal model for Norrie disease (ND): gene targeting of the mouse ND gene.
Berger, W; van de Pol, D; Bächner, D; Oerlemans, F; Winkens, H; Hameister, H; Wieringa, B; Hendriks, W; Ropers, H H
1996-01-01
In order to elucidate the cellular and molecular processes which are involved in Norrie disease (ND), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart. RNA in situ hybridization revealed expression in retina, brain and the olfactory bulb and epithelium of 2 week old mice. Hemizygous mice carrying a replacement mutation in exon 2 of the ND gene developed retrolental structures in the vitreous body and showed an overall disorganization of the retinal ganglion cell layer. The outer plexiform layer disappears occasionally, resulting in a juxtaposed inner and outer nuclear layer. At the same regions, the outer segments of the photoreceptor cell layer are no longer present. These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder.
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Identification of the human ApoAV gene as a novel ROR{alpha} target gene
Energy Technology Data Exchange (ETDEWEB)
Lind, Ulrika [Department of Molecular Pharmacology, AstraZeneca R and D Moelndal (Sweden); Nilsson, Tina [Department of Molecular Pharmacology, AstraZeneca R and D Moelndal (Sweden); McPheat, Jane [Department of Molecular Pharmacology, AstraZeneca R and D Moelndal (Sweden); Stroemstedt, Per-Erik [Department of Molecular Pharmacology, AstraZeneca R and D Moelndal (Sweden); Bamberg, Krister [Department of Molecular Pharmacology, AstraZeneca R and D Moelndal (Sweden); Balendran, Clare [Department of Molecular Pharmacology, AstraZeneca R and D Moelndal (Sweden); Kang, Daiwu [Department of Molecular Pharmacology, AstraZeneca R and D Moelndal (Sweden)
2005-04-29
Retinoic acid receptor-related orphan receptor-{alpha} (ROR{alpha}) (NR1F1) is an orphan nuclear receptor with a potential role in metabolism. Previous studies have shown that ROR{alpha} regulates transcription of the murine Apolipoprotein AI gene and human Apolipoprotein CIII genes. In the present study, we present evidence that ROR{alpha} also induces transcription of the human Apolipoprotein AV gene, a recently identified apolipoprotein associated with triglyceride levels. Adenovirus-mediated overexpression of ROR{alpha} increased the endogenous expression of ApoAV in HepG2 cells and ROR{alpha} also enhanced the activity of an ApoAV promoter construct in transiently transfected HepG2 cells. Deletion and mutation studies identified three AGGTCA motifs in the ApoAV promoter that mediate ROR{alpha} transactivation, one of which overlaps with a previously identified binding site for PPAR{alpha}. Together, these results suggest a novel mechanism whereby ROR{alpha} modulates lipid metabolism and implies ROR{alpha} as a potential target for the treatment of dyslipidemia and atherosclerosis.
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Subgraphs in vertex neighborhoods of K-free graphs
DEFF Research Database (Denmark)
Bang-Jensen, J.; Brandt, Stephan
2004-01-01
In a K-free graph, the neighborhood of every vertex induces a K-free subgraph. The K-free graphs with the converse property that every induced K-free subgraph is contained in the neighborhood of a vertex are characterized, based on the characterization in the case r = 3 due to Pach [8]....
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Neighborhood racial discrimination and the development of major depression.
Russell, Daniel W; Clavél, Frederick D; Cutrona, Carolyn E; Abraham, W Todd; Burzette, Rebecca G
2018-02-01
This study examined the impact of neighborhood racial discrimination on the development of major depressive disorder (MDD) in a sample of African American women. Participants were 499 women from Georgia and Iowa with no history of MDD who were followed for 9 to 11 years. Several neighborhood characteristics (community social disorder, community cohesion, and community racism) and individual characteristics (negative life events, financial strain, personal outlook, religious involvement, relationship quality, negative affectivity, and individual experiences of racism) were employed as predictors of whether or not the women met criteria for MDD during this period of time. In a multilevel logistic regression analysis, neighborhood-level discrimination as well as individual-level variables including the number of negative life events, financial strain, and negative affectivity were found to be significant predictors of developing MDD. Analyses of cross-level interactions indicated that the effects of neighborhood-level discrimination were moderated by the quality of individuals' relationships, such that better relationships with others served to lessen the effect of neighborhood discrimination on depression. Implications of these findings for understanding the negative effects of racial discrimination are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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Neighborhood, Family and Individual Influences on School Physical Victimization
Brooks-Gunn, Jeanne
2013-01-01
Few studies on the correlates of school violence include school and neighborhood influences. We use ecological systems theory and social disorganization theory to simultaneously incorporate neighborhood (e.g., concentrated poverty, residential instability, and immigrant concentration), school, family, and individual predictors of physical school victimization longitudinally among a large socio-economically and ethnically diverse (49% Hispanic; 34% African American) sample of 6 and 9 year olds (49% female) from the Project on Human Development in Chicago Neighborhoods (PHDCN). These children were followed up at Wave II at ages 8 and 11 (n=1425). Results of Hierarchical Generalized Linear Models reveal neighborhood residential instability increases school victimization net of family and individual correlates. Furthermore, cross-level interactions were also supported where residential family mobility has a stronger risk influence in areas of high residential instability. Also, the influence of residential family mobility is decreased in areas with higher levels of immigrant concentration. We also found cross-context connections where parent-to-child aggression in the home is connected to a higher risk of victimization at school. The role of neighborhood and family residential instability on victimization warrants further research. PMID:23263822
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ADOLESCENTS’ EXPOSURE TO COMMUNITY VIOLENCE: ARE NEIGHBORHOOD YOUTH ORGANIZATIONS PROTECTIVE?
Gardner, Margo; Brooks-Gunn, Jeanne
2009-01-01
Using data from the Project on Human Development in Chicago Neighborhoods (PHDCN), we identified a significant inverse association between the variety of youth organizations available at the neighborhood level and adolescents’ exposure to community violence. We examined two non-competing explanations for this finding. First, at the individual level, we tested the hypothesis that access to a greater variety of neighborhood youth organizations predicts adolescents’ participation in organized co...
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Municipality and Neighborhood Influences on Volunteering in Later Life.
Dury, Sarah; Willems, Jurgen; De Witte, Nico; De Donder, Liesbeth; Buffel, Tine; Verté, Dominique
2016-06-01
This article explores the relationships between municipality features and volunteering by older adults. In the literature, strong evidence exists of the influence of place on older people's health. However, the question how neighborhoods and municipalities promote or hinder volunteer participation remains under-explored. Data for the research are derived from the Belgian Aging Studies. We estimate logistic multilevel models for older individuals' engagement in volunteering across 141 municipalities in Belgium (N = 67,144). Analysis shows that neighborhood connectedness, neighborhood satisfaction, home ownership, and presence of services predict voluntary engagement at older ages. The findings support that perceptions and quality of social resources that relate to neighborhoods may be important factors to explain volunteering among older adults. Moreover, the findings suggest that volunteering in later life must be considered within a broader framework. © The Author(s) 2014.
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Quality over Quantity: Contribution of Urban Green Space to Neighborhood Satisfaction.
Zhang, Yang; Van den Berg, Agnes E; Van Dijk, Terry; Weitkamp, Gerd
2017-05-16
There is increasing evidence that the quality of green space significantly contributes to neighborhood satisfaction and well-being, independent of the mere amount of green space. In this paper, we examined residents' perceptions of the quality and beneficial affordances of green space in relation to objectively assessed accessibility and usability. We used data from a survey in two neighborhoods ( N = 223) of a medium-sized city in the Netherlands, which were similar in the amount of green space and other physical and socio-demographic characteristics, but differed in the availability of accessible and usable green spaces. Results show that residents of the neighborhood with a higher availability of accessible and usable green spaces were more satisfied with their neighborhood. This difference was statistically mediated by the higher level of perceived green space quality. Neighborhood satisfaction was significantly positively related to well-being. However, residents of the two neighborhoods did not differ in self-reported well-being and beneficial affordances of green space. These analyses contribute to a further understanding of how the accessibility and usability of green spaces may increase people's neighborhood satisfaction. It highlights the importance of perceived quality in addition to the amount of green space when examining the beneficial effects of green space.
