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Sample records for program influences gene

  1. Interacting Alleles of the Coinhibitory Immunoreceptor Genes Cytotoxic T-Lymphocyte Antigen 4 and Programmed Cell-Death 1 Influence Risk and Features of Primary Biliary Cirrhosis

    PubMed Central

    Juran, Brian D.; Atkinson, Elizabeth J.; Schlicht, Erik M.; Fridley, Brooke L.; Petersen, Gloria M.; Lazaridis, Konstantinos N.

    2012-01-01

    Autoimmune diseases such as primary biliary cirrhosis (PBC) result from failure in the immune mechanisms that establish and maintain self-tolerance. Evidence suggests that these processes are shared among the spectrum of autoimmune syndromes and are likely genetically determined. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell-death 1 (PDCD1) are two genes encoding coinhibitory immunoreceptors that harbor polymorphisms with demonstrated associations to multiple autoimmune disorders. We aimed to assess functional single nucleotide polymorphisms (SNPs) in these two genes for association with PBC. SNPs in CTLA4 and PDCD1 were genotyped in 351 PBC patients and 205 controls. Allele and genotype frequencies were evaluated for association with PBC and/or antimitochondrial antibody (AMA) positivity with logistic regression. Haplotypes were inferred with an expectation-maximization algorithm, and allelic interaction was analyzed by logistic regression modeling. Individual SNPs demonstrated no association to PBC. However, the GG genotype of CTLA4 49AG was significantly associated with AMA positivity among the PBC patients. Also, individual SNPs and a haplotype of CTLA4 as well as a rare genotype of the PDCD1 SNP PD1.3 were associated with orthotopic liver transplantation. As well, we identified the influence of an interaction between the putatively autoimmune-protective CTLA4 49AG:CT60 AA haplotype and autoimmune-risk PDCD1 PD1.3 A allele on development of PBC. Conclusion Our findings illustrate the complex nature of the genetically induced risk of PBC and emphasize the importance of considering definable subphenotypes of disease, such as AMA positivity, or definitive measures of disease severity/progression, like orthotopic liver transplantation, when genetic analyses are being performed. Comprehensive screening of genes involved with immune function will lead to a greater understanding of the genetic component of autoimmunity in PBC while furthering our

  2. Screening for Multiple Genes Influencing Dyslexia.

    ERIC Educational Resources Information Center

    Smith, Shelley D.; And Others

    1991-01-01

    Examines the "sib pair" method of linkage analysis designed to locate genes influencing dyslexia, which has several advantages over the "LOD" score method. Notes that the sib pair analysis was able to detect the same linkages as the LOD method, plus a possible third region. Confirms that the sib pair method is an effective means of screening. (RS)

  3. Sperm is epigenetically programmed to regulate gene transcription in embryos.

    PubMed

    Teperek, Marta; Simeone, Angela; Gaggioli, Vincent; Miyamoto, Kei; Allen, George E; Erkek, Serap; Kwon, Taejoon; Marcotte, Edward M; Zegerman, Philip; Bradshaw, Charles R; Peters, Antoine H F M; Gurdon, John B; Jullien, Jerome

    2016-08-01

    For a long time, it has been assumed that the only role of sperm at fertilization is to introduce the male genome into the egg. Recently, ideas have emerged that the epigenetic state of the sperm nucleus could influence transcription in the embryo. However, conflicting reports have challenged the existence of epigenetic marks on sperm genes, and there are no functional tests supporting the role of sperm epigenetic marking on embryonic gene expression. Here, we show that sperm is epigenetically programmed to regulate embryonic gene expression. By comparing the development of sperm- and spermatid-derived frog embryos, we show that the programming of sperm for successful development relates to its ability to regulate transcription of a set of developmentally important genes. During spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3 marks. Experimental removal of these epigenetic marks at fertilization de-regulates gene expression in the resulting embryos in a paternal chromatin-dependent manner. This demonstrates that epigenetic instructions delivered by the sperm at fertilization are required for correct regulation of gene expression in the future embryos. The epigenetic mechanisms of developmental programming revealed here are likely to relate to the mechanisms involved in transgenerational transmission of acquired traits. Understanding how parental experience can influence development of the progeny has broad potential for improving human health. PMID:27034506

  4. Sperm is epigenetically programmed to regulate gene transcription in embryos

    PubMed Central

    Teperek, Marta; Simeone, Angela; Gaggioli, Vincent; Miyamoto, Kei; Allen, George E.; Erkek, Serap; Kwon, Taejoon; Marcotte, Edward M.; Zegerman, Philip; Bradshaw, Charles R.; Peters, Antoine H.F.M.; Gurdon, John B.; Jullien, Jerome

    2016-01-01

    For a long time, it has been assumed that the only role of sperm at fertilization is to introduce the male genome into the egg. Recently, ideas have emerged that the epigenetic state of the sperm nucleus could influence transcription in the embryo. However, conflicting reports have challenged the existence of epigenetic marks on sperm genes, and there are no functional tests supporting the role of sperm epigenetic marking on embryonic gene expression. Here, we show that sperm is epigenetically programmed to regulate embryonic gene expression. By comparing the development of sperm- and spermatid-derived frog embryos, we show that the programming of sperm for successful development relates to its ability to regulate transcription of a set of developmentally important genes. During spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3 marks. Experimental removal of these epigenetic marks at fertilization de-regulates gene expression in the resulting embryos in a paternal chromatin-dependent manner. This demonstrates that epigenetic instructions delivered by the sperm at fertilization are required for correct regulation of gene expression in the future embryos. The epigenetic mechanisms of developmental programming revealed here are likely to relate to the mechanisms involved in transgenerational transmission of acquired traits. Understanding how parental experience can influence development of the progeny has broad potential for improving human health. PMID:27034506

  5. GAP: A computer program for gene assembly

    SciTech Connect

    Eisnstein, J.R.; Uberbacher, E.C.; Guan, X.; Mural, R.J.; Mann, R.C.

    1991-09-01

    A computer program, GAP (Gene Assembly Program), has been written to assemble and score hypothetical genes, given a DNA sequence containing the gene, and the outputs of several other programs which analyze the sequence. These programs include the codign-recognition and splice-junction-recognition modules developed in this laboratory. GAP is a prototype of a planned system in which it will be integrated with an expert system and rule base. Initial tests of GAP have been carried out with four sequences, the exons of which have been determined by biochemcial methods. The highest-scoring hypothetical genes for each of the four sequences had percent correct splice junctions ranging from 50 to 100% (average 81%) and percent correct bases ranging from 92 to 100% (average 96%). 9 refs., 1 tab.

  6. Influence of Rice Development on the Function of Bacterial Blight Resistance Genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disease resistance genes most commonly used in breeding programs are single, dominant, resistance (R) genes with relative effectiveness influenced by plant developmental stage. Knowing the developmental stages at which an R gene is functional is important for disease management. In rice, resistanc...

  7. Values, Influences, and Peers (VIP) Program Review.

    ERIC Educational Resources Information Center

    Fine, Judith

    This report reviews the Values, Influences, and Peers (VIP) program in the Peel, Ontario schools. Originally developed as a joint initiative of the Ministry of Education and the Ministry of the Solicitor General, the VIP program was first introduced in Peel in 1983 as a pilot initiative in one school. Launched as a response to an increase in…

  8. Radiopharmaceutical and Gene Therapy Program

    SciTech Connect

    Buchsbaum, Donald J.

    2006-02-09

    The objective of our research program was to determine whether novel receptors can be induced in solid cancers as a target for therapy with radiolabeled unmodified peptides that bind to the receptors. The hypothesis was that induction of a high number of receptors on the surface of these cancer cells would result in an increased uptake of the radiolabeled monomeric peptides as compared to published results with radiolabeled antibodies or peptides to naturally expressed antigens or receptors, and therefore a better therapeutic outcome. The following is a summary of published results.

  9. "Programmed packaging" for gene delivery.

    PubMed

    Hyodo, M; Sakurai, Y; Akita, H; Harashima, H

    2014-11-10

    We report on the development of a multifunctional envelope-type nano device (MEND) based on our packaging concept "Programmed packaging" to control not only intracellular trafficking but also the biodistribution of encapsulated compounds such as nucleic acids/proteins/peptides. Our strategy for achieving this is based on molecular mechanisms of cell biology such as endocytosis, vesicular trafficking, etc. In this review, we summarize the concept of programmed packaging and discuss some of our recent successful examples of using MENDs. Systematic evolution of ligands by exponential enrichment (SELEX) was applied as a new methodology for identifying a new ligand toward cell or mitochondria. The delivery of siRNA to tumors and the tumor vasculature was achieved using pH sensitive lipid (YSK05), which was newly designed and optimized under in vivo conditions. The efficient delivery of pDNA to immune cells such as dendritic cells has also been developed using the KALA ligand, which can be a breakthrough technology for DNA vaccine. Finally, ss-cleavable and pH-activated lipid-like surfactant (ssPalm) which is a lipid like material with pH-activatable and SS-cleavable properties is also introduced as a proof of our concept. PMID:24780263

  10. Genetic influences on smoking: candidate genes.

    PubMed Central

    Rossing, M A

    1998-01-01

    Twin studies consistently indicate important genetic influences on multiple aspects of smoking behavior, including both initiation and cessation; however, knowledge regarding the role of specific genes is extremely limited. Habit-forming actions of nicotine appear to be triggered primarily at nicotinic receptors on the cell bodies of dopaminergic neurons in the mesolimbic "reward" system of the brain, a region implicated in addiction to other substances including cocaine, opiates, and alcohol. Important aspects of the dopaminergic pathway include synthesis of dopamine in dopaminergic neurons, release of dopamine by presynaptic neurons, receptor activation of postsynaptic neurons, dopamine re-uptake by presynaptic neurons, and metabolism of released dopamine. Research examining the role of allelic variation in genes involved in these functions is being actively pursued with respect to addictive behavior as well as personality traits and psycho- and neuropathologic conditions and has implications for smoking research. In addition, genetic differences in nicotinic receptors or nicotine metabolism might reasonably be hypothesized to play a role in smoking addiction. A role of dopaminergic or other genes in smoking cessation is of particular potential importance, as research in this area may lead to the identification of subgroups of individuals for whom pharmacologic cessation aids may be most effective. PMID:9647893

  11. Genes that influence yield in tomato

    PubMed Central

    Ariizumi, Tohru; Shinozaki, Yoshihito; Ezura, Hiroshi

    2013-01-01

    Yield is the most important breeding trait of crops. For fruit-bearing plants such as Solanum lycopersicum (tomato), fruit formation directly affects yield. The final fruit size depends on the number and volume of cell layers in the pericarp of the fruit, which is determined by the degree of cell division and expansion in the fertilized ovaries. Thus, fruit yield in tomato is predominantly determined by the efficiency of fruit set and the final cell number and size of the fruits. Through domestication, tomato fruit yield has been markedly increased as a result of mutations associated with fruit size and genetic studies have identified the genes that influence the cell cycle, carpel number and fruit set. Additionally, several lines of evidence have demonstrated that plant hormones control fruit set and size through the delicate regulation of genes that trigger physiological responses associated with fruit expansion. In this review, we introduce the key genes involved in tomato breeding and describe how they affect the physiological processes that contribute to tomato yield. PMID:23641176

  12. The Influence of Gene-Gene and Gene-Environment Interactions on the Risk of Asbestosis

    PubMed Central

    Franko, A.; Dolžan, V.; Arnerić, N.; Dodič-Fikfak, M.

    2013-01-01

    This study investigated the influence of gene-gene and gene-environment interactions on the risk of developing asbestosis. The study comprised 262 cases with asbestosis and 265 controls with no asbestos-related disease previously studied for MnSOD, ECSOD, CAT, GSTT1, GSTM1, GSTP1, and iNOS polymorphisms. Data on cumulative asbestos and smoking were available for all subjects. To assess gene-gene and gene-environmental interactions, logistic regression was used. The associations between MnSOD Ala −9Val polymorphism and the risk of asbestosis and between iNOS genotypes and asbestosis were modified by CAT –262 C > T polymorphism (P = 0.038; P = 0.031). A strong interaction was found between GSTM1-null polymorphism and smoking (P = 0.007), iNOS (CCTTT)n polymorphism and smoking (P = 0.054), and between iNOS (CCTTT)n polymorphism and cumulative asbestos exposure (P = 0.037). The findings of this study suggest that the interactions between different genotypes, genotypes and smoking, and between genotypes and asbestos exposure have an important influence on the development of asbestosis and should be seriously considered in future research on occupational/environmental asbestos-related diseases. PMID:23984360

  13. Food-chain competition influences gene's size

    NASA Astrophysics Data System (ADS)

    Dembska, Marta; Dudek, Mirosław R.; Stauffer, Dietrich

    2006-11-01

    We have analyzed an effect of the Bak-Sneppen predator-prey food-chain self-organization on nucleotide content of evolving species. In our model, genomes of the species under consideration have been represented by their nucleotide genomic fraction and we have applied two-parameter Kimura model of substitutions to include the changes of the fraction in time. The initial nucleotide fraction and substitution rates were decided with the help of random number generator. Deviation of the genomic nucleotide fraction from its equilibrium value was playing the role of the fitness parameter, B, in Bak-Sneppen model. Our finding is, that the higher is the value of the threshold fitness, during the evolution course, the more frequent are large fluctuations in number of species with strongly differentiated nucleotide content; and it is more often the case that the oldest species, which survive the food-chain competition, might have specific nucleotide fraction making possible generating long genes.

  14. Computer programs for the characterization of protein coding genes.

    PubMed

    Pierno, G; Barni, N; Candurro, M; Cipollaro, M; Franzè, A; Juliano, L; Macchiato, M F; Mastrocinque, G; Moscatelli, C; Scarlato, V

    1984-01-11

    Computer programs, implemented on an Univac II00/80 computer system, for the identification and characterization of protein coding genes and for the analysis of nucleic acid sequences, are described. PMID:6546420

  15. Computer programs for the characterization of protein coding genes.

    PubMed Central

    Pierno, G; Barni, N; Candurro, M; Cipollaro, M; Franzè, A; Juliano, L; Macchiato, M F; Mastrocinque, G; Moscatelli, C; Scarlato, V

    1984-01-01

    Computer programs, implemented on an Univac II00/80 computer system, for the identification and characterization of protein coding genes and for the analysis of nucleic acid sequences, are described. PMID:6546420

  16. Exercise influences circadian gene expression in equine skeletal muscle.

    PubMed

    Murphy, B A; Wagner, A L; McGlynn, O F; Kharazyan, F; Browne, J A; Elliott, J A

    2014-07-01

    Circadian rhythms are endogenously generated 24-h oscillations that coordinate numerous aspects of mammalian physiology, metabolism and behaviour. The existence of a molecular circadian clock in equine skeletal muscle has previously been demonstrated. This study investigates how the circadian 24-h expression of exercise-relevant genes in skeletal muscle is influenced by a regular exercise regime. Mid-gluteal, percutaneous muscle biopsies were obtained over a 24-h period from six Thoroughbred mares before and after an 8-week exercise programme. Real-time qPCR assays were used to assess the expression patterns of core clock genes ARNTL, PER2, NR1D1, clock-controlled gene DBP, and muscle genes MYF6, UCP3, VEGFA, FOXO1, MYOD1, PPARGC1A, PPARGC1B, FBXO32 and PDK4. Two-way repeated measures ANOVA revealed a significant interaction between circadian time and exercise for muscle genes MYF6, UCP3, MYOD1 and PDK4. A significant effect of time was observed for all genes with the exception of VEGFA, where a main effect of exercise was observed. By cosinor analysis, the core clock genes, ARNTL (P <0.01) and NR1D1 (P <0.05), showed 24-h rhythmicity both pre- and post-exercise, while PER2 expression was rhythmic post-exercise (P <0.05) but not pre-exercise. The expression profiles of muscle genes MYOD1 and MYF6 showed significant fits to a 24-h cosine waveform indicative of circadian rhythmicity post-exercise only (P <0.01). This study suggests that the metabolic capacity of muscle is influenced by scheduled exercise and that optimal athletic performance may be achieved when exercise times and competition times coincide. PMID:24888677

  17. Influence of mitochondria on gene expression in a citrus cybrid.

    PubMed

    Bassene, Jean-Baptiste; Froelicher, Yann; Navarro, Luis; Ollitrault, Patrick; Ancillo, Gema

    2011-06-01

    The production of cybrids, combining nucleus of a species with alien cytoplasmic organelles, is a valuable method used for improvement of various crops. Several citrus cybrids have been created by somatic hybridization. These genotypes are interesting models to analyze the impact of cytoplasmic genome change on nuclear genome expression. Herein, we report genome-wide gene expression analysis in leaves of a citrus cybrid between C. reticulata cv 'Willowleaf mandarin' and C. limon cv 'Eureka lemon' compared with its lemon parent, using a Citrus 20K cDNA microarray. Molecular analysis showed that this cybrid possesses nuclear and chloroplast genomes of Eureka lemon plus mitochondria from Willowleaf mandarin and, therefore, can be considered as a lemon bearing foreign mitochondria. Mandarin mitochondria influenced the expression of a large set of lemon nuclear genes causing an over-expression of 480 of them and repression of 39 genes. Quantitative real-time RT-PCR further confirmed the credibility of microarray data. Genes over-expressed in cybrid leaves are predominantly attributed to the functional category "cellular protein metabolism" whereas in the down-regulated none functional category was enriched. Overall, mitochondria replacement affected different nuclear genes including particularly genes predicted to be involved in mitochondrial retrograde signaling. Mitochondria regulate all cell structures even chloroplast status. These results suggest that nuclear gene expression is modulated with respect to new information received from the foreign organelle, with the final objective to suit specific needs to ensure better cell physiological balance. PMID:21308470

  18. Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections

    PubMed Central

    Lipner, Ettie M.; Garcia, Benjamin J.; Strong, Michael

    2016-01-01

    Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects. PMID:26751573

  19. Evaluation of five ab initio gene prediction programs for the discovery of maize genes.

    PubMed

    Yao, Hong; Guo, Ling; Fu, Yan; Borsuk, Lisa A; Wen, Tsui-Jung; Skibbe, David S; Cui, Xiangqin; Scheffler, Brian E; Cao, Jun; Emrich, Scott J; Ashlock, Daniel A; Schnable, Patrick S

    2005-02-01

    Five ab initio programs (FGENESH, GeneMark.hmm, GENSCAN, GlimmerR and Grail) were evaluated for their accuracy in predicting maize genes. Two of these programs, GeneMark.hmm and GENSCAN had been trained for maize; FGENESH had been trained for monocots (including maize), and the others had been trained for rice or Arabidopsis. Initial evaluations were conducted using eight maize genes (gl8a, pdc2, pdc3, rf2c, rf2d, rf2e1, rth1, and rth3) of which the sequences were not released to the public prior to conducting this evaluation. The significant advantage of this data set for this evaluation is that these genes could not have been included in the training sets of the prediction programs. FGENESH yielded the most accurate and GeneMark.hmm the second most accurate predictions. The five programs were used in conjunction with RT-PCR to identify and establish the structures of two new genes in the a1-sh2 interval of the maize genome. FGENESH, GeneMark.hmm and GENSCAN were tested on a larger data set consisting of maize assembled genomic islands (MAGIs) that had been aligned to ESTs. FGENESH, GeneMark.hmm and GENSCAN correctly predicted gene models in 773, 625, and 371 MAGIs, respectively, out of the 1353 MAGIs that comprise data set 2. PMID:15830133

  20. Programmed cell death and the gene behind spinal muscular atrophy.

    PubMed Central

    Robinson, A

    1995-01-01

    A gene involved in the development of spinal muscular atrophy (SMA) has been found on human chromosome 5 after a 4-year search. Named the neuronal apoptosis inhibitor protein (NAIP) gene, it is believed to inhibit the normal process of apoptosis--the disintegration of single cells that results from programmed cell death--in motor neurons. The researchers who found the NAIP gene also discovered that healthy people carry one complete copy of the gene along with many other partial copies. Many children with SMA have the partial copies but not the complete gene. This discovery facilitates the accurate genetic diagnosis of SMA. But gene therapy for SMA will not be possible until researchers find a suitable vector to stably introduce activated and intact copies of the gene into the motor neurons of children with SMA in time to stop motor neuron loss. Images p1460-a PMID:7585374

  1. Perspectives on best practices for gene therapy programs.

    PubMed

    Cheever, Thomas R; Berkley, Dale; Braun, Serge; Brown, Robert H; Byrne, Barry J; Chamberlain, Jeffrey S; Cwik, Valerie; Duan, Dongsheng; Federoff, Howard J; High, Katherine A; Kaspar, Brian K; Klinger, Katherine W; Larkindale, Jane; Lincecum, John; Mavilio, Fulvio; McDonald, Cheryl L; McLaughlin, James; Weiss McLeod, Bonnie; Mendell, Jerry R; Nuckolls, Glen; Stedman, Hansell H; Tagle, Danilo A; Vandenberghe, Luk H; Wang, Hao; Wernett, Pamela J; Wilson, James M; Porter, John D; Gubitz, Amelie K

    2015-03-01

    With recent successes in gene therapy trials for hemophilia and retinal diseases, the promise and prospects for gene therapy are once again garnering significant attention. To build on this momentum, the National Institute of Neurological Disorders and Stroke and the Muscular Dystrophy Association jointly hosted a workshop in April 2014 on "Best Practices for Gene Therapy Programs," with a focus on neuromuscular disorders. Workshop participants included researchers from academia and industry as well as representatives from the regulatory, legal, and patient advocacy sectors to cover the gamut from preclinical optimization to intellectual property concerns and regulatory approval. The workshop focused on three key issues in the field: (1) establishing adequate scientific premise for clinical trials in gene therapy, (2) addressing regulatory process issues, and (3) intellectual property and commercialization issues as they relate to gene therapy. The outcomes from the discussions at this workshop are intended to provide guidance for researchers and funders in the gene therapy field. PMID:25654329

  2. Factors Influencing Student Participation in College Study Abroad Programs

    ERIC Educational Resources Information Center

    Bandyopadhyay, Soumava; Bandyopadhyay, Kakoli

    2015-01-01

    This paper proposes a theoretical framework to investigate the factors that influence student participation in college study abroad programs. The authors posit that students' general perceptions regarding the study abroad experience and their expectations of intercultural awareness from study abroad programs will impact their perceptions of…

  3. Factors Influencing the Occurrence of Adult Agricultural Education Programs.

    ERIC Educational Resources Information Center

    Christmas, Oren L.; Warmbrod, J. Robert

    A study examined the institutional factors the influence whether or not adult agricultural education programs are offered in high schools. All Ohio secondary schools that offered vocational agriculture programs in agricultural production or farm business management during 1985-1986 (a total of 260 schools) were included in the study. Data were…

  4. Low-Rank Regularization for Learning Gene Expression Programs

    PubMed Central

    Ye, Guibo; Tang, Mengfan; Cai, Jian-Feng; Nie, Qing; Xie, Xiaohui

    2013-01-01

    Learning gene expression programs directly from a set of observations is challenging due to the complexity of gene regulation, high noise of experimental measurements, and insufficient number of experimental measurements. Imposing additional constraints with strong and biologically motivated regularizations is critical in developing reliable and effective algorithms for inferring gene expression programs. Here we propose a new form of regulation that constrains the number of independent connectivity patterns between regulators and targets, motivated by the modular design of gene regulatory programs and the belief that the total number of independent regulatory modules should be small. We formulate a multi-target linear regression framework to incorporate this type of regulation, in which the number of independent connectivity patterns is expressed as the rank of the connectivity matrix between regulators and targets. We then generalize the linear framework to nonlinear cases, and prove that the generalized low-rank regularization model is still convex. Efficient algorithms are derived to solve both the linear and nonlinear low-rank regularized problems. Finally, we test the algorithms on three gene expression datasets, and show that the low-rank regularization improves the accuracy of gene expression prediction in these three datasets. PMID:24358148

  5. Benchmarking of gene prediction programs for metagenomic data.

    PubMed

    Yok, Non; Rosen, Gail

    2010-01-01

    This manuscript presents the most rigorous benchmarking of gene annotation algorithms for metagenomic datasets to date. We compare three different programs: GeneMark, MetaGeneAnnotator (MGA) and Orphelia. The comparisons are based on their performances over simulated fragments from one hundred species of diverse lineages. We defined four different types of fragments; two types come from the inter- and intra-coding regions and the other types are from the gene edges. Hoff et al. used only 12 species in their comparison; therefore, their sample is too small to represent an environmental sample. Also, no predecessors has separately examined fragments that contain gene edges as opposed to intra-coding regions. General observations in our results are that performances of all these programs improve as we increase the length of the fragment. On the other hand, intra-coding fragments of our data show low annotation error in all of the programs if compared to the gene edge fragments. Overall, we found an upper-bound performance by combining all the methods. PMID:21097156

  6. Gene identification programs in bread wheat: a comparison study.

    PubMed

    Nasiri, Jaber; Naghavi, Mohammadreza; Rad, Sara Naseri; Yolmeh, Tahereh; Shirazi, Milaveh; Naderi, Ramin; Nasiri, Mojtaba; Ahmadi, Sayvan

    2013-01-01

    Seven ab initio web-based gene prediction programs (i.e., AUGUSTUS, BGF, Fgenesh, Fgenesh+, GeneID, Genemark.hmm, and HMMgene) were assessed to compare their prediction accuracy using protein-coding sequences of bread wheat. At both nucleotide and exon levels, Fgenesh+ was deduced as the superior program and BGF followed by Fgenesh were resided in the next positions, respectively. Conversely, at gene level, Fgenesh with the value of predicting more than 75% of all the genes precisely, concluded as the best ones. It was also found out that programs such as Fgenesh+, BGF, and Fgenesh, because of harboring the highest percentage of correct predictive exons appear to be much more applicable in achieving more trustworthy results, while using both GeneID and HMMgene the percentage of false negatives would be expected to enhance. Regarding initial exon, overall, the frequency of accurate recognition of 3' boundary was significantly higher than that of 5' and the reverse was true if terminal exon is taken into account. Lastly, HMMgene and Genemark.hmm, overall, presented independent tendency against GC content, while the others appear to be slightly more sensitive if GC-poor sequences are employed. Our results, overall, exhibited that to make adequate opportunity in acquiring remarkable results, gene finders still need additional improvements. PMID:24124688

  7. Factors influencing candidates' choice of a pediatric dental residency program.

    PubMed

    da Fonseca, Marcio A; Pollock, Matthew; Majewski, Robert; Tootla, Ruwaida; Murdoch-Kinch, Carol Anne

    2007-09-01

    The goal of this study was to identify the factors and program characteristics that influenced the program ranking decisions of applicants to pediatric dentistry residency programs. A questionnaire was sent to the first-year resident class in 2005 with a response rate of 69.2 percent (n=260). Approximately 55 percent were female (104/180) and 61 percent were non-His-panic white (110/180). The respondents reported that they applied to an average of nine programs, of which five were ranked. Most applicants were interested in a program that had a hospital component with a duration of two years. A program's ability to prepare the resident for an academic career was a minimal influence for 48.6 percent (87/179), and 57.5 percent (103/179) were not interested in a master's or Ph.D. degree. Factors associated with program ranking included modern clinical facilities, high ratio of dental assistants and faculty to residents, availability of assistants for sedation and general anesthesia cases, availability of a salary or stipend, and amount of clinical experience. Important non-clinical factors included hospitality during the interview, geographic location, and perceived reputation of the program. Opportunity to speak with the current residents in private, observing the interaction between residents and faculty, and touring the facilities were also highly considered. These findings may help program directors tailor their interviews and programs to suit the needs of applicants. PMID:17761626

  8. Evaluation of gene-finding programs on mammalian sequences.

    PubMed

    Rogic, S; Mackworth, A K; Ouellette, F B

    2001-05-01

    We present an independent comparative analysis of seven recently developed gene-finding programs: FGENES, GeneMark.hmm, Genie, Genescan, HMMgene, Morgan, and MZEF. For evaluation purposes we developed a new, thoroughly filtered, and biologically validated dataset of mammalian genomic sequences that does not overlap with the training sets of the programs analyzed. Our analysis shows that the new generation of programs has substantially better results than the programs analyzed in previous studies. The accuracy of the programs was also examined as a function of various sequence and prediction features, such as G + C content of the sequence, length and type of exons, signal type, and score of the exon prediction. This approach pinpoints the strengths and weaknesses of each individual program as well as those of computational gene-finding in general. The dataset used in this analysis (HMR195) as well as the tables with the complete results are available at http://www.cs.ubc.ca/~rogic/evaluation/. PMID:11337477

  9. Factors influencing nursing career choices and choice of study program.

    PubMed

    Haron, Yafa; Reicher, Sima; Riba, Shoshana

    2014-01-01

    In advance of a recruitment campaign, Israeli first-year nursing students of all ethnicities were surveyed to elucidate what factors had influenced them to make nursing their career and what sort of training track they preferred. The responses made it clear that different factors influence different groups differently. There were noticeable differences by gender, age, and ethnicity. Overall, training institutions were chosen for their closeness to the student's home but other factors also operated among particular groups, such as institutional prestige and flexible entry criteria. There was a blatant preference for academic, particularly university-sited, programs over diploma programs. PMID:24878405

  10. Role of Energy Metabolism in the Brown Fat Gene Program

    PubMed Central

    Nam, Minwoo; Cooper, Marcus P.

    2015-01-01

    In murine and human brown adipose tissue (BAT), mitochondria are powerful generators of heat that safely metabolize fat, a feature that has great promise in the fight against obesity and diabetes. Recent studies suggest that the actions of mitochondria extend beyond their conventional role as generators of heat. There is mounting evidence that impaired mitochondrial respiratory capacity is accompanied by attenuated expression of Ucp1 and other BAT-selective genes, implying that mitochondria exert transcriptional control over the brown fat gene program. In this review, we discuss the current understanding of brown fat mitochondria, their potential role in transcriptional control of the brown fat gene program, and potential strategies to treat obesity in humans by leveraging thermogenesis in brown adipocytes. PMID:26175716

  11. Factors influencing perceived sustainability of Dutch community health programs.

    PubMed

    Vermeer, A J M; Van Assema, P; Hesdahl, B; Harting, J; De Vries, N K

    2015-09-01

    We assessed the perceived sustainability of community health programs organized by local intersectoral coalitions, as well as the factors that collaborating partners think might influence sustainability. Semi-structured interviews were conducted among 31 collaborating partners of 5 community health programs in deprived neighborhoods in the southern part of the Netherlands. The interview guide was based on a conceptual framework that includes factors related to the context, the leading organization, leadership, the coalition, collaborating partners, interventions and outcomes. Interviews were recorded, transcribed and content analyzed using NVivo 8.0. Participants in each of the programs varied in their perceptions of the sustainability of the program, but those people collaborating in pre-existing neighborhood structures expressed relatively high faith in their continuation. The participating citizens in particular believed that these structures would continue to address the health of the community in the future. We found factors from all categories of the conceptual framework that were perceived to influence sustainability. The program leaders appeared to be crucial to the programs, as they were frequently mentioned in close interaction with other factors. Program leaders should use a motivating and supportive leadership style and should act as 'program champions'. PMID:24021354

  12. Influence of neonatal hypothyroidism on hepatic gene expression and lipid metabolism in adulthood.

    PubMed

    Santana-Farré, Ruymán; Mirecki-Garrido, Mercedes; Bocos, Carlos; Henríquez-Hernández, Luis A; Kahlon, Nusrat; Herrera, Emilio; Norstedt, Gunnar; Parini, Paolo; Flores-Morales, Amilcar; Fernández-Pérez, Leandro

    2012-01-01

    Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. PMID:22666351

  13. Influence of Neonatal Hypothyroidism on Hepatic Gene Expression and Lipid Metabolism in Adulthood

    PubMed Central

    Bocos, Carlos; Henríquez-Hernández, Luis A.; Kahlon, Nusrat; Herrera, Emilio; Norstedt, Gunnar; Parini, Paolo; Flores-Morales, Amilcar; Fernández-Pérez, Leandro

    2012-01-01

    Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. PMID:22666351

  14. Influence of Funding Cuts on Texas School Tobacco Programs

    ERIC Educational Resources Information Center

    Gingiss, Phyllis M.; Boerm, Melynda

    2009-01-01

    Background: Following the Master Settlement Agreement, state tobacco prevention spending peaked in 2002, but has subsequently been diminishing annually. This study compared the influence of 2004 Texas tobacco program budget cuts on school practices a year after funding loss. Methods: Three school groups were compared: continuously funded for a…

  15. A Metacognitive Approach to Pair Programming: Influence on Metacognitive Awareness

    ERIC Educational Resources Information Center

    Breed, Betty; Mentz, Elsa; van der Westhuizen, Gert

    2014-01-01

    Introduction: The research focused on metacognition in a collaborative learning setting. Based on a comprehensive literature study the researchers designed a metacognitive teaching-learning strategy for pair programmers. Our purpose was to investigate the influence of this metacognitive teaching-learning strategy during pair programming in an…

  16. Alternative Administrative Certification: Socializing Factors Influencing Program Choice

    ERIC Educational Resources Information Center

    Bickmore, Dana L.; Bickmore, Steven T.; Raines, Sarah

    2013-01-01

    This study used an organizational socialization lens to examine factors influencing participants' decision to pursue the principalship and choice to engage in an alternate administration certification program. Through an analysis of participant focus groups and interviews, factors emerged from the codes that were compared with dimensions of…

  17. Attendees' Perceptions of Commercial Influence in Noncommercially Funded CME Programs

    ERIC Educational Resources Information Center

    Goldfarb, Elizabeth; Baer, Lee; Fromson, John A.; Gorrindo, Tristan; Iodice, Kristin E.; Birnbaum, Robert J.