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Directory of Open Access Journals (Sweden)
de los Reyes Benildo G
2008-04-01
Full Text Available Abstract Background Integrating data from multiple global assays and curated databases is essential to understand the spatio-temporal interactions within cells. Different experiments measure cellular processes at various widths and depths, while databases contain biological information based on established facts or published data. Integrating these complementary datasets helps infer a mutually consistent transcriptional regulatory network (TRN with strong similarity to the structure of the underlying genetic regulatory modules. Decomposing the TRN into a small set of recurring regulatory patterns, called network motifs (NM, facilitates the inference. Identifying NMs defined by specific transcription factors (TF establishes the framework structure of a TRN and allows the inference of TF-target gene relationship. This paper introduces a computational framework for utilizing data from multiple sources to infer TF-target gene relationships on the basis of NMs. The data include time course gene expression profiles, genome-wide location analysis data, binding sequence data, and gene ontology (GO information. Results The proposed computational framework was tested using gene expression data associated with cell cycle progression in yeast. Among 800 cell cycle related genes, 85 were identified as candidate TFs and classified into four previously defined NMs. The NMs for a subset of TFs are obtained from literature. Support vector machine (SVM classifiers were used to estimate NMs for the remaining TFs. The potential downstream target genes for the TFs were clustered into 34 biologically significant groups. The relationships between TFs and potential target gene clusters were examined by training recurrent neural networks whose topologies mimic the NMs to which the TFs are classified. The identified relationships between TFs and gene clusters were evaluated using the following biological validation and statistical analyses: (1 Gene set enrichment
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Human synthetic lethal inference as potential anti-cancer target gene detection
Directory of Open Access Journals (Sweden)
Solé Ricard V
2009-12-01
Full Text Available Abstract Background Two genes are called synthetic lethal (SL if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. Results In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases as well as on existent approved drugs (DrugBank database supports our selection of cancer-therapy candidates. Conclusions Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.
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Neighborhood Characteristics and Disability in Older Adults
Blaney, Shannon; Cerda, Magda; Frye, Victoria; Lovasi, Gina S.; Ompad, Danielle; Rundle, Andrew; Vlahov, David
2009-01-01
Objective To characterize the influence of the residential neighborhood of older adults on the prevalence of disability. Methods We combined Census data on disability in older adults living in New York City with environmental information from a comprehensive geospatial database. We used factor analysis to derive dimensions of compositional and physical neighborhood characteristics and linear regression to model their association with levels of disability. Measures of neighborhood collective efficacy were added to these models to explore the impact of the social environment. Results Low neighborhood socioeconomic status, residential instability, living in areas with low proportions of foreign born and high proportions of Black residents, and negative street characteristics were associated with higher prevalence of both “physical” disability and “going outside the home” disability. High crime levels were additionally associated with physical disability, although this relationship disappeared when misdemeanor arrests were removed from the crime variable. Low levels of collective efficacy were associated with more going-outside-the-home disability, with racial/ethnic composition dropping out of this model to be replaced by an interaction term. Conclusion The urban environment may have a substantial impact on whether an older adult with a given level of functional impairment is able to age actively and remain independent. PMID:19181694
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siRNAs targeting PB2 and NP genes potentially inhibit replication
Indian Academy of Sciences (India)
% and has caused the death or culling of millions of poultry since 2003. In this study, we have designed three siRNAs (PB2-2235, PB2-479 and NP-865) targeting PB2 and NP genes of avian influenza virus and evaluated their potential, ...
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Aging in Place in Gentrifying Neighborhoods: Implications for Physical and Mental Health.
Smith, Richard J; Lehning, Amanda J; Kim, Kyeongmo
2018-01-18
In the United States, the older adult population and the proportion of neighborhoods experiencing gentrification are both growing. However, there is limited scholarship on the effects of gentrification on older adults, with most work focusing on those who leave rather than stay. This study examines the effects of remaining in a gentrifying neighborhood on older adults' self-rated health and mental health, with particular attention to outcomes for those who are economically vulnerable. Data are from 6,810 community-dwelling respondents in metropolitan areas from the first wave of the National Health & Aging Trends Study combined with the 1970-2010 National Neighborhood Change Database. We estimate the effects of gentrification on self-rated health and mental health separately using a quasi-experimental approach and comparing two methods: matching design and linear regression. Economically vulnerable older adults in gentrifying neighborhoods reported higher self-rated health than economically vulnerable older adults in low-income neighborhoods. Both economically vulnerable and higher-income older adults in gentrifying neighborhoods had more depression and anxiety symptoms than those living in more affluent areas. Higher-income older adults in gentrifying neighborhoods had poorer mental health than their counterparts in low-income neighborhoods. Findings call attention to the complexity of gentrification, and the need for more research examining how the intersection of neighborhood and individual characteristics influences older adults' health. Results reinforce the need for neighborhood-level interventions as well as relocation support to promote health in later life and caution against an overemphasis on aging in place. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Health, Safety and Environment (HSE assessment of neighborhoods: A case study in Tehran Municipality
Directory of Open Access Journals (Sweden)
Narmin Hassanzadeh- Rangi
2014-09-01
Full Text Available Urbanization is growing rapidly in recent centuries. This phenomenon can cause many changes in various aspects of human life including the economy, education and public health This study was conducted to assess the Health, Safety and Environment (HSE problems in Tehran neighborhoods. A new instrument was developed based on the results of a literature review and formulated during a pilot study. Through cluster sampling, 10 neighborhoods were selected based from 374 neighborhoods of Tehran. Six observers completed observational items during the field studies. Secondary data were used to obtain non-observation characteristics. Standard descriptive statistics were used to compare the HSE characteristics in sampled neighborhoods. Furthermore, control chart was used to as a decision rule to identify specific variation among sampled neighborhoods. Niavaran neighborhood had the best HSE status (52.80%±25.03 whereas Khak Sefid neighborhood had the worst one (20.09%±27.51. Standard deviations of HSE characteristics were high in different parts of a neighborhood. Statistical analysis indicated that significant differences in HSE characteristics exist among sampled neighborhoods. HSE status was in warning situation in both rich and poor neighborhoods. Community-based interventions were suggested as health promotion programs to involve and empower people in neighborhoods.
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Stimulation of autophagy by the p53 target gene Sestrin2.
Maiuri, Maria Chiara; Malik, Shoaib Ahmad; Morselli, Eugenia; Kepp, Oliver; Criollo, Alfredo; Mouchel, Pierre-Luc; Carnuccio, Rosa; Kroemer, Guido
2009-05-15
The oncosuppressor protein p53 regulates autophagy in a dual fashion. The pool of cytoplasmic p53 protein represses autophagy in a transcription-independent fashion, while the pool of nuclear p53 stimulates autophagy through the transactivation of specific genes. Here we report the discovery that Sestrin2, a novel p53 target gene, is involved in the induction of autophagy. Depletion of Sestrin2 by RNA interference reduced the level of autophagy in a panel of p53-sufficient human cancer cell lines responding to distinct autophagy inducers. In quantitative terms, Sestrin2 depletion was as efficient in preventing autophagy induction as was the depletion of Dram, another p53 target gene. Knockout of either Sestrin2 or Dram reduced autophagy elicited by nutrient depletion, rapamycin, lithium or thapsigargin. Moreover, autophagy induction by nutrient depletion or pharmacological stimuli led to an increase in Sestrin2 expression levels in p53-proficient cells. In strict contrast, the depletion of Sestrin2 or Dram failed to affect autophagy in p53-deficient cells and did not modulate the inhibition of baseline autophagy by a cytoplasmic p53 mutant that was reintroduced into p53-deficient cells. We conclude that Sestrin2 acts as a positive regulator of autophagy in p53-proficient cells.
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Neighborhood deprivation and access to fast-food retailing: a national study.
Pearce, Jamie; Blakely, Tony; Witten, Karen; Bartie, Phil
2007-05-01
Obesogenic environments may be an important contextual explanation for the growing obesity epidemic, including its unequal social distribution. The objective of this study was to determine whether geographic access to fast-food outlets varied by neighborhood deprivation and school socioeconomic ranking, and whether any such associations differed to those for access to healthier food outlets. Data were collected on the location of fast-food outlets, supermarkets, and convenience stores across New Zealand. The data were geocoded and geographic information systems used to calculate travel distances from each census meshblock (i.e., neighborhood), and each school, to the closest fast-food outlet. Median travel distances are reported by a census-based index of socioeconomic deprivation for each neighborhood, and by a Ministry of Education measure of socioeconomic circumstances for each school. Analyses were repeated for outlets selling healthy food to allow comparisons. At the national level, statistically significant negative associations were found between neighborhood access to the nearest fast-food outlet and neighborhood deprivation (p<0.001) for both multinational fast-food outlets and locally operated outlets. The travel distances to both types of fast food outlet were at least twice as far in the least socially deprived neighborhoods compared to the most deprived neighborhoods. A similar pattern was found for outlets selling healthy food such as supermarkets and smaller food outlets (p<0.001). These relationships were broadly linear with travel distances tending to be shorter in more-deprived neighborhoods. There is a strong association between neighborhood deprivation and geographic access to fast food outlets in New Zealand, which may contribute to the understanding of environmental causes of obesity. However, outlets potentially selling healthy food (e.g., supermarkets) are patterned by deprivation in a similar way. These findings highlight the importance of
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HIV-derived vectors for gene therapy targeting dendritic cells.
Rossetti, Maura; Cavarelli, Mariangela; Gregori, Silvia; Scarlatti, Gabriella
2013-01-01
Human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LV) have the potential to mediate stable therapeutic gene transfer. However, similarly to other viral vectors, their benefit is compromised by the induction of an immune response toward transgene-expressing cells that closely mimics antiviral immunity. LV share with the parental HIV the ability to activate dendritic cells (DC), while lack the peculiar ability of subverting DC functions, which is responsible for HIV immune escape. Understanding the interaction between LV and DC, with plasmacytoid and myeloid DC playing fundamental and distinct roles, has paved the way to novel approaches aimed at regulating transgene-specific immune responses. Thanks to the ability to target either DC subsets LV might be a powerful tool to induce immunity (i.e., gene therapy of cancer), cell death (i.e., in HIV/AIDS infection), or tolerance (i.e., gene therapy strategies for monogenic diseases). In this chapter, similarities and differences between the LV-mediated and HIV-mediated induction of immune responses, with specific focus on their interactions with DC, are discussed.