    2012-01-01

    Introduction: The controversy surrounding commercial support for continuing medical education (CME) programs has led to policy changes, but data show no significant difference in perceived bias between commercial and noncommercial CME. Indeed, what attendees perceive as commercial influence is not fully understood. We sought to clarify what…

  18. The Learning Context: Influence on Learning to Program

    ERIC Educational Resources Information Center

    Govender, Irene

    2009-01-01

    In this paper the influence of the learning context is considered when learning to program. For the purposes of this study, the lectures, study process, previous knowledge or teaching experience and tests comprised the learning context. The article argues that students' experiences of the learning context have important implications for teaching…

  19. Using gene expression programming to infer gene regulatory networks from time-series data.

    PubMed

    Zhang, Yongqing; Pu, Yifei; Zhang, Haisen; Su, Yabo; Zhang, Lifang; Zhou, Jiliu

    2013-12-01

    Gene regulatory networks inference is currently a topic under heavy research in the systems biology field. In this paper, gene regulatory networks are inferred via evolutionary model based on time-series microarray data. A non-linear differential equation model is adopted. Gene expression programming (GEP) is applied to identify the structure of the model and least mean square (LMS) is used to optimize the parameters in ordinary differential equations (ODEs). The proposed work has been first verified by synthetic data with noise-free and noisy time-series data, respectively, and then its effectiveness is confirmed by three real time-series expression datasets. Finally, a gene regulatory network was constructed with 12 Yeast genes. Experimental results demonstrate that our model can improve the prediction accuracy of microarray time-series data effectively. PMID:24140883

  20. Perspectives on Best Practices for Gene Therapy Programs

    PubMed Central

    Cheever, Thomas R.; Berkley, Dale; Braun, Serge; Brown, Robert H.; Byrne, Barry J.; Chamberlain, Jeffrey S.; Cwik, Valerie; Duan, Dongsheng; Federoff, Howard J.; High, Katherine A.; Kaspar, Brian K.; Klinger, Katherine W.; Larkindale, Jane; Lincecum, John; Mavilio, Fulvio; McDonald, Cheryl L.; McLaughlin, James; Weiss McLeod, Bonnie; Mendell, Jerry R.; Nuckolls, Glen; Stedman, Hansell H.; Tagle, Danilo A.; Vandenberghe, Luk H.; Wang, Hao; Wernett, Pamela J.; Wilson, James M.; Porter, John D.

    2015-01-01

    Abstract With recent successes in gene therapy trials for hemophilia and retinal diseases, the promise and prospects for gene therapy are once again garnering significant attention. To build on this momentum, the National Institute of Neurological Disorders and Stroke and the Muscular Dystrophy Association jointly hosted a workshop in April 2014 on “Best Practices for Gene Therapy Programs,” with a focus on neuromuscular disorders. Workshop participants included researchers from academia and industry as well as representatives from the regulatory, legal, and patient advocacy sectors to cover the gamut from preclinical optimization to intellectual property concerns and regulatory approval. The workshop focused on three key issues in the field: (1) establishing adequate scientific premise for clinical trials in gene therapy, (2) addressing regulatory process issues, and (3) intellectual property and commercialization issues as they relate to gene therapy. The outcomes from the discussions at this workshop are intended to provide guidance for researchers and funders in the gene therapy field. PMID:25654329

  1. Factors that Influence the Effectiveness of Sanitation Programs.

    PubMed

    Fernandez-Haddad, Marilu; Ingram, Maia

    2015-01-01

    Local governments in both Mexico and the U.S. spend considerable money on public services, which do not always bring the expected results. For instance, a large part of the public budget is destined to solve social and health problems, such as public sanitation. Government has attacked the problem by providing public sanitation infrastructure (such as garbage and recycling receptacles) and by using social ad campaigns. However, these efforts do not always affect the habits of residents and bring the desired changes in city sanitation. This article presents a case study that used a participatory method to address an innovative city sanitation effort: The Clean City Program in Puebla, Mexico. This program adopted social marketing techniques, a discipline born in the 70s when the principles and practices developed to sell products and services started to be applied to sell ideas, attitudes, or behaviors. Social marketing programs have been adopted by governments to change attitudes and behavior in areas such as public services. The article first describes the context and strategies of the program, which included the use of the promotora model to engage community members. The researchers then make use of qualitative data gathered throughout program planning and implementation to evaluate the impact of the social marketing programs and its effectiveness. The article analyzes social, educational, economic, demographic, and cultural factors that influence the effectiveness of sanitation programs and presents recommendations for strategies to engage community members in community sanitation programs. PMID:26389106

  2. Factors that Influence the Effectiveness of Sanitation Programs

    PubMed Central

    Fernandez-Haddad, Marilu; Ingram, Maia

    2015-01-01

    Local governments in both Mexico and the U.S. spend considerable money on public services, which do not always bring the expected results. For instance, a large part of the public budget is destined to solve social and health problems, such as public sanitation. Government has attacked the problem by providing public sanitation infrastructure (such as garbage and recycling receptacles) and by using social ad campaigns. However, these efforts do not always affect the habits of residents and bring the desired changes in city sanitation. This article presents a case study that used a participatory method to address an innovative city sanitation effort: The Clean City Program in Puebla, Mexico. This program adopted social marketing techniques, a discipline born in the 70s when the principles and practices developed to sell products and services started to be applied to sell ideas, attitudes, or behaviors. Social marketing programs have been adopted by governments to change attitudes and behavior in areas such as public services. The article first describes the context and strategies of the program, which included the use of the promotora model to engage community members. The researchers then make use of qualitative data gathered throughout program planning and implementation to evaluate the impact of the social marketing programs and its effectiveness. The article analyzes social, educational, economic, demographic, and cultural factors that influence the effectiveness of sanitation programs and presents recommendations for strategies to engage community members in community sanitation programs. PMID:26389106

  3. Modeling dietary influences on offspring metabolic programming in Drosophila melanogaster.

    PubMed

    Brookheart, Rita T; Duncan, Jennifer G

    2016-09-01

    The influence of nutrition on offspring metabolism has become a hot topic in recent years owing to the growing prevalence of maternal and childhood obesity. Studies in mammals have identified several factors correlating with parental and early offspring dietary influences on progeny health; however, the molecular mechanisms that underlie these factors remain undiscovered. Mammalian metabolic tissues and pathways are heavily conserved in Drosophila melanogaster, making the fly an invaluable genetic model organism for studying metabolism. In this review, we discuss the metabolic similarities between mammals and Drosophila and present evidence supporting its use as an emerging model of metabolic programming. PMID:27450801

  4. Factors Influencing Learning Environments in an Integrated Experiential Program

    NASA Astrophysics Data System (ADS)

    Koci, Peter

    The research conducted for this dissertation examined the learning environment of a specific high school program that delivered the explicit curriculum through an integrated experiential manner, which utilized field and outdoor experiences. The program ran over one semester (five months) and it integrated the grade 10 British Columbian curriculum in five subjects. A mixed methods approach was employed to identify the students' perceptions and provide richer descriptions of their experiences related to their unique learning environment. Quantitative instruments were used to assess changes in students' perspectives of their learning environment, as well as other supporting factors including students' mindfulness, and behaviours towards the environment. Qualitative data collection included observations, open-ended questions, and impromptu interviews with the teacher. The qualitative data describe the factors and processes that influenced the learning environment and give a richer, deeper interpretation which complements the quantitative findings. The research results showed positive scores on all the quantitative measures conducted, and the qualitative data provided further insight into descriptions of learning environment constructs that the students perceived as most important. A major finding was that the group cohesion measure was perceived by students as the most important attribute of their preferred learning environment. A flow chart was developed to help the researcher conceptualize how the learning environment, learning process, and outcomes relate to one another in the studied program. This research attempts to explain through the consideration of this case study: how learning environments can influence behavioural change and how an interconnectedness among several factors in the learning process is influenced by the type of learning environment facilitated. Considerably more research is needed in this area to understand fully the complexity learning

  5. Factors influencing students to enroll in health information management programs.

    PubMed

    Safian, Shelley C

    2012-01-01

    This nonexperimental quantitative descriptive-correlative research study was performed to describe the sources with the greatest influence on the participants' decision to enroll in a postsecondary educational program with the intent of working toward a career in health information management. Participants were asked, "Which sources have the greatest influence on an individual's decision to enroll in a postsecondary educational program with the intent of working toward a career in health information management (HIM)?" The study population was composed of matriculated students enrolled in accredited postsecondary schools offering an undergraduate medical billing and coding program at a brick-and-mortar campus in a two-county area of a South Atlantic state. The study found that an environmental source, specifically career job opportunities, was statistically significant as the greatest source of influence for these participants. This research aims to support efforts to provide the health information management subsector of the healthcare industry with a sufficient number of trained professionals to fill the identified need for trained HIM professionals, particularly medical coding specialists. PMID:22783152

  6. Factors Influencing Students to Enroll in Health Information Management Programs

    PubMed Central

    Safian, Shelley C.

    2012-01-01

    This nonexperimental quantitative descriptive-correlative research study was performed to describe the sources with the greatest influence on the participants’ decision to enroll in a postsecondary educational program with the intent of working toward a career in health information management. Participants were asked, “Which sources have the greatest influence on an individual's decision to enroll in a postsecondary educational program with the intent of working toward a career in health information management (HIM)?” The study population was composed of matriculated students enrolled in accredited postsecondary schools offering an undergraduate medical billing and coding program at a brick-and-mortar campus in a two-county area of a South Atlantic state. The study found that an environmental source, specifically career job opportunities, was statistically significant as the greatest source of influence for these participants. This research aims to support efforts to provide the health information management subsector of the healthcare industry with a sufficient number of trained professionals to fill the identified need for trained HIM professionals, particularly medical coding specialists. PMID:22783152

  7. Characteristic features of the nucleotide sequences of yeast mitochondrial ribosomal protein genes as analyzed by computer program GeneMark.

    PubMed

    Isono, K; McIninch, J D; Borodovsky, M

    1994-01-01

    The nucleotide sequence data for yeast mitochondrial ribosomal protein (MRP) genes were analyzed by the computer program GeneMark which predicts the presence of likely genes in sequence data by calculating statistical biases in the appearance of consecutive nucleotides. The program uses a set of standard sequence data for this calculation. We used this program for the analysis of yeast nucleotide sequence data containing MRP genes, hoping to obtain information as to whether they share features in common that are different from other yeast genes. Sequence data sets for ordinary yeast genes and for 27 known MRP genes were used. The MRP genes were nicely predicted as likely genes regardless of the data sets used, whereas other yeast genes were predicted to be likely genes only when the data set for ordinary yeast genes was used. The assembled sequence data for chromosomes II, III, VIII and XI as well as the segmented data for chromosome V were analyzed in a similar manner. In addition to the known MRP genes, eleven ORF's were predicted to be likely MRP genes. Thus, the method seems very powerful in analyzing genes of heterologous origins. PMID:7719921

  8. Simulated microgravity influenced the expression of DNA damage repair genes

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Jiawei, Liu; Wang, Ting

    2016-07-01

    Ionizing radiation and microgravity were considered to be the most important stress factors of space environmental the respective study of the biological effects of the radiation and microgravity carried out earlier, but the interaction of the effects of radiation with microgravity started later, and due to difference of the materials and methods the result of this experiment were not consistent. To further investigate the influence of microgravity on the expression of the radiation damage repair genes, the seed of Arabidopsis (Col) and its gravity-insensitive mutant (PIN2) were exposed to 0.1Gy of the dose of energetic carbon-ion beam radiation (LET = 30KeV / μm), and the germinated seed were than fixed in the 3D random positioning apparatus immediately for a 10-day simulated microgravity. By measuring the deflection angle of root tip and the changes of the expression of Ku70 and RAD51 protein, we investigated the impact of microgravity effect on radiation damage repair systems. The results shown that radiation, microgravity and microgravity with radiation could increase the angle of the root of the Col significantly, but no obvious effect on PIN2 type. The radiation could increase the expression of Ku70 significantly in both Col and PIN2, microgravity does not affect the expression, but the microgravity with radiation could decrease the expression of Ku70. This result shown that the microgravity could influence the radiation damage repair systems in molecular level. Moreover, our findings were important to understand the molecular mechanism of the impact of microgravity effect on radiation damage repair systems in vivo.

  9. IL18 Gene Variants Influence the Susceptibility to Chagas Disease

    PubMed Central

    Leon Rodriguez, Daniel A; Carmona, F. David; Echeverría, Luis Eduardo; González, Clara Isabel; Martin, Javier

    2016-01-01

    Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control. PMID:27027876

  10. Computer-based construction of gene models using the GRAIL Gene Assembly Program

    SciTech Connect

    Einstein, J.R.; Mural, R.J.; Guan, X.; Uberbacher, E.C.

    1992-09-01

    The Gene Assembly Program (GAP), a module of GRAIL, assembles and scores gene models, given a DNA sequence and the outputs of other GRAIL modules for the sequence. The latter modules determine the positions of coding regions, the positions and scores of possible splice junctions, the positions of possible translation-initiation sites, the coding strand for the gene, and the probable-translation-frame function over the sequence. GAP tests combinations of those splice junctions which are within acceptable distances from the initial estimated edges of the coding regions. Every complete gene model, comprising translation-initiation site, splice junctions and stop codon, which agrees with GAP`s set of rules is scored, and the ten highest-scoring models are saved. Each gene-model score depends on the input scores of splice junctions used in the model, their positions relative to the initial estimated edges of the included coding regions, and the degree of agreement of the entire model with the probable-translation-frame function. If error conditions are detected, the present version of GAP attempts to correct them by the insertion and/or deletion of one or more coding regions. These insertions and deletions have resulted in a net improvement of gene models, and a particularly large improvement in the recognition and characterization of very short coding regions. The results of GRAIL including the GAP module for 26 sequences from GenBank, each with a biochemically characterized single gene, are quite promising and demonstrate the feasibility of constructing largely accurate gene models strictly on the basis of sequence data.

  11. Computer-based construction of gene models using the GRAIL Gene Assembly Program

    SciTech Connect

    Einstein, J.R.; Mural, R.J.; Guan, X.; Uberbacher, E.C.

    1992-09-01

    The Gene Assembly Program (GAP), a module of GRAIL, assembles and scores gene models, given a DNA sequence and the outputs of other GRAIL modules for the sequence. The latter modules determine the positions of coding regions, the positions and scores of possible splice junctions, the positions of possible translation-initiation sites, the coding strand for the gene, and the probable-translation-frame function over the sequence. GAP tests combinations of those splice junctions which are within acceptable distances from the initial estimated edges of the coding regions. Every complete gene model, comprising translation-initiation site, splice junctions and stop codon, which agrees with GAP's set of rules is scored, and the ten highest-scoring models are saved. Each gene-model score depends on the input scores of splice junctions used in the model, their positions relative to the initial estimated edges of the included coding regions, and the degree of agreement of the entire model with the probable-translation-frame function. If error conditions are detected, the present version of GAP attempts to correct them by the insertion and/or deletion of one or more coding regions. These insertions and deletions have resulted in a net improvement of gene models, and a particularly large improvement in the recognition and characterization of very short coding regions. The results of GRAIL including the GAP module for 26 sequences from GenBank, each with a biochemically characterized single gene, are quite promising and demonstrate the feasibility of constructing largely accurate gene models strictly on the basis of sequence data.

  12. Evolution of the CNS myelin gene regulatory program.

    PubMed

    Li, Huiliang; Richardson, William D

    2016-06-15

    Myelin is a specialized subcellular structure that evolved uniquely in vertebrates. A myelinated axon conducts action potentials many times faster than an unmyelinated axon of the same diameter; for the same conduction speed, the unmyelinated axon would need a much larger diameter and volume than its myelinated counterpart. Hence myelin speeds information transfer and saves space, allowing the evolution of a powerful yet portable brain. Myelination in the central nervous system (CNS) is controlled by a gene regulatory program that features a number of master transcriptional regulators including Olig1, Olig2 and Myrf. Olig family genes evolved from a single ancestral gene in non-chordates. Olig2, which executes multiple functions with regard to oligodendrocyte identity and development in vertebrates, might have evolved functional versatility through post-translational modification, especially phosphorylation, as illustrated by its evolutionarily conserved serine/threonine phospho-acceptor sites and its accumulation of serine residues during more recent stages of vertebrate evolution. Olig1, derived from a duplicated copy of Olig2 in early bony fish, is involved in oligodendrocyte development and is critical to remyelination in bony vertebrates, but is lost in birds. The origin of Myrf orthologs might be the result of DNA integration between an invading phage or bacterium and an early protist, producing a fusion protein capable of self-cleavage and DNA binding. Myrf seems to have adopted new functions in early vertebrates - initiation of the CNS myelination program as well as the maintenance of mature oligodendrocyte identity and myelin structure - by developing new ways to interact with DNA motifs specific to myelin genes. This article is part of a Special Issue entitled SI: Myelin Evolution. PMID:26474911

  13. RUNX1 represses the erythroid gene expression program during megakaryocytic differentiation.

    PubMed

    Kuvardina, Olga N; Herglotz, Julia; Kolodziej, Stephan; Kohrs, Nicole; Herkt, Stefanie; Wojcik, Bartosch; Oellerich, Thomas; Corso, Jasmin; Behrens, Kira; Kumar, Ashok; Hussong, Helge; Urlaub, Henning; Koch, Joachim; Serve, Hubert; Bonig, Halvard; Stocking, Carol; Rieger, Michael A; Lausen, Jörn

    2015-06-01

    The activity of antagonizing transcription factors represents a mechanistic paradigm of bidirectional lineage-fate control during hematopoiesis. At the megakaryocytic/erythroid bifurcation, the cross-antagonism of krueppel-like factor 1 (KLF1) and friend leukemia integration 1 (FLI1) has such a decisive role. However, how this antagonism is resolved during lineage specification is poorly understood. We found that runt-related transcription factor 1 (RUNX1) inhibits erythroid differentiation of murine megakaryocytic/erythroid progenitors and primary human CD34(+) progenitor cells. We show that RUNX1 represses the erythroid gene expression program during megakaryocytic differentiation by epigenetic repression of the erythroid master regulator KLF1. RUNX1 binding to the KLF1 locus is increased during megakaryocytic differentiation and counterbalances the activating role of T-cell acute lymphocytic leukemia 1 (TAL1). We found that corepressor recruitment by RUNX1 contributes to a block of the KLF1-dependent erythroid gene expression program. Our data indicate that the repressive function of RUNX1 influences the balance between erythroid and megakaryocytic differentiation by shifting the balance between KLF1 and FLI1 in the direction of FLI1. Taken together, we show that RUNX1 is a key player within a network of transcription factors that represses the erythroid gene expression program. PMID:25911237

  14. Factors influencing utilization of postdischarge cognitive rehabilitation programs.

    PubMed

    Gummow, L J; Gregory, V R; Macnamara, S E

    1990-04-01

    A decision to add a new treatment program has widespread and long-lasting implications for both the patient and the organization. Information about the interactions among the institution, the patient, and the treatment modality are seldom available. Cognitive rehabilitation is a relatively new treatment modality that is being adopted in a number of programs. This report examined characteristics of stroke patients that (1) precluded their selection for cognitive rehabilitation treatment and (2) were associated with patient refusal to participate in cognitive rehabilitation. The records of stroke patients treated in three rehabilitation facilities were examined for their ability to participate in an outpatient cognitive rehabilitation program. Due to stringent criteria for the research project, fewer than half of the stroke patient population were cognitively able to participate. Of eligible patients, many declined postdischarge cognitive rehabilitation. Several variables influenced patient participation. Female stroke patients were much less likely to participate than were male patients. In addition, distance from the medical facility providing cognitive rehabilitation was a major barrier to treatment participation. Individuals who opted to participate were well educated, affluent or both. The sample of cognitive rehabilitation patients was not, therefore, representative of the population. These results suggest that medical facilities considering the addition of a centralized outpatient postdischarge cognitive rehabilitation program should first evaluate the characteristics of the target population. Suggestions about the institutional considerations involved in making the decision to add a cognitive rehabilitation program are made. PMID:2158490

  15. The role of genes involved in lipolysis on weight loss program in overweight and obese individuals.

    PubMed

    Luglio, Harry Freitag; Sulistyoningrum, Dian Caturini; Susilowati, Rina

    2015-09-01

    The ability of obese people to reduce weight in the same treatment varied. Genetic make up as well as the behavioral changes are important for the successfulness of the program. One of the most proposed genetic variations that have been reported in many intervention studies was genes that control lipolysis process. This review summarizes studies that were done showing the influence of genetic polymorphisms in lipolysis pathway and weight loss in a weight loss treatment program. Some studies had shown that certain enzymes involved in this process were related to successfulness of weight loss program. Single Nucleotide Polymorphism (SNP) in PLIN (11482G>A) and ADRB3 (Trp64Arg) are the most studied polymorphisms that have effect on weight loss intervention. However, those studies were not conclusive because of limited number of subjects used and controversies in the results. Thus, replication and confirmation on the role of those genes in weight loss are important due to their potential to be used as predictors of the results of the program. PMID:26388665

  16. The role of genes involved in lipolysis on weight loss program in overweight and obese individuals

    PubMed Central

    Luglio, Harry Freitag; Sulistyoningrum, Dian Caturini; Susilowati, Rina

    2015-01-01

    The ability of obese people to reduce weight in the same treatment varied. Genetic make up as well as the behavioral changes are important for the successfulness of the program. One of the most proposed genetic variations that have been reported in many intervention studies was genes that control lipolysis process. This review summarizes studies that were done showing the influence of genetic polymorphisms in lipolysis pathway and weight loss in a weight loss treatment program. Some studies had shown that certain enzymes involved in this process were related to successfulness of weight loss program. Single Nucleotide Polymorphism (SNP) in PLIN (11482G>A) and ADRB3 (Trp64Arg) are the most studied polymorphisms that have effect on weight loss intervention. However, those studies were not conclusive because of limited number of subjects used and controversies in the results. Thus, replication and confirmation on the role of those genes in weight loss are important due to their potential to be used as predictors of the results of the program. PMID:26388665

  17. A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis

    PubMed Central

    Pimentel, Harold; Parra, Marilyn; Gee, Sherry L.; Mohandas, Narla; Pachter, Lior; Conboy, John G.

    2016-01-01

    Differentiating erythroblasts execute a dynamic alternative splicing program shown here to include extensive and diverse intron retention (IR) events. Cluster analysis revealed hundreds of developmentally-dynamic introns that exhibit increased IR in mature erythroblasts, and are enriched in functions related to RNA processing such as SF3B1 spliceosomal factor. Distinct, developmentally-stable IR clusters are enriched in metal-ion binding functions and include mitoferrin genes SLC25A37 and SLC25A28 that are critical for iron homeostasis. Some IR transcripts are abundant, e.g. comprising ∼50% of highly-expressed SLC25A37 and SF3B1 transcripts in late erythroblasts, and thereby limiting functional mRNA levels. IR transcripts tested were predominantly nuclear-localized. Splice site strength correlated with IR among stable but not dynamic intron clusters, indicating distinct regulation of dynamically-increased IR in late erythroblasts. Retained introns were preferentially associated with alternative exons with premature termination codons (PTCs). High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with other tissues but ultimately is unique to erythropoiesis. We conclude that IR is a multi-dimensional set of processes that post-transcriptionally regulate diverse gene groups during normal erythropoiesis, misregulation of which could be responsible for human disease. PMID:26531823

  18. A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis

    DOE PAGESBeta

    Pimentel, Harold; Parra, Marilyn; Gee, Sherry L.; Mohandas, Narla; Pachter, Lior; Conboy, John G.

    2015-11-03

    Differentiating erythroblasts execute a dynamic alternative splicing program shown here to include extensive and diverse intron retention (IR) events. Cluster analysis revealed hundreds of developmentallydynamic introns that exhibit increased IR in mature erythroblasts, and are enriched in functions related to RNA processing such as SF3B1 spliceosomal factor. Distinct, developmentally-stable IR clusters are enriched in metal-ion binding functions and include mitoferrin genes SLC25A37 and SLC25A28 that are critical for iron homeostasis. Some IR transcripts are abundant, e.g. comprising ~50% of highly-expressed SLC25A37 and SF3B1 transcripts in late erythroblasts, and thereby limiting functional mRNA levels. IR transcripts tested were predominantly nuclearlocalized. Splicemore » site strength correlated with IR among stable but not dynamic intron clusters, indicating distinct regulation of dynamically-increased IR in late erythroblasts. Retained introns were preferentially associated with alternative exons with premature termination codons (PTCs). High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with other tissues but ultimately is unique to erythropoiesis. Finally, we conclude that IR is a multi-dimensional set of processes that post-transcriptionally regulate diverse gene groups during normal erythropoiesis, misregulation of which could be responsible for human disease.« less

  19. A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis

    SciTech Connect

    Pimentel, Harold; Parra, Marilyn; Gee, Sherry L.; Mohandas, Narla; Pachter, Lior; Conboy, John G.

    2015-11-03

    Differentiating erythroblasts execute a dynamic alternative splicing program shown here to include extensive and diverse intron retention (IR) events. Cluster analysis revealed hundreds of developmentallydynamic introns that exhibit increased IR in mature erythroblasts, and are enriched in functions related to RNA processing such as SF3B1 spliceosomal factor. Distinct, developmentally-stable IR clusters are enriched in metal-ion binding functions and include mitoferrin genes SLC25A37 and SLC25A28 that are critical for iron homeostasis. Some IR transcripts are abundant, e.g. comprising ~50% of highly-expressed SLC25A37 and SF3B1 transcripts in late erythroblasts, and thereby limiting functional mRNA levels. IR transcripts tested were predominantly nuclearlocalized. Splice site strength correlated with IR among stable but not dynamic intron clusters, indicating distinct regulation of dynamically-increased IR in late erythroblasts. Retained introns were preferentially associated with alternative exons with premature termination codons (PTCs). High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with other tissues but ultimately is unique to erythropoiesis. Finally, we conclude that IR is a multi-dimensional set of processes that post-transcriptionally regulate diverse gene groups during normal erythropoiesis, misregulation of which could be responsible for human disease.

  20. A dynamic intron retention program enriched in RNA processing genes regulates gene expression during terminal erythropoiesis.

    PubMed

    Pimentel, Harold; Parra, Marilyn; Gee, Sherry L; Mohandas, Narla; Pachter, Lior; Conboy, John G

    2016-01-29

    Differentiating erythroblasts execute a dynamic alternative splicing program shown here to include extensive and diverse intron retention (IR) events. Cluster analysis revealed hundreds of developmentally-dynamic introns that exhibit increased IR in mature erythroblasts, and are enriched in functions related to RNA processing such as SF3B1 spliceosomal factor. Distinct, developmentally-stable IR clusters are enriched in metal-ion binding functions and include mitoferrin genes SLC25A37 and SLC25A28 that are critical for iron homeostasis. Some IR transcripts are abundant, e.g. comprising ∼50% of highly-expressed SLC25A37 and SF3B1 transcripts in late erythroblasts, and thereby limiting functional mRNA levels. IR transcripts tested were predominantly nuclear-localized. Splice site strength correlated with IR among stable but not dynamic intron clusters, indicating distinct regulation of dynamically-increased IR in late erythroblasts. Retained introns were preferentially associated with alternative exons with premature termination codons (PTCs). High IR was observed in disease-causing genes including SF3B1 and the RNA binding protein FUS. Comparative studies demonstrated that the intron retention program in erythroblasts shares features with other tissues but ultimately is unique to erythropoiesis. We conclude that IR is a multi-dimensional set of processes that post-transcriptionally regulate diverse gene groups during normal erythropoiesis, misregulation of which could be responsible for human disease. PMID:26531823

  1. StrateGene: object-oriented programming in molecular biology.

    PubMed

    Carhart, R E; Cash, H D; Moore, J F

    1988-03-01

    This paper describes some of the ways that object-oriented programming methodologies have been used to represent and manipulate biological information in a working application. When running on a Xerox 1100 series computer, StrateGene functions as a genetic engineering workstation for the management of information about cloning experiments. It represents biological molecules, enzymes, fragments, and methods as classes, subclasses, and members in a hierarchy of objects. These objects may have various attributes, which themselves can be defined and classified. The attributes and their values can be passed from the classes of objects down to the subclasses and members. The user can modify the objects and their attributes while using them. New knowledge and changes to the system can be incorporated relatively easily. The operations on the biological objects are associated with the objects themselves. This makes it easier to invoke them correctly and allows generic operations to be customized for the particular object. PMID:3164229

  2. How the Number of Alleles Influences Gene Expression

    NASA Astrophysics Data System (ADS)

    Hat, Beata; Paszek, Pawel; Kimmel, Marek; Piechor, Kazimierz; Lipniacki, Tomasz

    2007-07-01

    The higher organisms, eukaryotes, are diploid and most of their genes have two homological copies (alleles). However, the number of alleles in a cell is not constant. In the S phase of the cell cycle all the genome is duplicated and then in the G2 phase and mitosis, which together last for several hours, most of the genes have four copies instead of two. Cancer development is, in many cases, associated with a change in allele number. Several genetic diseases are caused by haploinsufficiency: Lack of one of the alleles or its improper functioning. In the paper we consider the stochastic expression of a gene having a variable number of copies. We applied our previously developed method in which the reaction channels are split into slow (connected with change of gene state) and fast (connected with mRNA/protein synthesis/decay), the later being approximated by deterministic reaction rate equations. As a result we represent gene expression as a piecewise deterministic time-continuous Markov process, which is further related with a system of partial differential hyperbolic equations for probability density functions (pdfs) of protein distribution. The stationary pdfs are calculated analytically for haploidal gene or numerically for diploidal and tetraploidal ones. We distinguished nine classes of simultaneous activation of haploid, diploid and tetraploid genes. This allows for analysis of potential consequences of gene duplication or allele loss. We show that when gene activity is autoregulated by a positive feedback, the change in number of gene alleles may have dramatic consequences for its regulation and may not be compensated by the change of efficiency of mRNA synthesis per allele.

  3. Genes influencing circadian differences in blood pressure in hypertensive mice.

    PubMed

    Marques, Francine Z; Campain, Anna E; Davern, Pamela J; Yang, Yee Hwa J; Head, Geoffrey A; Morris, Brian J

    2011-01-01

    Essential hypertension is a common multifactorial heritable condition in which increased sympathetic outflow from the central nervous system is involved in the elevation in blood pressure (BP), as well as the exaggerated morning surge in BP that is a risk factor for myocardial infarction and stroke in hypertensive patients. The Schlager BPH/2J mouse is a genetic model of hypertension in which increased sympathetic outflow from the hypothalamus has an important etiological role in the elevation of BP. Schlager hypertensive mice exhibit a large variation in BP between the active and inactive periods of the day, and also show a morning surge in BP. To investigate the genes responsible for the circadian variation in BP in hypertension, hypothalamic tissue was collected from BPH/2J and normotensive BPN/3J mice at the 'peak' (n = 12) and 'trough' (n = 6) of diurnal BP. Using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays, validation by quantitative real-time PCR and a statistical method that adjusted for clock genes, we identified 212 hypothalamic genes whose expression differed between 'peak' and 'trough' BP in the hypertensive strain. These included genes with known roles in BP regulation, such as vasopressin, oxytocin and thyrotropin releasing hormone, as well as genes not recognized previously as regulators of BP, including chemokine (C-C motif) ligand 19, hypocretin and zinc finger and BTB domain containing 16. Gene ontology analysis showed an enrichment of terms for inflammatory response, mitochondrial proton-transporting ATP synthase complex, structural constituent of ribosome, amongst others. In conclusion, we have identified genes whose expression differs between the peak and trough of 24-hour circadian BP in BPH/2J mice, pointing to mechanisms responsible for diurnal variation in BP. The findings may assist in the elucidation of the mechanism for the morning surge in BP in essential hypertension. PMID:21541337

  4. Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula.

    PubMed

    Zhang, Beilin; Gao, Yanxia; Li, Yang; Yang, Jing; Zhao, Hua

    2016-01-01

    Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis. PMID:27413249

  5. Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula

    PubMed Central

    Gao, Yanxia

    2016-01-01

    Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis. PMID:27413249

  6. Sociopolitical Influences on Federal Government Funding of Gifted and Talented and Bilingual Education Programs.

    ERIC Educational Resources Information Center

    Casanova, Ursula; Chavez, Sheila

    1992-01-01

    Examines the influence of various sociopolitical factors on government policies in two federal programs, those for the gifted and talented and those for bilingual education. Traces the evolution of these programs and compares their backgrounds to determine the influences shaping federal funding and program implementation. (GLR)

  7. Color and scent: how single genes influence pollinator attraction.

    PubMed

    Sheehan, H; Hermann, K; Kuhlemeier, C

    2012-01-01

    A major function of angiosperm flowers is the recruitment of animal pollinators that serve to transfer pollen among conspecific plants. Distinct sets of floral characteristics, called pollination syndromes, are correlated with visitation by specific groups of pollinators. Switches among pollination syndromes have occurred in many plant families. Such switches must have involved coordinated changes in multiple traits and multiple genes. Two well-studied floral traits affecting pollinator attraction are petal color and scent production. We review current knowledge about the biosynthetic pathways for floral color and scent production and their interaction at the genetic and biochemical levels. A key question in the field concerns the genes that underlie natural variation in color and scent and how such genes affect pollinator preference, reproductive isolation, and ultimately speciation. PMID:23467550

  8. Coeliac disease-associated polymorphisms influence thymic gene expression.

    PubMed

    Amundsen, S S; Viken, M K; Sollid, L M; Lie, B A

    2014-09-01

    Significant associations between coeliac disease (CD) and single nucleotide polymorphisms (SNPs) distributed over 40 genetic regions have been established. The majority of these SNPs are non-coding and 20 SNPs were, by expression quantitative trait loci (eQTL) analysis, found to harbour cis regulatory potential in peripheral blood mononuclear cells (PBMC). Almost all regions contain genes with an immunological relevant function, of which many act in the same biological pathways. One such pathway is T-cell development in the thymus, a pathway previously not explored in CD pathogenesis. The aim of our study was to explore the regulatory potential of the CD-associated SNPs (n=50) by eQTL analysis in thymic tissue from 42 subjects. In total, 43 nominal significant (P<0.05) eQTLs were found within 24 CD-associated chromosomal regions, corresponding to 27 expression-altering SNPs (eSNPs) and 40 probes (eProbes) that represents 39 unique genes (eGenes). Nine significant probe-SNP pairs (corresponding to 8 eSNPs and 7 eGenes) overlapped with previous findings in PBMC (rs12727642-PARK7, rs296547-DDX59, rs917997-IL18RAP, rs842647-AHSA2, rs13003464-AHSA2, rs6974491-ELMO1, rs2074404-NSF (two independent probes) and rs2298428-UBE2L3). When compared across more tissues, we found that 14 eQTLs could represent potentially novel thymus-specific eQTLs. This implies that CD risk polymorphisms could affect gene regulation in thymus. PMID:24871462

  9. The relative influence of natural selection and geography on gene flow in guppies.

    PubMed

    Crispo, Erika; Bentzen, Paul; Reznick, David N; Kinnison, Michael T; Hendry, Andrew P

    2006-01-01

    Two general processes may influence gene flow among populations. One involves divergent selection, wherein the maladaptation of immigrants and hybrids impedes gene flow between ecological environments (i.e. ecological speciation). The other involves geographic features that limit dispersal. We determined the relative influence of these two processes in natural populations of Trinidadian guppies (Poecilia reticulata). If selection is important, gene flow should be reduced between different selective environments. If geography is important, gene flow should be impeded by geographic distance and physical barriers. We examined how genetic divergence, long-term gene flow, and contemporary dispersal within a watershed were influenced by waterfalls, geographic distance, predation, and habitat features. We found that waterfalls and geographic distance increased genetic divergence and reduced dispersal and long-term gene flow. Differences in predation or habitat features did not influence genetic divergence or gene flow. In contrast, differences in predation did appear to reduce contemporary dispersal. We suggest that the standard predictions of ecological speciation may be heavily nuanced by the mating behaviour and life history strategies of guppies. PMID:16367829

  10. Cystic gene dosage influences kidney lesions after nephron reduction.

    PubMed

    Le Corre, Stéphanie; Viau, Amandine; Burtin, Martine; El-Karoui, Khalil; Cnops, Yvette; Terryn, Sara; Debaix, Huguette; Bérissi, Sophie; Gubler, Marie-Claire; Devuyst, Olivier; Terzi, Fabiola

    2015-01-01

    Cystic kidney disease is characterized by the progressive development of multiple fluid-filled cysts. Cysts can be acquired, or they may appear during development or in postnatal life due to specific gene defects and lead to renal failure. The most frequent form of this disease is the inherited polycystic kidney disease (PKD). Experimental models of PKD showed that an increase of cellular proliferation and apoptosis as well as defects in apico-basal and planar cell polarity or cilia play a critical role in cyst development. However, little is known about the mechanisms and the mediators involved in acquired cystic kidney diseases (ACKD). In this study, we used the nephron reduction as a model to study the mechanisms underlying cyst development in ACKD. We found that tubular dilations after nephron reduction recapitulated most of the morphological features of ACKD. The development of tubular dilations was associated with a dramatic increase of cell proliferation. In contrast, the apico-basal polarity and cilia did not seem to be affected. Interestingly, polycystin 1 and fibrocystin were markedly increased and polycystin 2 was decreased in cells lining the dilated tubules, whereas the expression of several other cystic genes did not change. More importantly, Pkd1 haploinsufficiency accelerated the development of tubular dilations after nephron reduction, a phenotype that was associated to a further increase of cell proliferation. These data were relevant to humans ACKD, as cystic genes expression and the rate of cell proliferation were also increased. In conclusion, our study suggests that the nephron reduction can be considered a suitable model to study ACKD and that dosage of genes involved in PKD is also important in ACKD. PMID:25531116

  11. The Limits of Family Influence: Genes, Experience, and Behavior.

    ERIC Educational Resources Information Center

    Rowe, David C.