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Boro, Aleksandar; Prêtre, Kathya; Rechfeld, Florian; Thalhammer, Verena; Oesch, Susanne; Wachtel, Marco; Schäfer, Beat W; Niggli, Felix K
2012-11-01
Ewing's sarcoma family of tumors (EFT) is characterized by the presence of chromosomal translocations leading to the expression of oncogenic transcription factors such as, in the majority of cases, EWS/FLI1. Because of its key role in Ewing's sarcoma development and maintenance, EWS/FLI1 represents an attractive therapeutic target. Here, we characterize PHLDA1 as a novel direct target gene whose expression is repressed by EWS/FLI1. Using this gene and additional specific well-characterized target genes such as NROB1, NKX2.2 and CAV1, all activated by EWS/FLI1, as a read-out system, we screened a small-molecule compound library enriched for FDA-approved drugs that modulated the expression of EWS/FLI1 target genes. Among a hit-list of nine well-known drugs such as camptothecin, fenretinide, etoposide and doxorubicin, we also identified the kinase inhibitor midostaurin (PKC412). Subsequent experiments demonstrated that midostaurin is able to induce apoptosis in a panel of six Ewing's sarcoma cell lines in vitro and can significantly suppress xenograft tumor growth in vivo. These results suggest that midostaurin might be a novel drug that is active against Ewing's cells, which might act by modulating the expression of EWS/FLI1 target genes. Copyright © 2012 UICC.
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The temporal stability of children's neighborhood experiences: A follow-up from birth to age 15
Directory of Open Access Journals (Sweden)
Tom Kleinepier
2017-06-01
Full Text Available Background: Despite increasing attention being paid to the temporal dynamics of childhood disadvantage, children's neighborhood characteristics are still frequently measured at a single point in time. Whether such cross-sectional measures serve as reliable proxies for children's long-run neighborhood conditions depends on the stability in children's neighborhood experiences over time. Objective: We investigate stability in children's neighborhood environment over time, focusing on two of the most commonly studied neighborhood socioeconomic conditions: The ethnic composition and mean income of the neighborhood. Methods: Drawing on data from the Dutch population registers, an entire cohort of children born in the Netherlands in 1999 (n=179,166 is followed from birth up until age 15. We use year-to-year correlations in the percentage of non-Western ethnic minorities and the mean logged income in the neighborhood to evaluate the temporal stability of children's neighborhood experiences. Results: Results indicate that children's neighborhood characteristics are more stable over time with regard to ethnic composition than with regard to the mean income. Children who had moved at least once had less stability in neighborhood characteristics than children who never moved. Finally, neighborhood experiences were found to be more stable over time for ethnic minority children, although differences were small with regard to mean income in the neighborhood. Conclusions: We conclude that single point-in-time measurements of neighborhood characteristics are reasonable proxies for the long-run ethnic composition of children's neighborhood environment, but rather noisy proxies for the long-run income status of their neighborhood, particularly for those who moved. Contribution: We examine the temporal stability of children's neighborhood experiences over almost the entire childhood life course in the European context.
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Derraugh, Lesley S; Neath, Ian; Surprenant, Aimée M; Beaudry, Olivia; Saint-Aubin, Jean
2017-03-01
The word-length effect, the finding that lists of short words are better recalled than lists of long words, is 1 of the 4 benchmark phenomena that guided development of the phonological loop component of working memory. However, previous work has noted a confound in word-length studies: The short words used had more orthographic neighbors (valid words that can be made by changing a single letter in the target word) than long words. The confound is that words with more neighbors are better recalled than otherwise comparable words with fewer neighbors. Two experiments are reported that address criticisms of the neighborhood-size account of the word-length effect by (1) testing 2 new stimulus sets, (2) using open rather than closed pools of words, and (3) using stimuli from a language other than English. In both experiments, words from large neighborhoods were better recalled than words from small neighborhoods. The results add to the growing number of studies demonstrating the substantial contribution of long-term memory to what have traditionally been identified as working memory tasks. The data are more easily explained by models incorporating the concept of redintegration rather than by frameworks such as the phonological loop that posit decay offset by rehearsal. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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Impact of neighborhood separation on the spatial reciprocity in the prisoner’s dilemma game
International Nuclear Information System (INIS)
Xia, Chengyi; Miao, Qin; Zhang, Juanjuan
2013-01-01
Highlights: • We present a novel game model in which interaction and learning neighborhood is not identical. • The separation between interaction and learning neighborhood can largely influence the cooperative behaviors. • Monte Carlo simulations are utilized to verify the evolution of cooperation. • When IN is fixed to be 4, medium-sized LN = 8 is the optimal size to promote the cooperation. • When LN is fixed to be 4, the cooperation can also be highly enhanced when IN > 4. -- Abstract: The evolutionary game theory is a very powerful tool to understand the collective cooperation behavior in many real-world systems. In the spatial game model, the payoff is often first obtained within a specific neighborhood (i.e., interaction neighborhood) and then the focal player imitates or learns the behavior of a randomly selected one inside another neighborhood which is named after the learning neighborhood. However, most studies often assume that the interaction neighborhood is identical with the learning neighborhood. Beyond this assumption, we present a spatial prisoner’s dilemma game model to discuss the impact of separation between interaction neighborhood and learning neighborhood on the cooperative behaviors among players on the square lattice. Extensive numerical simulations demonstrate that separating the interaction neighborhood from the learning neighborhood can dramatically affect the density of cooperators (ρ C ) in the population at the stationary state. In particular, compared to the standard case, we find that the medium-sized learning (interaction) neighborhood allows the cooperators to thrive and substantially favors the evolution of cooperation and ρ C can be greatly elevated when the interaction (learning) neighborhood is fixed, that is, too little or much information is not beneficial for players to make the contributions for the collective cooperation. Current results are conducive to further analyzing and understanding the emergence of
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Gerrish, Michael
2009-01-01
Blue collar doesn't have to mean drab and dull. At least, not to Troy, New York, historian Mike Esposito, who is a member of a neighborhood revitalization movement seeking to celebrate the people and events that brought diversity, prosperity, and vitality to this upstate New York community more than 100 years ago. Esposito and others invited…
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Loss of Trust in the Neighborhood: The Experience of Older African Americans in Detroit.
Fritz, Heather; Cutchin, Malcolm P; Cummins, Emily R
2018-02-19
Although evidence suggests that neighborhood conditions are related to stress and health, the processes connecting neighborhood conditions and stress for older minorities is little explored. The purpose of this analysis is to contribute new insights into this issue. We conducted a qualitative analysis as part of a larger mixed methods study of 100 African Americans aged 55 and older living in neighborhoods of varying quality in Detroit, Michigan. A subsample of (n = 20) older adults took photographs of bothersome aspects of their neighborhoods and participated in in-depth photo-elicitation interviews. Data were analyzed using a grounded theory approach. 'Loss of trust in the neighborhood' emerged as the core category to explain how older African Americans in our sample experienced neighborhood stressors in their daily lives. Loss of trust in physical, social, and institutional dimensions of the neighborhood contributed to the core category. The life course of neighborhoods and the trust placed in them appears to be intimately connected to the well-being of older African Americans. We therefore hypothesize that a fundamental pathway through which neighborhood stressors are experienced for older African Americans in U.S. 'Rust Belt' cities is the multifaceted loss of trust in the neighborhood.
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Perceived neighborhood characteristics predict severity and emotional response to daily stressors.
Scott, Stacey B; Munoz, Elizabeth; Mogle, Jacqueline A; Gamaldo, Alyssa A; Smyth, Joshua M; Almeida, David M; Sliwinski, Martin J
2018-03-01
Neighborhood characteristics may influence health and well-being outcomes through stressors in daily life. This study tested whether a varied set of perceived characteristics of neighborhood (i.e., social cohesion, safety, aesthetic quality, violence) predicted stressor frequency and severity as well as negative emotional responses to stressors. We predicted greater reported cohesion and safety and less violence would be associated with less frequent stressor exposure and severity and less intense negative affect following stressors; we conducted subsequent tests of neighborhood aesthetic quality as a predictor. Participants (n = 233, age 25-65 years) were residents in a socio-economically, racially, and ethnically diverse zip code in Bronx, New York, most who participated in the Effects of Stress on Cognitive Aging, Physiology and Emotion study between 2012 and 2013. They provided demographic information and neighborhood ratings, then participated in the EMA protocol in which they completed brief smartphone surveys of current negative affect and stressor exposure, severity, and recency, five times daily for 14 days. No coded neighborhood characteristic was related to the frequency of stressors. Individuals who reported greater neighborhood violence, however, rated their stressors as more severe. Individuals rating their neighborhood lower in safety or aesthetic quality, or higher in violence, had greater negative affect following stressors. Even among people living within the same zip code, individual differences in perceptions of neighborhood predict how stressful they appraised stressors in daily life to be and how much negative affect they reported following stressors. Copyright © 2017 Elsevier Ltd. All rights reserved.