    This book examines socialization science, which is the empirical effort to understand how children acquire traits from their families and cultures. This work proposes that one part of the family influence process--broad differences in family environments, except for those that are neglectful, abusive, or without opportunity--may exert little…

  12. Limited influence of local and landscape factors on finescale gene flow in two pond-breeding amphibians.

    PubMed

    Coster, Stephanie S; Babbitt, Kimberly J; Cooper, Andrew; Kovach, Adrienne I

    2015-02-01

    Dispersal and gene flow within animal populations are influenced by the composition and configuration of the landscape. In this study, we evaluated hypotheses about the impact of natural and anthropogenic factors on genetic differentiation in two amphibian species, the spotted salamander (Ambystoma maculatum) and the wood frog (Lithobates sylvaticus) in a commercial forest in central Maine. We conducted this analysis at two scales: a local level, focused on factors measured at each breeding pond, and a landscape level, focused on factors measured between ponds. We investigated the effects of a number of environmental factors in six categories including Productivity, Physical, Land Composition, Land Configuration, Isolation and Location. Embryos were sampled from 56 spotted salamander breeding ponds and 39 wood frog breeding ponds. We used a hierarchical Bayesian approach in the program GESTE at each breeding pond and a random forest algorithm in conjunction with a network analysis between the ponds. We found overall high genetic connectivity across distances up to 17 km for both species and a limited effect of natural and anthropogenic factors on gene flow. We found the null models best explained patterns of genetic differentiation at a local level and found several factors at the landscape level that weakly influenced gene flow. This research indicates multiscale investigations that incorporate local and landscape factors are valuable for understanding patterns of gene flow. Our findings suggest that dispersal rates in this system are high enough to minimize genetic structuring and that current forestry practices do not significantly impede dispersal. PMID:25580642

  13. Gene--gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis.

    PubMed

    Scapoli, C; Mamolini, E; Carrieri, A; Guarnelli, M E; Annunziata, M; Guida, L; Romano, F; Aimetti, M; Trombelli, L

    2011-09-01

    Aggressive periodontitis (AgP) is a multifactorial disease. The distinctive aspect of periodontitis is that this disease must deal with a large number of genes interacting with one another and forming complex networks. Thus, it is reasonable to expect that gene-gene interaction may have a crucial role. Therefore, we carried out a pilot case-control study to identify the association of candidate epistatic interactions between genetic risk factors and susceptibility to AgP, by using both conventional parametric analyses and a higher order interactions model, based on the nonparametric Multifactor Dimensionality Reduction algorithm. We analyzed 122 AgP patients and 246 appropriate periodontally healthy individuals, and genotyped 28 polymorphisms, located within 14 candidate genes, chosen among the principal genetic variants pointed out from literature and having a role in inflammation and immunity. Our analyses provided significant evidence for gene--gene interactions in the development of AgP, in particular, present results: (a) indicate a possible role of two new polymorphisms, within SEPS1 and TNFRSF1B genes, in determining host individual susceptibility to AgP; (b) confirm the potential association between of IL-6 and Fc γ- receptor polymorphisms and the disease; (c) exclude an essential contribution of IL-1 cluster gene polymorphisms to AgP in our Caucasian-Italian population. PMID:21593780

  14. The Program of Gene Transcription for a Single Differentiating Cell Type during Sporulation in Bacillus subtilis

    PubMed Central

    2004-01-01

    Asymmetric division during sporulation by Bacillus subtilis generates a mother cell that undergoes a 5-h program of differentiation. The program is governed by a hierarchical cascade consisting of the transcription factors: σE, σK, GerE, GerR, and SpoIIID. The program consists of the activation and repression of 383 genes. The σE factor turns on 262 genes, including those for GerR and SpoIIID. These DNA-binding proteins downregulate almost half of the genes in the σE regulon. In addition, SpoIIID turns on ten genes, including genes involved in the appearance of σK. Next, σK activates 75 additional genes, including that for GerE. This DNA-binding protein, in turn, represses half of the genes that had been activated by σK while switching on a final set of 36 genes. Evidence is presented that repression and activation contribute to proper morphogenesis. The program of gene expression is driven forward by its hierarchical organization and by the repressive effects of the DNA-binding proteins. The logic of the program is that of a linked series of feed-forward loops, which generate successive pulses of gene transcription. Similar regulatory circuits could be a common feature of other systems of cellular differentiation. PMID:15383836

  15. Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression

    PubMed Central

    Kohannim, Omid; Hibar, Derrek P.; Stein, Jason L.; Jahanshad, Neda; Hua, Xue; Rajagopalan, Priya; Toga, Arthur W.; Jack, Clifford R.; Weiner, Michael W.; de Zubicaray, Greig I.; McMahon, Katie L.; Hansell, Narelle K.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.

    2012-01-01

    We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8 ± 2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain. PMID:22888310

  16. Automated Eukaryotic Gene Structure Annotation Using EVidenceModeler and the Program to Assemble Spliced Alignments

    SciTech Connect

    Haas, B J; Salzberg, S L; Zhu, W; Pertea, M; Allen, J E; Orvis, J; White, O; Buell, C R; Wortman, J R

    2007-12-10

    EVidenceModeler (EVM) is presented as an automated eukaryotic gene structure annotation tool that reports eukaryotic gene structures as a weighted consensus of all available evidence. EVM, when combined with the Program to Assemble Spliced Alignments (PASA), yields a comprehensive, configurable annotation system that predicts protein-coding genes and alternatively spliced isoforms. Our experiments on both rice and human genome sequences demonstrate that EVM produces automated gene structure annotation approaching the quality of manual curation.

  17. A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary

    PubMed Central

    Gill, Mark E.; Mueller, Jacob L.; van Oudenaarden, Alexander; Page, David C.

    2015-01-01

    The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, particularly in organisms with a segregated germline. We characterized the gene regulatory program of meiotic prophase as it occurs in the mouse fetal ovary. By profiling gene expression in the mouse fetal ovary in mutants with whole tissue and single-cell techniques, we identified 104 genes expressed specifically in pre-meiotic to pachytene germ cells. We characterized the regulation of these genes by 1) retinoic acid (RA), which induces meiosis, 2) Dazl, which is required for germ cell competence to respond to RA, and 3) Stra8, a downstream target of RA required for the chromosomal program of meiotic prophase. Initial induction of practically all identified meiotic prophase genes requires Dazl. In the presence of Dazl, RA induces at least two pathways: one Stra8-independent, and one Stra8-dependent. Genes vary in their induction by Stra8, spanning fully Stra8-independent, partially Stra8-independent, and fully Stra8-dependent. Thus, Stra8 regulates the entirety of the chromosomal program but plays a more nuanced role in governing the gene expression program. We propose that Stra8-independent gene expression enables the stockpiling of selected meiotic structural proteins prior to the commencement of the chromosomal program. Unexpectedly, we discovered that Stra8 is required for prompt down-regulation of itself and Rec8. Germ cells that have expressed and down-regulated Stra8 are refractory to further Stra8 expression. Negative feedback of Stra8, and subsequent resistance to further Stra8 expression, may ensure a single, restricted pulse of Stra8 expression. Collectively, our findings reveal a gene regulatory logic by which germ cells prepare for the chromosomal program of

  18. Dyslexia susceptibility genes influence brain atrophy in frontotemporal dementia

    PubMed Central

    Paternicó, Donata; Premi, Enrico; Alberici, Antonella; Archetti, Silvana; Bonomi, Elisa; Gualeni, Vera; Gasparotti, Roberto; Padovani, Alessandro

    2015-01-01

    Objective: In this study, we evaluated whether variations within genes specifically associated with dyslexia, namely KIAA0319, DCDC2, and CNTNAP2, were associated with greater damage of language-related regions in patients with frontotemporal dementia (FTD) and primary progressive aphasia (PPA) in particular. Methods: A total of 118 patients with FTD, 84 with the behavioral variant of FTD (bvFTD) and 34 with PPA, underwent neuropsychological examination, genetic analyses, and brain MRI. KIAA0319 rs17243157 G/A, DCDC2 rs793842 A/G, and CNTNAP2 rs17236239 A/G genetic variations were assessed. Patients were grouped according to clinical phenotype and genotype status (GA/AA or GG). Gray matter (GM) and white matter (WM) differences were assessed by voxel-based morphometry and structural intercorrelation pattern analyses. Results: Patients carrying KIAA0319 A* (GA or AA) showed greater GM and WM atrophy in the left middle and inferior temporal gyri, as compared with KIAA0319 GG (p < 0.001). The effect of KIAA0319 polymorphism was mainly reported in patients with PPA. In patients with PPA carrying at-risk polymorphism, temporal damage led to loss of interhemispheric and intrahemispheric GM and WM structural association. No effect of DCDC2 and CNTNAP2 was found. Conclusions: Genes involved in dyslexia susceptibility, such as KIAA0319, result in language network vulnerability in FTD, and in PPA in particular. PMID:27066561

  19. Transcriptome analysis of a barley breeding program examines gene expression diversity and reveals target genes for malting quality improvement

    PubMed Central

    2010-01-01

    Background Advanced cycle breeding utilizes crosses among elite lines and is a successful method to develop new inbreds. However, it results in a reduction in genetic diversity within the breeding population. The development of malting barley varieties requires the adherence to a narrow malting quality profile and thus the use of advanced cycle breeding strategies. Although attention has been focused on diversity in gene expression and its association with genetic diversity, there are no studies performed in a single breeding program examining the implications that consecutive cycles of breeding have on gene expression variation and identifying the variability still available for future improvement. Results Fifteen lines representing the historically important six-rowed malting barley breeding program of the University of Minnesota were genotyped with 1,524 SNPs, phenotypically examined for six malting quality traits, and analyzed for transcript accumulation during germination using the Barley1 GeneChip array. Significant correlation was detected between genetic and transcript-level variation. We observed a reduction in both genetic and gene expression diversity through the breeding process, although the expression of many genes have not been fixed. A high number of quality-related genes whose expression was fixed during the breeding process was identified, indicating that much of the diversity reduction was associated with the improvement of the complex phenotype "malting quality", the main goal of the University of Minnesota breeding program. We also identified 49 differentially expressed genes between the most recent lines of the program that were correlated with one or more of the six primary malting quality traits. These genes constitute potential targets for the improvement of malting quality within the breeding program. Conclusions The present study shows the repercussion of advanced cycle breeding on gene expression diversity within an important barley

  20. Genes influence the amplitude and timing of brain hemodynamic responses.

    PubMed

    Shan, Zuyao Y; Vinkhuyzen, Anna A E; Thompson, Paul M; McMahon, Katie L; Blokland, Gabriëlla A M; de Zubicaray, Greig I; Calhoun, Vince; Martin, Nicholas G; Visscher, Peter M; Wright, Margaret J; Reutens, David C

    2016-01-01

    In functional magnetic resonance imaging (fMRI), the hemodynamic response function (HRF) reflects regulation of regional cerebral blood flow in response to neuronal activation. The HRF varies significantly between individuals. This study investigated the genetic contribution to individual variation in HRF using fMRI data from 125 monozygotic (MZ) and 149 dizygotic (DZ) twin pairs. The resemblance in amplitude, latency, and duration of the HRF in six regions in the frontal and parietal lobes was compared between MZ and DZ twin pairs. Heritability was estimated using an ACE (Additive genetic, Common environmental, and unique Environmental factors) model. The genetic influence on the temporal profile and amplitude of HRF was moderate to strong (24%-51%). The HRF may be used in the genetic analysis of diseases with a cerebrovascular etiology. PMID:26375212

  1. Influence of Isoflurane on Immediate-Early Gene Expression

    PubMed Central

    Bunting, Kristopher M.; Nalloor, Rebecca I.; Vazdarjanova, Almira

    2016-01-01

    Background: Anterograde amnesia is a hallmark effect of volatile anesthetics. Isoflurane is known to affect both the translation and transcription of plasticity-associated genes required for normal memory formation in many brain regions. What is not known is whether isoflurane anesthesia prevents the initiation of transcription or whether it halts transcription already in progress. We tested the hypothesis that general anesthesia with isoflurane prevents learning-induced initiation of transcription of several memory-associated immediate-early genes (IEGs) correlated with amnesia; we also assessed whether it stops transcription initiated prior to anesthetic administration. Methods: Using a Tone Fear Conditioning paradigm, rats were trained to associate a tone with foot-shock. Animals received either no anesthesia, anesthesia immediately after training, or anesthesia before, during, and after training. Animals were either sacrificed after training or tested 24 h later for long-term memory. Using Cellular Compartment Analysis of Temporal Activity by Fluorescence in situ Hybridization (catFISH), we examined the percentage of neurons expressing the IEGs Arc/Arg3.1 and Zif268/Egr1/Ngfi-A/Krox-24 in the dorsal hippocampus, primary somatosensory cortex, and primary auditory cortex. Results: On a cellular level, isoflurane administered at high doses (general anesthesia) prevented initiation of transcription, but did not stop transcription of Arc and Zif268 mRNA initiated prior to anesthesia. On a behavioral level, the same level of isoflurane anesthesia produced anterograde amnesia for fear conditioning when administered before and during training, but did not produce retrograde amnesia when administered immediately after training. Conclusion: General anesthesia with isoflurane prevents initiation of learning-related transcription but does not stop ongoing transcription of two plasticity-related IEGs, Arc and Zif268, a pattern of disruption that parallels the effects of

  2. Quantitative influence of macromolecular crowding on gene regulation kinetics

    PubMed Central

    Tabaka, Marcin; Kalwarczyk, Tomasz; Hołyst, Robert

    2014-01-01

    We introduce macromolecular crowding quantitatively into the model for kinetics of gene regulation in Escherichia coli. We analyse and compute the specific-site searching time for 180 known transcription factors (TFs) regulating 1300 operons. The time is between 160 s (e.g. for SoxS Mw = 12.91 kDa) and 1550 s (e.g. for PepA6 of Mw = 329.28 kDa). Diffusion coefficients for one-dimensional sliding are between for large proteins up to for small monomers or dimers. Three-dimensional diffusion coefficients in the cytoplasm are 2 orders of magnitude larger than 1D sliding coefficients, nevertheless the sliding enhances the binding rates of TF to specific sites by 1–2 orders of magnitude. The latter effect is due to ubiquitous non-specific binding. We compare the model to experimental data for LacI repressor and find that non-specific binding of the protein to DNA is activation- and not diffusion-limited. We show that the target location rate by LacI repressor is optimized with respect to microscopic rate constant for association to non-specific sites on DNA. We analyse the effect of oligomerization of TFs and DNA looping effects on searching kinetics. We show that optimal searching strategy depends on TF abundance. PMID:24121687

  3. Complexity, Post-genomic Biology and Gene Expression Programs

    NASA Astrophysics Data System (ADS)

    Williams, Rohan B. H.; Luo, Oscar Junhong

    Gene expression represents the fundamental phenomenon by which information encoded in a genome is utilised for the overall biological objectives of the organism. Understanding this level of information transfer is therefore essential for dissecting the mechanistic basis of form and function of organisms. We survey recent developments in the methodology of the life sciences that is relevant for understanding the organisation and function of the genome and review our current understanding of the regulation of gene expression, and finally, outline some new approaches that may be useful in understanding the organisation of gene regulatory systems.

  4. Transcriptome Analysis in Rat Kidneys: Importance of Genes Involved in Programmed Hypertension

    PubMed Central

    Tain, You-Lin; Huang, Li-Tung; Chan, Julie Y. H.; Lee, Chien-Te

    2015-01-01

    Suboptimal conditions in pregnancy can elicit long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether there are common genes and pathways in the kidney are responsible for generating programmed hypertension among three different models using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received dexamethasone (DEX, 0.1 mg/kg) from gestational day 16 to 22, 60% high-fructose (HF) diet, or NG-nitro-l-arginine-methyester (l-NAME, 60 mg/kg/day) to conduct DEX, HF, or l-NAME model respectively. All three models elicited programmed hypertension in adult male offspring. We observed five shared genes (Bcl6, Dmrtc1c, Egr1, Inmt, and Olr1668) among three different models. The identified differential genes (DEGs) that are related to regulation of blood pressure included Aqp2, Ptgs1, Eph2x, Hba-a2, Apln, Guca2b, Hmox1, and Npy. RNA-Seq identified genes in arachidonic acid metabolism are potentially gatekeeper genes contributing to programmed hypertension. In addition, HF and DEX increased expression and activity of soluble epoxide hydrolase (Ephx2 gene encoding protein). Conclusively, the DEGs in arachidonic acid metabolism are potentially gatekeeper genes in programmed hypertension. The roles of DEGs identified by the RNA-Seq in this study deserve further clarification, to develop the potential interventions in the prevention of programmed hypertension. PMID:25739086

  5. Genome size diversity in angiosperms and its influence on gene space.

    PubMed

    Dodsworth, Steven; Leitch, Andrew R; Leitch, Ilia J

    2015-12-01

    Genome size varies c. 2400-fold in angiosperms (flowering plants), although the range of genome size is skewed towards small genomes, with a mean genome size of 1C=5.7Gb. One of the most crucial factors governing genome size in angiosperms is the relative amount and activity of repetitive elements. Recently, there have been new insights into how these repeats, previously discarded as 'junk' DNA, can have a significant impact on gene space (i.e. the part of the genome comprising all the genes and gene-related DNA). Here we review these new findings and explore in what ways genome size itself plays a role in influencing how repeats impact genome dynamics and gene space, including gene expression. PMID:26605684

  6. Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression

    PubMed Central

    Hendrickson, Sher L.; Lautenberger, James A.; Chinn, Leslie Wei; Malasky, Michael; Sezgin, Efe; Kingsley, Lawrence A.; Goedert, James J.; Kirk, Gregory D.; Gomperts, Edward D.; Buchbinder, Susan P.; Troyer, Jennifer L.; O'Brien, Stephen J.

    2010-01-01

    Background The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression. Methodology/Principal Findings Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 European American patients from five US AIDS cohorts. Successfully genotyped SNPs gave 50% or better haplotype coverage for 679 of known NEMP genes. With a Bonferroni adjustment for the number of genes and tests examined, multiple SNPs within two NEMP genes showed significant association with AIDS progression: acyl-CoA synthetase medium-chain family member 4 (ACSM4) on chromosome 12 and peroxisomal D3,D2-enoyl-CoA isomerase (PECI) on chromosome 6. Conclusions Our previous studies on mitochondrial DNA showed that European haplogroups with presumed functional differences were associated with AIDS progression and HAART mediated adverse events. The modest influences of nuclear-encoded mitochondrial genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS pathogenesis. PMID:20877624

  7. Data and programs in support of network analysis of genes and their association with diseases.

    PubMed

    Kontou, Panagiota I; Pavlopoulou, Athanasia; Dimou, Niki L; Pavlopoulos, Georgios A; Bagos, Pantelis G

    2016-09-01

    The network-based approaches that were employed in order to depict the relationships between human genetic diseases and their associated genes are described. Towards this direction, monopartite disease-disease and gene-gene networks were constructed from bipartite gene-disease association networks. The latter were created by collecting and integrating data from three diverse resources, each one with different content, covering from rare monogenic disorders to common complex diseases. Moreover, topological and clustering graph analyses were performed. The methodology and the programs presented in this article are related to the research article entitled "Network analysis of genes and their association with diseases" [1]. PMID:27508260

  8. The Influence of Perceived Characteristics of Management Development Programs on Employee Outcomes

    ERIC Educational Resources Information Center

    Ardts, Joost C. A.; van der Velde, Mandy E. G.; Maurer, Todd J.

    2010-01-01

    Employees' perceptions of Management Development (MD) programs is the topic of this study. The purpose is to examine the influence of three important perceived characteristics of MD programs on relevant MD outcomes. The MD characteristics are: availability of role models, perceived control, and understanding the MD program. Outcomes are:…

  9. A Computer Program to Assist Counseling Trainees in Understanding Interpersonal Influence Processes in Their Counseling.

    ERIC Educational Resources Information Center

    Lichtenberg, James W.

    This paper describes a computer program based on the premise that successful counseling can be viewed as an interpersonal influence process composed of three basic features: sequentiality, flexibility, and constraint. An introduction to the INTERACT program explains how the program analyzes counselor/client and client/counselor transitions or…

  10. The Influence of Advertising on Attendance at Park Programs

    ERIC Educational Resources Information Center

    Reyburn, Jerry H.; Knudson, Douglas M.

    1975-01-01

    Investigated were the effects on attendance of four types of pre-program advertising: no advertising, personal invitation, signs, and innovation. All three advertising treatments increased program attendance over no advertising. Each advertising technique has advantages and disadvantages. Signs are impersonal, but effective. Personal invitation is…

  11. Modelling Programming Performance: Beyond the Influence of Learner Characteristics

    ERIC Educational Resources Information Center

    Lau, Wilfred W. F.; Yuen, Allan H. K.

    2011-01-01

    In the 21st century, the ubiquitous nature of technology today is evident and to a large extent, most of us benefit from the modern convenience brought about by technology. Yet to be technology literate, it is argued that learning to program still plays an important role. One area of research in programming concerns the identification of…

  12. Learning to Program with Personal Robots: Influences on Student Motivation

    ERIC Educational Resources Information Center

    McGill, Monica M.

    2012-01-01

    One of the goals of using robots in introductory programming courses is to increase motivation among learners. There have been several types of robots that have been used extensively in the classroom to teach a variety of computer science concepts. A more recently introduced robot designed to teach programming to novice students is the Institute…

  13. Genetic Influences on Brain Gene Expression in Rats Selected for Tameness and Aggression

    PubMed Central

    Heyne, Henrike O.; Lautenschläger, Susann; Nelson, Ronald; Besnier, François; Rotival, Maxime; Cagan, Alexander; Kozhemyakina, Rimma; Plyusnina, Irina Z.; Trut, Lyudmila; Carlborg, Örjan; Petretto, Enrico; Kruglyak, Leonid; Pääbo, Svante; Schöneberg, Torsten; Albert, Frank W.

    2014-01-01

    Interindividual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior toward humans for >64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40, and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals. PMID:25189874

  14. Major Histocompatibility Complex and Background Genes in Chickens Influence Susceptibility to High Pathogenicity Avian Influenza Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chicken’s major histocompatibility complex (MHC) haplotype has profound influence on the resistance or susceptibility to certain pathogens such as B21 MHC haplotype confers resistance to Marek’s disease (MD). However, non-MHC genes are also important in disease resistance. For example, both line...

  15. Multi-Vendor Loyalty Programs: Influencing Customer Behavioral Loyalty?

    PubMed Central

    Villacé-Molinero, Teresa; Reinares-Lara, Pedro; Reinares-Lara, Eva

    2016-01-01

    Loyalty programs are a consolidated marketing instrument whose adoption in many sectors has not been associated with appropriate comprehension of either their management elements or their effects. The purpose of this research is to contribute to knowledge about the effect of loyalty programs on repeat purchase behavior. More specifically, it seeks to discover whether joining a program changes the buying behavior of its members, and, if so, to study the profile of those whose behavior changes most. The intention was also to provide new study variables pertaining to multi-vendor loyalty programs, such as where they are joined or purchases in associated outlets as a result of behavioral loyalty. Research was carried out using a sample of 1200 individuals (31,746 purchases) belonging to a multi-vendor loyalty program. The study period was 13 years, 4 months, and split into two phases: before and after the joining the program. Different methodological approaches, such as the use of transactional databases that included pre-program-enrollment data and of the same sampling units throughout the study, were incorporated into the research with the aim of advancing academic knowledge regarding multi-vendor loyalty programs. Moreover, a type of program and market hardly dealt with in the relevant literature was analyzed. The results showed while the loyalty program had managed to reduce the time between purchases, it had not affected purchase volume or average expenditure. They also demonstrated the existence of a differential profile of customers who had changed their buying behavior to a greater extent. Finally, recency was identified as being the decisive variable in behavioral change. PMID:26941677

  16. The Influence of the Global Gene Expression Shift on Downstream Analyses

    PubMed Central

    Xu, Qifeng; Zhang, Xuegong

    2016-01-01

    The assumption that total abundance of RNAs in a cell is roughly the same in different cells is underlying most studies based on gene expression analyses. But experiments have shown that changes in the expression of some master regulators such as c-MYC can cause global shift in the expression of almost all genes in some cell types like cancers. Such shift will violate this assumption and can cause wrong or biased conclusions for standard data analysis practices, such as detection of differentially expressed (DE) genes and molecular classification of tumors based on gene expression. Most existing gene expression data were generated without considering this possibility, and are therefore at the risk of having produced unreliable results if such global shift effect exists in the data. To evaluate this risk, we conducted a systematic study on the possible influence of the global gene expression shift effect on differential expression analysis and on molecular classification analysis. We collected data with known global shift effect and also generated data to simulate different situations of the effect based on a wide collection of real gene expression data, and conducted comparative studies on representative existing methods. We observed that some DE analysis methods are more tolerant to the global shift while others are very sensitive to it. Classification accuracy is not sensitive to the shift and actually can benefit from it, but genes selected for the classification can be greatly affected. PMID:27092944

  17. Genes influencing spinal bone mineral density in inbred F344, LEW, COP, and DA rats

    PubMed Central

    Alam, Imranul; Sun, Qiwei; Koller, Daniel L.; Liu, Lixiang; Liu, Yunlong; Edenberg, Howard J.; Foroud, Tatiana

    2009-01-01

    Previously, we identified the regions of chromosomes 10q12–q31 and 15p16–q21 harbor quantitative trait loci (QTLs) for lumbar volumetric bone mineral density (vBMD) in female F2 rats derived from Fischer 344 (F344) × Lewis (LEW) and Copenhagen 2331 (COP) × Dark Agouti (DA) crosses. The purpose of this study is to identify the candidate genes within these QTL regions contributing to the variation in lumbar vBMD. RNA was extracted from bone tissue of F344, LEW, COP, and DA rats. Microarray analysis was performed using Affymetrix Rat Genome 230 2.0 Arrays. Genes differentially expressed among the rat strains were then ranked based on the strength of the correlation with lumbar vBMD in F2 animals derived from these rats. Quantitative PCR (qPCR) analysis was performed to confirm the prioritized candidate genes. A total of 285 genes were differentially expressed among all strains of rats with a false discovery rate less than 10%. Among these genes, 18 candidate genes were prioritized based on their strong correlation (r2 > 0.90) with lumbar vBMD. Of these, 14 genes (Akap1, Asgr2, Esd, Fam101b, Irf1, Lcp1, Ltc4s, Mdp-1, Pdhb, Plxdc1, Rabep1, Rhot1, Slc2a4, Xpo4) were confirmed by qPCR. We identified several novel candidate genes influencing spinal vBMD in rats. PMID:19841953

  18. COMT but not serotonin-related genes modulates the influence of childhood abuse on anger traits

    PubMed Central

    Perroud, Nader; Jaussent, Isabelle; Guillaume, Sébastien; Bellivier, Frank; Baud, Patrick; Jollant, Fabrice; Leboyer, Marion; Lewis, Cathryn; Malafosse, Alain; Courtet, Philippe

    2010-01-01

    Anger-related traits are regulated by genes as well as early environmental factors. Both childhood maltreatment and genes underlie vulnerability to suicidal behaviors, possibly by affecting the constitution of intermediate phenotypes such as anger traits. The aim of this study was to test the interaction between nine candidate genes and childhood maltreatment in modulating anger-related traits in 875 adult suicide attempters. The State-Trait Anger Expression Inventory and the Childhood Trauma Questionnaire were used to examine anger traits and traumatic childhood experiences respectively. The functional polymorphism of the catecholamine-O-methyl-transferase (COMT) gene Val158Met significantly modulated the association between sexual abuse and anger-trait level (p=0.001). In the presence of sexual abuse, individuals carrying the Val high-activity allele displayed greater disposition towards anger than individuals homozygous for the Met allele (p=0.0003). Notably, none of the serotonin-related genes influenced the effect of childhood abuse on anger traits. The results of the present study suggest that anger-trait level is influenced by the interaction between childhood abuse and functional polymorphism in the COMT gene. This study was carried out in a population with a high frequency of childhood abuse and a high disposition towards anger, and replication in healthy subjects is needed. PMID:20002200

  19. Phosphorylation events in the multiple gene regulator of group A Streptococcus significantly influence global gene expression and virulence.

    PubMed

    Sanson, Misu; Makthal, Nishanth; Gavagan, Maire; Cantu, Concepcion; Olsen, Randall J; Musser, James M; Kumaraswami, Muthiah

    2015-06-01

    Whole-genome sequencing analysis of ∼800 strains of group A Streptococcus (GAS) found that the gene encoding the multiple virulence gene regulator of GAS (mga) is highly polymorphic in serotype M59 strains but not in strains of other serotypes. To help understand the molecular mechanism of gene regulation by Mga and its contribution to GAS pathogenesis in serotype M59 GAS, we constructed an isogenic mga mutant strain. Transcriptome studies indicated a significant regulatory influence of Mga and altered metabolic capabilities conferred by Mga-regulated genes. We assessed the phosphorylation status of Mga in GAS cell lysates with Phos-tag gels. The results revealed that Mga is phosphorylated at histidines in vivo. Using phosphomimetic and nonphosphomimetic substitutions at conserved phosphoenolpyruvate:carbohydrate phosphotransferase regulation domain (PRD) histidines of Mga, we demonstrated that phosphorylation-mimicking aspartate replacements at H207 and H273 of PRD-1 and at H327 of PRD-2 are inhibitory to Mga-dependent gene expression. Conversely, non-phosphorylation-mimicking alanine substitutions at H273 and H327 relieved inhibition, and the mutant strains exhibited a wild-type phenotype. The opposing regulatory profiles observed for phosphorylation- and non-phosphorylation-mimicking substitutions at H273 extended to global gene regulation by Mga. Consistent with these observations, the H273D mutant strain attenuated GAS virulence, whereas the H273A strain exhibited a wild-type virulence phenotype in a mouse model of necrotizing fasciitis. Together, our results demonstrate phosphoregulation of Mga and its direct link to virulence in M59 GAS strains. These data also lay a foundation toward understanding how naturally occurring gain-of-function variations in mga, such as H201R, may confer an advantage to the pathogen and contribute to M59 GAS pathogenesis. PMID:25824840

  20. Phosphorylation Events in the Multiple Gene Regulator of Group A Streptococcus Significantly Influence Global Gene Expression and Virulence

    PubMed Central

    Sanson, Misu; Makthal, Nishanth; Gavagan, Maire; Cantu, Concepcion; Olsen, Randall J.; Musser, James M.