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2012-01-01
Background MicroRNA (miRNA) target genes tend to have relatively long and conserved 3' untranslated regions (UTRs), but to what degree these characteristics contribute to miRNA targeting is poorly understood. Different high-throughput experiments have, for example, shown that miRNAs preferentially regulate genes with both short and long 3' UTRs and that target site conservation is both important and irrelevant for miRNA targeting. Results We have analyzed several gene context-dependent features, including 3' UTR length, 3' UTR conservation, and messenger RNA (mRNA) expression levels, reported to have conflicting influence on miRNA regulation. By taking into account confounding factors such as technology-dependent experimental bias and competition between transfected and endogenous miRNAs, we show that two factors - target gene expression and competition - could explain most of the previously reported experimental differences. Moreover, we find that these and other target site-independent features explain about the same amount of variation in target gene expression as the target site-dependent features included in the TargetScan model. Conclusions Our results show that it is important to consider confounding factors when interpreting miRNA high throughput experiments and urge special caution when using microarray data to compare average regulatory effects between groups of genes that have different average gene expression levels. PMID:22325809
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Geurts, J.; Joosten, L.A.B.; Takahashi, N.; Arntz, O.J.; Gluck, A.; Bennink, M.B.; Berg, W.B. van den; Loo, F.A.J. van de
2009-01-01
The promoter regions of genes that are differentially regulated in the synovial membrane during the course of rheumatoid arthritis (RA) represent attractive candidates for application in transcriptionally targeted gene therapy. In this study, we applied an unbiased computational approach to define
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Directory of Open Access Journals (Sweden)
Samuel Campbell
2018-04-01
Full Text Available The previously developed adeno-associated virus/phage (AAVP vector, a hybrid between M13 bacteriophage (phage viruses that infect bacteria only and human Adeno-Associated Virus (AAV, is a promising tool in targeted gene therapy against cancer. AAVP can be administered systemically and made tissue specific through the use of ligand-directed targeting. Cancer cells and tumor-associated blood vessels overexpress the αν integrin receptors, which are involved in tumor angiogenesis and tumor invasion. AAVP is targeted to these integrins via a double cyclic RGD4C ligand displayed on the phage capsid. Nevertheless, there remain significant host-defense hurdles to the use of AAVP in targeted gene delivery and subsequently in gene therapy. We previously reported that histone deacetylation in cancer constitutes a barrier to AAVP. Herein, to improve AAVP-mediated gene delivery to cancer cells, we combined the vector with selective adjuvant chemicals that inhibit specific histone deacetylases (HDAC. We examined the effects of the HDAC inhibitor C1A that mainly targets HDAC6 and compared this to sodium butyrate, a pan-HDAC inhibitor with broad spectrum HDAC inhibition. We tested the effects on melanoma, known for HDAC6 up-regulation, and compared this side by side with a normal human kidney HEK293 cell line. Varying concentrations were tested to determine cytotoxic levels as well as effects on AAVP gene delivery. We report that the HDAC inhibitor C1A increased AAVP-mediated transgene expression by up to ~9-fold. These findings indicate that selective HDAC inhibition is a promising adjuvant treatment for increasing the therapeutic value of AAVP.
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Non-viral gene therapy that targets motor neurons in vivo
Directory of Open Access Journals (Sweden)
Mary-Louise eRogers
2014-10-01
Full Text Available A major challenge in neurological gene therapy is safe delivery of transgenes to sufficient cell numbers from the circulation or periphery. This is particularly difficult for diseases involving spinal cord motor neurons such as amyotrophic lateral sclerosis (ALS. We have examined the feasibility of non-viral gene delivery to spinal motor neurons from intraperitoneal injections of plasmids carried by ‘immunogene’ nanoparticles targeted for axonal retrograde transport using antibodies. PEGylated polyethylenimine (PEI-PEG12 as DNA carrier was conjugated to an antibody (MLR2 to the neurotrophin receptor p75 (p75NTR. We used a plasmid (pVIVO2 designed for in vivo gene delivery that produces minimal immune responses, has improved nuclear entry into post mitotic cells and also expresses green fluorescent protein (GFP. MLR2-PEI-PEG12 carried pVIVO2 and was specific for mouse motor neurons in mixed cultures containing astrocytes. While only 8% of motor neurons expressed GFP 72 h post transfection in vitro, when the immunogene was given intraperitonealy to neonatal C57BL/6J mice GFP specific motor neuron expression was observed in 25.4% of lumbar, 18.3% of thoracic and 17.0 % of cervical motor neurons, 72 h post transfection. PEI-PEG12 carrying pVIVO2 by itself did not transfect motor neurons in vivo, demonstrating the need for specificity via the p75NTR antibody MLR2. This is the first time that specific transfection of spinal motor neurons has been achieved from peripheral delivery of plasmid DNA as part of a non-viral gene delivery agent. These results stress the specificity and feasibility of immunogene delivery targeted for p75NTR expressing motor neurons, but suggests that further improvements are required to increase the transfection efficiency of motor neurons in vivo.
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Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system
Wang, Xiaolong; Yu, Honghao; Lei, Anmin; Zhou, Jiankui; Zeng, Wenxian; Zhu, Haijing; Dong, Zhiming; Niu, Yiyuan; Shi, Bingbo; Cai, Bei; Liu, Jinwang; Huang, Shuai; Yan, Hailong; Zhao, Xiaoe; Zhou, Guangxian; He, Xiaoling; Chen, Xiaoxu; Yang, Yuxin; Jiang, Yu; Shi, Lei; Tian, Xiue; Wang, Yongjun; Ma, Baohua; Huang, Xingxu; Qu, Lei; Chen, Yulin
2015-01-01
Recent advances in the study of the CRISPR/Cas9 system have provided a precise and versatile approach for genome editing in various species. However, the applicability and efficiency of this method in large animal models, such as the goat, have not been extensively studied. Here, by co-injection of one-cell stage embryos with Cas9 mRNA and sgRNAs targeting two functional genes (MSTN and FGF5), we successfully produced gene-modified goats with either one or both genes disrupted. The targeting efficiency of MSTN and FGF5 in cultured primary fibroblasts was as high as 60%, while the efficiency of disrupting MSTN and FGF5 in 98 tested animals was 15% and 21% respectively, and 10% for double gene modifications. The on- and off-target mutations of the target genes in fibroblasts, as well as in somatic tissues and testis of founder and dead animals, were carefully analyzed. The results showed that simultaneous editing of several sites was achieved in large animals, demonstrating that the CRISPR/Cas9 system has the potential to become a robust and efficient gene engineering tool in farm animals, and therefore will be critically important and applicable for breeding. PMID:26354037
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Newbury, Joanne; Arseneault, Louise; Caspi, Avshalom; Moffitt, Terrie E; Odgers, Candice L; Fisher, Helen L
2016-11-01
Urban upbringing is associated with a 2-fold adulthood psychosis risk, and this association replicates for childhood psychotic symptoms. No study has investigated whether specific features of urban neighborhoods increase children's risk for psychotic symptoms, despite these early psychotic phenomena elevating risk for schizophrenia and other psychiatric disorders in adulthood. Analyses were conducted on over 2000 children from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of UK-born twins. Neighborhood-level characteristics were assessed for each family via: a geodemographic discriminator indexing neighborhood-level deprivation, postal surveys of over 5000 residents living alongside the children, and in-home interviews with the children's mothers. Children were interviewed about psychotic symptoms at age 12. Analyses were adjusted for important family-level confounders including socioeconomic status (SES), psychiatric history, and maternal psychosis. Urban residency at age-5 (OR = 1.80, 95% CI = 1.16-2.77) and age-12 (OR = 1.76, 95% CI = 1.15-2.69) were both significantly associated with childhood psychotic symptoms, but not with age-12 anxiety, depression, or antisocial behavior. The association was not attributable to family SES, family psychiatric history, or maternal psychosis, each implicated in childhood mental health. Low social cohesion, together with crime victimization in the neighborhood explained nearly a quarter of the association between urbanicity and childhood psychotic symptoms after considering family-level confounders. Low social cohesion and crime victimization in the neighborhood partly explain why children in cities have an elevated risk of developing psychotic symptoms. Greater understanding of the mechanisms leading from neighborhood-level exposures to psychotic symptoms could help target interventions for emerging childhood psychotic symptoms. © The Author 2016. Published by Oxford University
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Workplace Neighborhoods, Walking, Physical Activity, Weight Status, and Perceived Health
Forsyth, Ann; Oakes, J.
2014-01-01
Recent interest has focused on how the built environment in residential neighborhoods affects walking and other physical activity. The neighborhood around the workplace has been examined far less. This study explored the neighborhood around the workplace and its correlation with the amount of walking, level of physical activity, body mass index, and perceived health of those who (a) worked away from home (N = 446) and (b) were retired or unemployed (N = 207). Study participants were recruited...