    2015-01-01

    Whole-genome sequencing analysis of ∼800 strains of group A Streptococcus (GAS) found that the gene encoding the multiple virulence gene regulator of GAS (mga) is highly polymorphic in serotype M59 strains but not in strains of other serotypes. To help understand the molecular mechanism of gene regulation by Mga and its contribution to GAS pathogenesis in serotype M59 GAS, we constructed an isogenic mga mutant strain. Transcriptome studies indicated a significant regulatory influence of Mga and altered metabolic capabilities conferred by Mga-regulated genes. We assessed the phosphorylation status of Mga in GAS cell lysates with Phos-tag gels. The results revealed that Mga is phosphorylated at histidines in vivo. Using phosphomimetic and nonphosphomimetic substitutions at conserved phosphoenolpyruvate:carbohydrate phosphotransferase regulation domain (PRD) histidines of Mga, we demonstrated that phosphorylation-mimicking aspartate replacements at H207 and H273 of PRD-1 and at H327 of PRD-2 are inhibitory to Mga-dependent gene expression. Conversely, non-phosphorylation-mimicking alanine substitutions at H273 and H327 relieved inhibition, and the mutant strains exhibited a wild-type phenotype. The opposing regulatory profiles observed for phosphorylation- and non-phosphorylation-mimicking substitutions at H273 extended to global gene regulation by Mga. Consistent with these observations, the H273D mutant strain attenuated GAS virulence, whereas the H273A strain exhibited a wild-type virulence phenotype in a mouse model of necrotizing fasciitis. Together, our results demonstrate phosphoregulation of Mga and its direct link to virulence in M59 GAS strains. These data also lay a foundation toward understanding how naturally occurring gain-of-function variations in mga, such as H201R, may confer an advantage to the pathogen and contribute to M59 GAS pathogenesis. PMID:25824840

  1. Influence of sex on gene expression in the mouse lacrimal gland.

    PubMed

    Richards, Stephen M; Jensen, Roderick V; Liu, Meng; Sullivan, Benjamin D; Lombardi, Michael J; Rowley, Patricia; Schirra, Frank; Treister, Nathaniel S; Suzuki, Tomo; Steagall, Rebecca J; Yamagami, Hiroko; Sullivan, David A

    2006-01-01

    Significant, sex-associated differences exist in the physiology and pathophysiology of the lacrimal gland. We hypothesize that many of these differences are due to fundamental variations in gene expression. The purpose of this study was to determine the extent to which sex-related differences in gene expression are present in the lacrimal gland. Lacrimal glands were obtained from adult male and female BALB/c mice (n=5-10mice/sex/experiment), pooled according to sex and processed for the isolation of RNA. Samples were analyzed for differentially expressed mRNAs by using Atlas Mouse cDNA Expression Arrays, cDNA amplification techniques, GEM 1 and 2 gene chips, CodeLink bioarrays and quantitative real-time PCR (qPCR) procedures. Quantitative evaluation of Atlas Array gene expression was performed with an image analysis system developed in our laboratory, whereas gene chip data were analyzed with Rosetta Resolver and GeneSifter.Net software. Statistical significance was determined by using Student's t-test. Our results with CodeLink bioarrays show that sex has a significant influence on the expression of over 490 genes in the mouse lacrimal gland. These genes are involved in a wide range of biological processes, molecular functions and cellular components, including such activities as development, growth, transcription, metabolism, signal transduction, transport, receptor activity and protein and nucleic acid binding. The expression of selected genes was confirmed by the use of GEM gene chips and qPCR. Our findings also demonstrate that certain methodological approaches are less useful in attempting to assess the magnitude of sex-associated differences in the lacrimal gland. These results support our hypothesis that sex-related differences in gene expression play a role in the sexual dimorphism of the lacrimal gland. PMID:15979613

  2. Development of Genomic Resources for a thraustochytrid Pathogen and Investigation of Temperature Influences on Gene Expression

    PubMed Central

    Garcia-Vedrenne, Ana Elisa; Groner, Maya; Page-Karjian, Annie; Siegmund, Gregor-Fausto; Singhal, Sonia; Sziklay, Jamie; Roberts, Steven

    2013-01-01

    Understanding how environmental changes influence the pathogenicity and virulence of infectious agents is critical for predicting epidemiological patterns of disease. Thraustochytrids, part of the larger taxonomic class Labyrinthulomycetes, contain several highly pathogenic species, including the hard clam pathogen quahog parasite unknown (QPX). QPX has been associated with large-scale mortality events along the northeastern coast of North America. Growth and physiology of QPX is temperature-dependent, and changes in local temperature profiles influence pathogenicity. In this study we characterize the partial genome of QPX and examine the influence of temperature on gene expression. Genes involved in several biological processes are differentially expressed upon temperature change, including those associated with altered growth and metabolism and virulence. The genomic and transcriptomic resources developed in this study provide a foundation for better understanding virulence, pathogenicity and life history of thraustochytrid pathogens. PMID:24069279

  3. Development of genomic resources for a thraustochytrid pathogen and investigation of temperature influences on gene expression.

    PubMed

    Garcia-Vedrenne, Ana Elisa; Groner, Maya; Page-Karjian, Annie; Siegmund, Gregor-Fausto; Singhal, Sonia; Sziklay, Jamie; Roberts, Steven

    2013-01-01

    Understanding how environmental changes influence the pathogenicity and virulence of infectious agents is critical for predicting epidemiological patterns of disease. Thraustochytrids, part of the larger taxonomic class Labyrinthulomycetes, contain several highly pathogenic species, including the hard clam pathogen quahog parasite unknown (QPX). QPX has been associated with large-scale mortality events along the northeastern coast of North America. Growth and physiology of QPX is temperature-dependent, and changes in local temperature profiles influence pathogenicity. In this study we characterize the partial genome of QPX and examine the influence of temperature on gene expression. Genes involved in several biological processes are differentially expressed upon temperature change, including those associated with altered growth and metabolism and virulence. The genomic and transcriptomic resources developed in this study provide a foundation for better understanding virulence, pathogenicity and life history of thraustochytrid pathogens. PMID:24069279

  4. Advancing Translational Research Through the NHLBI Gene Therapy Resource Program (GTRP)

    PubMed Central

    Benson, Janet; Cornetta, Kenneth; Diggins, Margaret; Johnston, Julie C.; Sepelak, Susan; Wang, Gensheng; Wilson, James M.; Wright, J. Fraser; Skarlatos, Sonia I.

    2013-01-01

    Abstract Translational research is a lengthy, complex, and necessary endeavor in order to bring basic science discoveries to clinical fruition. The NIH offers several programs to support translational research including an important resource established specifically for gene therapy researchers—the National Heart, Lung, and Blood Institute (NHLBI) Gene Therapy Resource Program (GTRP). This paper reviews the core components of the GTRP and describes how the GTRP provides researchers with resources that are critical to advancing investigational gene therapy products into clinical testing. PMID:23692378

  5. The Tibetan medicine Zuotai influences clock gene expression in the liver of mice

    PubMed Central

    Li, Huan; Li, Wen-Kai; Lu, Yuan-Fu; Wei, Li-Xin

    2016-01-01

    Background. The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and “detoxification,” and is mainly composed of metacinnabar (β-HgS). The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice. Materials and methods. Mice were orally given Zuotai (10 mg/kg, 1.5-fold of clinical dose) daily for 7 days, and livers were collected every 4 h during the 24 h period. Total RNA was extracted and subjected to real-time RT-PCR analysis of circadian clock gene expression. Results. Zuotai decreased the oscillation amplitude of the clock core gene Clock, neuronal PAS domain protein 2 (Npas2), Brain and muscle Arnt-like protein-1 (Bmal1) at 10:00. For the clock feedback negative control genes, Zuotai had no effect on the oscillation of the clock gene Cryptochrome (Cry1) and Period genes (Per1–3). For the clock-driven target genes, Zuotai increased the oscillation amplitude of the PAR-bZip family member D-box-binding protein (Dbp), decreased nuclear factor interleukin 3 (Nfil3) at 10:00, but had no effect on thyrotroph embryonic factor (Tef); Zuotai increased the expression of nuclear receptor Rev-Erbα (Nr1d1) at 18:00, but had little influence on the nuclear receptor Rev-Erbβ (Nr1d2) and RORα. Conclusion. The Tibetan medicine Zuotai could influence the expression of clock genes, which could contribute to pharmacological and/or toxicological effects of Zuotai. PMID:26855871

  6. Study of the influence of genes related to muscle oxidative processes on beef color.

    PubMed

    Falomir-Lockhart, A H; Rogberg-Muñoz, A; Papaleo-Mazzucco, J; Goszczynski, D E; Lirón, J P; Fernández, M E; Añon, M C; Melucci, L M; Giovambattista, G

    2015-10-01

    The biochemical bases of meat color are determined by the concentration and redox state of myoglobin, hemoglobin, cytochromes, and other pigments. Post-mortem depletion of cellular oxygen results in oxidative stresses that consume NADH and affects reducing activity, while enzymatic detoxification influences the cellular oxidative processes, both affecting meat color. The aim of this work was to study the influence of several genes related to cellular oxidative processes that could affect CIELAB meat color parameters. The study was performed in steers that received a grass-based diet combined with grain, hays and silages. Results suggest a possible link between colorimetric parameters (a*, b* and chroma) and SNPs in the GSTP1 gene (P<0.05). Although the influence of the enzymes, encoded by GSTP1 gene, on meat color has been proposed previously at biochemical level and protein expression level, further association studies in different populations and functional studies of proteins are needed to confirm the genetic determination of that gene on meat color. PMID:26010991

  7. Enamel Formation Genes Influence Enamel Microhardness Before and After Cariogenic Challenge

    PubMed Central

    Shimizu, Takehiko; Ho, Bao; Deeley, Kathleen; Briseño-Ruiz, Jessica; Faraco, Italo M.; Schupack, Brett I.; Brancher, João A.; Pecharki, Giovana D.; Küchler, Erika C.; Tannure, Patricia N.; Lips, Andrea; Vieira, Thays C. S.; Patir, Asli; Yildirim, Mine; Poletta, Fernando A.; Mereb, Juan C.; Resick, Judith M.; Brandon, Carla A.; Orioli, Iêda M.; Castilla, Eduardo E.; Marazita, Mary L.; Seymen, Figen; Costa, Marcelo C.; Granjeiro, José M.; Trevilatto, Paula C.; Vieira, Alexandre R.

    2012-01-01

    There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes may contribute to caries. For the present study, we used DNA samples collected from 1,831 individuals from various population data sets. Single nucleotide polymorphism markers were genotyped in selected genes (ameloblastin, amelogenin, enamelin, tuftelin, and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Associations with caries experience can be detected but they are not necessarily replicated in all population groups and the most expressive results was for a marker in AMELX (p = 0.0007). To help interpret these results, we evaluated if enamel microhardness changes under simulated cariogenic challenges are associated with genetic variations in these same genes. After creating an artificial caries lesion, associations could be seen between genetic variation in TUFT1 (p = 0.006) and TUIP11 (p = 0.0006) with enamel microhardness. Our results suggest that the influence of genetic variation of enamel formation genes may influence the dynamic interactions between the enamel surface and the oral cavity. PMID:23028741

  8. Fear in Outdoor Education: The Influence of Gender and Program.

    ERIC Educational Resources Information Center

    Young, Anderson B.; Ewert, Alan

    The purpose of this study was to identify and measure the situational fears and anxieties held by participants before, during, and after participation in an outdoor program. Subjects in the study were college students with recreation and physical education majors, who were completing separate, but similar Outdoor Education Practicum (OEP) courses…

  9. Deviant Peer Influences in Programs for Youth Problems and Solutions

    ERIC Educational Resources Information Center

    Dodge, Kenneth A., Ed.; Dishion, Thomas J., Ed.; Lansford, Jennifer E., Ed.

    2006-01-01

    Most interventions for at-risk youth are group based. Yet, emerging research indicates that young people often learn to become deviant by interacting with deviant peers. In this important volume, leading intervention and prevention experts from psychology, education, criminology, and related fields analyze how, and to what extent, programs that…

  10. Factors Influencing the ABT Phenomenon among Graduate Students in a Master Program in Mexico

    ERIC Educational Resources Information Center

    Gonzalez-Castillo, Vicente; Cisneros-Cohernour, Edith J.

    2007-01-01

    This paper presents the findings of a study examining the factors that influence the ABT phenomenon (all but thesis) among graduate students of a Master in Education program in the Southeast of Mexico. Findings of the study identified individual and organizational factors influencing ABT. The study allowed for a better understanding about how…

  11. The Influence of the CAS Standards on Academic Advisors and Advising Programs

    ERIC Educational Resources Information Center

    Keeling, Sarah

    2010-01-01

    Research on the influence of the Council for the Advancement of Standards in Higher Education (CAS) on academic advising is limited. Using a comparative case study method, I respond to this research gap by exploring how the standards influence practices of academic advising programs. Study results indicate that participating advisors knew little…

  12. Interethnic differences of cytochrome P450 gene polymorphisms may influence outcome of taxane therapy in Roma and Hungarian populations.

    PubMed

    Szalai, Renata; Ganczer, Alma; Magyari, Lili; Matyas, Petra; Bene, Judit; Melegh, Bela

    2015-12-01

    Taxanes are widely used microtubule-stabilizing chemotherapeutic agents in the treatment of cancers. Several cytochrome P450 gene variants have been proven to influence taxane metabolism and therapy. The purpose of this work was to determine the distribution of genetic variations of CYP1B1, CYP2C8 and CYP3A5 genes as the first report on taxane metabolizer cytochrome P450 gene polymorphisms in Roma and Hungarian populations. A total of 397 Roma and 412 Hungarian healthy subjects were genotyped for CYP1B1 c.4326C > G, CYP2C8 c.792C > G and CYP3A5 c.6986A > G variant alleles by PCR-RFLP assay and direct sequencing. We found significant differences in the frequencies of homozygous variant genotypes of CYP1B1 4326 GG (p = 0.002) and CYP3A5 6986 GG (p < 0.001) between Roma and Hungarian populations. Regarding minor allele frequencies, for CYP2C8 a significantly increased prevalence was found in 792G allele frequency in the Hungarian population compared to the Roma population (5.83% vs. 2.14%, p = 0.001). Our results can be used as possible predictive factors in population specific treatment algorithms to developing effective programs for a better outcome in patients treated with taxanes. PMID:26507668

  13. Multiscale analysis of Hymenocallis coronaria (Amaryllidaceae) genetic diversity, genetic structure, and gene movement under the influence of unidirectional stream flow.

    PubMed

    Markwith, Scott H; Scanlon, Michael J

    2007-02-01

    Understanding gene movement patterns in unidirectional flow environments and their effect on patterns of genetic diversity and genetic structure is necessary to manage these systems. Hypotheses and models to explain genetic patterns in streams are rare, and the results of macrophyte studies are inconsistent. This study addresses Ritland's (Canadian Journal of Botany 67: 2017-2024) unidirectional diversity hypothesis, the one-dimensional stepping stone model, and the metapopulation model within and among populations. Hymenocallis coronaria, an aquatic macrophyte of rocky river shoals of the SE USA, was sampled in four river basins. Within populations and among populations <16.2 km apart had significant isolation by distance. However, the rate of gene flow decay was not consistent with a one-dimensional stepping stone model, nor was evidence strong or consistent for Ritland's hypothesis. Some evidence indicates that localized metapopulation processes may be affecting genetic diversity and structure; however, gene flow patterns inconsistent with the assumptions of the linear and unidirectional models are also a possible influence. We discuss three variants on the one-dimensional stepping stone model. Future research in linear environments should examine the expectations of these models. This study is also one of the first efforts to calculate population genetic parameters using a new program, TETRASAT. PMID:21642217

  14. MEF2 Transcription Factors Regulate Distinct Gene Programs in Mammalian Skeletal Muscle Differentiation*

    PubMed Central

    Estrella, Nelsa L.; Desjardins, Cody A.; Nocco, Sarah E.; Clark, Amanda L.; Maksimenko, Yevgeniy; Naya, Francisco J.

    2015-01-01

    Skeletal muscle differentiation requires precisely coordinated transcriptional regulation of diverse gene programs that ultimately give rise to the specialized properties of this cell type. In Drosophila, this process is controlled, in part, by MEF2, the sole member of an evolutionarily conserved transcription factor family. By contrast, vertebrate MEF2 is encoded by four distinct genes, Mef2a, -b, -c, and -d, making it far more challenging to link this transcription factor to the regulation of specific muscle gene programs. Here, we have taken the first step in molecularly dissecting vertebrate MEF2 transcriptional function in skeletal muscle differentiation by depleting individual MEF2 proteins in myoblasts. Whereas MEF2A is absolutely required for proper myoblast differentiation, MEF2B, -C, and -D were found to be dispensable for this process. Furthermore, despite the extensive redundancy, we show that mammalian MEF2 proteins regulate a significant subset of nonoverlapping gene programs. These results suggest that individual MEF2 family members are able to recognize specific targets among the entire cohort of MEF2-regulated genes in the muscle genome. These findings provide opportunities to modulate the activity of MEF2 isoforms and their respective gene programs in skeletal muscle homeostasis and disease. PMID:25416778

  15. Response to "Exploring the Influence of the ROC Integrated High School Program"

    ERIC Educational Resources Information Center

    Elrick, Michael

    2007-01-01

    In this article, the author provides a response to Scott Caspell's article "Exploring the Influence of the ROC Integrated High School Program." The author states that Caspell picked an excellent time frame to interview former students as they had participated in the integrated program between 10 and 13 years ago. Ideally, then, participants would…

  16. Socio-Cultural Influences in Eating Disorders: Focus on Sports/Fitness Program.

    ERIC Educational Resources Information Center

    Moriarty, Dick; Moriarty, Mary

    This report notes that eating disorders are frequently described as a diet and fitness program gone wild. It outlines and describes five sociocultural influences which have been identified for eating disorders: (1) emphasis on thinness; (2) glorification of youth; (3) changing roles of women; (4) emphasis on fitness and sport programs; and (5) the…

  17. The Life Skills Program IPSY: Positive Influences on School Bonding and Prevention of Substance Misuse

    ERIC Educational Resources Information Center

    Wenzel, Victoria; Weichold, Karina; Silbereisen, Rainer K.

    2009-01-01

    The present study investigated whether a life skills program (LSP) for the prevention of adolescent substance misuse can have positive influences on a school context and on school bonding. The study also explored whether effects on alcohol use are mediated by positive effects on school bonding resulting from program participation. The LSP IPSY…

  18. IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability.

    PubMed

    Furlan, Larissa Lazzarini; Marson, Fernando Augusto Lima; Ribeiro, José Dirceu; Bertuzzo, Carmen Sílvia; Salomão Junior, João Batista; Souza, Dorotéia Rossi Silva

    2016-08-01

    The severity of cystic fibrosis (CF) is associated with classes of mutations in the CFTR gene (cystic fibrosis transmembrane regulator), physical environment and modifier genes interaction. The IL8 gene (interleukin 8), according to its respective polymorphisms, influences inflammatory responses. This study analyzed IL8 gene polymorphisms (rs4073, rs2227306 and rs2227307), by means of PCR/RFLP, and their association with pulmonary function markers and clinical severity scores in 186 patients with CF, considering the CFTR genotype. There was an association between rs2227307 and precocity of the disease. The severity of lung disease was associated with the following markers: transcutaneous arterial hemoglobin oxygen saturation (SaO2) (regardless of CFTR genotype, for the polymorphisms rs4073, rs2227306 and rs2227307); mucoid Pseudomonas aeruginosa (regardless of CFTR genotype, for the polymorphisms rs2227306 and rs2227307). Pulmonary function markers (SaO2 and spirometric variables) and clinical severity scores were also associated with IL8 gene polymorphisms. This study identified the IL8 gene, represented by rs4073 and rs2227306 polymorphisms, and particularly the rs2227307 polymorphism, as potentiating factors for the degree of variability in the severity of CF, especially in pulmonary clinical manifestation correlated with increased morbidity and mortality. PMID:27209008

  19. The Equine Embryo Influences Immune-Related Gene Expression in the Oviduct.

    PubMed

    Smits, Katrien; De Coninck, Dieter I M; Van Nieuwerburgh, Filip; Govaere, Jan; Van Poucke, Mario; Peelman, Luc; Deforce, Dieter; Van Soom, Ann

    2016-02-01

    Although the equine oviduct clearly affects early embryo development and the selective transport of equine embryos through the oviduct indicates a reciprocal interaction, the influence of the embryo on gene expression in the oviduct remains to be determined in the horse. The aim of this study was to examine this by means of RNA sequencing. Four days after ovulation, epithelial cells ipsilateral and contralateral to the ovulation side from five cyclic and five pregnant mares were collected from the oviduct. RNA was extracted, samples were sequenced, and data analysis was performed to determine differentially expressed genes (DEGs) (P value ≤0.05 and absolute fold change ≥2) and to provide functional interpretation. A total of 10 743 transcripts were identified and 253 genes were found to be upregulated and 108 to be downregulated in the pregnant ipsilateral oviduct when compared to the cyclic ipsilateral oviduct. Comparison of the ipsilateral and the contralateral oviduct indicated 164 DEGs in pregnant mares and 77 DEGs in cyclic mares. Enriched functional categories were detected only in the comparison of pregnant and cyclic ipsilateral oviducts and showed that the equine embryo affects the expression of immune response-related genes in the oviduct, with marked upregulation of interferon-associated genes. This research represents the foundation for further assessment of the role of specific genes in the early embryo-maternal dialogue of the horse. PMID:26740593

  20. Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain

    PubMed Central

    Contet, Candice

    2013-01-01

    Sensitivity to ethanol intoxication, propensity to drink ethanol and vulnerability to develop alcoholism are all influenced by genetic factors. Conversely, exposure to ethanol or subsequent withdrawal produce gene expression changes, which, in combination with environmental variables, may participate in the emergence of compulsive drinking and relapse. The present review offers an integrated perspective on brain gene expression profiling in rodent models of predisposition to differential ethanol sensitivity or consumption, in rats and mice subjected to acute or chronic ethanol exposure, as well as in human alcoholics. The functional categories over-represented among differentially expressed genes suggest that the transcriptional effects of chronic ethanol consumption contribute to the neuroplasticity and neurotoxicity characteristic of alcoholism. Importantly, ethanol produces distinct transcriptional changes within the different brain regions involved in intoxication, reinforcement and addiction. Special emphasis is put on recent profiling studies that have provided some insights into the molecular mechanisms potentially mediating genome-wide regulation of gene expression by ethanol. In particular, current evidence for a role of transcription factors, chromatin remodeling and microRNAs in coordinating the expression of large sets of genes in animals predisposed to excessive ethanol drinking or exposed to protracted abstinence, as well as in human alcoholics, is presented. Finally, studies that have compared ethanol with other drugs of abuse have highlighted common gene expression patterns that may play a central role in drug addiction. The availability of novel technologies and a focus on mechanistic approaches are shaping the future of ethanol transcriptomics. PMID:24078902

  1. Genetic influences on insight problem solving: the role of catechol-O-methyltransferase (COMT) gene polymorphisms

    PubMed Central

    Jiang, Weili; Shang, Siyuan; Su, Yanjie

    2015-01-01

    People may experience an “aha” moment, when suddenly realizing a solution of a puzzling problem. This experience is called insight problem solving. Several findings suggest that catecholamine-related genes may contribute to insight problem solving, among which the catechol-O-methyltransferase (COMT) gene is the most promising candidate. The current study examined 753 healthy individuals to determine the associations between 7 candidate single nucleotide polymorphisms on the COMT gene and insight problem-solving performance, while considering gender differences. The results showed that individuals carrying A allele of rs4680 or T allele of rs4633 scored significantly higher on insight problem-solving tasks, and the COMT gene rs5993883 combined with gender interacted with correct solutions of insight problems, specifically showing that this gene only influenced insight problem-solving performance in males. This study presents the first investigation of the genetic impact on insight problem solving and provides evidence that highlights the role that the COMT gene plays in insight problem solving. PMID:26528222

  2. The social status of the male Nile tilapia (Oreochromis niloticus) influences testis structure and gene expression.

    PubMed

    Pfennig, Frank; Kurth, Thomas; Meissner, Stefan; Standke, Andrea; Hoppe, Markus; Zieschang, Freia; Reitmayer, Christine; Göbel, Andy; Kretzschmar, Georg; Gutzeit, Herwig O

    2012-01-01

    Dominant and territorial behaviour are known social phenomena in cichlids and social stress influences reproduction and growth. The gonadotropic hormones trigger spermatogenesis and subordinate males have typically lower levels of gonadotropins than dominant males. In this study, we compared testis morphology and gene expression of dominant and subordinate Nile tilapia males (d- and s-males) in socially stable communities. The d-males had the highest gonadosomatic index but they were not the largest animals in the majority of studied cases. Long-term d-males showed large groups of Leydig cells and hyperplasia of the tunica albuginea due to numerous cytochrome-P450-11β-hydroxylase (Cyp11b) expressing myoid cells. Increased Cyp11b expression in d-males was reflected by elevated 11-ketotestosterone plasma values. However, immunofluorescence microscopy and expression analysis of selected genes revealed that most s-males conserved their capability for spermatogenesis and are, therefore, ready for reproduction when the social environment changes. Moreover, in s-males gene expression analysis by quantitative RT-PCR showed increased transcript levels for germ line-specific genes (vasa, sox2 and dmc1) and Sertoli-specific genes (amh, amhrII and dmrt1) whereas gene expression of key factors for steroid production (sf1 and cyp11b) were reduced. The Nile tilapia is a promising model to study social cues and gonadotropic signals on testis development in vertebrates. PMID:22031714

  3. Array data extractor (ADE): a LabVIEW program to extract and merge gene array data

    PubMed Central

    2013-01-01

    Background Large data sets from gene expression array studies are publicly available offering information highly valuable for research across many disciplines ranging from fundamental to clinical research. Highly advanced bioinformatics tools have been made available to researchers, but a demand for user-friendly software allowing researchers to quickly extract expression information for multiple genes from multiple studies persists. Findings Here, we present a user-friendly LabVIEW program to automatically extract gene expression data for a list of genes from multiple normalized microarray datasets. Functionality was tested for 288 class A G protein-coupled receptors (GPCRs) and expression data from 12 studies comparing normal and diseased human hearts. Results confirmed known regulation of a beta 1 adrenergic receptor and further indicate novel research targets. Conclusions Although existing software allows for complex data analyses, the LabVIEW based program presented here, “Array Data Extractor (ADE)”, provides users with a tool to retrieve meaningful information from multiple normalized gene expression datasets in a fast and easy way. Further, the graphical programming language used in LabVIEW allows applying changes to the program without the need of advanced programming knowledge. PMID:24289243

  4. Burkholderia cenocepacia ShvR-regulated genes that influence colony morphology, biofilm formation, and virulence.

    PubMed

    Subramoni, Sujatha; Nguyen, David T; Sokol, Pamela A

    2011-08-01

    Burkholderia cenocepacia is an opportunistic pathogen that primarily infects cystic fibrosis (CF) patients. Previously, we reported that ShvR, a LysR regulator, influences colony morphology, virulence, and biofilm formation and regulates the expression of an adjacent 24-kb genomic region encoding 24 genes. In this study, we report the functional characterization of selected genes in this region. A Tn5 mutant with shiny colony morphology was identified with a polar mutation in BCAS0208, predicted to encode an acyl-coenzyme A dehydrogenase. Mutagenesis of BCAS0208 and complementation analyses revealed that BCAS0208 is required for rough colony morphology, biofilm formation, and virulence on alfalfa seedlings. It was not possible to complement with BCAS0208 containing a mutation in the catalytic site. BCAS0201, encoding a putative flavin adenine dinucleotide (FAD)-dependent oxidoreductase, and BCAS0207, encoding a putative citrate synthase, do not influence colony morphology but are required for optimum levels of biofilm formation and virulence. Both BCAS0208 and BCAS0201 contribute to pellicle formation, although individual mutations in each of these genes had no appreciable effect on pellicle formation. A mutant with a polar insertion in BCAS0208 was significantly less virulent in a rat model of chronic lung infection as well as in the alfalfa model. Genes in this region were shown to influence utilization of branched-chain fatty acids, tricarboxylic acid cycle substrates, l-arabinose, and branched-chain amino acids. Together, our data show that the ShvR-regulated genes BCAS0208 to BCAS0201 are required for the rough colony morphotype, biofilm and pellicle formation, and virulence in B. cenocepacia. PMID:21690240

  5. Identification of landscape features influencing gene flow: How useful are habitat selection models?

    USGS Publications Warehouse

    Roffler, Gretchen H.; Schwartz, Michael K.; Pilgrim, Kristy L.; Talbot, Sandra; Sage, Kevin; Adams, Layne G.; Luikart, Gordon

    2016-01-01

    Understanding how dispersal patterns are influenced by landscape heterogeneity is critical for modeling species connectivity. Resource selection function (RSF) models are increasingly used in landscape genetics approaches. However, because the ecological factors that drive habitat selection may be different from those influencing dispersal and gene flow, it is important to consider explicit assumptions and spatial scales of measurement. We calculated pairwise genetic distance among 301 Dall's sheep (Ovis dalli dalli) in southcentral Alaska using an intensive noninvasive sampling effort and 15 microsatellite loci. We used multiple regression of distance matrices to assess the correlation of pairwise genetic distance and landscape resistance derived from an RSF, and combinations of landscape features hypothesized to influence dispersal. Dall's sheep gene flow was positively correlated with steep slopes, moderate peak normalized difference vegetation indices (NDVI), and open land cover. Whereas RSF covariates were significant in predicting genetic distance, the RSF model itself was not significantly correlated with Dall's sheep gene flow, suggesting that certain habitat features important during summer (rugged terrain, mid-range elevation) were not influential to effective dispersal. This work underscores that consideration of both habitat selection and landscape genetics models may be useful in developing management strategies to both meet the immediate survival of a species and allow for long-term genetic connectivity.

  6. Identification of landscape features influencing gene flow: How useful are habitat selection models?

    PubMed

    Roffler, Gretchen H; Schwartz, Michael K; Pilgrim, Kristy L; Talbot, Sandra L; Sage, George K; Adams, Layne G; Luikart, Gordon

    2016-07-01

    Understanding how dispersal patterns are influenced by landscape heterogeneity is critical for modeling species connectivity. Resource selection function (RSF) models are increasingly used in landscape genetics approaches. However, because the ecological factors that drive habitat selection may be different from those influencing dispersal and gene flow, it is important to consider explicit assumptions and spatial scales of measurement. We calculated pairwise genetic distance among 301 Dall's sheep (Ovis dalli dalli) in southcentral Alaska using an intensive noninvasive sampling effort and 15 microsatellite loci. We used multiple regression of distance matrices to assess the correlation of pairwise genetic distance and landscape resistance derived from an RSF, and combinations of landscape features hypothesized to influence dispersal. Dall's sheep gene flow was positively correlated with steep slopes, moderate peak normalized difference vegetation indices (NDVI), and open land cover. Whereas RSF covariates were significant in predicting genetic distance, the RSF model itself was not significantly correlated with Dall's sheep gene flow, suggesting that certain habitat features important during summer (rugged terrain, mid-range elevation) were not influential to effective dispersal. This work underscores that consideration of both habitat selection and landscape genetics models may be useful in developing management strategies to both meet the immediate survival of a species and allow for long-term genetic connectivity. PMID:27330556

  7. Pasture-feeding of Charolais steers influences skeletal muscle metabolism and gene expression.

    PubMed

    Cassar-Malek, I; Jurie, C; Bernard, C; Barnola, I; Micol, D; Hocquette, J-F

    2009-10-01

    Extensive beef production systems on pasture are promoted to improve animal welfare and beef quality. This study aimed to compare the influence on muscle characteristics of two management approaches representative of intensive and extensive production systems. One group of 6 Charolais steers was fed maize-silage indoors and another group of 6 Charolais steers grazed on pasture. Activities of enzymes representative of glycolytic and oxidative (Isocitrate dehydrogenase [ICDH], citrate synthase [CS], hydroxyacyl-CoA dehydrogenase [HAD]) muscle metabolism were assessed in Rectus abdominis (RA) and Semitendinosus (ST) muscles. Activities of oxidative enzymes ICDH, CS and HAD were higher in muscles from grazing animals demonstrating a plasticity of muscle metabolism according to the production and feeding system. Gene expression profiling in RA and ST muscles was performed on both production groups using a multi-tissue bovine cDNA repertoire. Variance analysis showed an effect of the muscle type and of the production system on gene expression (P<0.001). A list of the 212 most variable genes according to the production system was established, of which 149 genes corresponded to identified genes. They were classified according to their gene function annotation mainly in the "protein metabolism and modification", "signal transduction", "cell cycle", "developmental processes" and "muscle contraction" biological processes. Selenoprotein W was found to be underexpressed in pasture-fed animals and could be proposed as a putative gene marker of the grass-based system. In conclusion, enzyme-specific adaptations and gene expression modifications were observed in response to the production system and some of them could be candidates for grazing or grass-feeding traceability. PMID:19996487

  8. Common genetic variants in NEFL influence gene expression and neuroblastoma risk

    PubMed Central

    Capasso, Mario; Diskin, Sharon; Cimmino, Flora; Acierno, Giovanni; Totaro, Francesca; Petrosino, Giuseppe; Pezone, Lucia; Diamond, Maura; McDaniel, Lee; Hakonarson, Hakon; Iolascon, Achille; Devoto, Marcella; Maris, John M

    2014-01-01

    The genetic etiology of sporadic neuroblastoma is still largely obscure. In a genome-wide association study, we identified single nucleotide polymorphisms (SNP) associated with neuroblastoma at the LINC00340, BARD1, LMO1, DUSP12, HSD17B12, HACE1 and LIN28B gene loci, but these explain only a small fraction of neuroblastoma heritability. Other neuroblastoma susceptibility genes are likely hidden among signals discarded by the multiple testing corrections. In this study, we evaluated 8 additional genes selected as candidates for further study based on proven involvement in neuroblastoma differentiation. SNP at these candidate genes were tested for association with disease susceptibility in 2101 cases and 4202 controls, with the associations found replicated in an independent cohort of 459 cases and 809 controls. Replicated associations were further studied for cis-effect using gene expression, transient overexpression, silencing and cellular differentiation assays. The neurofilament gene NEFL harbored three SNP associated with neuroblastoma (rs11994014; Pcombined=0.0050; OR=0.88, rs2979704; Pcombined=0.0072; OR=0.87, rs105911; Pcombined=0.0049; OR=0.86). The protective allele of rs1059111 correlated with increased NEFL expression. Biological investigations showed that ectopic overexpression of NEFL inhibited cell growth specifically in neuroblastoma cells carrying the protective allele. NEFL overexpression also enhanced differentiation and impaired the proliferation and anchorage-independent growth of cells with protective allele and basal NEFL expression, while impairing invasiveness and proliferation of cells homozygous for the risk genotype. Clinically, high levels of NEFL expression in primary neuroblastoma specimens was associated with better overall survival (P=0.03; HR=0.68). Our results show that common variants of NEFL influence neuroblastoma susceptibility and they establish that NEFL expression influences disease initiation and progression. PMID:25312269

  9. Tobacco industry sociological programs to influence public beliefs about smoking.

    PubMed

    Landman, Anne; Cortese, Daniel K; Glantz, Stanton

    2008-02-01

    The multinational tobacco companies responded to arguments about the social costs of smoking and hazards of secondhand smoke by quietly implementing the Social Costs/Social Values project (1979-1989), which relied upon the knowledge and authoritative power of social scientists to construct an alternate cultural repertoire of smoking. Social scientists created and disseminated non-health based, pro-tobacco arguments without fully acknowledging their relationship with the industry. After the US Surgeon General concluded that nicotine was addictive in 1988, the industry responded by forming "Associates for Research in the Science of Enjoyment" (c.1988-1999), whose members toured the world promoting the health benefits of the use of legal substances, including tobacco, for stress relief and relaxation, without acknowledging the industry's role. In this paper we draw on previously secret tobacco industry documents, now available on the Internet to show how both of these programs utilized academic sociologists, political scientists, anthropologists, psychologists, philosophers and economists, and allowed the industry to develop and widely disseminate friendly research through credible channels. Strategies included creating favorable surveys and opinions, infusing them into the lay press and media through press releases, articles and conferences, publishing, promoting and disseminating books, commissioning and placing favorable book reviews, providing media training for book authors and organizing media tours. These programs allowed the tobacco industry to affect public and academic discourse on the social acceptability of smoking. PMID:18164524

  10. Tobacco industry sociological programs to influence public beliefs about smoking

    PubMed Central

    Glantz, Stanton; Landman, Anne; Cortese, Daniel K

    2008-01-01

    The multinational tobacco companies responded to arguments about the social costs of smoking and hazards of secondhand smoke by quietly implementing the Social Costs/Social Values project (1979–1989), which relied upon the knowledge and authoritative power of social scientists to construct an alternate cultural repertoire of smoking. Social scientists created and disseminated non-health based, pro-tobacco arguments without fully acknowledging their relationship with the industry. After the U.S. Surgeon General concluded that nicotine was addictive in 1988, the industry responded by forming “Associates for Research in the Science of Enjoyment” (c.1988–1999), whose members toured the world promoting the health benefits of the use of legal substances, including tobacco, for stress relief and relaxation, without acknowledging the industry’s role. In this paper we draw on previously secret tobacco industry documents, now available on the internet to show how both of these programs utilized academic sociologists, political scientists, anthropologists, psychologists, philosophers and economists, and allowed the industry to develop and widely disseminate friendly research through credible channels. Strategies included creating favorable surveys and opinions, infusing them into the lay press and media through press releases, articles and conferences, publishing, promoting and disseminating books, commissioning and placing favorable book reviews, providing media training for book authors and organizing media tours. These programs allowed the tobacco industry to affect public and academic discourse on the social acceptability of smoking. PMID:18164524

  11. Detecting horizontal gene transfer with T-REX and RHOM programs.

    PubMed

    Li, Zuofeng; Wang, Li; Zhong, Yang

    2005-12-01

    As the Human Genome Project and other genome projects experience remarkable success and a flood of biological data is produced by means of high-throughout sequencing techniques, detection of horizontal gene transfer (HGT) becomes a promising field in bioinformatics. This review describes two freeware programs: T-REX for MS Windows and RHOM for Linux. T-REX is a graphical user interface program that offers functions to reconstruct the HGT network among the donor and receptor hosts from the gene and species distance matrices. RHOM is a set of command-line driven programs used to detect HGT in genomes. While T-REX impresses with a user-friendly interface and drawing of the reticulation network, the strength of RHOM is an extensive statistical framework of genome and the graphical display of the estimated sequence position probabilities for the candidate horizontally transferred genes. PMID:16420738

  12. Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats

    PubMed Central

    2013-01-01

    18. Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by metabolic syndrome. Conclusions Metabolic syndrome significantly alters cardiac gene expression profile which may be involved in development of cardiac pathologies in the presence of metabolic syndrome. PMID:23320804

  13. The influence of reduced oxygen availability on pathogenicity and gene expression in Mycobacterium tuberculosis.

    PubMed

    Bacon, Joanna; James, Brian W; Wernisch, Lorenz; Williams, Ann; Morley, Kim A; Hatch, Graham J; Mangan, Joseph A; Hinds, Jason; Stoker, Neil G; Butcher, Philip D; Marsh, Philip D

    2004-01-01

    We investigated how Mycobacterium tuberculosis responded to a reduced oxygen tension in terms of its pathogenicity and gene expression by growing cells under either aerobic or low-oxygen conditions in chemostat culture. The chemostat enabled us to control and vary the oxygen tension independently of other environmental parameters, so that true cause-and-effect relationships of reduced oxygen availability could be established. Cells grown under low oxygen were more pathogenic for guinea pigs than those grown aerobically. The effect of reduced oxygen on global gene expression was determined using DNA microarray. Spearman rank correlation confirmed that microarray expression profiles were highly reproducible between repeat cultures. Using microarray analysis we have identified genes that respond to a low-oxygen environment without the influence of other parameters such as nutrient depletion. Some of these genes appear to be involved in the biosynthesis of cell wall precursors and their induction may have contributed to increased infectivity in the guinea pig. This study has shown that a combination of chemostat culture and microarray presents a biologically robust and statistically reliable experimental approach for studying the effect of relevant and specific environmental stimuli on mycobacterial virulence and gene expression. PMID:15207490

  14. Language impairment and dyslexia genes influence language skills in children with autism spectrum disorders

    PubMed Central

    Eicher, John D.; Gruen, Jeffrey R.

    2014-01-01

    Language and communication development is a complex process influenced by numerous environmental and genetic factors. Many neurodevelopment disorders include deficits in language and communication skills in their diagnostic criteria, including autism spectrum disorders (ASD), language impairment (LI), and dyslexia. These disorders are polygenic and complex with a significant genetic component contributing to each. The similarity of language phenotypes and comorbidity of these disorders suggest that they may share genetic contributors. To test this, we examined the association of genes previously implicated in dyslexia, LI, and/or language-related traits with language skills in children with ASD. We used genetic and language data collected in the Autism Genome Research Exchange (AGRE) and Simons Simplex Collection (SSC) cohorts to perform a meta-analysis on performance on a receptive vocabulary task. There were associations with LI risk gene ATP2C2 and dyslexia risk gene MRPL19. Additionally, we found suggestive evidence of association with CMIP, GCFC2, KIAA0319L, the DYX2 locus (ACOT13, GPLD1, and FAM65B), and DRD2. Our results show that LI and dyslexia genes also contribute to language traits in children with ASD. These associations add to the growing literature of generalist genes that contribute to multiple related neurobehavioral traits. Future studies should examine whether other genetic contributors may be shared among these disorders and how risk variants interact with each other and the environment to modify clinical presentations. PMID:25448322

  15. Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen

    PubMed Central

    Joyce-Tan, Siew Mei; Zain, Shamsul Mohd; Abdul Sattar, Munavvar Zubaid; Abdullah, Nor Azizan

    2016-01-01

    Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P = 0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15–3.20, permuted P = 0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk. PMID:26682227

  16. Language impairment and dyslexia genes influence language skills in children with autism spectrum disorders.

    PubMed

    Eicher, John D; Gruen, Jeffrey R

    2015-04-01

    Language and communication development is a complex process influenced by numerous environmental and genetic factors. Many neurodevelopment disorders include deficits in language and communication skills in their diagnostic criteria, including autism spectrum disorders (ASD), language impairment (LI), and dyslexia. These disorders are polygenic and complex with a significant genetic component contributing to each. The similarity of language phenotypes and comorbidity of these disorders suggest that they may share genetic contributors. To test this, we examined the association of genes previously implicated in dyslexia, LI, and/or language-related traits with language skills in children with ASD. We used genetic and language data collected in the Autism Genome Research Exchange (AGRE) and Simons Simplex Collection (SSC) cohorts to perform a meta-analysis on performance on a receptive vocabulary task. There were associations with LI risk gene ATP2C2 and dyslexia risk gene MRPL19. Additionally, we found suggestive evidence of association with CMIP, GCFC2, KIAA0319L, the DYX2 locus (ACOT13, GPLD1, and FAM65B), and DRD2. Our results show that LI and dyslexia genes also contribute to language traits in children with ASD. These associations add to the growing literature of generalist genes that contribute to multiple related neurobehavioral traits. Future studies should examine whether other genetic contributors may be shared among these disorders and how risk variants interact with each other and the environment to modify clinical presentations. PMID:25448322

  17. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

    NASA Astrophysics Data System (ADS)

    Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

    2000-02-01

    The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

  18. Evidence for a major gene influencing 7-year increases in diastolic blood pressure with age

    SciTech Connect

    Li Shu-Chuan Cheng; Carmelli, D.; Hunt, S.C.

    1995-11-01

    The contribution of genetic factors to blood pressure levels is well established. The contribution of genes to the longitudinal change in blood pressure has been less well studied, because of the lack of longitudinal family data. The present study investigated a possible major-gene effect on the observed increase with age in diastolic blood pressure (DBP) levels. Subjects included 965 unmedicated adults (age {ge}18 years) in 73 pedigrees collected in Utah as part of a longitudinal cardiovascular family study. Segregation analysis of DBP change over 7.2 years of follow-up identified a recessive major-gene effect with a gene frequency of p = .23. There was also a significant age effect on the genotypic means, which decreased expression of the major gene at older ages. For those inferred to have the genotype responsible for large DBP increases, DBP increased 32.3%, compared with a 1.5% increase in the nonsusceptible group (P < .0001). The relative risk of developing hypertension between the susceptible and nonsusceptible groups after 7.2 years was 2.4 (P = .006). Baseline DBP reactivities to mental arithmetic (P < .0001) and isometric hand-grip (P < .0001) stress tests were greatest in those assigned to the susceptible genotype. We conclude that age-related changes in DBP are influenced by a major gene. Characteristics of this major-gene effect for greater age-related blood pressure increases include greater reactivity to mental and physical stressors. The present study thus provides evidence for genetic control of changes in blood pressure, in addition to the previously suggested genetic control of absolute blood pressure level. 28 refs., 6 tabs.

  19. Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

    PubMed Central

    Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P.; Nir, Talia M.; Toga, Arthur W.; Jack, Clifford R.; Saykin, Andrew J.; Green, Robert C.; Weiner, Michael W.; Medland, Sarah E.; Montgomery, Grant W.; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.; Weiner, Michael; Aisen, Paul; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Liu, Enchi; Green, Robert C.; Montine, Tom; Petersen, Ronald; Aisen, Paul; Gamst, Anthony; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Beckett, Laurel; Harvey, Danielle; Gamst, Anthony; Donohue, Michael; Kornak, John; Jack, Clifford R.; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Jagust, William; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Morris, John; Cairns, Nigel J.; Taylor-Reinwald, Lisa; Trojanowki, J.Q.; Shaw, Les; Lee, Virginia M.Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Khachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Coleman, R. Edward; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Lu, Po H.; Bartzokis, George; Silverman, Daniel H.S.; Graff-Radford, Neill R.; Parfitt, Francine; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Bwayo, Salome K.; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabeth; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick

    2013-01-01

    Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases. PMID:23471985

  20. Creating Programs to Help Latino Youth Thrive at School: The Influence of Latino Parent Involvement Programs

    ERIC Educational Resources Information Center

    Behnke, Andrew O.; Kelly, Christine

    2011-01-01

    Parent involvement programs can play an essential role in the academic success of Latino youth. This article reports the effectiveness and evaluation of two new Extension programs that help Latino parents become more involved in their youths' academics. The Latino Parent and Family Advocacy and Support Training (LPFAST) targets parents of K- 8th…

  1. Sociocultural Influences and Teacher Education Programs. Research on Sociocultural Influences on Motivation and Learning.

    ERIC Educational Resources Information Center

    McInerney, Dennis M., Ed.; Van Etten, Shawn, Ed.

    This collection of papers describes exemplary programs in teacher education that attempt to address issues of diversity and the achievement gap between different groups of students. After "Introduction: Teacher Preparation for Diverse Settings," (Dennis M. McInerney and Shawn Van Etten), the 10 papers are: (1) "Can Teacher Education Close the…

  2. Development of a gene expression database and related analysis programs for evaluation of anticancer compounds.

    PubMed

    Ushijima, Masaru; Mashima, Tetsuo; Tomida, Akihiro; Dan, Shingo; Saito, Sakae; Furuno, Aki; Tsukahara, Satomi; Seimiya, Hiroyuki; Yamori, Takao; Matsuura, Masaaki

    2013-03-01

    Genome-wide transcriptional expression analysis is a powerful strategy for characterizing the biological activity of anticancer compounds. It is often instructive to identify gene sets involved in the activity of a given drug compound for comparison with different compounds. Currently, however, there is no comprehensive gene expression database and related application system that is; (i) specialized in anticancer agents; (ii) easy to use; and (iii) open to the public. To develop a public gene expression database of antitumor agents, we first examined gene expression profiles in human cancer cells after exposure to 35 compounds including 25 clinically used anticancer agents. Gene signatures were extracted that were classified as upregulated or downregulated after exposure to the drug. Hierarchical clustering showed that drugs with similar mechanisms of action, such as genotoxic drugs, were clustered. Connectivity map analysis further revealed that our gene signature data reflected modes of action of the respective agents. Together with the database, we developed analysis programs that calculate scores for ranking changes in gene expression and for searching statistically significant pathways from the Kyoto Encyclopedia of Genes and Genomes database in order to analyze the datasets more easily. Our database and the analysis programs are available online at our website (http://scads.jfcr.or.jp/db/cs/). Using these systems, we successfully showed that proteasome inhibitors are selectively classified as endoplasmic reticulum stress inducers and induce atypical endoplasmic reticulum stress. Thus, our public access database and related analysis programs constitute a set of efficient tools to evaluate the mode of action of novel compounds and identify promising anticancer lead compounds. PMID:23176546

  3. Epigenetic Influence of Dam Methylation on Gene Expression and Attachment in Uropathogenic Escherichia coli

    PubMed Central

    Stephenson, Stacy Ann-Marie; Brown, Paul D.

    2016-01-01

    Urinary tract infections (UTI) are among the most frequently encountered infections in clinical practice globally. Predominantly a burden among female adults and infants, UTIs primarily caused by uropathogenic Escherichia coli (UPEC) results in high morbidity and fiscal health strains. During pathogenesis, colonization of the urinary tract via fimbrial adhesion to mucosal cells is the most critical point in infection and has been linked to DNA methylation. Furthermore, with continuous exposure to antibiotics as the standard therapeutic strategy, UPEC has evolved to become highly adaptable in circumventing the effect of antimicrobial agents and host defenses. Hence, the need for alternative treatment strategies arises. Since differential DNA methylation is observed as a critical precursor to virulence in various pathogenic bacteria, this body of work sought to assess the influence of the DNA adenine methylase (dam) gene on gene expression and cellular adhesion in UPEC and its potential as a therapeutic target. To monitor the influence of dam on attachment and FQ resistance, selected UPEC dam mutants created via one-step allelic exchange were transformed with cloned qnrA and dam complement plasmid for comparative analysis of growth rate, antimicrobial susceptibility, biofilm formation, gene expression, and mammalian cell attachment. The absence of DNA methylation among dam mutants was apparent. Varying deficiencies in cell growth, antimicrobial resistance and biofilm formation, alongside low-level increases in gene expression (recA and papI), and adherence to HEK-293 and HTB-9 mammalian cells were also detected as a factor of SOS induction to result in increased mutability. Phenotypic characteristics of parental strains were restored in dam complement strains. Dam’s vital role in DNA methylation and gene expression in local UPEC isolates was confirmed. Similarly to dam-deficient Enterohemorrhagic E. coli (EHEC), these findings suggest unsuccessful therapeutic use

  4. Factors influencing overweight children's commencement of and continuation in a resistance training program

    PubMed Central

    2010-01-01

    Background In light of the child overweight and obesity problem in Australia, resistance training programs have been trialled as an innovative way of assisting children increase lean body mass and reduce body fat. The purpose of this study was to investigate the factors influencing overweight children's participation in a resistance training trial program. Method Parent-child pairs who participated in the trial program were invited to take part in a follow-up individual interview to discuss their program experiences. In total, 22 semi-structured interviews were conducted with 11 parent-child pairs. Results The factors found to be most relevant to program commencement among parents were a desire for their child to lose weight and gain confidence, the proximity of the venue, and no cost for participation. For children, the most relevant factors were the opportunity to build strength and improve fitness and having supportive parents who facilitated program initiation. The factors most relevant to continuation for parents were the quality of the program management, being able to stay for the sessions, the child's improved weight status, coordination, and confidence, and no cost for participation. Weight loss and improved confidence were also motivators for continuation among the children, along with pleasant social interaction with peers and trainers and ongoing parental support. Conclusion Different factors variably influence program commencement and program continuation in both parents and children. This has important implications for future interventions that aim to successfully recruit and retain intervention participants. PMID:21083936

  5. IL-7 signalling represses Bcl-6 and the TFH gene program.

    PubMed

    McDonald, Paul W; Read, Kaitlin A; Baker, Chandra E; Anderson, Ashlyn E; Powell, Michael D; Ballesteros-Tato, André; Oestreich, Kenneth J

    2016-01-01

    The transcriptional repressor Bcl-6 is linked to the development of both CD4(+) T follicular helper (TFH) and central memory T (TCM) cells. Here, we demonstrate that in response to decreased IL-2 signalling, T helper 1 (TH1) cells upregulate Bcl-6 and co-initiate TFH- and TCM-like gene programs, including expression of the cytokine receptors IL-6Rα and IL-7R. Exposure of this potentially bi-potent cell population to IL-6 favours the TFH gene program, whereas IL-7 signalling represses TFH-associated genes including Bcl6 and Cxcr5, but not the TCM-related genes Klf2 and Sell. Mechanistically, IL-7-dependent activation of STAT5 contributes to Bcl-6 repression. Importantly, antigen-specific IL-6Rα(+)IL-7R(+) CD4(+) T cells emerge from the effector population at late time points post influenza infection. These data support a novel role for IL-7 in the repression of the TFH gene program and evoke a divergent regulatory mechanism by which post-effector TH1 cells may contribute to long-term cell-mediated and humoral immunity. PMID:26743592

  6. Encoding four gene expression programs in the activation dynamics of a single transcription factor.

    PubMed

    Hansen, Anders S; O'Shea, Erin K

    2016-04-01

    Cellular signaling response pathways often exhibit a bow-tie topology [1,2]: multiple upstream stress signals converge on a single shared transcription factor, which is thought to induce different downstream gene expression programs (Figure 1A). However, if several different signals activate the same transcription factor, can each signal then induce a specific gene expression response? A growing body of literature supports a temporal coding theory where information about environmental signals can be encoded, at least partially, in the temporal dynamics of the shared transcription factor [1,2]. For example, in the case of the budding yeast transcription factor Msn2, different stresses induce distinct Msn2 activation dynamics: Msn2 shows pulsatile nuclear activation with dose-dependent frequency under glucose limitation, but sustained nuclear activation with dose-dependent amplitude under oxidative stress [3]. These dynamic patterns can then lead to differential gene expression responses [3-5], but it is not known how much specificity can be obtained. Thus, a major question of this temporal coding theory is how many gene response programs or cellular functions can be robustly encoded by dynamic control of a single transcription factor. Here we provide the first direct evidence that, simply by regulating the activation dynamics of a single transcription factor, it is possible to preferentially induce four distinct gene expression programs. PMID:27046808

  7. Supplemental dietary inulin influences expression of iron and inflammation related genes in young pigs.

    PubMed

    Yasuda, Koji; Dawson, Harry D; Wasmuth, Elizabeth V; Roneker, Carol A; Chen, Celine; Urban, Joseph F; Welch, Ross M; Miller, Dennis D; Lei, Xin Gen

    2009-11-01

    We have previously shown improved hemoglobin (Hb) repletion efficiency by supplementing a 50:50 mixture of short (P95) and long-chain (HP) inulin (Synergy 1, BENEO-Orafti) into a corn-soybean meal-basal diet (BD) for young pigs. In this study, weanling pigs (5 or 6 wk old) were fed the BD or the BD + 4% of P95, HP, or Synergy 1 (50:50 mixtures of HP and P95) for 5-7 wk. Blood Hb concentrations of pigs were measured weekly and digesta samples were collected at the end of the trial. In a replicate experiment, total RNA was isolated from the liver and mucosa of duodenum, ileum, cecum, and colon of all pigs at the end of the trial. Relative mRNA expression of 27 genes, including iron and inflammation-related genes, was quantified using real-time quantitative-PCR. Although all 3 types of inulin resulted in similar improvements (P < 0.05) in blood Hb concentration and liver ferritin protein amount, neither type of inulin was detectable in the digesta of cecum or colon. Supplemental inulin enhanced the expression of iron-storing protein genes but decreased that of inflammation-related genes. Such effects were more pronounced (P < 0.05) in the mucosa of the lower than the upper gut and were seen on 7 genes in liver. In conclusion, all 3 types of inulin shared similar efficacy and possibly similar modes of action in improving dietary iron utilization by young pigs. Suppressing inflammation-induced genes that can negatively influence iron metabolism might help explain the benefit of inulin. PMID:19776179

  8. Genetic Influences on Adolescent Sexual Behavior: Why Genes Matter for Environmentally-Oriented Researchers

    PubMed Central

    Harden, K. Paige

    2013-01-01

    There are dramatic individual differences among adolescents in how and when they become sexually active adults, and “early” sexual activity is frequently cited as a cause of concern for scientists, policymakers, and the general public. Understanding the causes and developmental impact of adolescent sexual activity can be furthered by considering genes as a source of individual differences. Quantitative behavioral genetics (i.e., twin and family studies) and candidate gene association studies now provide clear evidence for the genetic underpinnings of individual differences in adolescent sexual behavior and related phenotypes. Genetic influences on sexual behavior may operate through a variety of direct and indirect mechanisms, including pubertal development, testosterone levels, and dopaminergic systems. Genetic differences may be systematically associated with exposure to environments that are commonly treated as causes of sexual behavior (gene-environment correlation). Possible gene-environment correlations pose a serious challenge for interpreting the results of much behavioral research. Multivariate, genetically-informed research on adolescent sexual behavior compares twins and family members as a form of “quasi-experiment”: How do twins who differ in their sexual experiences differ in their later development? The small but growing body of genetically-informed research has already challenged dominant assumptions regarding the etiology and sequelae of adolescent sexual behavior, with some studies indicating possible positive effects of teenage sexuality. Studies of gene × environment interaction may further elucidate the mechanisms by which genes and environments combine to shape the development of sexual behavior and its psychosocial consequences. Overall, the existence of heritable variation in adolescent sexual behavior has profound implications for environmentally-oriented theory and research. PMID:23855958

  9. Determinants of nucleosome positioning and their influence on plant gene expression

    PubMed Central

    Liu, Ming-Jung; Seddon, Alexander E.; Tsai, Zing Tsung-Yeh; Major, Ian T.; Floer, Monique; Howe, Gregg A.; Shiu, Shin-Han

    2015-01-01

    Nucleosome positioning influences the access of transcription factors (TFs) to their binding sites and gene expression. Studies in plant, animal, and fungal models demonstrate similar nucleosome positioning patterns along genes and correlations between occupancy and expression. However, the relationships among nucleosome positioning, cis-regulatory element accessibility, and gene expression in plants remain undefined. Here we showed that plant nucleosome depletion occurs on specific 6-mer motifs and this sequence-specific nucleosome depletion is predictive of expression levels. Nucleosome-depleted regions in Arabidopsis thaliana tend to have higher G/C content, unlike yeast, and are centered on specific G/C-rich 6-mers, suggesting that intrinsic sequence properties, such as G/C content, cannot fully explain plant nucleosome positioning. These 6-mer motif sites showed higher DNase I hypersensitivity and are flanked by strongly phased nucleosomes, consistent with known TF binding sites. Intriguingly, this 6-mer-specific nucleosome depletion pattern occurs not only in promoter but also in genic regions and is significantly correlated with higher gene expression level, a phenomenon also found in rice but not in yeast. Among the 6-mer motifs enriched in genes responsive to treatment with the defense hormone jasmonate, there are no significant changes in nucleosome occupancy, suggesting that these sites are potentially preconditioned to enable rapid response without changing chromatin state significantly. Our study provides a global assessment of the joint contribution of nucleosome occupancy and motif sequences that are likely cis-elements to the control of gene expression in plants. Our findings pave the way for further understanding the impact of chromatin state on plant transcriptional regulatory circuits. PMID:26063739

  10. Influence of Populus Genotype on Gene Expression by the Wood Decay Fungus Phanerochaete chrysosporium

    PubMed Central

    Gaskell, Jill; Marty, Amber; Mozuch, Michael; Kersten, Philip J.; Splinter BonDurant, Sandra; Sabat, Grzegorz; Azarpira, Ali; Ralph, John; Skyba, Oleksandr; Mansfield, Shawn D.; Blanchette, Robert A.

    2014-01-01

    We examined gene expression patterns in the lignin-degrading fungus Phanerochaete chrysosporium when it colonizes hybrid poplar (Populus alba × tremula) and syringyl (S)-rich transgenic derivatives. A combination of microarrays and liquid chromatography-tandem mass spectrometry (LC-MS/MS) allowed detection of a total of 9,959 transcripts and 793 proteins. Comparisons of P. chrysosporium transcript abundance in medium containing poplar or glucose as a sole carbon source showed 113 regulated genes, 11 of which were significantly higher (>2-fold, P < 0.05) in transgenic line 64 relative to the parental line. Possibly related to the very large amounts of syringyl (S) units in this transgenic tree (94 mol% S), several oxidoreductases were among the upregulated genes. Peptides corresponding to a total of 18 oxidoreductases were identified in medium consisting of biomass from line 64 or 82 (85 mol% S) but not in the parental clone (65 mol% S). These results demonstrate that P. chrysosporium gene expression patterns are substantially influenced by lignin composition. PMID:25015893

  11. Factors influencing law enforcement decisions to adopt an evidence-based robbery prevention program.

    PubMed

    Cabell, A; Casteel, C; Chronister, T; Nocera, M; Vladutiu, C J; Peek-Asa, C

    2013-12-01

    Homicide is the leading cause of workplace death among small retail and service businesses in the United States. Evidence-based programs have been shown to reduce robbery and robbery-related crimes in small retail businesses; however, reaching small businesses with programs has been difficult. As small businesses typically have no corporate backing or trade affiliation, police departments have been identified as potential vehicles for program dissemination. A national sample of 300 law enforcement agencies was surveyed to identify facilitators and barriers to adoption and sustainability of an evidence-based program. The questionnaire was developed using behavioral theory concepts and administered via telephone. Preliminary findings suggest the primary facilitators to program adoption included organizational capacity factors such as staff buy-in, dedicated personnel and financial support. Competing responsibilities was the primary barrier identified by agencies. Agency size and program complexity were identified as potential predictors of program adoption. Identifying agency and program-specific characteristics that influence program adoption by law enforcement agencies will be valuable for marketing programs to agencies that have the infrastructure to support and sustain program dissemination. Understanding these factors will optimize the reach of evidence-based strategies to small businesses. PMID:24057272

  12. Internal and External Influences on Program-Level Curriculum Development in Higher Education Fashion Merchandising Programs

    ERIC Educational Resources Information Center

    King, Janice E.

    2010-01-01

    In an ever changing global economy, higher education experiences accountability issues in educating the workforce. Graduates require the knowledge and skills necessary to succeed in the global workplace. For graduates to have the opportunity to attain this understanding and expertise, it is critical to identify what influences curriculum…

  13. Var Gene promoter activation in clonal Plasmodium falciparum isolates follows a hierarchy and suggests a conserved switching program that is independent of genetic background.

    PubMed

    Enderes, Corinna; Kombila, Davy; Dal-Bianco, Matthias; Dzikowski, Ron; Kremsner, Peter; Frank, Matthias

    2011-11-15

    Antigenic variation of Plasmodium falciparum is mediated by a mutually exclusive expression mechanism that limits expression to an individual member of the multicopy var gene family. This process determines the antigenic and adhesive phenotype of the infected red blood cell. Previously, we showed that var gene switching is influenced by chromosomal position. Here, we address whether var gene transcription follows a general conserved pattern in long-term laboratory parasites and in recently culture-adapted field parasites. Activation of the var gene family was monitored in biological replicates in each parasite isolate every 3-5 generations for up to 3 months. We used transgenic parasites carrying a drug-selectable marker at a defined var locus to characterize var gene activation after the exclusive expression of the transgene. Transgenic parasites exhibited a repeatable hierarchy of var gene activation and a fluctuating transcriptional activity of the transgenic var locus. Transcriptional profiling of wild-type laboratory and field parasites showed a universal bias toward transcription of UpsC var genes and a fluctuating transcriptional activity of the dominant var promoter. The data suggest the existence of an intrinsic var gene transcription program that is independent of genetic background. PMID:21926380

  14. Influence factors and gene expression patterns during MeJa-induced gummosis in peach.

    PubMed

    Li, Minji; Liu, Meiyan; Peng, Futian; Fang, Long

    2015-06-15

    Jasmonates (JAs) play important roles in gummosis in peach. Mechanical damage, methyl jasmonate (MeJa), and ethylene can induce gummosis on peach shoots in the field. In this study, we used MeJa (2%, w/w) to induce gummosis on current-year shoots in peach on high temperature (35°C). Based on the experimental model, we studied the influence of factors on the development of peach gummosis. Our experimental results showed that high temperature could promote gummosis development induced by MeJa. Exogenous CaCl2 treatment reduced the degree of gummosis by increasing the calcium content in shoots, which is conducive to the synthesis and maintenance of the cell wall. Using digital gene expression (DGE), 3831 differentially expressed genes were identified in the MeJa treatment versus the control. By analyzing changes in gene expression associated with cell wall degradation, genes encoding pectin methylesterase (PME) and endo-polygalacturonase (PG) were found to be significantly induced, suggesting that they are key enzymes in cell wall degradation that occurs during MeJa-induced gummosis. Genes for glycosyltransferase (GT) and cellulose synthase (CS) were also significantly upregulated by MeJa. This result suggests that MeJa treatment not only promotes the degradation of polysaccharides to destroy the cell wall, but also promotes the synthesis of new polysaccharides. We also analyzed changes in gene expression associated with sugar metabolism, senescence, and defense. MeJa treatment affected the expression of genes related to sugar metabolism and promoted plant senescence. Among the defense genes, the expression pattern of phenylalanine ammonium lyase (PAL) suggested that PAL may play an important role in protecting against the effects of MeJa treatment. Our experimental results showed that MeJa treatment can promote the biosynthesis and signal transduction of ethylene in peach shoots; they can induce gummosis on peach shoots respectively, and there are overlaps between

  15. The Gene Expression Program for the Formation of Wing Cuticle in Drosophila.

    PubMed

    Sobala, Lukasz F; Adler, Paul N

    2016-05-01

    The cuticular exoskeleton of insects and other arthropods is a remarkably versatile material with a complex multilayer structure. We made use of the ability to isolate cuticle synthesizing cells in relatively pure form by dissecting pupal wings and we used RNAseq to identify genes expressed during the formation of the adult wing cuticle. We observed dramatic changes in gene expression during cuticle deposition, and combined with transmission electron microscopy, we were able to identify candidate genes for the deposition of the different cuticular layers. Among genes of interest that dramatically change their expression during the cuticle deposition program are ones that encode cuticle proteins, ZP domain proteins, cuticle modifying proteins and transcription factors, as well as genes of unknown function. A striking finding is that mutations in a number of genes that are expressed almost exclusively during the deposition of the envelope (the thin outermost layer that is deposited first) result in gross defects in the procuticle (the thick chitinous layer that is deposited last). An attractive hypothesis to explain this is that the deposition of the different cuticle layers is not independent with the envelope instructing the formation of later layers. Alternatively, some of the genes expressed during the deposition of the envelope could form a platform that is essential for the deposition of all cuticle layers. PMID:27232182

  16. The Gene Expression Program for the Formation of Wing Cuticle in Drosophila

    PubMed Central

    Adler, Paul N.

    2016-01-01

    The cuticular exoskeleton of insects and other arthropods is a remarkably versatile material with a complex multilayer structure. We made use of the ability to isolate cuticle synthesizing cells in relatively pure form by dissecting pupal wings and we used RNAseq to identify genes expressed during the formation of the adult wing cuticle. We observed dramatic changes in gene expression during cuticle deposition, and combined with transmission electron microscopy, we were able to identify candidate genes for the deposition of the different cuticular layers. Among genes of interest that dramatically change their expression during the cuticle deposition program are ones that encode cuticle proteins, ZP domain proteins, cuticle modifying proteins and transcription factors, as well as genes of unknown function. A striking finding is that mutations in a number of genes that are expressed almost exclusively during the deposition of the envelope (the thin outermost layer that is deposited first) result in gross defects in the procuticle (the thick chitinous layer that is deposited last). An attractive hypothesis to explain this is that the deposition of the different cuticle layers is not independent with the envelope instructing the formation of later layers. Alternatively, some of the genes expressed during the deposition of the envelope could form a platform that is essential for the deposition of all cuticle layers. PMID:27232182

  17. YHV-responsive gene expression under the influence of PmRelish regulation.

    PubMed

    Visetnan, Suwattana; Supungul, Premruethai; Tang, Sureerat; Hirono, Ikuo; Tassanakajon, Anchalee; Rimphanitchayakit, Vichien

    2015-11-01

    In animals, infection by Gram-negative bacteria and certain viruses activates the Imd signaling pathway wherein the a NF-κB transcription factor, Relish, is a key regulatory protein for the synthesis of antimicrobial proteins. Infection by yellow head virus (YHV) activates the Imd pathway. To investigate the expression of genes involved in YHV infection and under the influence of PmRelish regulation, RNA interference and suppression subtractive hybridization (SSH) are employed. The genes in forward library expressed in shrimp after YHV infection and under the activity of PmRelish were obtained by subtracting the cDNAs from YHV-infected and PmRelish-knockdown shrimp with cDNAs from YHV-infected shrimp. Opposite subtraction gave a reverse library whereby an alternative set of genes under YHV infection and no PmRelish expression were obtained. Nucleotide sequences of 252 and 99 cDNA clones from the forward and reverse libraries, respectively, were obtained and annotated through blast search against the GenBank sequences. Genes involved in defense and homeostasis were abundant in both libraries, 31% and 23% in the forward and reverse libraries, respectively. They were predominantly antimicrobial proteins, proteinases and proteinase inhibitors. The expression of antimicrobial protein genes, ALFPm3, crustinPm1, penaeidin3 and penaeidin5 were tested under PmRelish silencing and Gram-negative bacterium Vibrio harveyi infection. Together with the results using YHV infection previously reported, the expression of penaeidin5 and also penaeidin3 but not ALFPm3 and crustinPm1 were under the regulation of PmRelish in the Imd pathway. PMID:26434714

  18. Analysis of HLA and disease susceptibility: Chromosome 6 genes and sex influence long-QT phenotype

    SciTech Connect

    Weitkamp, L.R.; Moss, A.J.; Hall, W.J.; Robinson, J.L.; Guttormsen, S.A.; Lewis, R.A.; MacCluer, J.W.; Schwartz, P.J.; Locati, E.H.; Tzivoni, D.

    1994-12-01

    The long-QT (LQT) syndrome is a genetically complex disorder that is characterized by syncope and fatal ventricular arrhythmias. LQT syndrome, as defined by a prolonged electrocardiographic QT interval, has a higher incidence in females than in males and does not exhibit Mendelian transmission patterns in all families. Among those families that are nearly consistent with Mendelian transmission, linkage between a locus for LQT syndrome and the H-ras-1 locus on the short arm of chromosome 11 has been reported in some families but not in others. Earlier analyses suggesting that LQT syndrome might be caused by a gene in the HLA region of chromosome 6 were not confirmed by standard linkage analyses. Here, we present an analysis of HLA haplotype sharing among affected pedigree members, showing an excess of haplotype sharing in a previously published Japanese pedigree and possibly also in 15 families of European descent. The haplotypes shared by affected individuals derive from both affected and unaffected parents. In an analysis of independent (unrelated) HLA haplotypes, we also found a nonrandom distribution of HLA-DR genes in LQT syndrome patients compared with controls, suggesting an association between the LQT phenotype and specific HLA-DR genes. Our data indicate that DR2 has a protective effect and, particularly in males, that DR7 may increase susceptibility to the LQT syndrome. Thus, LQT syndrome may be influenced by genes on chromosomes 11 and 6, possibly with a sex-specific effect. These results provide a model for an effect of HLA-region genes inherited from either parent on the expression of an illness that may be determined principally by alleles at loci not linked to HLA.

  19. A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis

    PubMed Central

    Pimentel, Harold; Parra, Marilyn; Gee, Sherry; Ghanem, Dana; An, Xiuli; Li, Jie; Mohandas, Narla; Pachter, Lior; Conboy, John G.