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Brown, David A; Di Cerbo, Vincenzo; Feldmann, Angelika; Ahn, Jaewoo; Ito, Shinsuke; Blackledge, Neil P; Nakayama, Manabu; McClellan, Michael; Dimitrova, Emilia; Turberfield, Anne H; Long, Hannah K; King, Hamish W; Kriaucionis, Skirmantas; Schermelleh, Lothar; Kutateladze, Tatiana G; Koseki, Haruhiko; Klose, Robert J
2017-09-05
Chromatin modifications and the promoter-associated epigenome are important for the regulation of gene expression. However, the mechanisms by which chromatin-modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live-cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed gene promoters through CFP1, which engages in a form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3). CFP1 defines SET1 complex occupancy on chromatin, and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed, suggesting that normal targeting and function of the SET1 complex are central to creating an appropriately functioning vertebrate promoter-associated epigenome. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Melak, Tilahun; Gakkhar, Sunita
2015-12-01
In spite of the implementations of several strategies, tuberculosis (TB) is overwhelmingly a serious global public health problem causing millions of infections and deaths every year. This is mainly due to the emergence of drug-resistance varieties of TB. The current treatment strategies for the drug-resistance TB are of longer duration, more expensive and have side effects. This highlights the importance of identification and prioritization of targets for new drugs. This study has been carried out to prioritize potential drug targets of Mycobacterium tuberculosis H37Rv based on their flow to resistance genes. The weighted proteome interaction network of the pathogen was constructed using a dataset from STRING database. Only a subset of the dataset with interactions that have a combined score value ≥770 was considered. Maximum flow approach has been used to prioritize potential drug targets. The potential drug targets were obtained through comparative genome and network centrality analysis. The curated set of resistance genes was retrieved from literatures. Detail literature review and additional assessment of the method were also carried out for validation. A list of 537 proteins which are essential to the pathogen and non-homologous with human was obtained from the comparative genome analysis. Through network centrality measures, 131 of them were found within the close neighborhood of the centre of gravity of the proteome network. These proteins were further prioritized based on their maximum flow value to resistance genes and they are proposed as reliable drug targets of the pathogen. Proteins which interact with the host were also identified in order to understand the infection mechanism. Potential drug targets of Mycobacterium tuberculosis H37Rv were successfully prioritized based on their flow to resistance genes of existing drugs which is believed to increase the druggability of the targets since inhibition of a protein that has a maximum flow to
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Seret, Marie-Line; Baret, Philippe V
2011-01-01
Comparative sequence analysis is widely used to infer gene function and study genome evolution and requires proper ortholog identification across different genomes. We have developed a program for the Identification of Orthologs in one-to-one relationship by Neighborhood and Similarity (IONS) between closely related species. The algorithm combines two levels of evidence to determine co-ancestrality at the genome scale: sequence similarity and shared neighborhood. The method was initially designed to provide anchor points for syntenic blocks within the Génolevures project concerning nine hemiascomycetous yeasts (about 50,000 genes) and is applicable to different input databases. Comparison based on use of a Rand index shows that the results are highly consistent with the pillars of the Yeast Gene Order Browser, a manually curated database. Compared with SYNERGY, another algorithm reporting homology relationships, our method's main advantages are its automation and the absence of dataset-dependent parameters, facilitating consistent integration of newly released genomes.
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Seret, Marie-Line; Baret, Philippe V.
2011-01-01
Comparative sequence analysis is widely used to infer gene function and study genome evolution and requires proper ortholog identification across different genomes. We have developed a program for the Identification of Orthologs in one-to-one relationship by Neighborhood and Similarity (IONS) between closely related species. The algorithm combines two levels of evidence to determine co-ancestrality at the genome scale: sequence similarity and shared neighborhood. The method was initially designed to provide anchor points for syntenic blocks within the Génolevures project concerning nine hemiascomycetous yeasts (about 50,000 genes) and is applicable to different input databases. Comparison based on use of a Rand index shows that the results are highly consistent with the pillars of the Yeast Gene Order Browser, a manually curated database. Compared with SYNERGY, another algorithm reporting homology relationships, our method’s main advantages are its automation and the absence of dataset-dependent parameters, facilitating consistent integration of newly released genomes. PMID:21918595
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Durham Neighborhood Compass Block Groups
City and County of Durham, North Carolina — The Durham Neighborhood Compass is a quantitative indicators project with qualitative values, integrating data from local government, the Census Bureau and other...
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Garimella, Rama; Tadikonda, Priyanka; Tawfik, Ossama; Gunewardena, Sumedha; Rowe, Peter; Van Veldhuizen, Peter
2017-01-01
Osteosarcoma (OS) is an aggressive malignancy of bone affecting children, adolescents and young adults. Understanding vitamin D metabolism and vitamin D regulated genes in OS is an important aspect of vitamin D/cancer paradigm, and in evaluating vitamin D as adjuvant therapy for human OS. Vitamin D treatment of 143B OS cells induced significant and novel changes in the expression of genes that regulate: (a) inflammation and immunity; (b) formation of reactive oxygen species, metabolism of cyclic nucleotides, sterols, vitamins and mineral (calcium), quantity of gap junctions and skeletogenesis; (c) bone mineral density; and (d) cell viability of skeletal cells, aggregation of bone cancer cells and exocytosis of secretory vesicles. Ingenuity pathway analysis revealed significant reduction in Runx2 target genes such as fibroblast growth factor -1, -12 (FGF1 and FGF12), bone morphogenetic factor-1 (BMP1), SWI/SNF related, matrix associated actin dependent regulator of chromatin subfamily a, member 4 (SMARCA4), Matrix extracellular phosphoglycoprotein (MEPE), Integrin, β4 (ITGBP4), Matrix Metalloproteinase -1, -28 (MMP1 and MMP28), and signal transducer and activator of transcription-4 (STAT4) in vitamin D treated 143B OS cells. These genes interact with the inflammation, oxidative stress and membrane vesicle biogenesis gene networks. Vitamin D not only inhibited the expression of Runx2 target genes MMP1, MMP28 and kallikrein related peptidase-7 (KLK7), but also migration and invasion of 143B OS cells. Vitamin D regulated Runx2 target genes or their products represent potential therapeutic targets and laboratory biomarkers for applications in translational oncology. PMID:28300755
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Neighborhood Poverty and Maternal Fears of Children's Outdoor Play
Kimbro, Rachel Tolbert; Schachter, Ariela
2011-01-01
Investigating children's outdoor play unites scholarship on neighborhoods, parental perceptions of safety, and children's health. Utilizing the Fragile Families and Child Well-being Study (N = 3,448), we examine mothers' fear of their 5-year-old children playing outdoors, testing associations with neighborhood social characteristics, city-level…
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Beheshti, Afshin
2018-01-01
GeneLab as a general tool for the scientific community; Utilizing GeneLab datasets to generate hypothesis and determining potential biological targets against health risks due to long-term space missions; How can OpenTarget be used to discover novel drugs to test as countermeasures that can be utilized by astronauts.
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Directory of Open Access Journals (Sweden)
Hongkai Ji
Full Text Available The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP, global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs. We further document that a Myc core signature (MCS set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells.
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Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis.
Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan
2017-07-01
Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.
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Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis
Directory of Open Access Journals (Sweden)
Cuiyuan Huang
2017-07-01
Full Text Available Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble–mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.
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Genome-wide analysis of PDX1 target genes in human pancreatic progenitors
Directory of Open Access Journals (Sweden)
Xianming Wang
2018-03-01
Full Text Available Objective: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4. Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing β-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult β-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. Methods: In this study, we have generated a novel induced pluripotent stem cell (iPSC line that efficiently differentiates into human pancreatic progenitors (PPs. Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. Results: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation
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Bringing urban governance back in: Neighborhood conflicts and depression.