    2014-01-01

    Alternative pre-messenger RNA splicing remodels the human transcriptome in a spatiotemporal manner during normal development and differentiation. Here we explored the landscape of transcript diversity in the erythroid lineage by RNA-seq analysis of five highly purified populations of morphologically distinct human erythroblasts, representing the last four cell divisions before enucleation. In this unique differentiation system, we found evidence of an extensive and dynamic alternative splicing program encompassing genes with many diverse functions. Alternative splicing was particularly enriched in genes controlling cell cycle, organelle organization, chromatin function and RNA processing. Many alternative exons exhibited differentiation-associated switches in splicing efficiency, mostly in late-stage polychromatophilic and orthochromatophilic erythroblasts, in concert with extensive cellular remodeling that precedes enucleation. A subset of alternative splicing switches introduces premature translation termination codons into selected transcripts in a differentiation stage-specific manner, supporting the hypothesis that alternative splicing-coupled nonsense-mediated decay contributes to regulation of erythroid-expressed genes as a novel part of the overall differentiation program. We conclude that a highly dynamic alternative splicing program in terminally differentiating erythroblasts plays a major role in regulating gene expression to ensure synthesis of appropriate proteome at each stage as the cells remodel in preparation for production of mature red cells. PMID:24442673

  20. A dynamic alternative splicing program regulates gene expression during terminal erythropoiesis.

    PubMed

    Pimentel, Harold; Parra, Marilyn; Gee, Sherry; Ghanem, Dana; An, Xiuli; Li, Jie; Mohandas, Narla; Pachter, Lior; Conboy, John G

    2014-04-01

    Alternative pre-messenger RNA splicing remodels the human transcriptome in a spatiotemporal manner during normal development and differentiation. Here we explored the landscape of transcript diversity in the erythroid lineage by RNA-seq analysis of five highly purified populations of morphologically distinct human erythroblasts, representing the last four cell divisions before enucleation. In this unique differentiation system, we found evidence of an extensive and dynamic alternative splicing program encompassing genes with many diverse functions. Alternative splicing was particularly enriched in genes controlling cell cycle, organelle organization, chromatin function and RNA processing. Many alternative exons exhibited differentiation-associated switches in splicing efficiency, mostly in late-stage polychromatophilic and orthochromatophilic erythroblasts, in concert with extensive cellular remodeling that precedes enucleation. A subset of alternative splicing switches introduces premature translation termination codons into selected transcripts in a differentiation stage-specific manner, supporting the hypothesis that alternative splicing-coupled nonsense-mediated decay contributes to regulation of erythroid-expressed genes as a novel part of the overall differentiation program. We conclude that a highly dynamic alternative splicing program in terminally differentiating erythroblasts plays a major role in regulating gene expression to ensure synthesis of appropriate proteome at each stage as the cells remodel in preparation for production of mature red cells. PMID:24442673

  1. Assessing the Positive Influence of Music Activities in Community Development Programs

    ERIC Educational Resources Information Center

    Dillon, Steve

    2006-01-01

    This article describes a framework for assessing the positive influence of music activities in community development programs. It examines hybrid music, health and rich media approaches to creative case study with the purpose of developing more compelling evidence based advocacy that examines the claims of a causal link. This preliminary study…

  2. The Influence of Leadership Practices on Faculty Job Satisfaction in Baccalaureate Degree Nursing Program

    ERIC Educational Resources Information Center

    Afam, Clifford C.

    2012-01-01

    Using a correlational, cross-sectional study design with self-administered questionnaires, this study explored the extent to which leadership practices of deans and department heads influence faculty job satisfaction in baccalaureate degree nursing programs. Using a simple random sampling technique, the study survey was sent to 400 faculty…

  3. The Transactional Influence of Parents and Children in a Parent-Administered School Readiness Program

    ERIC Educational Resources Information Center

    Mathis, Erin T.; Bierman, Karen L.

    2014-01-01

    This study examines changes in parent support and child emergent literacy skills over time as children moved from Head Start into kindergarten. It compares the transactional parent-child influences in families randomly assigned in Head Start to receive an enriched home visiting program that emphasized parents as teachers relative to a control…

  4. Limitations on Change: Current Conditions Influencing Academic Intransigence in Educational Administration Programs.

    ERIC Educational Resources Information Center

    Logan, Connie Stokes; Pounder, Diana G.

    An analysis of academic intransigence (resistance to change) in educational administrative preparation programs is presented in this paper. Drawing upon two conceptual frameworks, the stakeholder perspective and Porter's (1980) five-force model of industry structure and competitive influence, two factors contributing to academic intransigence are…

  5. Influence of Multiculturalism on the Study Programs in Malaysian Public Universities: International Students' Perceptions

    ERIC Educational Resources Information Center

    Pandian, Ambigapathy; Baboo, Shanthi Balraj; Mahfoodh, Omer Hassan Ali

    2016-01-01

    In response to the emphasis on the benefits of enhanced multicultural educational experiences of international students in higher education, this study examined international students' perceptions of the influence of multiculturalism on the study programs in Malaysian public universities. Both quantitative and qualitative data were collected. The…

  6. Network Influences on Dissemination of Evidence-Based Guidelines in State Tobacco Control Programs

    ERIC Educational Resources Information Center

    Luke, Douglas A.; Wald, Lana M.; Carothers, Bobbi J.; Bach, Laura E.; Harris, Jenine K.

    2013-01-01

    Little is known regarding the social network relationships that influence dissemination of evidence-based public health practices and policies. In public health, it is critical that evidence-based guidelines, such as the Centers for Disease Control and Prevention's "Best Practices for Comprehensive Tobacco Control Programs," are…

  7. The Influence of Precollege Access Programs on Postsecondary Enrollment and Persistence

    ERIC Educational Resources Information Center

    Glennie, Elizabeth J.; Dalton, Ben W.; Knapp, Laura G.

    2015-01-01

    Using a nationally representative longitudinal data-set, we examine the influence of precollege access programs on high school achievement, college preparation, postsecondary enrollment, and postsecondary persistence. Results do not show much difference in the level of academic preparation between participants and non-participants. However,…

  8. Government Influence and Community Involvement on Abstinence-Only Programs in 1999 and 2003

    ERIC Educational Resources Information Center

    Gusrang, Jamie L.; Cheng, Simon

    2010-01-01

    In this study, we compare federal government influence on abstinence-only programs in 1999 and 2003 to better see how shifts in the federal government's sex education polices impacted other government and community actors. Using data from the Sex Education in America Surveys (SEAS), we find that changes in federal policy, particularly after the…

  9. Examining the Influence of Campus Leadership Programs at a Catholic University

    ERIC Educational Resources Information Center

    Whitney, Rich; Meents-DeCaigny, Ellen

    2014-01-01

    This study uses the socially responsible leadership and leadership efficacy scales in the Multi-Institutional Study of Leadership (MSL) to examine leadership programs at one Catholic campus, and their influence on socially responsible leadership and leadership efficacy. Examining students that identified as involved in 14 campus leadership…

  10. FACTORS INFLUENCING PERCEPTIONS OF THE IDEAL ADULT VOCATIONAL PROGRAM FOR PUBLIC SECONDARY SCHOOLS.

    ERIC Educational Resources Information Center

    FRANK, HARRY ELMER, JR.

    TO ASCERTAIN THE INFLUENCE OF SELECTED SITUATIONAL AND PERSONAL FACTORS ON THE PERCEPTION OF THE IDEAL ADULT VOCATIONAL PROGRAM FOR PUBLIC SECONDARY SCHOOLS, OPINIONNAIRES RETURNED BY 388 VOCATIONAL TEACHERS AND ADMINISTRATORS IN OKLAHOMA PUBLIC SECONDARY SCHOOLS WERE STUDIED. OPINIONNAIRES CONTAINED 38 STATEMENTS OF CONDITIONS IDENTIFIED AS…

  11. Activating Interpersonal Influence in Health Promotion: A Field Test of Iowa's Program Against Smoking.

    ERIC Educational Resources Information Center

    Burke, Julie A.; And Others

    This study examined a smoking intervention program, which employed group competitions with rewards, to determine its effects on adolescents' smoking-relevant beliefs, their subjective norms, and peer influence. Initially, 1,187 seventh graders in Burlington, Clinton, and Muscatine, Iowa were surveyed in 1984. Data were gathered from a re-survey…

  12. The Influence of Selected Academic, Demographic, and Instructional Program Related Factors on Elementary Student Retention Rates

    ERIC Educational Resources Information Center

    Scott, Marshall, III

    2011-01-01

    The purpose of this study was to examine the influence of selected academic, demographic, and instructional program related factors on the retention rates of elementary school students. More specifically, this study was concerned with the relationship and predictability of the reading and mathematics variables scores, gender, ethnicity, program…

  13. Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects.

    PubMed

    Granata, Simona; Dalla Gassa, Alessandra; Carraro, Amedeo; Brunelli, Matteo; Stallone, Giovanni; Lupo, Antonio; Zaza, Gianluigi

    2016-01-01

    Sirolimus (SRL) and everolimus (EVR) are mammalian targets of rapamycin inhibitors (mTOR-I) largely employed in renal transplantation and oncology as immunosuppressive/antiproliferative agents. SRL was the first mTOR-I produced by the bacterium Streptomyces hygroscopicus and approved for several medical purposes. EVR, derived from SRL, contains a 2-hydroxy-ethyl chain in the 40th position that makes the drug more hydrophilic than SRL and increases oral bioavailability. Their main mechanism of action is the inhibition of the mTOR complex 1 and the regulation of factors involved in a several crucial cellular functions including: protein synthesis, regulation of angiogenesis, lipid biosynthesis, mitochondrial biogenesis and function, cell cycle, and autophagy. Most of the proteins/enzymes belonging to the aforementioned biological processes are encoded by numerous and tightly regulated genes. However, at the moment, the polygenic influence on SRL/EVR cellular effects is still not completely defined, and its comprehension represents a key challenge for researchers. Therefore, to obtain a complete picture of the cellular network connected to SRL/EVR, we decided to review major evidences available in the literature regarding the genetic influence on mTOR-I biology/pharmacology and to build, for the first time, a useful and specific "SRL/EVR genes-focused pathway", possibly employable as a starting point for future in-depth research projects. PMID:27187382

  14. Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects

    PubMed Central

    Granata, Simona; Dalla Gassa, Alessandra; Carraro, Amedeo; Brunelli, Matteo; Stallone, Giovanni; Lupo, Antonio; Zaza, Gianluigi

    2016-01-01

    Sirolimus (SRL) and everolimus (EVR) are mammalian targets of rapamycin inhibitors (mTOR-I) largely employed in renal transplantation and oncology as immunosuppressive/antiproliferative agents. SRL was the first mTOR-I produced by the bacterium Streptomyces hygroscopicus and approved for several medical purposes. EVR, derived from SRL, contains a 2-hydroxy-ethyl chain in the 40th position that makes the drug more hydrophilic than SRL and increases oral bioavailability. Their main mechanism of action is the inhibition of the mTOR complex 1 and the regulation of factors involved in a several crucial cellular functions including: protein synthesis, regulation of angiogenesis, lipid biosynthesis, mitochondrial biogenesis and function, cell cycle, and autophagy. Most of the proteins/enzymes belonging to the aforementioned biological processes are encoded by numerous and tightly regulated genes. However, at the moment, the polygenic influence on SRL/EVR cellular effects is still not completely defined, and its comprehension represents a key challenge for researchers. Therefore, to obtain a complete picture of the cellular network connected to SRL/EVR, we decided to review major evidences available in the literature regarding the genetic influence on mTOR-I biology/pharmacology and to build, for the first time, a useful and specific “SRL/EVR genes-focused pathway”, possibly employable as a starting point for future in-depth research projects. PMID:27187382

  15. Influence of involvement in the girls on track program on early adolescent girls' self-perceptions.

    PubMed

    Waldron, Jennifer J

    2007-12-01

    The Model of Competence Motivation (Harteg 1978) higlights how self-perceptions are influenced by individual and socialization fac tors. Using this model the present study investigated, quantitatively with a pretest and posttest design (N=34) and qualitatively via individual interviews (N=8), how involvement in the Girls on Track pogram (GOT) influenced the perceived competence and self-worth of sixth-grade girls. GOT is a program that uses training for a 5-km race as a means to teach life skills. The self-perceptions of the particapants showed increasing trends from pre- to posttest. Interviewed girls discussed their acquisition of interpersonal skills and ofpositive feelings about themselves. The discussion emphasizes how program involvement can influence the development of self-perceptions in early adolescent girls. PMID:18274223

  16. Quadruplex-single nucleotide polymorphisms (Quad-SNP) influence gene expression difference among individuals

    PubMed Central

    Baral, Aradhita; Kumar, Pankaj; Halder, Rashi; Mani, Prithvi; Yadav, Vinod Kumar; Singh, Ankita; Das, Swapan K.; Chowdhury, Shantanu

    2012-01-01

    Non-canonical guanine quadruplex structures are not only predominant but also conserved among bacterial and mammalian promoters. Moreover recent findings directly implicate quadruplex structures in transcription. These argue for an intrinsic role of the structural motif and thereby posit that single nucleotide polymorphisms (SNP) that compromise the quadruplex architecture could influence function. To test this, we analysed SNPs within quadruplex motifs (Quad-SNP) and gene expression in 270 individuals across four populations (HapMap) representing more than 14 500 genotypes. Findings reveal significant association between quadruplex-SNPs and expression of the corresponding gene in individuals (P < 0.0001). Furthermore, analysis of Quad-SNPs obtained from population-scale sequencing of 1000 human genomes showed relative selection bias against alteration of the structural motif. To directly test the quadruplex-SNP-transcription connection, we constructed a reporter system using the RPS3 promoter—remarkable difference in promoter activity in the ‘quadruplex-destabilized’ versus ‘quadruplex-intact’ promoter was noticed. As a further test, we incorporated a quadruplex motif or its disrupted counterpart within a synthetic promoter reporter construct. The quadruplex motif, and not the disrupted-motif, enhanced transcription in human cell lines of different origin. Together, these findings build direct support for quadruplex-mediated transcription and suggest quadruplex-SNPs may play significant role in mechanistically understanding variations in gene expression among individuals. PMID:22238381

  17. Genetic variation in the serotonin transporter gene influences ERP old/new effects during recognition memory.

    PubMed

    Ross, Robert S; Medrano, Paolo; Boyle, Kaitlin; Smolen, Andrew; Curran, Tim; Nyhus, Erika

    2015-11-01

    Recognition memory is defined as the ability to recognize a previously encountered stimulus and has been associated with spatially and temporally distinct event-related potentials (ERPs). Allelic variations of the serotonin transporter gene (SLC6A4) have recently been shown to impact memory performance. Common variants of the serotonin transporter-linked polymorphic region (5HTTLPR) of the SLC6A4 gene result in long (l) and short (s) allelic variants with carriers of the s allele having lowered transcriptional efficiency. Thus, the current study examines the effects polymorphisms of the SLC6A4 gene have on performance and ERP amplitudes commonly associated with recognition memory. Electroencephalogram (EEG), genetic, and behavioral data were collected from sixty participants as they performed an item and source memory recognition task. In both tasks, participants studied and encoded 200 words, which were then mixed with 200 new words during retrieval. Participants were monitored with EEG during the retrieval portion of each memory task. EEG electrodes were grouped into four ROIs, left anterior superior, right anterior superior, left posterior superior, and right posterior superior. ERP mean amplitudes during hits in the item and source memory task were compared to correctly recognizing new items (correct rejections). Results show that s-carriers have decreased mean hit amplitudes in both the right anterior superior ROI 1000-1500ms post stimulus during the source memory task and the left anterior superior ROI 300-500ms post stimulus during the item memory task. These results suggest that individual differences due to genetic variation of the serotonin transporter gene influences recognition memory. PMID:26423665

  18. Identification of Gender-Specific Candidate Genes That Influence Bone Microarchitecture in Chromosome 1

    PubMed Central

    Mohan, Subburaman; Hu, Yan; Edderkaoui, Bouchra

    2016-01-01

    The studies on the identification of the genetic basis for sexual dimorphism in peak bone mass are obviously important toward providing novel therapeutic approaches to prevent or treat metabolic bone diseases. Our goal in this study is to identify the bone microstructure that could lead to differences in volumetric (v) bone mineral density (BMD) and identify new candidate genes that regulate the gender effect on bone. Therefore, we used a congenic line of mice that carry the BMD1-4 locus from CAST/EiJ (CAST) mice in a C57BL/6J (B6) background and show greater vBMD in female but not male congenics compared to age and gender matched B6 mice. To assess the vBMD variations between the two lines of mice, we performed micro-CT measurements and found no difference in cortical bone volume by tissue volume (BV/TV) between congenics and B6 mice. However, trabecular BV/TV was significantly greater in female but not male congenics compared to corresponding B6 mice which was due to increased trabecular thickness but not reduced trabecular separation suggesting that a bone formation but not a bone resorption is responsible for the trabecular bone phenotype observed in the female but not male congenics. To identify the gender candidate genes, we have determined the polymorphisms between B6 and CAST within the BMD1-4 locus and performed gene expression profiling. We have identified ef-hand calcium binding domain (Efcab2), consortin, connexin sorting protein (Cnst) and presenilin 2 (Psen2) as potential candidate genes that regulate bone mass by influencing trabecular thickness in a gender specific manner. PMID:23263656

  19. Influence of kynurenine 3-monooxygenase (KMO) gene polymorphism on cognitive function in schizophrenia✰,✰✰

    PubMed Central

    Wonodi, Ikwunga; McMahon, Robert P.; Krishna, Nithin; Mitchell, Braxton D.; Liu, Judy; Glassman, Matthew; Hong, L. Elliot; Gold, James M.

    2015-01-01

    Background Cognitive deficits compromise quality of life and productivity for individuals with schizophrenia and have no effective treatments. Preclinical data point to the kynurenine pathway of tryptophan metabolism as a potential target for pro-cognitive drug development. We have previously demonstrated association of a kynurenine 3-monooxygenase (KMO) gene variant with reduced KMO gene expression in postmortem schizophrenia cortex, and neurocognitive endophenotypic deficits in a clinical sample. KMO encodes kynurenine 3-monooxygenase (KMO), the rate-limiting microglial enzyme of cortical kynurenine metabolism. Aberration of the KMO gene might be the proximal cause of impaired cortical kynurenine metabolism observed in schizophrenia. However, the relationship between KMO variation and cognitive function in schizophrenia is unknown. This study examined the effects of the KMO rs2275163C>T C (risk) allele on cognitive function in schizophrenia. Methods We examined the association of KMO polymorphisms with general neuropsychological performance and P50 gating in a sample of 150 schizophrenia and 95 healthy controls. Results Consistent with our original report, the KMO rs2275163C>T C (risk) allele was associated with deficits in general neuropsychological performance, and this effect was more marked in schizophrenia compared with controls. Additionally, the C (Arg452) allele of the missense rs1053230C>T variant (KMO Arg452Cys) showed a trend effect on cognitive function. Neither variant affected P50 gating. Conclusions These data suggest that KMO variation influences a range of cognitive domains known to predict functional outcome. Extensive molecular characterization of this gene would elucidate its role in cognitive function with implications for vertical integration with basic discovery. PMID:25464917

  20. The influence of horizontal gene transfer on the mean fitness of unicellular populations in static environments.

    PubMed

    Raz, Yoav; Tannenbaum, Emmanuel

    2010-05-01

    Horizontal gene transfer (HGT) is believed to be a major source of genetic variation, particularly for prokaryotes. It is believed that horizontal gene transfer plays a major role in shaping bacterial genomes and is also believed to be responsible for the relatively rapid dissemination and acquisition of new, adaptive traits across bacterial strains. Despite the importance of horizontal gene transfer as a major source of genetic variation, the bulk of research on theoretical evolutionary dynamics and population genetics has focused on point mutations (sometimes coupled with gene duplication events) as the main engine of genomic change. Here, we seek to specifically model HGT processes in bacterial cells, by developing a mathematical model describing the influence that conjugation-mediated HGT has on the mutation-selection balance in an asexually reproducing population of unicellular, prokaryotic organisms. It is assumed that mutation-selection balance is reached in the presence of a fixed background concentration of antibiotic, to which the population must become resistant to survive. We find that HGT has a nontrivial effect on the mean fitness of the population. However, one of the central results that emerge from our analysis is that, at mutation-selection balance, conjugation-mediated HGT has a slightly deleterious effect on the mean fitness of a population. Therefore, we conclude that HGT does not confer a selection advantage in static environments. Rather, its advantage must lie in its ability to promote faster adaptation in dynamic environments, an interpretation that is consistent with the observation that HGT can be promoted by environmental stresses on a population. PMID:20194966

  1. Novel candidate genes influencing natural variation in potato tuber cold sweetening identified by comparative proteomics and association mapping

    PubMed Central

    2013-01-01

    Background Higher plants evolved various strategies to adapt to chilling conditions. Among other transcriptional and metabolic responses to cold temperatures plants accumulate a range of solutes including sugars. The accumulation of the reducing sugars glucose and fructose in mature potato tubers during exposure to cold temperatures is referred to as cold induced sweetening (CIS). The molecular basis of CIS in potato tubers is of interest not only in basic research on plant adaptation to environmental stress but also in applied research, since high amounts of reducing sugars affect negatively the quality of processed food products such as potato chips. CIS-tolerance varies considerably among potato cultivars. Our objective was to identify by an unbiased approach genes and cellular processes influencing natural variation of tuber sugar content before and during cold storage in potato cultivars used in breeding programs. We compared by two-dimensional polyacrylamide gel electrophoresis the tuber proteomes of cultivars highly diverse for CIS. DNA polymorphisms in genomic sequences encoding differentially expressed proteins were tested for association with tuber starch content, starch yield and processing quality. Results Pronounced natural variation of CIS was detected in tubers of a population of 40 tetraploid potato cultivars. Significant differences in protein expression were detected between CIS-tolerant and CIS-sensitive cultivars before the onset as well as during cold storage. Identifiable differential proteins corresponded to protease inhibitors, patatins, heat shock proteins, lipoxygenase, phospholipase A1 and leucine aminopeptidase (Lap). Association mapping based on single nucleotide polymorphisms supported a role of Lap in the natural variation of the quantitative traits tuber starch and sugar content. Conclusions The combination of comparative proteomics and association genetics led to the discovery of novel candidate genes for influencing the natural

  2. Juvenile hormone and colony conditions differentially influence cytochrome P450 gene expression in the termite Reticulitermes flavipes.

    PubMed

    Zhou, X; Song, C; Grzymala, T L; Oi, F M; Scharf, M E

    2006-12-01

    In lower termites, the worker caste is a totipotent immature stage that is capable of differentiating into other adult caste phenotypes. We investigated the diversity of family 4 cytochrome P450 (CYP4) genes in Reticulitermes flavipes workers, with the specific goal of identifying P450s potentially involved in regulating caste differentiation. Seven novel CYP4 genes were identified. Quantitative real-time PCR revealed the tissue distribution of expression for the seven CYP4s, as well as temporal expression changes in workers in association with a release from colony influences and during juvenile hormone (JH)-induced soldier caste differentiation. Several fat-body-related CYP4 genes were differentially expressed after JH treatment. Still other genes changed expression in association with removal from colony influences, suggesting that primer pheromones and/or other colony influences impact their expression. These findings add to a growing database of candidate termite caste-regulatory genes, and provide explicit evidence that colony factors influence termite gene expression. PMID:17201768

  3. Factors that influence exercise activity among women post hip fracture participating in the Exercise Plus Program

    PubMed Central

    Resnick, Barbara; Orwig, Denise; D’Adamo, Christopher; Yu-Yahiro, Janet; Hawkes, William; Shardell, Michelle; Golden, Justine; Zimmerman, Sheryl; Magaziner, Jay

    2007-01-01

    Using a social ecological model, this paper describes selected intra- and interpersonal factors that influence exercise behavior in women post hip fracture who participated in the Exercise Plus Program. Model testing of factors that influence exercise behavior at 2, 6 and 12 months post hip fracture was done. The full model hypothesized that demographic variables; cognitive, affective, physical and functional status; pain; fear of falling; social support for exercise, and exposure to the Exercise Plus Program would influence self-efficacy, outcome expectations, and stage of change both directly and indirectly influencing total time spent exercising. Two hundred and nine female hip fracture patients (age 81.0 ± 6.9), the majority of whom were Caucasian (97%), participated in this study. The three predictive models tested across the 12 month recovery trajectory suggest that somewhat different factors may influence exercise over the recovery period and the models explained 8 to 21% of the variance in time spent exercising. To optimize exercise activity post hip fracture, older adults should be helped to realistically assess their self-efficacy and outcome expectations related to exercise, health care providers and friends/peers should be encouraged to reinforce the positive benefits of exercise post hip fracture, and fear of falling should be addressed throughout the entire hip fracture recovery trajectory. PMID:18044192

  4. Distributed Function Mining for Gene Expression Programming Based on Fast Reduction.

    PubMed

    Deng, Song; Yue, Dong; Yang, Le-chan; Fu, Xiong; Feng, Ya-zhou

    2016-01-01

    For high-dimensional and massive data sets, traditional centralized gene expression programming (GEP) or improved algorithms lead to increased run-time and decreased prediction accuracy. To solve this problem, this paper proposes a new improved algorithm called distributed function mining for gene expression programming based on fast reduction (DFMGEP-FR). In DFMGEP-FR, fast attribution reduction in binary search algorithms (FAR-BSA) is proposed to quickly find the optimal attribution set, and the function consistency replacement algorithm is given to solve integration of the local function model. Thorough comparative experiments for DFMGEP-FR, centralized GEP and the parallel gene expression programming algorithm based on simulated annealing (parallel GEPSA) are included in this paper. For the waveform, mushroom, connect-4 and musk datasets, the comparative results show that the average time-consumption of DFMGEP-FR drops by 89.09%%, 88.85%, 85.79% and 93.06%, respectively, in contrast to centralized GEP and by 12.5%, 8.42%, 9.62% and 13.75%, respectively, compared with parallel GEPSA. Six well-studied UCI test data sets demonstrate the efficiency and capability of our proposed DFMGEP-FR algorithm for distributed function mining. PMID:26751200

  5. A comparative analysis of the perceived influence of advanced placement and honors programs upon science instruction

    NASA Astrophysics Data System (ADS)

    Herr, Norman Edward

    These are two major models for advanced science instruction in American high schools, the traditional honors program and the Advanced Placement (AP) program of the College Entrance Examination Board. Using the self-reports of teachers who were experienced in teaching honors and AP courses to students of similar academic preparation and ability, the author examined the perceived influences of program format upon the use of basic teaching techniques, the laboratory experience, the pace of the course, curricular freedom, and student creativity. One of the most notable aspects of the AP program is the speed at which teachers move through the curriculum. In the rush to prepare students for the exam, most AP teachers adopt a strong lecture format and minimize student-centered activities such as laboratory experimentation, student projects, and student presentations. When laboratory work is not assessed on the national AP examination, such experiences are sacrificed to provide time for lecture. When laboratory experiments are assessed, however, teachers respond by allocating more time for laboratory work, and by upgrading their exercises to make them more quantitative and experimental than those used previously or those used in honors classes. Although AP is associated with a loss in curricular freedom and flexibility, teachers perceive no clear influence of program format upon student creativity.

  6. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1).

    PubMed

    Terranova, Christopher; Narla, Sridhar T; Lee, Yu-Wei; Bard, Jonathan; Parikh, Abhirath; Stachowiak, Ewa K; Tzanakakis, Emmanuel S; Buck, Michael J; Birkaya, Barbara; Stachowiak, Michal K

    2015-01-01

    Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development. PMID:25923916

  7. Genetic Influences on Hand Osteoarthritis in Finnish Women – A Replication Study of Candidate Genes

    PubMed Central

    Hämäläinen, Satu; Solovieva, Svetlana; Vehmas, Tapio; Luoma, Katariina; Leino-Arjas, Päivi; Hirvonen, Ari

    2014-01-01

    Objectives Our aims were to replicate some previously reported associations of single nucleotide polymorphisms (SNPs) in five genes (A2BP1, COG5, GDF5, HFE, ESR1) with hand osteoarthritis (OA), and to examine whether genes (BCAP29, DIO2, DUS4L, DVWA, HLA, PTGS2, PARD3B, TGFB1 and TRIB1) associated with OA at other joint sites were associated with hand OA among Finnish women. Design We examined the bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45 to 63 and classified them according to the presence of OA by using reference images. Data regarding finger joint pain and other risk factors were collected using a questionnaire. We defined two hand OA phenotypes: radiographic OA in at least three joints (ROA) and symptomatic DIP OA. The genotypes were determined by PCR-based methods. In statistical analysis, we used SNPStats software, the chi-square test and logistic regression. Results Of the SNPs, rs716508 in A2BP1 was associated with ROA (OR = 0.7, 95% CI 0.5–0.9) and rs1800470 in TGFB1 with symptomatic DIP OA (1.8, 1.2–2.9). We found an interaction between ESR1 (rs9340799) and occupation: teachers with the minor allele were at an increased risk of symptomatic DIP OA (2.8, 1.3–6.5). We saw no association among the dentists. We also found that the carriage of the COG5 rs3757713 C allele increased the risk of ROA only among women with the BCAP29 rs10953541 CC genotype (2.6; 1.1–6.1). There was also a suggestive interaction between the HFE rs179945 and the ESR1 rs9340799, and the carriage of the minor allele of either of these SNPs was associated with an increased risk of symptomatic DIP OA (2.1, 1.3–2.5). Conclusions Our results support the earlier findings of A2BP1 and TBGF1 being OA susceptibility genes and provide evidence of a possible gene-gene interaction in the genetic influence on hand OA predisposition. PMID:24825461

  8. The bdr gene families of the Lyme disease and relapsing fever spirochetes: potential influence on biology, pathogenesis, and evolution.

    PubMed

    Roberts, D M; Carlyon, J A; Theisen, M; Marconi, R T

    2000-01-01

    Species of the genus Borrelia cause human and animal infections, including Lyme disease, relapsing fever, and epizootic bovine abortion. The borrelial genome is unique among bacterial genomes in that it is composed of a linear chromosome and a series of linear and circular plasmids. The plasmids exhibit significant genetic redundancy and carry 175 paralogous gene families, most of unknown function. Homologous alleles on different plasmids could influence the organization and evolution of the Borrelia genome by serving as foci for interplasmid homologous recombination. The plasmid-carried Borrelia direct repeat (bdr) gene family encodes polymorphic, acidic proteins with putative phosphorylation sites and transmembrane domains. These proteins may play regulatory roles in Borrelia. We describe recent progress in the characterization of the Borrelia bdr genes and discuss the possible influence of this gene family on the biology, pathogenesis, and evolution of the Borrelia genome. PMID:10756144

  9. Evidence for a gene on chromosome 13 influencing postural systolic blood pressure change and body mass index.

    PubMed

    North, Kari E; Rose, Kathryn M; Borecki, Ingrid B; Oberman, Albert; Hunt, Steven C; Miller, Michael B; Blangero, John; Almasy, Laura; Pankow, James S

    2004-04-01

    Previous analysis in the Hypertension Genetic Epidemiology Network (HyperGEN) of the National Heart Lung and Blood Institute (NHLBI) Family Blood Pressure Program, a multicenter study of genetic and environmental factors related to hypertension, indicated regions of linkage for blood pressure traits together with several coincident regions for phenotypically correlated traits, including systolic blood pressure (SBP) response to a postural challenge and body mass index (BMI). Motivated by these findings and by our desire to better understand the physiology of these traits, we conducted bivariate linkage analysis of postural SBP change and BMI. Sibships in HyperGEN were recruited from 5 field centers in Massachusetts, North Carolina, Minnesota, Utah, and Alabama. All available affected siblings, their parents, and selected nonmedicated offspring were recruited. Among 1636 whites and 1747 blacks, we performed a maximum likelihood bivariate genome scan for quantitative trait loci influencing postural SBP change and BMI, similarly adjusted for race, study center, sex, age, and age-by-sex interactions. Genome scans were performed using SOLAR (version 2.0) and race-specific marker allele frequencies derived from founders. The maximum genome-wide logarithm of odds (LOD) score of 3.2 was detected on chromosome 13 at 24 cM. This marker (D13S493) lies within 20 cM of a marker previously linked to BMI in the Family Heart Study and is substantially higher than the univariate linkage for each trait (LOD scores for BMI and postural SBP change were 2.4 and 0.9, respectively). These findings suggest that a gene(s) on chromosome 13q jointly regulates the SBP response to postural change and BMI. PMID:14967843

  10. Operating under the influence: Three year recidivism rates for motivation-enhancing versus standard care programs.

    PubMed

    Beadnell, Blair; Crisafulli, Michele A; Stafford, Pamela A; Rosengren, David B; DiClemente, Carlo C

    2015-07-01

    Operating a motor vehicle under the influence of alcohol (OUI) is an international problem. In the United States, one intervention strategy is to require offenders to attend group-delivered interventions. We compared three year rearrest rates among 12,267 individuals in Maine receiving either a motivation-enhancing (ME) program, Prime For Life(®), or historical standard care (SC) programs. We created two cohorts, one when Maine used SC (9/1/1999-8/31/2000) and one after the ME program was implemented (9/1/2002-8/31/2003). Adjusted for control variables, rearrest rates among people not completing an assigned program did not differ for the ME versus SC cohorts (12.1% and 11.6%, respectively; OR=1.05, ns). In contrast, ME compared to SC program completers had lower rearrest rates (7.4% versus 9.9%, OR=0.73, p<.05). The same pattern occurred for people required to take these programs plus substance use treatment (12.1% versus 14.7%, OR=0.82, p<.01). For those rearrested, time to rearrest did not differ between ME and SC cohorts. Among those required to have substance abuse treatment, ME and SC arrest rates did not differ for younger individuals; otherwise, the ME cohort's lower rearrest rates occurred across gender, age, having a previous OUI, and having completed a previous intervention program. PMID:25879708

  11. Genetic Polymorphisms Influence the Ovarian Response to rFSH Stimulation in Patients Undergoing In Vitro Fertilization Programs with ICSI

    PubMed Central

    Boudjenah, Radia; Molina-Gomes, Denise; Torre, Antoine; Bergere, Marianne; Bailly, Marc; Boitrelle, Florence; Taieb, Stéphane; Wainer, Robert; Benahmed, Mohamed; de Mazancourt, Philippe; Selva, Jacqueline; Vialard, François

    2012-01-01

    Introduction Obtaining an adequate number of high-quality oocytes is a major challenge in controlled ovarian hyperstimulation (COH). To date, a range of hormonal and clinical parameters have been used to optimize COH but none have significant predictive value. This variability could be due to the genetic predispositions of single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the ovarian response to rFSH stimulation for patients undergoing intracytoplasmic sperm injection program (ICSI). Results Univariate analysis revealed that only FSHR, ESR2 and p53 SNPs influenced the number of mature oocytes. The association was statistically significant for FSHR (p=0.0047) and ESR2 (0.0017) in the overall study population and for FSHR (p=0.0009) and p53 (p=0.0048) in subgroup that was more homogeneous in terms of clinical variables. After Bonferroni correction and a multivariate analysis, only the differences for FSHR and ESR2 polymorphisms were still statistically significant. In a multilocus analysis, only the FSHR and AMH SNP combination significantly influenced oocyte numbers in both population (p<0.01). Discussion We confirmed the impact of FSHR and ESR2 polymorphisms on the IVF outcome. Furthermore, we showed for the first time that a p53 polymorphism (which is already known to impact embryo implantation) could influence the ovarian response. However, given that this result lost its statistical significance after multivariate analysis, more data are needed to draw firm conclusions. Only the FSHR and AMH polymorphism combination appears to influence mature oocyte numbers but this finding also needs to be confirmed. Materials and Methods A 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(−397T>C), BMP15(−9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(−725C>G), VEGF(+405G>C), TNFα(−308A>G), AMHR

  12. Influence of interactions between genes and childhood trauma on refractoriness in psychiatric disorders.

    PubMed

    Kim, Ji Sun; Lee, Seung-Hwan

    2016-10-01

    Psychiatric disorders are excellent disease models in which gene-environmental interaction play a significant role in the pathogenesis. Childhood trauma has been known as a significant environmental factor in the progress of, and prognosis for psychiatric illness. Patients with refractory illness usually have more severe symptoms, greater disability, lower quality of life and are at greater risk of suicide than other psychiatric patients. Our literature review uncovered some important clinical factors which modulate response to treatment in psychiatric patients who have experienced childhood trauma. Childhood trauma seems to be a critical determinant of treatment refractoriness in psychotic disorder, bipolar disorder, major depressive disorder, and post-traumatic stress disorder. In patients with psychotic disorders, the relationship between childhood trauma and treatment-refractoriness appears to be mediated by cognitive impairment. In the case of bipolar disorder, the relationship appears to be mediated by greater affective disturbance and earlier onset, while in major depressive disorder the mediating factors are persistent, severe symptoms and frequent recurrence. In suicidal individuals, childhood maltreatment was associated with violent suicidal attempts. In the case of PTSD patients, it appears that childhood trauma makes the brain more vulnerable to subsequent trauma, thus resulting in more severe, refractory symptoms. Given that several studies have suggested that there are distinct subtypes of genetic vulnerability to childhood trauma, it is important to understand how gene-environment interactions influence the course of psychiatric illnesses in order to improve therapeutic strategies. PMID:26827636

  13. Evidence for a gene influencing reading disability on chromosome 6p in two populations

    SciTech Connect

    Smith, S.D.; Brower, A.M.; Kimberling, W.J.

    1994-09-01

    A genetic contribution to specific reading disability has been demonstrated by twin studies, and segregation analysis has supported a dominant gene effect. In an effort to localize genes influencing reading disability, we have ascertained two independent populations of families: kindreds which were selected to have a three generation history of reading diability in an autosomal dominant pattern; and families with dizygotic twins, at least one of which has been diagnosed with reading disability. All available family members were given a battery of tests to measure reading and spelling ability and intelligence, and qualitative and quantitative phenotypes for reading disability were derived. Blood samples were obtained for genotyping on all consenting family members, in concordance with IRB requirements. Linkage analysis was performed by the sib pair method utilizing the S.A.G.E. (1992) package and by a differential regression technique developed by DeFries and Fulker (1985). In both populations and by both linkage techniques, several markers in the HLA region of chromosome 6p showed results suggestive of linkage, with the effect most pronounced in the twin families. Significance levels were enhanced when only the more severely affected subjects were analyzed with the differential regression technique.

  14. Deletion of the PDR16 gene influences the plasma membrane properties of the yeast Kluyveromyces lactis.

    PubMed

    Toth Hervay, Nora; Goffa, Eduard; Svrbicka, Alexandra; Simova, Zuzana; Griac, Peter; Jancikova, Iva; Gaskova, Dana; Morvova, Marcela; Sikurova, Libusa; Gbelska, Yvetta

    2015-04-01

    The plasma membrane is the first line of cell defense against changes in external environment, thus its integrity and functionality are of utmost importance. The plasma membrane properties depend on both its protein and lipid composition. The PDR16 gene is involved in the control of Kluyveromyces lactis susceptibility to drugs and alkali metal cations. It encodes the homologue of the major K. lactis phosphatidylinositol transfer protein Sec14p. Sec14p participates in protein secretion, regulation of lipid synthesis, and turnover in vivo. We report here that the plasma membrane of the Klpdr16Δ mutant is hyperpolarized and its fluidity is lower than that of the parental strain. In addition, protoplasts prepared from the Klpdr16Δ cells display decreased stability when subjected to hypo-osmotic conditions. These changes in membrane properties lead to an accumulation of radiolabeled fluconazole and lithium cations inside mutant cells. Our results point to the fact that the PDR16 gene of K. lactis (KlPDR16) influences the plasma membrane properties in K. lactis that lead to subsequent changes in susceptibility to a broad range of xenobiotics. PMID:25742422

  15. Influence of birth weight and gender on lipid status and adipose tissue gene expression in lambs.

    PubMed

    Wallace, Jacqueline M; Milne, John S; Aitken, Raymond P; Adam, Clare L

    2014-08-01

    Intrauterine growth restriction (IUGR) is a risk factor for obesity, particularly when offspring are born into an unrestricted nutritional environment. In this study, we investigated the impact of IUGR and gender on circulating lipids and on expression of adipogenic, lipogenic and adipokine genes in perirenal adipose tissue. Singleton lambs born to overnourished adolescent dams were normal birth weight (N) or IUGR (32% lower birth weight due to placental insufficiency). IUGR lambs exhibited increased fractional growth rates but remained smaller than N lambs at necropsy (d77). At 48 days, fasting plasma triglycerides, non-esterified fatty acids and glycerol were elevated predominantly in IUGR males. Body fat content was independent of prenatal growth but higher in females than in males. In perirenal fat, relative to male lambs, females had larger adipocytes; higher lipoprotein lipase, fatty acid synthase and leptin and lower IGF1, IGF2, IGF1R, IGF2R and hormone-sensitive lipase mRNA expression levels, and all were independent of prenatal growth category; peroxisome proliferator-activated receptor gamma and glycerol-3-phosphate dehydrogenase (G3PDH) mRNA expression were not affected by IUGR or gender. Adiposity indices were inversely related to G3PDH mRNA expression, and for the population as a whole the expression of IGF system genes in perirenal fat was negatively correlated with plasma leptin, fat mass and adipocyte size, and positively correlated with circulating IGF1 levels. Higher plasma lipid levels in IUGR males may predict later adverse metabolic health and obesity, but in early postnatal life gender has the dominant influence on adipose tissue gene expression, reflecting the already established sexual dimorphism in body composition. PMID:24928206

  16. Temperature influences β-carotene production in recombinant Saccharomyces cerevisiae expressing carotenogenic genes from Phaffia rhodozyma.

    PubMed

    Shi, Feng; Zhan, Wubing; Li, Yongfu; Wang, Xiaoyuan

    2014-01-01

    Red yeast Phaffia rhodozyma is a prominent microorganism able to synthesize carotenoid. Here, three carotenogenic cDNAs of P. rhodozyma CGMCC 2.1557, crtE, crtYB and crtI, were cloned and introduced into Saccharomyces cerevisiae INVSc1. The recombinant Sc-EYBI cells could synthesize 258.8 ± 43.8 μg g(-1) dry cell weight (DCW) of β-carotene when growing at 20 °C, about 59-fold higher than in those growing at 30 °C. Additional expression of the catalytic domain of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from S. cerevisiae (Sc-EYBIH) increased the β-carotene level to 528.8 ± 13.3 μg g(-1) DCW as cells growing at 20 °C, 27-fold higher than cells growing at 30 °C, although cells grew faster at 30 °C than at 20 °C. Consistent with the much higher β-carotene level in cells growing at 20 °C, transcription level of three crt genes and cHMG1 gene in cells growing at 20 °C was a little higher than in those growing at 30 °C. Meanwhile, expression of three carotenogenic genes and accumulation of β-carotene promoted cell growth. These results reveal the influence of temperature on β-carotene biosynthesis and may be helpful for improving β-carotene production in recombinant S. cerevisiae. PMID:23861041

  17. Influence of transcriptional and translational control sequences on the expression of foreign genes in Caulobacter crescentus.

    PubMed Central

    Yap, W H; Thanabalu, T; Porter, A G

    1994-01-01

    The influence of expression control sequences (ECSs; promoters and ribosome-binding sites [RBSs]), transcriptional terminators, and gene orientation on the expression of the Escherichia coli lacZ gene in the gram-negative microorganisms Caulobacter crescentus and E. coli was investigated. A series of broad-host-range expression vectors, based on the RK2 plasmid derivative pRK248, were constructed. The ECSs included the tac promoter, the promoter for the surface layer protein of C. crescentus, and promoters from a number of gram-positive bacteria together with their associated RBSs. In addition, synthetic ECSs were constructed by using different combinations of promoters and RBSs. lacZ expression was found to be dependent on the nature of the promoter and RBS and, to a lesser extent, on the presence of a transcriptional terminator and the orientation of the promoter-lacZ construct in pRK248. The relative efficiencies of the various ECSs in driving lacZ expression differed markedly in C. crescentus and E. coli. In C. crescentus, the ECS ptac1 (tac promoter and consensus RBS for C. crescentus mRNAs) appeared to be the most efficient, producing 12-fold-higher activity than did pSL (promoter for the surface layer protein of C. crescentus and its putative RBS). pSL was not transcribed in E. coli, whereas various promoters from gram-positive microorganisms were transcribed in both C. crescentus and E. coli. A number of ECSs were also used to drive mosquitocidal toxin gene expression in C. crescentus, and a correlation between toxin expression and lacZ expression was observed. PMID:8169208

  18. LncRNA-Dependent Mechanisms of Androgen Receptor-regulated Gene Activation Programs

    PubMed Central

    Jin, Chunyu; Yang, Joy C.; Tanasa, Bogdan; Li, Wenbo; Merkurjev, Daria; Ohgi, Kenneth A.; Meng, Da; Zhang, Jie; Evans, Christopher P.; Rosenfeld, Michael G.

    2014-01-01

    While recent studies indicated roles of long non-coding RNAs (lncRNAs) in physiologic aspects of cell-type determination and tissue homeostasis1 yet their potential involvement in regulated gene transcription programs remain rather poorly understood. Androgen receptor (AR) regulates a large repertoire of genes central to the identity and behavior of prostate cancer cells2, and functions in a ligand-independent fashion in many prostate cancers when they become hormone refractory after initial androgen deprivation therapy3. Here, we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 and PCGEM1, bind successively to the AR and strongly enhance both ligand-dependent and ligand-independent AR-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the C-terminally acetylated AR on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM1, to the DOT1L-mediated methylated AR N-terminus. Unexpectedly, recognition of specific protein marks by PCGEM1-recruited Pygopus2 PHD domain proves to enhance selective looping of AR-bound enhancers to target gene promoters in these cells. In “resistant” prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for, the robust activation of both truncated and full length AR, causing ligand-independent activation of the AR transcriptional program and cell proliferation. Conditionally-expressed short hairpin RNA (shRNA) targeting of these lncRNAs in castration-resistant prostate cancer (CRPC) cell lines strongly suppressed tumor xenograft growth in vivo. Together, these results suggest that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumors. PMID:23945587

  19. Genes influence young children's human figure drawings and their association with intelligence a decade later.

    PubMed

    Arden, Rosalind; Trzaskowski, Maciej; Garfield, Victoria; Plomin, Robert

    2014-10-01

    Drawing is ancient; it is the only childhood cognitive behavior for which there is any direct evidence from the Upper Paleolithic. Do genes influence individual differences in this species-typical behavior, and is drawing related to intelligence (g) in modern children? We report on the first genetically informative study of children's figure drawing. In a study of 7,752 pairs of twins, we found that genetic differences exert a greater influence on children's figure drawing at age 4 than do between-family environmental differences. Figure drawing was as heritable as g at age 4 (heritability of .29 for both). Drawing scores at age 4 correlated significantly with g at age 4 (r = .33, p < .001, n = 14,050) and with g at age 14 (r = .20, p < .001, n = 4,622). The genetic correlation between drawing at age 4 and g at age 14 was .52, 95% confidence interval = [.31, .75]. Individual differences in this widespread behavior have an important genetic component and a significant genetic link with g. PMID:25143430

  20. Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia

    PubMed Central

    Wright, C; Gupta, C N; Chen, J; Patel, V; Calhoun, V D; Ehrlich, S; Wang, L; Bustillo, J R; Perrone-Bizzozero, N I; Turner, J A

    2016-01-01

    Evidence suggests that microRNA-137 (miR-137) is involved in the genetic basis of schizophrenia. Risk variants within the miR-137 host gene (MIR137HG) influence structural and functional brain-imaging measures, and miR-137 itself is predicted to regulate hundreds of genes. We evaluated the influence of a MIR137HG risk variant (rs1625579) in combination with variants in miR-137-regulated genes TCF4, PTGS2, MAPK1 and MAPK3 on gray matter concentration (GMC). These genes were selected based on our previous work assessing schizophrenia risk within possible miR-137-regulated gene sets using the same cohort of subjects. A genetic risk score (GRS) was determined based on genotypes of these four schizophrenia risk-associated genes in 221 Caucasian subjects (89 schizophrenia patients and 132 controls). The effects of the rs1625579 genotype with the GRS of miR-137-regulated genes in a three-way interaction with diagnosis on GMC patterns were assessed using a multivariate analysis. We found that schizophrenia subjects homozygous for the MIR137HG risk allele show significant decreases in occipital, parietal and temporal lobe GMC with increasing miR-137-regulated GRS, whereas those carrying the protective minor allele show significant increases in GMC with GRS. No correlations of GMC and GRS were found in control subjects. Variants within or upstream of genes regulated by miR-137 in combination with the MIR137HG risk variant may influence GMC in schizophrenia-related regions in patients. Given that the genes evaluated here are involved in protein kinase A signaling, dysregulation of this pathway through alterations in miR-137 biogenesis may underlie the gray matter loss seen in the disease. PMID:26836412

  1. Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia

    DOE PAGESBeta

    Wright, C.; Gupta, C. N.; Chen, J.; Patel, V.; Calhoun, V. D.; Ehrlich, S.; Wang, L.; Bustillo, J. R.; Perrone-Bizzozero, N. I.; Turner, J. A.

    2016-02-02

    Evidence suggests that microRNA-137 (miR-137) is involved in the genetic basis of schizophrenia. Risk variants within the miR-137 host gene (MIR137HG) influence structural and functional brain-imaging measures, and miR-137 itself is predicted to regulate hundreds of genes. We evaluated the influence of a MIR137HG risk variant (rs1625579) in combination with variants in miR-137- regulated genes TCF4, PTGS2, MAPK1 and MAPK3 on gray matter concentration (GMC). These genes were selected based on our previous work assessing schizophrenia risk within possible miR-137-regulated gene sets using the same cohort of subjects. A genetic risk score (GRS) was determined based on genotypes of thesemore » four schizophrenia risk-associated genes in 221 Caucasian subjects (89 schizophrenia patients and 132 controls). The effects of the rs1625579 genotype with the GRS of miR-137-regulated genes in a three-way interaction with diagnosis on GMC patterns were assessed using a multivariate analysis. We found that schizophrenia subjects homozygous for the MIR137HG risk allele show significant decreases in occipital, parietal and temporal lobe GMC with increasing miR-137-regulated GRS, whereas those carrying the protective minor allele show significant increases in GMC with GRS. No correlations of GMC and GRS were found in control subjects. Variants within or upstream of genes regulated by miR-137 in combination with the MIR137HG risk variant may influence GMC in schizophrenia-related regions in patients. Furthermore, given that the genes evaluated here are involved in protein kinase A signaling, dysregulation of this pathway through alterations in miR-137 biogenesis may underlie the gray matter loss seen in the disease.« less

  2. A Genome-Scale Investigation of How Sequence, Function, and Tree-Based Gene Properties Influence Phylogenetic Inference

    PubMed Central

    Shen, Xing-Xing; Salichos, Leonidas; Rokas, Antonis

    2016-01-01

    Molecular phylogenetic inference is inherently dependent on choices in both methodology and data. Many insightful studies have shown how choices in methodology, such as the model of sequence evolution or optimality criterion used, can strongly influence inference. In contrast, much less is known about the impact of choices in the properties of the data, typically genes, on phylogenetic inference. We investigated the relationships between 52 gene properties (24 sequence-based, 19 function-based, and 9 tree-based) with each other and with three measures of phylogenetic signal in two assembled data sets of 2,832 yeast and 2,002 mammalian genes. We found that most gene properties, such as evolutionary rate (measured through the percent average of pairwise identity across taxa) and total tree length, were highly correlated with each other. Similarly, several gene properties, such as gene alignment length, Guanine-Cytosine content, and the proportion of tree distance on internal branches divided by relative composition variability (treeness/RCV), were strongly correlated with phylogenetic signal. Analysis of partial correlations between gene properties and phylogenetic signal in which gene evolutionary rate and alignment length were simultaneously controlled, showed similar patterns of correlations, albeit weaker in strength. Examination of the relative importance of each gene property on phylogenetic signal identified gene alignment length, alongside with number of parsimony-informative sites and variable sites, as the most important predictors. Interestingly, the subsets of gene properties that optimally predicted phylogenetic signal differed considerably across our three phylogenetic measures and two data sets; however, gene alignment length and RCV were consistently included as predictors of all three phylogenetic measures in both yeasts and mammals. These results suggest that a handful of sequence-based gene properties are reliable predictors of phylogenetic signal

  3. A Genome-Scale Investigation of How Sequence, Function, and Tree-Based Gene Properties Influence Phylogenetic Inference.

    PubMed

    Shen, Xing-Xing; Salichos, Leonidas; Rokas, Antonis

    2016-01-01

    Molecular phylogenetic inference is inherently dependent on choices in both methodology and data. Many insightful studies have shown how choices in methodology, such as the model of sequence evolution or optimality criterion used, can strongly influence inference. In contrast, much less is known about the impact of choices in the properties of the data, typically genes, on phylogenetic inference. We investigated the relationships between 52 gene properties (24 sequence-based, 19 function-based, and 9 tree-based) with each other and with three measures of phylogenetic signal in two assembled data sets of 2,832 yeast and 2,002 mammalian genes. We found that most gene properties, such as evolutionary rate (measured through the percent average of pairwise identity across taxa) and total tree length, were highly correlated with each other. Similarly, several gene properties, such as gene alignment length, Guanine-Cytosine content, and the proportion of tree distance on internal branches divided by relative composition variability (treeness/RCV), were strongly correlated with phylogenetic signal. Analysis of partial correlations between gene properties and phylogenetic signal in which gene evolutionary rate and alignment length were simultaneously controlled, showed similar patterns of correlations, albeit weaker in strength. Examination of the relative importance of each gene property on phylogenetic signal identified gene alignment length, alongside with number of parsimony-informative sites and variable sites, as the most important predictors. Interestingly, the subsets of gene properties that optimally predicted phylogenetic signal differed considerably across our three phylogenetic measures and two data sets; however, gene alignment length and RCV were consistently included as predictors of all three phylogenetic measures in both yeasts and mammals. These results suggest that a handful of sequence-based gene properties are reliable predictors of phylogenetic signal

  4. Assessment of the influence of field size on maize gene flow using SSR analysis.

    PubMed

    Palaudelmàs, M; Melé, E; Monfort, A; Serra, J; Salvia, J; Messeguer, J

    2012-06-01

    One of the factors that may influence the rate of cross-fertilization is the relative size of the pollen donor and receptor fields. We designed a spatial distribution with four varieties of genetically-modified (GM) yellow maize to generate different sized fields while maintaining a constant distance to neighbouring fields of conventional white kernel maize. Samples of cross-fertilized, yellow kernels in white cobs were collected from all of the adjacent fields at different distances. A special series of samples was collected at distances of 0, 2, 5, 10, 20, 40, 80 and 120 m following a transect traced in the dominant down-wind direction in order to identify the origin of the pollen through SSR analysis. The size of the receptor fields should be taken into account, especially when they extend in the same direction than the GM pollen flow is coming. From collected data, we then validated a function that takes into account the gene flow found in the field border and that is very useful for estimating the % of GM that can be found in any point of the field. It also serves to predict the total GM content of the field due to cross fertilization. Using SSR analysis to identify the origin of pollen showed that while changes in the size of the donor field clearly influence the percentage of GMO detected, this effect is moderate. This study demonstrates that doubling the donor field size resulted in an approximate increase of GM content in the receptor field of 7%. This indicates that variations in the size of the donor field have a smaller influence on GM content than variations in the size of the receptor field. PMID:21898271

  5. DNASynth: A Computer Program for Assembly of Artificial Gene Parts in Decreasing Temperature

    PubMed Central

    Nowak, Robert M.; Wojtowicz-Krawiec, Anna; Plucienniczak, Andrzej

    2015-01-01

    Artificial gene synthesis requires consideration of nucleotide sequence development as well as long DNA molecule assembly protocols. The nucleotide sequence of the molecule must meet many conditions including particular preferences of the host organism for certain codons, avoidance of specific regulatory subsequences, and a lack of secondary structures that inhibit expression. The chemical synthesis of DNA molecule has limitations in terms of strand length; thus, the creation of artificial genes requires the assembly of long DNA molecules from shorter fragments. In the approach presented, the algorithm and the computer program address both tasks: developing the optimal nucleotide sequence to encode a given peptide for a given host organism and determining the long DNA assembly protocol. These tasks are closely connected; a change in codon usage may lead to changes in the optimal assembly protocol, and the lack of a simple assembly protocol may be addressed by changing the nucleotide sequence. The computer program presented in this study was tested with real data from an experiment in a wet biological laboratory to synthesize a peptide. The benefit of the presented algorithm and its application is the shorter time, compared to polymerase cycling assembly, needed to produce a ready synthetic gene. PMID:25629047

  6. Rapid gene expression changes in peripheral blood lymphocytes upon practice of a comprehensive yoga program.

    PubMed

    Qu, Su; Olafsrud, Solveig Mjelstad; Meza-Zepeda, Leonardo A; Saatcioglu, Fahri

    2013-01-01

    One of the most common integrative medicine (IM) modalities is yoga and related practices. Previous work has shown that yoga may improve wellness in healthy people and have benefits for patients. However, the mechanisms of how yoga may positively affect the mind-body system are largely unknown. Here we have assessed possible rapid changes in global gene expression profiles in the peripheral blood mononuclear cells (PBMCs) in healthy people that practiced either a comprehensive yoga program or a control regimen. The experimental sessions included gentle yoga postures, breathing exercises, and meditation (Sudarshan Kriya and Related Practices--SK&P) compared with a control regimen of a nature walk and listening to relaxing music. We show that the SK&P program has a rapid and significantly greater effect on gene expression in PBMCs compared with the control regimen. These data suggest that yoga and related practices result in rapid gene expression alterations which may be the basis for their longer term cell biological and higher level health effects. PMID:23613970

  7. Prediction of cancer class with majority voting genetic programming classifier using gene expression data.

    PubMed

    Paul, Topon Kumar; Iba, Hitoshi

    2009-01-01

    In order to get a better understanding of different types of cancers and to find the possible biomarkers for diseases, recently, many researchers are analyzing the gene expression data using various machine learning techniques. However, due to a very small number of training samples compared to the huge number of genes and class imbalance, most of these methods suffer from overfitting. In this paper, we present a majority voting genetic programming classifier (MVGPC) for the classification of microarray data. Instead of a single rule or a single set of rules, we evolve multiple rules with genetic programming (GP) and then apply those rules to test samples to determine their labels with majority voting technique. By performing experiments on four different public cancer data sets, including multiclass data sets, we have found that the test accuracies of MVGPC are better than those of other methods, including AdaBoost with GP. Moreover, some of the more frequently occurring genes in the classification rules are known to be associated with the types of cancers being studied in this paper. PMID:19407358

  8. Influence of a quality improvement learning collaborative program on team functioning in primary healthcare.

    PubMed

    Kotecha, Jyoti; Brown, Judith Belle; Han, Han; Harris, Stewart B; Green, Michael; Russell, Grant; Roberts, Sharon; Webster-Bogaert, Susan; Fournie, Meghan; Thind, Amardeep; Reichert, Sonja M; Birtwhistle, Richard

    2015-09-01

    Quality improvement (QI) programs are frequently implemented to support primary healthcare (PHC) team development and to improve care outcomes. In Ontario, Canada, the Quality Improvement and Innovation Partnership (QIIP) offered a learning collaborative (LC) program to support the development of interdisciplinary team function and improve chronic disease management, disease prevention, and access to care. A qualitative study using a phenomenological approach was conducted as part of a mixed-method evaluation to explore the influence of the program on team functioning in participating PHC teams. A purposive sampling strategy was used to identify PHC teams (n = 10), from which participants of different professional roles were selected through a purposeful recruitment process to reflect maximum variation of team roles. Additionally, QI coaches working with the interview participants and the LC administrators were also interviewed. Data were collected through semistructured telephone interviews that were audiotaped and transcribed verbatim. Thematic analysis was conducted through an iterative and interpretive approach. The shared experience of participating in the program appeared to improve team functioning. Participants described increased trust and respect for each other's clinical and administrative roles and were inspired by learning about different approaches to interdisciplinary care. This appeared to enhance collegial relationships, collapse professional silos, improve communication, and increase interdisciplinary collaboration. Teamwork involves more than just physically grouping healthcare providers from multiple disciplines and mandating them to work together. The LC program provided opportunities for participants to learn how to work collaboratively, and participation in the LC program appeared to enhance team functioning. PMID:25799255

  9. A polymorphic (GA/CT)n- SSR influences promoter activity of Tryptophan decarboxylase gene in Catharanthus roseus L. Don.

    PubMed

    Kumar, Santosh; Bhatia, Sabhyata

    2016-01-01

    Simple Sequence Repeats (SSRs) of polypurine-polypyrimidine type motifs occur very frequently in the 5' flanks of genes in plants and have recently been implicated to have a role in regulation of gene expression. In this study, 2 accessions of Catharanthus roseus having (CT)8 and (CT)21 varying motifs in the 5'UTR of Tryptophan decarboxylase (Tdc) gene, were investigated for its role in regulation of gene expression. Extensive Tdc gene expression analysis in the 2 accessions was carried out both at the level of transcription and translation. Transcript abundance was estimated using Northern analysis and qRT-PCR, whereas the rate of Tdc gene transcription was assessed using in-situ nuclear run-on transcription assay. Translation status of Tdc gene was monitored by quantification of polysome associated Tdc mRNA using qRT-PCR. These observations were validated through transient expression analysis using the fusion construct [CaM35S:(CT)8-21:GUS]. Our study demonstrated that not only does the length of (CT)n -SSRs influences the promoter activity, but the presence of SSRs per se in the 5'-UTR significantly enhances the level of gene expression. We termed this phenomenon as "microsatellite mediated enhancement" (MME) of gene expression. Results presented here will provide leads for engineering plants with enhanced amounts of medicinally important alkaloids. PMID:27623355

  10. The influence of contract type in program execution/V-22 Osprey: A case study

    NASA Astrophysics Data System (ADS)

    Smith, Danny Roy

    1989-12-01

    The purpose of this study was to look at the impact of a fixed price type contract on program execution of a major weapon system. The full scale development phase of the V-22 Osprey program was used as a case study. The focus of this thesis was to determine the affects of this contract type and identify the actions program management took to address it's influences. The predominant conclusion brought out by this research was that based on the political, historical, and economic circumstances of the period, the fixed price incentive fee contract was the best contractual instrument for the government to use. The major recommendations are: in future contracts, ensure an appropriate spread between ceiling and target price in order to adequately incentivize the contractor; in teaming arrangements, employ incentives to guarantee the appropriate transfer of technical information; and incentivize comprehensive production plans and Production Readiness Reviews.

  11. Automatic design of synthetic gene circuits through mixed integer non-linear programming.

    PubMed

    Huynh, Linh; Kececioglu, John; Köppe, Matthias; Tagkopoulos, Ilias

    2012-01-01

    Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits. PMID:22536398

  12. Factors influencing decisions to enroll in the health informatics educational programs.

    PubMed

    Alshammari, Fares

    2016-01-01

    The aim of this study was to identify the most important factors associated with undergraduate students' decisions to enroll in the health informatics program at Hail University in Saudi Arabia. A cross-sectional survey was conducted among the population of 73 students (second to fourth year; 52 females, 21 males; age range 19-25 years). A hierarchy of perceived sources of influence was identified. Counselors, teachers and other professionals, and promotional materials, including information in the media, as well as the high quality characteristics of the institution, had the strongest influence. Other students, friends and family, the academic reputation of the University and the health informatics department faculty, together with interactions in the academic environment (e.g. segregation by gender) and financial, job, career, and postgraduate opportunities, were perceived to be weaker sources of influence. The strengths of the sources of influence varied significantly with respect to the socio-demographic characteristics of the students, as well as the categories associated with the decision-making process. Strong sources of influence were particularly important for the increasing number of female students who often made the final decision to enroll. These findings will support policy and decision makers to make better plans for health informatics education by understanding the influential sources that attract students into the health informatics profession, and will also assist the health care sector's attempts to avoid a deficiency in this rapidly expanding professional field. PMID:25710093

  13. Innate-like functions of natural killer T cell subsets result from highly divergent gene programs.

    PubMed

    Engel, Isaac; Seumois, Grégory; Chavez, Lukas; Samaniego-Castruita, Daniela; White, Brandie; Chawla, Ashu; Mock, Dennis; Vijayanand, Pandurangan; Kronenberg, Mitchell

    2016-06-01

    Natural killer T cells (NKT cells) have stimulatory or inhibitory effects on the immune response that can be attributed in part to the existence of functional subsets of NKT cells. These subsets have been characterized only on the basis of the differential expression of a few transcription factors and cell-surface molecules. Here we have analyzed purified populations of thymic NKT cell subsets at both the transcriptomic level and epigenomic level and by single-cell RNA sequencing. Our data indicated that despite their similar antigen specificity, the functional NKT cell subsets were highly divergent populations with many gene-expression and epigenetic differences. Therefore, the thymus 'imprints' distinct gene programs on subsets of innate-like NKT cells that probably impart differences in proliferative capacity, homing, and effector functions. PMID:27089380

  14. Combining classifiers generated by multi-gene genetic programming for protein fold recognition using genetic algorithm.

    PubMed

    Bardsiri, Mahshid Khatibi; Eftekhari, Mahdi; Mousavi, Reza

    2015-01-01

    In this study the problem of protein fold recognition, that is a classification task, is solved via a hybrid of evolutionary algorithms namely multi-gene Genetic Programming (GP) and Genetic Algorithm (GA). Our proposed method consists of two main stages and is performed on three datasets taken from the literature. Each dataset contains different feature groups and classes. In the first step, multi-gene GP is used for producing binary classifiers based on various feature groups for each class. Then, different classifiers obtained for each class are combined via weighted voting so that the weights are determined through GA. At the end of the first step, there is a separate binary classifier for each class. In the second stage, the obtained binary classifiers are combined via GA weighting in order to generate the overall classifier. The final obtained classifier is superior to the previous works found in the literature in terms of classification accuracy. PMID:25786796

  15. The hnRNPs F and H2 bind to similar sequences to influence gene expression

    PubMed Central

    Alkan, Serkan A.; Martincic, Kathleen; Milcarek, Christine

    2005-01-01

    The hnRNPs (heterogeneous nuclear ribonucleoproteins) F and H2 share a similar protein structure. Both have been implicated as regulating polyadenylation, but hnRNP H2 had a positive effect, whereas hnRNP F acted negatively. We therefore carried out side-by-side comparisons of their RNA-binding and in vivo actions. The binding of the CstF2 (64 kDa cleavage stimulatory factor) to SV40 (simian virus 40) late pre-mRNA substrates containing a downstream GRS (guanine-rich sequence) was reduced by hnRNP F, but not by hnRNP H2, in a UV-cross-linking assay. Point mutations of the 14-nt GRS influenced the binding of purified hnRNP F or H2 in parallel. Co-operative binding of the individual proteins to RNA was lost with mutations of the GRS in the G1−5 or G12−14 regions; both regions seem to be necessary for optimal interactions. Using a reporter green fluorescent protein assay with the GRS inserted downstream of the poly(A) (polyadenine) signal, expression in vivo was diminished by a mutant G1−5 sequence which decreased binding of both hnRNPs (SAA20) and was enhanced by a 12–14-nt mutant that showed enhanced hnRNP F or H2 binding (SAA10). Using small interfering RNA, down-regulation of hnRNP H2 levels diminished reporter expression, confirming that hnRNP H2 confers a positive influence; in contrast, decreasing hnRNP F levels had a negligible influence on reporter expression with the intact GRS. A pronounced diminution in reporter expression was seen with the SAA20 mutant for both. Thus the relative levels of hnRNP F and H2 in cells, as well as the target sequences in the downstream GRS on pre-mRNA, influence gene expression. PMID:16171461

  16. Using Single-nucleotide Polymorphisms and Genetic Mapping to find Candidate Genes that Influence Varroa-Specific Hygiene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Varroa-sensitive hygienic (VSH) behavior is one of two behaviors identified that are most important for controlling the growth of Varroa mite populations in bee hives. A study was conducted to map quantitative trait loci (QTL) that influence VSH so that resistance genes could be identified. Crosses ...

  17. Maternal pre-gravid body mass index and adiposity influence umbilical cord gene expression at term in AGA infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While maternal obesity is associated with unfavorable maternal and fetal outcomes, the influence of maternal obesity on fetal gene expression is less clear. Umbilical cords (UC) from 12 lean (pre-gravid BMI < 25) and 10 overweight/obese (OB, pre-gravid BMI =25) women without gestational diabetes wer...

  18. Major histocompatibility complex and host background genes in chickens influence resistance to high pathogenicity avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chicken’s major histocompatibility complex (MHC) haplotype has a profound influence on the resistance or susceptibility to certain pathogens such as B21 MHC haplotype confers resistance to Marek’s disease (MD). However, non-MHC genes are also important in disease resistance. For example, both li...

  19. Prostaglandins A1 and E1 influence gene expression in an established insect cell line (BCIRL-HzAM1)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In work to determine the biochemical mechanisms of prostaglandin (PG) action in insect cells, we posed the hypothesis that prostaglandins (PGs) influence gene expression. In separate experiments, we exposed the BCIRL-HzAM1 cell line (derived from pupal ovarian tissue of the cotton bollworm, Helicov...

  20. γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.