Fu, Qiang
2018-01-01
Urban governance and its impact on contentious politics have received remarkably little attention in existing studies on mental health. Drawing on a measure of neighborhood conflicts developed in a survey of thirty-nine urban neighborhoods in Guangzhou, China, this article investigates the potential link between urban governance and mental health. Net of sociodemographic, relational, and environmental measures, it finds that among residents' conflicts with different entities of urban governance, only those with local/grassroots governments are significantly associated with more depressive symptoms. Moreover, these subgroups of government-oriented conflicts associated with more depressive symptoms are related to neighborhood planning and communal properties, reflecting a dilemma in the Chinese model of urban governance. By offering a relational interpretation of neighborhood conflicts, this study not only challenges the previous view that community building in China improves mental health, but calls attention to the significance of urban governance in research on mental health. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Tropism-Modification Strategies for Targeted Gene Delivery Using Adenoviral Vectors
Directory of Open Access Journals (Sweden)
Andrew H. Baker
2010-10-01
Full Text Available Achieving high efficiency, targeted gene delivery with adenoviral vectors is a long-standing goal in the field of clinical gene therapy. To achieve this, platform vectors must combine efficient retargeting strategies with detargeting modifications to ablate native receptor binding (i.e. CAR/integrins/heparan sulfate proteoglycans and “bridging” interactions. “Bridging” interactions refer to coagulation factor binding, namely coagulation factor X (FX, which bridges hepatocyte transduction in vivo through engagement with surface expressed heparan sulfate proteoglycans (HSPGs. These interactions can contribute to the off-target sequestration of Ad5 in the liver and its characteristic dose-limiting hepatotoxicity, thereby significantly limiting the in vivo targeting efficiency and clinical potential of Ad5-based therapeutics. To date, various approaches to retargeting adenoviruses (Ad have been described. These include genetic modification strategies to incorporate peptide ligands (within fiber knob domain, fiber shaft, penton base, pIX or hexon, pseudotyping of capsid proteins to include whole fiber substitutions or fiber knob chimeras, pseudotyping with non-human Ad species or with capsid proteins derived from other viral families, hexon hypervariable region (HVR substitutions and adapter-based conjugation/crosslinking of scFv, growth factors or monoclonal antibodies directed against surface-expressed target antigens. In order to maximize retargeting, strategies which permit detargeting from undesirable interactions between the Ad capsid and components of the circulatory system (e.g. coagulation factors, erythrocytes, pre-existing neutralizing antibodies, can be employed simultaneously. Detargeting can be achieved by genetic ablation of native receptor-binding determinants, ablation of “bridging interactions” such as those which occur between the hexon of Ad5 and coagulation factor X (FX, or alternatively, through the use of polymer
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A PCA3 gene-based transcriptional amplification system targeting primary prostate cancer
Neveu, Bertrand; Jain, Pallavi; T?tu, Bernard; Wu, Lily; Fradet, Yves; Pouliot, Fr?d?ric
2015-01-01
Targeting specifically primary prostate cancer (PCa) cells for immune therapy, gene therapy or molecular imaging is of high importance. The PCA3 long non-coding RNA is a unique PCa biomarker and oncogene that has been widely studied. This gene has been mainly exploited as an accurate diagnostic urine biomarker for PCa detection. In this study, the PCA3 promoter was introduced into a new transcriptional amplification system named the 3-Step Transcriptional Amplification System (PCA3-3STA) and ...
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Neighborhood differences in social capital: a compositional artifact or a contextual construct?
Subramanian, S V; Lochner, Kimberly A; Kawachi, Ichiro
2003-03-01
Assessment of social capital at the neighborhood level is often based on aggregating individual perceptions of trust and reciprocity. Individual perceptions, meanwhile, are influenced through a range of individual attributes. This paper examines the socioeconomic and demographic attributes that systematically correlate with individual perception of social capital and determines the extent to which such attributes account for neighborhood differences in social capital. Using improved multilevel modeling procedures, we ascertain the extent to which differences in social capital perception can be ascribed to true neighborhood-level variations. The analysis is based on the 1994-95 Community Survey of the Project on Human Development in Chicago Neighborhoods (PHDCN). The response measure is based on survey respondent's perceptions of whether people in their neighborhood can be trusted. The results suggest that even after accounting for individual demographic (age, sex, race, marital status) and socioeconomic characteristics (income, education), significant neighborhood differences remain in individual perceptions of trust, substantiating the notion of social capital as a true contextual construct.
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Do Sleep and Psychological Distress Mediate the Association Between Neighborhood Factors and Pain?
Brooks Holliday, Stephanie; Dubowitz, Tamara; Ghosh-Dastidar, Bonnie; Beckman, Robin; Buysse, Daniel; Hale, Lauren; Buman, Matthew; Troxel, Wendy
2018-05-14
Pain affects millions of American adults. However, individuals from socioeconomically disadvantaged groups experience higher rates of pain, and individuals from racial/ethnic minorities report greater pain severity and pain-related disability. Some studies find an association between neighborhood socioeconomic status and pain. The present study aimed to further understand the association between neighborhood disadvantage and pain, including the role of objective (e.g., crime rates) and subjective neighborhood characteristics (e.g., perceived safety, neighborhood satisfaction), and to examine sleep and psychological distress as potential mediators of these associations. The sample included 820 participants from two predominantly African American socioeconomically disadvantaged neighborhoods. Trained data collectors interviewed participants on a number of self-report measures, and objective neighborhood characteristics were obtained from city crime data and street segment audits. Subjective characteristics, specifically perceived infrastructure and perceived safety, were associated with pain. Based on bootstrapped regression models, sleep efficiency and psychological distress were tested as mediators of the association between these neighborhood factors and pain. Results of mediation testing indicated that psychological distress served as a significant mediator. Though sleep efficiency was not a mediator, it had a significant independent association with pain. Understanding the contribution of sleep problems and psychological distress to pain among at-risk individuals living in disadvantaged neighborhoods is important to identifying ways that individual- and neighborhood-level interventions may be leveraged to reduce pain-related disparities.
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The impact of childhood neighborhood disadvantage on adult joblessness and income.
Alvarado, Steven Elías
2018-02-01
Research on residential inequality focuses heavily on adult economic outcomes as crucial components of the intergenerational transmission of poverty. Yet, empirical evidence on whether youth neighborhoods have a lasting impact on adult economic outcomes at the national level is scarce. Further, we know little about how youth neighborhood effects on adult economic outcomes manifest. This study uses 26 years (14 waves) of restricted panel data from the NLSY79 and the NLSY Children and Young Adults cohorts - data that have never been used to analyze long-term neighborhood effects - to examine whether youth neighborhood disadvantage impacts adult economic outcomes through sensitive years in childhood, teen socialization, duration effects, or cumulative effects. Sibling fixed effects models that net out unobserved effects of shared family characteristics suggest that youth neighborhood disadvantage increases joblessness and reduces income in adulthood. However, exposure across specific developmental stages of youth does not appear to act as a significant moderator while sustained exposure yields pernicious effects on adult economic outcomes. Moreover, these results are robust to alternative variable specifications and cousin fixed effects that net out potentially unobserved confounders, such as the inheritance of neighborhood disadvantage across three generations. Copyright © 2017. Published by Elsevier Inc.
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The Challenge of Parenting Girls in Neighborhoods of Different Perceived Quality
Directory of Open Access Journals (Sweden)
Lia Ahonen
2014-08-01
Full Text Available It is well-known that disadvantaged neighborhoods, as officially identified through census data, harbor higher numbers of delinquent individuals than advantaged neighborhoods. What is much less known is whether parents’ perception of the neighborhood problems predicts low parental engagement with their girls and, ultimately, how this is related to girls’ delinquency, including violence. This paper elucidates these issues by examining data from the Pittsburgh Girls Study, including parent-report of neighborhood problems and level of parental engagement and official records and girl-reported delinquency at ages 15, 16, and 17. Results showed higher stability over time for neighborhood problems and parental engagement than girls’ delinquency. Parents’ perception of their neighborhood affected the extent to which parents engaged in their girls’ lives, but low parental engagement did not predict girls being charged for offending at age 15, 16 or 17. These results were largely replicated for girls’ self-reported delinquency with the exception that low parental engagement at age 16 was predictive of the frequency of girls’ self-reported delinquency at age 17 as well. The results, because of their implications for screening and early interventions, are relevant to policy makers as well as practitioners.
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Peptide-conjugated micelles as a targeting nanocarrier for gene delivery
Energy Technology Data Exchange (ETDEWEB)
Lin, Wen Jen, E-mail: wjlin@ntu.edu.tw; Chien, Wei Hsuan [National Taiwan University, School of Pharmacy, Graduate Institute of Pharmaceutical Sciences (China)
2015-09-15
The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly(d,l-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells.
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Lei, Lei
2018-05-01
Along with the economic reforms, rapid urbanization, and the growth of a free land market, Chinese cities witness new forms of neighborhood poverty and increasing residential segregation by social class, migration status, and housing tenure. But little is known about the consequences of the growing social-spatial differentiation for children's educational achievement in China. Using national-scale survey data from the China Family Panel Studies in 2010, this study examines the relationship between neighborhood socioeconomic status (SES) and children's test scores in urban China, and explores the mechanisms through which neighborhood environment is associated with children's academic achievement. The results show that neighborhood SES is positively associated with children's verbal and math test scores after accounting for myriad individual and family characteristics. The relationship between neighborhood SES and test scores is partially explained by neighborhood educational institutions and collective socialization. Peer contagion, neighborhood social organization, or neighborhood physical environment do not explain this relationship. Copyright © 2018 Elsevier Inc. All rights reserved.
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The evolution of gene expression in primates
Tashakkori Ghanbarian, Avazeh
2015-01-01
The evolution of a gene’s expression profile is commonly assumed to be independent of its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between expression of neighboring genes in extant taxa. Indeed, in all eukaryotic genomes, genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their e...
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Increasing overweight and obesity erodes engagement in one's neighborhood by women, but not men.
Schuster, Roseanne C; Han, Seung Yong; Brewis, Alexandra A; Wutich, Amber
2018-06-01
Obesity is socially stigmatized in the U.S., especially for women. Significant research has focused on the role that the social and built environments of neighborhoods play in shaping obesity. However, the role of obesity in shaping neighborhood social structure has been largely overlooked. We test the hypothesis that large body size inhibits an individual's engagement in his or her neighborhood. Our study objectives are to assess if (1) body size (body mass index) interacts with gender to predict engagement in one's neighborhood (neighborhood engagement) and (2) if bonding social capital interacts with gender to predict neighborhood engagement independent of body size. We used data collected from the cross-sectional 2011 Phoenix Area Social Survey (PASS), which systematically sampled residents across four neighborhood types (core urban, urban fringe, suburban, retirement) across the Phoenix Metopolitian Area. Survey data was analyzed using logistic regression for 804 participants, including 35% for whom missing data was computed using multiple imputation. We found that as body size increases, women-but not men-have reduced engagement in their neighborhood, independent of bonding social capital and other key covariates (objective 1). We did not observe the interaction between gender and bonding social capital associated with neighborhood engagement (objective 2). Prior scholarship suggests obesity clusters in neighborhoods due to processes of social, economic, and environmental disadvantage. This finding suggests bi-directionality: obesity could, in turn, undermine neighborhood engagement through the mechanism of weight stigma and discrimination.
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Neighborhood, Socioeconomic, and Racial Influence on Chronic Pain.
Maly, Angelika; Vallerand, April Hazard
2018-02-01
The purpose of this review is to highlight the neighborhood, socioeconomic, and racial influences on chronic pain. Negative influences on the experience of chronic pain are explored and defined as any adverse stressor common in low socioeconomic, urban neighborhoods that potentially contributes to health disparity in African Americans experiencing chronic pain. The multifactorial influences on chronic pain disparity in African Americans are explored and expounded upon in this review of existing evidence. Databases used for the search included CINAHL, PubMed, and PsycArticles. The experience of chronic pain is multifaceted, existing with multiple comorbidities and lasting consequences. To improve the burden of chronic pain requires a multifactorial assessment that considers neighborhood risk factors, emphasis on environmental stressors, limitations to support networks, barriers to physical activity, and access to primary care providers with whom communication is open and without bias. A comprehensive assessment of barriers will aid in the development of interventions that reach beyond the physical factors of chronic pain, also considering the psychosocial barriers to improving the burden of chronic pain in African Americans living in impoverished urban neighborhoods. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.
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Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy.
Barar, Jaleh; Omidi, Yadollah
2013-01-01
It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called "tumor microenvironment (TME)", in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs) that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF) functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.
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Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy
Directory of Open Access Journals (Sweden)
Jaleh Barar
2013-02-01
Full Text Available It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called “tumor microenvironment (TME”, in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.
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Li, Hang; Jiang, Weihua; Zhang, Zan; Xing, Yanru; Li, Fei
2013-01-01
The beet armyworm, Spodoptera exigua (Hübner), is a serious pest worldwide that causes significant losses in crops. Unfortunately, genetic resources for the beet armyworm is extremely scarce. To improve these resources we sequenced the transcriptome of S. exigua representing all stages including eggs, 1(st) to 5(th) instar larvae, pupae, male and female adults using the Illumina Solexa platform. We assembled the transcriptome with Trinity that yielded 31,414 contigs. Of these contigs, 18,592 were annotated as protein coding genes by Blast searches against the NCBI nr database. It has been shown that knockdown of important insect genes by dsRNAs or siRNAs is a feasible mechanism to control insect pests. The first key step towards developing an efficient RNAi-mediated pest control technique is to find suitable target genes. To screen for effective target genes in the beet armyworm, we selected nine candidate genes. The sequences of these genes were amplified using the RACE strategy. Then, siRNAs were designed and chemically synthesized. We injected 2 µl siRNA (2 µg/µl) into the 4(th) instar larvae to knock down the respective target genes. The mRNA abundance of target genes decreased to different levels (∼20-94.3%) after injection of siRNAs. Knockdown of eight genes including chitinase7, PGCP, chitinase1, ATPase, tubulin1, arf2, tubulin2 and arf1 caused a significantly high level of mortality compared to the negative control (Ppest control.
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Li, Zhiqing; Cheng, Daojun; Mon, Hiroaki; Tatsuke, Tsuneyuki; Zhu, Li; Xu, Jian; Lee, Jae Man; Xia, Qingyou; Kusakabe, Takahiro
2012-01-01
Polycomb group (PcG) proteins are evolutionarily conserved chromatin modifiers and act together in three multimeric complexes, Polycomb repressive complex 1 (PRC1), Polycomb repressive complex 2 (PRC2), and Pleiohomeotic repressive complex (PhoRC), to repress transcription of the target genes. Here, we identified Polycomb target genes in Bombyx mori with holocentric centromere using genome-wide expression screening based on the knockdown of BmSCE, BmESC, BmPHO, or BmSCM gene, which represent ...
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Perceived neighborhood social resources as determinants of prosocial behavior in early adolescence.
Lenzi, Michela; Vieno, Alessio; Perkins, Douglas D; Pastore, Massimiliano; Santinello, Massimo; Mazzardis, Sonia
2012-09-01
The present study aims to develop an integrative model that links neighborhood behavioral opportunities and social resources (neighborhood cohesion, neighborhood friendship and neighborhood attachment) to prosocial (sharing, helping, empathic) behavior in early adolescence, taking into account the potential mediating role of perceived support of friends. Path analysis was used to test the proposed theoretical model in a sample of 1,145 Italian early adolescents (6th through 8th graders). More perceived opportunities and social resources in the neighborhood are related to higher levels of adolescent prosocial behavior, and this relationship is partially mediated by perceived social support from friends. The results offer promising implications for future research and intervention programs that aim to modify social systems to improve child and adolescent social competencies.
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Planning and Partnerships for the Renewal of Urban Neighborhoods
Sterrett, Stephen A.
2009-01-01
Urban universities are a key resource for municipal government, businesses, community organizations, and citizens to foster partnerships for successful renewal of distressed urban neighborhoods. From its experience over the past decade, the Ohio State University has created a successful model for engagement with its neighborhoods and the City of…
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Directory of Open Access Journals (Sweden)
Paul D Goetsch
2017-11-01
Full Text Available The DREAM (Dp/Retinoblastoma(Rb-like/E2F/MuvB transcriptional repressor complex acts as a gatekeeper of the mammalian cell cycle by establishing and maintaining cellular quiescence. How DREAM's three functional components, the E2F-DP heterodimer, the Rb-like pocket protein, and the MuvB subcomplex, form and function at target gene promoters remains unknown. The current model invokes that the pocket protein links E2F-DP and MuvB and is essential for gene repression. We tested this model by assessing how the conserved yet less redundant DREAM system in Caenorhabditis elegans is affected by absence of the sole C. elegans pocket protein LIN-35. Using a LIN-35 protein null mutant, we analyzed the assembly of E2F-DP and MuvB at promoters that are bound by DREAM and the level of expression of those "DREAM target genes" in embryos. We report that LIN-35 indeed mediates the association of E2F-DP and MuvB, a function that stabilizes DREAM subunit occupancy at target genes. In the absence of LIN-35, the occupancy of E2F-DP and MuvB at most DREAM target genes decreases dramatically and many of those genes become upregulated. The retention of E2F-DP and MuvB at some target gene promoters in lin-35 null embryos allowed us to test their contribution to DREAM target gene repression. Depletion of MuvB, but not E2F-DP, in the sensitized lin-35 null background caused further upregulation of DREAM target genes. We conclude that the pocket protein functions primarily to support MuvB-mediated repression of DREAM targets and that transcriptional repression is the innate function of the evolutionarily conserved MuvB complex. Our findings provide important insights into how mammalian DREAM assembly and disassembly may regulate gene expression and the cell cycle.
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Neighborhood walkability and hospital treatment costs: A first assessment.
Yu, Yan; Davey, Rachel; Cochrane, Tom; Learnihan, Vincent; Hanigan, Ivan C; Bagheri, Nasser
2017-06-01
Health system expenditure is a global concern, with hospital cost a major component. Built environment has been found to affect physical activity and health outcomes. The purpose of the study was a first assessment of the relationship between neighborhood walkability and hospital treatment costs. For 88 neighborhoods in the Australian Capital Territory (ACT), 2011-2013, a total of 30,690 public hospital admissions for the treatment of four diagnostic groups (cancers, endocrine, nutritional and metabolic diseases, circulatory diseases and respiratory diseases) were extracted from the ACT admitted patient care database and analyzed in relation to the Walk Score® index as a measure of walkability. Hospital cost was calculated according to the cost weight of the diagnosis related group assigned to each admission. Linear regressions were used to analyze the associations of walkability with hospital cost per person, admissions per person and cost per admission at the neighborhood level. An inverse association with neighborhood walkability was found for cost per person and admissions per person, but not cost per admission. After adjusting for age, sex and socioeconomic status, a 20-unit increase in walkability was associated with 12.1% (95% CI: 7.1-17.0%) lower cost and 12.5% (8.1-17.0%) fewer admissions. These associations did not vary by neighborhood socioeconomic status. This exploratory analysis suggests the potential for improved population health and reduced hospital cost with greater neighborhood walkability. Further research should replicate the analysis with data from other urban settings, and focus on the behavioral mechanisms underlying the inverse walkability-hospital cost association. Copyright © 2017 Elsevier Inc. All rights reserved.
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Xiao, Qian; Hale, Lauren
2018-04-25
Earlier studies have linked neighborhood disadvantage with poor sleep outcomes. However, little is known about the association between changes in one's neighborhood over time and night sleep and napping. In over 300,000 middle-to-old aged Americans, we examined neighborhood socioeconomic status (SES) and change in neighborhood SES in relation to nocturnal sleep duration and napping. Nocturnal sleep duration and daytime napping were self-reported at baseline (1995-1996). Participants also reported baseline residential addresses, which were linked to US censuses. We derived a neighborhood SES index using census variables and calculated the baseline level and change (1990-2000) in neighborhood SES. Multinomial logistic regression was used to estimate the associations between neighborhood SES over time and nocturnal sleep and napping. Lower baseline neighborhood SES was associated short sleep, long sleep and napping. When compared with the highest quintile of neighborhood SES, the lowest was associated with 46% and 72% increase in relative risk (RR) of reporting very short (nap in men and women, respectively. Moreover, a decrease in neighborhood SES was associated with higher RR of reporting very short sleep in women; while an improvement in neighborhood SES was associated with an increase in RR of long sleep in men. Neighborhood disadvantage and worsening neighborhood conditions were associated with unhealthy sleep behaviors. These results reinforce a growing literature on the potential importance of neighborhood context for understanding sleep health.
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Hibbs, Shayna; Rankin, Kristin M; David, Richard J; Collins, James W
2016-07-01
Objectives We investigated the contributions of cigarette smoking to the age-related patterns of preterm (White women within the context of lifelong neighborhood income. Methods Stratified and multilevel logistic regression analyses were performed on an Illinois transgenerational dataset of non-Hispanic White and African-American infants (1989-1991) and their mothers (1956-1976) with appended US census income information. Among non-smoking African-American women (n = 20,107) with a lifelong residence in lower income neighborhoods, PTB rates decreased from 18.5 % for teens to 15.0 % for 30-35 year-olds, p smokers (n = 5936) with a lifelong residence in lower income neighborhoods, p smokers (n = 756), PTB rates increased from 11.1 % for teens to 24.9 % for 30-35 year-olds, p White women, even cigarette smokers with a lifelong residence in lower income neighborhoods, exhibited weathering with regard to PTB. Conclusions A weathering pattern of rising PTB rates with advancing age occurs only among African-American women cigarette smokers with an early-life or lifelong residence in lower income neighborhoods, underscoring the public health policy importance of targeted smoking cessation programs in eliminating the racial disparity in the age-related patterns of PTB rates.
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Neighborhood Effects in a Behavioral Randomized Controlled Trial
Pruitt, Sandi L.; Leonard, Tammy; Murdoch, James; Hughes, Amy; McQueen, Amy; Gupta, Samir
2014-01-01
Randomized controlled trials (RCTs) of interventions intended to modify health behaviors may be influenced by neighborhood effects which can impede unbiased estimation of intervention effects. Examining a RCT designed to increase colorectal cancer (CRC) screening (N=5,628), we found statistically significant neighborhood effects: average CRC test use among neighboring study participants was significantly and positively associated with individual patient’s CRC test use. This potentially import...
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The Synergy of Family and Neighborhood on Rural Dating Violence Victimization.
Foshee, Vangie A; Chang, Ling-Yin; McNaughton Reyes, H Luz; Chen, May S; Ennett, Susan T
2015-09-01
Rural adolescents are at high risk for dating violence victimization (DVV), which has serious negative consequences. Understanding more about the conditions that increase DVV risk for rural adolescents is needed to inform prevention efforts. In response to calls for examining the influence of upper levels of the social ecology on adolescent dating violence, this study examined whether associations between the family context and physical DVV were conditioned by the characteristics of the neighborhoods in which the family resided. Data were from a multi-wave longitudinal study of 3,236 rural adolescents nested in 65 block groups, which defined neighborhoods. Data were collected between 2003 and 2005. Multilevel growth curve modeling was conducted in 2014 to test hypothesized synergistic effects of the family and neighborhood on trajectories of physical DVV from grade 8 to 12. Low parental closeness was a DVV risk in residentially stable (pFamily aggression was a DVV risk, regardless of neighborhood characteristics (p=0.001). Low parental monitoring and rule setting were not DVV risks and their effects were not moderated by neighborhood characteristics. Neighborhood ethnic heterogeneity was significantly (pviolence were not associated with DVV. None of the effects varied by sex of the adolescent, across time (grade), or by the combination of sex and time. Findings demonstrate the importance of considering the family and neighborhood, and particularly their synergistic effects in efforts to prevent adolescent DVV. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Raul A Cernadas
2014-02-01
Full Text Available Bacterial leaf streak of rice, caused by Xanthomonas oryzae pv. oryzicola (Xoc is an increasingly important yield constraint in this staple crop. A mesophyll colonizer, Xoc differs from X. oryzae pv. oryzae (Xoo, which invades xylem to cause bacterial blight of rice. Both produce multiple distinct TAL effectors, type III-delivered proteins that transactivate effector-specific host genes. A TAL effector finds its target(s via a partially degenerate code whereby the modular effector amino acid sequence identifies nucleotide sequences to which the protein binds. Virulence contributions of some Xoo TAL effectors have been shown, and their relevant targets, susceptibility (S genes, identified, but the role of TAL effectors in leaf streak is uncharacterized. We used host transcript profiling to compare leaf streak to blight and to probe functions of Xoc TAL effectors. We found that Xoc and Xoo induce almost completely different host transcriptional changes. Roughly one in three genes upregulated by the pathogens is preceded by a candidate TAL effector binding element. Experimental analysis of the 44 such genes predicted to be Xoc TAL effector targets verified nearly half, and identified most others as false predictions. None of the Xoc targets is a known bacterial blight S gene. Mutational analysis revealed that Tal2g, which activates two genes, contributes to lesion expansion and bacterial exudation. Use of designer TAL effectors discriminated a sulfate transporter gene as the S gene. Across all targets, basal expression tended to be higher than genome-average, and induction moderate. Finally, machine learning applied to real vs. falsely predicted targets yielded a classifier that recalled 92% of the real targets with 88% precision, providing a tool for better target prediction in the future. Our study expands the number of known TAL effector targets, identifies a new class of S gene, and improves our ability to predict functional targeting.
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White, Rebecca M B; Roosa, Mark W; Zeiders, Katharine H
2012-10-01
We present an integrated model for understanding Mexican American youth mental health within family, neighborhood, and cultural contexts. We combined two common perspectives on neighborhood effects to hypothesize that (a) parents' perceptions of neighborhood risk would negatively impact their children's mental health by disrupting key parenting and family processes, and (b) objective neighborhood risk would alter the effect parent and family processes had on youth mental health. We further incorporated a cultural perspective to hypothesize that an ethnic minority group's culture-specific values may support parents to successfully confront neighborhood risk. We provided a conservative test of the integrated model by simultaneously examining three parenting and family process variables: maternal warmth, maternal harsh parenting, and family cohesion. The hypothesized model was estimated prospectively in a diverse, community-based sample of Mexican American adolescents and their mothers (N = 749) living in the southwestern United States. Support for specific elements of the hypothesized model varied depending on the parenting or family process variable examined. For family cohesion results were consistent with the combined neighborhood perspectives. The effects of maternal warmth on youth mental health were altered by objective neighborhood risk. For harsh parenting, results were somewhat consistent with the cultural perspective. The value of the integrated model for research on the impacts of family, neighborhood, and cultural contexts on youth mental health are discussed, as are implications for preventive interventions for Mexican American families and youth. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
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White, Rebecca M. B.; Roosa, Mark W.; Zeiders, Katharine H.
2012-01-01
We present an integrated model for understanding Mexican American youth mental health within family, neighborhood, and cultural contexts. We combined two common perspectives on neighborhood effects to hypothesize that (a) parents’ perceptions of neighborhood risk would negatively impact their children’s mental health by disrupting key parenting and family processes, and (b) objective neighborhood risk would alter the effect parent and family processes had on youth mental health. We further incorporated a cultural perspective to hypothesize that an ethnic minority group’s culture-specific values may support parents to successfully confront neighborhood risk. We provided a conservative test of the integrated model by simultaneously examining three parenting and family process variables: maternal warmth, maternal harsh parenting, and family cohesion. The hypothesized model was estimated prospectively in a diverse, community-based sample of Mexican American adolescents and their mothers (N = 749) living in the Southwestern, U.S. Support for specific elements of the hypothesized model varied depending on the parenting or family process variable examined. For family cohesion results were consistent with the combined neighborhood perspectives. The effects of maternal warmth on youth mental health were altered by objective neighborhood risk. For harsh parenting results were somewhat consistent with the cultural perspective. The value of the integrated model for research on the impacts of family, neighborhood, and cultural contexts on youth mental health are discussed, as are implications for preventive interventions for Mexican American families and youth. PMID:22866932
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Reacting to Neighborhood Cues?
DEFF Research Database (Denmark)
Danckert, Bolette; Dinesen, Peter Thisted; Sønderskov, Kim Mannemar
2017-01-01
is founded on politically sophisticated individuals having a greater comprehension of news and other mass-mediated sources, which makes them less likely to rely on neighborhood cues as sources of information relevant for political attitudes. Based on a unique panel data set with fine-grained information...