    PubMed

    Kim, Sung-Eun; Hinoue, Toshinori; Kim, Michael S; Sohn, Kyoung-Jin; Cho, Robert C; Cole, Peter D; Weisenberger, Daniel J; Laird, Peter W; Kim, Young-In

    2015-01-01

    γ-Glutamyl hydrolase (GGH) plays an important role in folate homeostasis by catalyzing hydrolysis of polyglutamylated folate into monoglutamates. Polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence, GGH modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression, in the maintenance of DNA integrity and stability, and in chromatin modifications, and aberrant or dysregulation of DNA methylation has been mechanistically linked to the development of human diseases including cancer. Using a recently developed in vitro model of GGH modulation in HCT116 colon and MDA-MB-435 breast cancer cells, we investigated whether GGH modulation would affect global and gene-specific DNA methylation and whether these alterations were associated with significant gene expression changes. In both cell lines, GGH overexpression decreased global DNA methylation and DNA methyltransferase (DNMT) activity, while GGH inhibition increased global DNA methylation and DNMT activity. Epigenomic and gene expression analyses revealed that GGH modulation influenced CpG promoter DNA methylation and gene expression involved in important biological pathways including cell cycle, cellular development, and cellular growth and proliferation. Some of the observed altered gene expression appeared to be regulated by changes in CpG promoter DNA methylation. Our data suggest that the GGH modulation-induced changes in total intracellular folate concentrations and content of long-chain folylpolyglutamates are associated with functionally significant DNA methylation alterations in several important biological pathways. PMID:25502219

  1. Dietary intake alters gene expression in colon tissue: possible underlying mechanism for the influence of diet on disease

    PubMed Central

    Pellatt, Andrew J.; Mullany, Lila E.; Wolff, Roger K.; Pellatt, Daniel F.

    2016-01-01

    Background Although the association between diet and disease is well documented, the biologic mechanisms involved have not been entirely elucidated. In this study, we evaluate how dietary intake influences gene expression to better understand the underlying mechanisms through which diet operates. Methods We used data from 144 individuals who had comprehensive dietary intake and gene expression data from RNAseq using normal colonic mucosa. Using the DESeq2 statistical package, we identified genes that showed statistically significant differences in expression between individuals in high-intake and low-intake categories for several dietary variables of interest adjusting for age and sex. We examined total calories, total fats, vegetable protein, animal protein, carbohydrates, trans-fatty acids, mutagen index, red meat, processed meat, whole grains, vegetables, fruits, fiber, folate, dairy products, calcium, and prudent and western dietary patterns. Results Using a false discovery rate of less than 0.1, meat-related foods were statistically associated with 68 dysregulated genes, calcium with three dysregulated genes, folate with four dysregulated genes, and nonmeat-related foods with 65 dysregulated genes. With a more stringent false discovery rate of less than 0.05, there were nine meat-related dysregulated genes and 23 nonmeat-related genes. Ingenuity pathway analysis identified three major networks among genes identified as dysregulated with respect to meat-related dietary variables and three networks among genes identified as dysregulated with respect to nonmeat-related variables. The top networks (Ingenuity Pathway Analysis network score >30) associated with meat-related genes were (i) cancer, organismal injury, and abnormalities, tumor morphology, and (ii) cellular function and maintenance, cellular movement, cell death, and survival. Among genes related to nonmeat consumption variables, the top networks were (i) hematological system development and function

  2. Influence of earthworm activity on gene transfer from Pseudomonas fluorescens to indigenous soil bacteria.

    PubMed

    Daane, L L; Molina, J A; Berry, E C; Sadowsky, M J

    1996-02-01

    We have developed a model system to assess the influence of earthworm activity on the transfer of plasmid pJP4 from an inoculated donor bacterium, Pseudomonas fluorescens C5t (pJP4), to indigenous soil microorganisms. Three different earthworm species (Lumbricus terrestris, Lumbricus rubellus, and Aporrectodea trapezoides), each with unique burrowing, casting, and feeding behaviors, were evaluated. Soil columns were inoculated on the surface with 10(8) cells per g of soil of the donor bacterium, and after a 2-week incubation period, donor, transconjugant, and total bacteria were enumerated at 5-cm-depth intervals. Transconjugants were confirmed by use of colony hybridization with a mer gene probe. In situ gene transfer of plasmid pJP4 from P. fluorescens C5t to indigenous soil bacteria was detected in all inoculated microcosms. In the absence of earthworms, the depth of recovery was limited to the top 5 cm of the column, with approximately 10(3) transconjugants per g of soil. However, the total number of transconjugants recovered from soil was significantly greater in microcosms containing either L. rubellus or A. trapezoides, with levels reaching about 10(5) CFU/g of soil. In addition, earthworms distributed donor and transconjugant bacteria throughout the microcosm columns, with the depth of recovery dependent on the burrowing behavior of each earthworm species. Donor and transconjugant bacteria were also recovered from earthworm casts and inside developing cocoons. Transconjugant bacteria from the indigenous soil microflora were classified as belonging to Acidovorax spp., Acinetobacter spp., Agrobacterium spp., Pasteurella spp., Pseudomonas spp., and Xanthomonas spp. PMID:8593052

  3. The Aeromonas caviae AHA0618 gene modulates cell length and influences swimming and swarming motility

    PubMed Central

    Lowry, Rebecca C; Parker, Jennifer L; Kumbhar, Ramhari; Mesnage, Stephane; Shaw, Jonathan G; Stafford, Graham P

    2015-01-01

    Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. The polar flagellum also has a role in cellular adherence and biofilm formation. The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6–8 serine and threonine residues within the central region of these proteins. This modification is essential for the formation of the flagellum. Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering

  4. Influence of earthworm activity on gene transfer from Pseudomonas fluorescens to indigenous soil bacteria.

    PubMed Central

    Daane, L L; Molina, J A; Berry, E C; Sadowsky, M J

    1996-01-01

    We have developed a model system to assess the influence of earthworm activity on the transfer of plasmid pJP4 from an inoculated donor bacterium, Pseudomonas fluorescens C5t (pJP4), to indigenous soil microorganisms. Three different earthworm species (Lumbricus terrestris, Lumbricus rubellus, and Aporrectodea trapezoides), each with unique burrowing, casting, and feeding behaviors, were evaluated. Soil columns were inoculated on the surface with 10(8) cells per g of soil of the donor bacterium, and after a 2-week incubation period, donor, transconjugant, and total bacteria were enumerated at 5-cm-depth intervals. Transconjugants were confirmed by use of colony hybridization with a mer gene probe. In situ gene transfer of plasmid pJP4 from P. fluorescens C5t to indigenous soil bacteria was detected in all inoculated microcosms. In the absence of earthworms, the depth of recovery was limited to the top 5 cm of the column, with approximately 10(3) transconjugants per g of soil. However, the total number of transconjugants recovered from soil was significantly greater in microcosms containing either L. rubellus or A. trapezoides, with levels reaching about 10(5) CFU/g of soil. In addition, earthworms distributed donor and transconjugant bacteria throughout the microcosm columns, with the depth of recovery dependent on the burrowing behavior of each earthworm species. Donor and transconjugant bacteria were also recovered from earthworm casts and inside developing cocoons. Transconjugant bacteria from the indigenous soil microflora were classified as belonging to Acidovorax spp., Acinetobacter spp., Agrobacterium spp., Pasteurella spp., Pseudomonas spp., and Xanthomonas spp. PMID:8593052

  5. Genetic Variation in Autophagy-Related Genes Influences the Risk and Phenotype of Buruli Ulcer

    PubMed Central

    Capela, Carlos; Dossou, Ange Dodji; Silva-Gomes, Rita; Sopoh, Ghislain Emmanuel; Makoutode, Michel; Menino, João Filipe; Fraga, Alexandra Gabriel; Cunha, Cristina; Carvalho, Agostinho; Rodrigues, Fernando; Pedrosa, Jorge

    2016-01-01

    Introduction Buruli ulcer (BU) is a severe necrotizing human skin disease caused by Mycobacterium ulcerans. Clinically, presentation is a sum of these diverse pathogenic hits subjected to critical immune-regulatory mechanisms. Among them, autophagy has been demonstrated as a cellular process of critical importance. Since microtubules and dynein are affected by mycolactone, the critical pathogenic exotoxin produced by M. ulcerans, cytoskeleton-related changes might potentially impair the autophagic process and impact the risk and progression of infection. Objective Genetic variants in the autophagy-related genes NOD2, PARK2 and ATG16L1 has been associated with susceptibility to mycobacterial diseases. Here, we investigated their association with BU risk, its severe phenotypes and its progression to an ulcerative form. Methods Genetic variants were genotyped using KASPar chemistry in 208 BU patients (70.2% with an ulcerative form and 28% in severe WHO category 3 phenotype) and 300 healthy endemic controls. Results The rs1333955 SNP in PARK2 was significantly associated with increased susceptibility to BU [odds ratio (OR), 1.43; P = 0.05]. In addition, both the rs9302752 and rs2066842 SNPs in NOD2 gee significantly increased the predisposition of patients to develop category 3 (OR, 2.23; P = 0.02; and OR 12.7; P = 0.03, respectively, whereas the rs2241880 SNP in ATG16L1 was found to significantly protect patients from presenting the ulcer phenotype (OR, 0.35; P = 0.02). Conclusion Our findings indicate that specific genetic variants in autophagy-related genes influence susceptibility to the development of BU and its progression to severe phenotypes. PMID:27128681

  6. Aerosol delivery of programmed cell death protein 4 using polysorbitol-based gene delivery system for lung cancer therapy.

    PubMed

    Kim, You-Kyoung; Xing, Lei; Chen, Bao-An; Xu, Fengguo; Jiang, Hu-Lin; Zhang, Can

    2014-11-01

    The development of a safe and effective gene delivery system is the most challenging obstacle to the broad application of gene therapy in the clinic. In this study, we report the development of a polysorbitol-based gene delivery system as an alternative gene carrier for lung cancer therapy. The copolymer was prepared by a Michael addition reaction between sorbitol diacrylate (SD) and spermine (SPE); the SD-SPE copolymer effectively condenses with DNA on the nanoscale and protects it from nucleases. SD-SPE/DNA complexes showed excellent transfection with low toxicity both in vitro and in vivo, and aerosol delivery of SD-SPE complexes with programmed cell death protein 4 DNA significantly suppressed lung tumorigenesis in K-ras(LA1) lung cancer model mice. These results demonstrate that SD-SPE has great potential as a gene delivery system based on its excellent biocompatibility and high gene delivery efficiency for lung cancer gene therapy. PMID:24983766

  7. Human clusterin gene expression is confined to surviving cells during in vitro programmed cell death.

    PubMed Central

    French, L E; Wohlwend, A; Sappino, A P; Tschopp, J; Schifferli, J A

    1994-01-01

    Clusterin is a serum glycoprotein endowed with cell aggregating, complement inhibitory, and lipid binding properties, and is also considered as a specific marker of dying cells, its expression being increased in various tissues undergoing programmed cell death (PCD). However, no study has so far directly shown that cells expressing clusterin in these tissues are actually apoptotic as defined by morphological and biochemical criteria. We have studied cellular clusterin gene expression in vitro using three different models of PCD: (a) ultraviolet B (UV-B) irradiation of human U937, HeLa, and A431 cell lines, (b) in vitro aging of human peripheral blood neutrophils (PMNs), and (c) dexamethasone-induced cell death of the human lymphoblastoid cell line CEM-C7. In all three models, the classical morphological and biochemical features of PCD observed did not correlate with an increase, but with either a marked decrease or an absence of clusterin gene expression as assessed by Northern blot analysis. In situ hybridization of U937 and A431 cells after UV-B irradiation revealed, in addition, that only morphologically normal cells that are surviving continue to express the clusterin gene. Our results demonstrate that in the human myeloid, lymphoid, and epithelial cell types studied, clusterin gene expression is not a prerequisite to their death by apoptosis. In addition, and most interestingly, in situ hybridization of U937 and A431 cells revealed that only surviving cells express the clusterin gene after the induction of PCD, thus providing novel evidence suggesting that clusterin may be associated with cell survival within tissues regressing as a consequence of PCD. Images PMID:8113419

  8. Gene expression programs of mouse endothelial cells in kidney development and disease.

    PubMed

    Brunskill, Eric W; Potter, S Steven

    2010-01-01

    Endothelial cells are remarkably heterogeneous in both morphology and function, and they play critical roles in the formation of multiple organ systems. In addition endothelial cell dysfunction can contribute to disease processes, including diabetic nephropathy, which is a leading cause of end stage renal disease. In this report we define the comprehensive gene expression programs of multiple types of kidney endothelial cells, and analyze the differences that distinguish them. Endothelial cells were purified from Tie2-GFP mice by cell dissociation and fluorescent activated cell sorting. Microarrays were then used to provide a global, quantitative and sensitive measure of gene expression levels. We examined renal endothelial cells from the embryo and from the adult glomerulus, cortex and medulla compartments, as well as the glomerular endothelial cells of the db/db mutant mouse, which represents a model for human diabetic nephropathy. The results identified the growth factors, receptors and transcription factors expressed by these multiple endothelial cell types. Biological processes and molecular pathways were characterized in exquisite detail. Cell type specific gene expression patterns were defined, finding novel molecular markers and providing a better understanding of compartmental distinctions. Further, analysis of enriched, evolutionarily conserved transcription factor binding sites in the promoters of co-activated genes begins to define the genetic regulatory network of renal endothelial cell formation. Finally, the gene expression differences associated with diabetic nephropathy were defined, providing a global view of both the pathogenic and protective pathways activated. These studies provide a rich resource to facilitate further investigations of endothelial cell functions in kidney development, adult compartments, and disease. PMID:20706631

  9. Gene Expression Programs of Mouse Endothelial Cells in Kidney Development and Disease

    PubMed Central

    Brunskill, Eric W.; Potter, S. Steven

    2010-01-01

    Endothelial cells are remarkably heterogeneous in both morphology and function, and they play critical roles in the formation of multiple organ systems. In addition endothelial cell dysfunction can contribute to disease processes, including diabetic nephropathy, which is a leading cause of end stage renal disease. In this report we define the comprehensive gene expression programs of multiple types of kidney endothelial cells, and analyze the differences that distinguish them. Endothelial cells were purified from Tie2-GFP mice by cell dissociation and fluorescent activated cell sorting. Microarrays were then used to provide a global, quantitative and sensitive measure of gene expression levels. We examined renal endothelial cells from the embryo and from the adult glomerulus, cortex and medulla compartments, as well as the glomerular endothelial cells of the db/db mutant mouse, which represents a model for human diabetic nephropathy. The results identified the growth factors, receptors and transcription factors expressed by these multiple endothelial cell types. Biological processes and molecular pathways were characterized in exquisite detail. Cell type specific gene expression patterns were defined, finding novel molecular markers and providing a better understanding of compartmental distinctions. Further, analysis of enriched, evolutionarily conserved transcription factor binding sites in the promoters of co-activated genes begins to define the genetic regulatory network of renal endothelial cell formation. Finally, the gene expression differences associated with diabetic nephropathy were defined, providing a global view of both the pathogenic and protective pathways activated. These studies provide a rich resource to facilitate further investigations of endothelial cell functions in kidney development, adult compartments, and disease. PMID:20706631

  10. A Comprehensive Examination of the Influence of State Tobacco Control Programs and Policies on Youth Smoking

    PubMed Central

    Loomis, Brett R.; Han, Beth; Gfroerer, Joe; Kuiper, Nicole; Couzens, G. Lance; Dube, Shanta; Caraballo, Ralph S.

    2013-01-01

    Objectives. We examined the influence of tobacco control policies (tobacco control program expenditures, smoke-free air laws, youth access law compliance, and cigarette prices) on youth smoking outcomes (smoking susceptibility, past-year initiation, current smoking, and established smoking). Methods. We combined data from the 2002 to 2008 National Surveys on Drug Use and Health with state and municipality population data from the US Census Bureau to assess the associations between state tobacco control policy variables and youth smoking outcomes, focusing on youths aged 12 to 17 years. We also examined the influence of policy variables on youth access when these variables were held at 2002 levels. Results. Per capita funding for state tobacco control programs was negatively associated with all 4 smoking outcomes. Smoke-free air laws were negatively associated with all outcomes except past-year initiation, and cigarette prices were associated only with current smoking. We found no association between these outcomes and retailer compliance with youth access laws. Conclusions. Smoke-free air laws and state tobacco control programs are effective strategies for curbing youth smoking. PMID:23327252

  11. HIV-1 gp140 epitope recognition is influenced by immunoglobulin DH gene segment sequence.

    PubMed

    Wang, Yuge; Kapoor, Pratibha; Parks, Robert; Silva-Sanchez, Aaron; Alam, S Munir; Verkoczy, Laurent; Liao, Hua-Xin; Zhuang, Yingxin; Burrows, Peter; Levinson, Michael; Elgavish, Ada; Cui, Xiangqin; Haynes, Barton F; Schroeder, Harry

    2016-02-01

    Complementarity Determining Region 3 of the immunoglobulin (Ig) H chain (CDR-H3) lies at the center of the antigen-binding site where it often plays a decisive role in antigen recognition and binding. Amino acids encoded by the diversity (DH) gene segment are the main component of CDR-H3. Each DH has the potential to rearrange into one of six DH reading frames (RFs), each of which exhibits a characteristic amino acid hydrophobicity signature that has been conserved among jawed vertebrates by natural selection. A preference for use of RF1 promotes the incorporation of tyrosine into CDR-H3 while suppressing the inclusion of hydrophobic or charged amino acids. To test the hypothesis that these evolutionary constraints on DH sequence influence epitope recognition, we used mice with a single DH that has been altered to preferentially use RF2 or inverted RF1. B cells in these mice produce a CDR-H3 repertoire that is enriched for valine or arginine in place of tyrosine. We serially immunized this panel of mice with gp140 from HIV-1 JR-FL isolate and then used enzyme-linked immunosorbent assay (ELISA) or peptide microarray to assess antibody binding to key or overlapping HIV-1 envelope epitopes. By ELISA, serum reactivity to key epitopes varied by DH sequence. By microarray, sera with Ig CDR-H3s enriched for arginine bound to linear peptides with a greater range of hydrophobicity but had a lower intensity of binding than sera containing Ig CDR-H3s enriched for tyrosine or valine. We conclude that patterns of epitope recognition and binding can be heavily influenced by DH germ line sequence. This may help explain why antibodies in HIV-infected patients must undergo extensive somatic mutation in order to bind to specific viral epitopes and achieve neutralization. PMID:26687685

  12. The influence of maternal health literacy and child's age on participation in social welfare programs.

    PubMed

    Pati, Susmita; Siewert, Elizabeth; Wong, Angie T; Bhatt, Suraj K; Calixte, Rose E; Cnaan, Avital

    2014-07-01

    The objective of this study is to determine the influence of maternal health literacy and child's age on participation in social welfare programs benefiting children. In a longitudinal prospective cohort study of 560 Medicaid-eligible mother-infant dyads recruited in Philadelphia, maternal health literacy was assessed using the test of functional health literacy in adults (short version). Participation in social welfare programs [Temporary Assistance to Needy Families (TANF), Supplemental Nutrition Assistance Program (SNAP), Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), child care subsidy, and public housing] was self-reported at child's birth, and at the 6, 12, 18, 24 month follow-up interviews. Generalized estimating equations quantified the strength of maternal health literacy as an estimator of program participation. The mothers were primarily African-Americans (83%), single (87%), with multiple children (62%). Nearly 24% of the mothers had inadequate or marginal health literacy. Children whose mothers had inadequate health literacy were less likely to receive child care subsidy (adjusted OR = 0.54, 95% CI 0.34-0.85) than children whose mothers had adequate health literacy. Health literacy was not a significant predictor for TANF, SNAP, WIC or housing assistance. The predicted probability for participation in all programs decreased from birth to 24 months. Most notably, predicted WIC participation declined rapidly after age one. During the first 24 months, mothers with inadequate health literacy could benefit from simplified or facilitated child care subsidy application processes. Targeted outreach and enrollment efforts conducted by social welfare programs need to take into account the changing needs of families as children age. PMID:23990157

  13. FrameD: a flexible program for quality check and gene prediction in prokaryotic genomes and noisy matured eukaryotic sequences

    PubMed Central

    Schiex, Thomas; Gouzy, Jérôme; Moisan, Annick; de Oliveira, Yannick

    2003-01-01

    We describe FrameD, a program that predicts coding regions in prokaryotic and matured eukaryotic sequences. Initially targeted at gene prediction in bacterial GC rich genomes, the gene model used in FrameD also allows to predict genes in the presence of frameshifts and partially undetermined sequences which makes it also very suitable for gene prediction and frameshift correction in unfinished sequences such as EST and EST cluster sequences. Like recent eukaryotic gene prediction programs, FrameD also includes the ability to take into account protein similarity information both in its prediction and its graphical output. Its performances are evaluated on different bacterial genomes. The web site (http://genopole.toulouse.inra.fr/bioinfo/FrameD/FD) allows direct prediction, sequence correction and translation and the ability to learn new models for new organisms. PMID:12824407

  14. FrameD: A flexible program for quality check and gene prediction in prokaryotic genomes and noisy matured eukaryotic sequences.

    PubMed

    Schiex, Thomas; Gouzy, Jérôme; Moisan, Annick; de Oliveira, Yannick

    2003-07-01

    We describe FrameD, a program that predicts coding regions in prokaryotic and matured eukaryotic sequences. Initially targeted at gene prediction in bacterial GC rich genomes, the gene model used in FrameD also allows to predict genes in the presence of frameshifts and partially undetermined sequences which makes it also very suitable for gene prediction and frameshift correction in unfinished sequences such as EST and EST cluster sequences. Like recent eukaryotic gene prediction programs, FrameD also includes the ability to take into account protein similarity information both in its prediction and its graphical output. Its performances are evaluated on different bacterial genomes. The web site (http://genopole.toulouse.inra.fr/bioinfo/FrameD/FD) allows direct prediction, sequence correction and translation and the ability to learn new models for new organisms. PMID:12824407

  15. Influence of Intron II microsatellite polymorphism in human toll-like receptor 2 gene in leprosy.

    PubMed

    Suryadevara, Naveen Chandra; Neela, Venkata Sanjeev Kumar; Devalraju, Kamakshi Prudhula; Jain, Suman; SivaSai, Krovvidi S R; Valluri, Vijaya Lakshmi; Jonnalagada, Subbanna; Anandaraj, M P J S

    2013-08-01

    Leprosy is a chronic granulomatous infection caused by the obligate intracellular organism Mycobacterium leprae. TLR2 plays a key role when activated by M. leprae lipoproteins initiating protective responses which induce bacterial killing and therefore control of disease spread. Microsatellite polymorphisms in intron2 of TLR2 gene have been reported to be associated with development of clinical features of several infectious diseases. The study aims to evaluate the influence of GT microsatellite on the expression of TLR2 which could make humans prone to M. leprae infections. A total of 279 individuals were enrolled in the study, 88 were leprosy patients, 95 were house hold contacts (HHC) and 96 were healthy controls (HC). Genotyping was done using PCR-Sequencing method. TLR2 mRNA expression was analyzed by RT-PCR. IL-10 and IFN-γ levels were measured using ELISA in MLSA stimulated cell culture supernatants. Statistical analysis was performed using Chi-Square (χ(2)) test and t-tests. Allele/genotype of TLR2 microsatellite which includes longer GT repeats was associated with low TLR2 mRNA expression and high IL-10 production while that including shorter GT repeats was associated with high TLR2 mRNA expression and low IL-10 production. High IL10 producing allele of TLR2 microsatellite might predispose house hold contacts to leprosy. PMID:23619473

  16. A test of the influence of continental axes of orientation on patterns of human gene flow

    PubMed Central

    Ramachandran, Sohini; Rosenberg, Noah A.

    2012-01-01

    The geographic distribution of genetic variation reflects trends in past population migrations, and can be used to make inferences about these migrations. It has been proposed that the east-west orientation of the Eurasian landmass facilitated the rapid spread of ancient technological innovations across Eurasia, while the north-south orientation of the Americas led to a slower diffusion of technology there. If the diffusion of technology was accompanied by gene flow, then this hypothesis predicts that genetic differentiation in the Americas along lines of longitude will be greater than that in Eurasia along lines of latitude. We use 678 microsatellite loci from 68 indigenous populations in Eurasia and the Americas to investigate the spatial axes that underlie population-genetic variation. We find that genetic differentiation increases more rapidly along lines of longitude in the Americas than along lines of latitude in Eurasia. Distance along lines of latitude explains a sizeable portion of genetic distance in Eurasia, whereas distance along lines of longitude does not explain a large proportion of Eurasian genetic variation. Genetic differentiation in the Americas occurs along both latitudinal and longitudinal axes and has a greater magnitude than corresponding differentiation in Eurasia, even when adjusting for the lower level of genetic variation in the American populations. These results support the view that continental orientation has influenced migration patterns and has played an important role in determining both the structure of human genetic variation and the distribution and spread of cultural traits. (240 words) PMID:21913175

  17. Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program.

    PubMed

    Shao, Mengle; Ishibashi, Jeff; Kusminski, Christine M; Wang, Qiong A; Hepler, Chelsea; Vishvanath, Lavanya; MacPherson, Karen A; Spurgin, Stephen B; Sun, Kai; Holland, William L; Seale, Patrick; Gupta, Rana K

    2016-06-14

    The transcriptional regulators Ebf2 and Prdm16 establish and maintain the brown and/or beige fat cell identity. However, the mechanisms operating in white adipocytes to suppress the thermogenic gene program and maintain an energy-storing phenotype are less understood. Here, we report that the transcriptional regulator Zfp423 is critical for maintaining white adipocyte identity through suppression of the thermogenic gene program. Zfp423 expression is enriched in white versus brown adipocytes and suppressed upon cold exposure. Doxycycline-inducible inactivation of Zfp423 in mature adipocytes, combined with β-adrenergic stimulation, triggers a conversion of differentiated adiponectin-expressing inguinal and gonadal adipocytes into beige-like adipocytes; this reprogramming event is sufficient to prevent and reverse diet-induced obesity and insulin resistance. Mechanistically, Zfp423 acts in adipocytes to inhibit the activity of Ebf2 and suppress Prdm16 activation. These data identify Zfp423 as a molecular brake on adipocyte thermogenesis and suggest a therapeutic strategy to unlock the thermogenic potential of white adipocytes in obesity. PMID:27238639

  18. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development

    PubMed Central

    Camp, J. Gray; Badsha, Farhath; Florio, Marta; Kanton, Sabina; Gerber, Tobias; Wilsch-Bräuninger, Michaela; Lewitus, Eric; Sykes, Alex; Hevers, Wulf; Lancaster, Madeline; Knoblich, Juergen A.; Lachmann, Robert; Pääbo, Svante; Huttner, Wieland B.; Treutlein, Barbara

    2015-01-01

    Cerebral organoids—3D cultures of human cerebral tissue derived from pluripotent stem cells—have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. PMID:26644564

  19. Induction of a program gene expression during osteoblast differentiation with strontium ranelate

    SciTech Connect

    Zhu Lingling; Zaidi, Samir; Peng Yuanzhen; Zhou Hang; Moonga, Baljit S.; Blesius, Alexia; Dupin-Roger, Isabelle; Zaidi, Mone . E-mail: mone.zaidi@mssm.edu; Sun Li

    2007-04-06

    Strontium ranelate, a new agent for the treatment of osteoporosis, has been shown stimulate bone formation in various experimental models. This study examines the effect of strontium ranelate on gene expression in osteoblasts, as well as the formation of mineralized (von Kossa-positive) colony-forming unit-osteoblasts (CFU-obs). Bone marrow-derived stromal cells cultured for 21 days under differentiating conditions, when exposed to strontium ranelate, displayed a significant time- and concentration-dependent increase in the expression of the master gene, Runx2, as well as bone sialoprotein (BSP), but interestingly without effects on osteocalcin. This was associated with a significant increase in the formation of CFU-obs at day 21 of culture. In U-33 pre-osteoblastic cells, strontium ranelate significantly enhanced the expression of Runx2 and osteocalcin, but not BSP. Late, more mature osteoblastic OB-6 cells showed significant elevations in BSP and osteocalcin, but with only minimal effects on Runx2. In conclusion, strontium ranelate stimulates osteoblast differentiation, but the induction of the program of gene expression appears to be cell type-specific. The increased osteoblastic differentiation is the likely basis underlying the therapeutic bone-forming actions of strontium ranelate.

  20. Evaluating the effectiveness of an intervention program to influence attitudes of students towards peers with disabilities.

    PubMed

    de Boer, Anke; Pijl, Sip Jan; Minnaert, Alexander; Post, Wendy

    2014-03-01

    In this study we examine the effectiveness of an intervention program to influence attitudes of elementary school students towards peers with intellectual, physical and severe physical and intellectual disabilities. A quasi-experimental longitudinal study was designed with an experimental group and a control group, both comprising two rural schools. An intervention program was developed for kindergarten (n(experimental) = 22, n(control) = 31) and elementary school students without disabilities (n(experimental) = 91, n(control) = 127) (age range 4-12 years old). This intervention consisted of a 3 weeks education project comprising six lessons about disabilities. The Acceptance Scale for Kindergarten-revised and the Attitude Survey to Inclusive Education were used to measure attitudes at three moments: prior to the start of the intervention, after the intervention and 1 year later. The outcomes of the multilevel analysis showed positive, immediate effects on attitudes of kindergarten students, but limited effects on elementary school students' attitudes. PMID:23982486

  1. Contamination with bacterial zoonotic pathogen genes in U.S. streams influenced by varying types of animal agriculture.

    PubMed

    Haack, Sheridan K; Duris, Joseph W; Kolpin, Dana W; Focazio, Michael J; Meyer, Michael T; Johnson, Heather E; Oster, Ryan J; Foreman, William T

    2016-09-01

    Animal waste, stream water, and streambed sediment from 19 small (<32km(2)) watersheds in 12U.S. states having either no major animal agriculture (control, n=4), or predominantly beef (n=4), dairy (n=3), swine (n=5), or poultry (n=3) were tested for: 1) cholesterol, coprostanol, estrone, and fecal indicator bacteria (FIB) concentrations, and 2) shiga-toxin producing and enterotoxigenic Escherichia coli, Salmonella, Campylobacter, and pathogenic and vancomycin-resistant enterococci by polymerase chain reaction (PCR) on enrichments, and/or direct quantitative PCR. Pathogen genes were most frequently detected in dairy wastes, followed by beef, swine and poultry wastes in that order; there was only one detection of an animal-source-specific pathogen gene (stx1) in any water or sediment sample in any control watershed. Post-rainfall pathogen gene numbers in stream water were significantly correlated with FIB, cholesterol and coprostanol concentrations, and were most highly correlated in dairy watershed samples collected from 3 different states. Although collected across multiple states and ecoregions, animal-waste gene profiles were distinctive via discriminant analysis. Stream water gene profiles could also be discriminated by the watershed animal type. Although pathogen genes were not abundant in stream water or streambed samples, PCR on enrichments indicated that many genes were from viable organisms, including several (shiga-toxin producing or enterotoxigenic E. coli, Salmonella, vancomycin-resistant enterococci) that could potentially affect either human or animal health. Pathogen gene numbers and types in stream water samples were influenced most by animal type, by local factors such as whether animals had stream access, and by the amount of local rainfall, and not by studied watershed soil or physical characteristics. Our results indicated that stream water in small agricultural U.S. watersheds was susceptible to pathogen gene inputs under typical agricultural

  2. Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q.

    PubMed

    North, Kari E; Miller, Michael B; Coon, Hilary; Martin, Lisa J; Peacock, James M; Arnett, Donna; Zhang, Binbin; Province, Michael; Oberman, Albert; Blangero, John; Almasy, Laura; Ellison, R Curtis; Heiss, Gerardo

    2005-03-01

    High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are strong predictors of cardiovascular disease risk. Motivated by previous evidence for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage analysis of LDL cholesterol and TG concentration among participants of the Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive siblings and their first-degree relatives were recruited. Both phenotypes were similarly adjusted for ethnicity, study center, sex, age, age-by-sex interactions, smoking, alcohol consumption, hormone use, diabetes medication use, and waist circumference. Variance component linkage analysis was performed as implemented in SOLAR, using ethnicity-specific marker allele frequencies derived from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide empirical LOD score of 3.9 was detected on chromosome 21 at 54cM, between markers D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three other studies and is suggestive of one or more genes on chromosome 21q jointly regulating LDL cholesterol and TG concentration. PMID:15721017

  3. LIN28A Modulates Splicing and Gene Expression Programs in Breast Cancer Cells.

    PubMed

    Yang, Jun; Bennett, Brian D; Luo, Shujun; Inoue, Kaoru; Grimm, Sara A; Schroth, Gary P; Bushel, Pierre R; Kinyamu, H Karimi; Archer, Trevor K

    2015-09-01

    LIN28 is an evolutionarily conserved RNA-binding protein with critical functions in developmental timing and cancer. However, the molecular mechanisms underlying LIN28's oncogenic properties are yet to be described. RNA-protein immunoprecipitation coupled with genome-wide sequencing (RIP-Seq) analysis revealed significant LIN28 binding within 843 mRNAs in breast cancer cells. Many of the LIN28-bound mRNAs are implicated in the regulation of RNA and cell metabolism. We identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a protein with multiple roles in mRNA metabolism, as a LIN28-interacting partner. Subsequently, we used a custom computational method to identify differentially spliced gene isoforms in LIN28 and hnRNP A1 small interfering RNA (siRNA)-treated cells. The results reveal that these proteins regulate alternative splicing and steady-state mRNA expression of genes implicated in aspects of breast cancer biology. Notably, cells lacking LIN28 undergo significant isoform switching of the ENAH gene, resulting in a decrease in the expression of the ENAH exon 11a isoform. The expression of ENAH isoform 11a has been shown to be elevated in breast cancers that express HER2. Intriguingly, analysis of publicly available array data from the Cancer Genome Atlas (TCGA) reveals that LIN28 expression in the HER2 subtype is significantly different from that in other breast cancer subtypes. Collectively, our data suggest that LIN28 may regulate splicing and gene expression programs that drive breast cancer subtype phenotypes. PMID:26149387

  4. LIN28A Modulates Splicing and Gene Expression Programs in Breast Cancer Cells

    PubMed Central

    Yang, Jun; Bennett, Brian D.; Luo, Shujun; Inoue, Kaoru; Grimm, Sara A.; Schroth, Gary P.; Bushel, Pierre R.

    2015-01-01

    LIN28 is an evolutionarily conserved RNA-binding protein with critical functions in developmental timing and cancer. However, the molecular mechanisms underlying LIN28's oncogenic properties are yet to be described. RNA-protein immunoprecipitation coupled with genome-wide sequencing (RIP-Seq) analysis revealed significant LIN28 binding within 843 mRNAs in breast cancer cells. Many of the LIN28-bound mRNAs are implicated in the regulation of RNA and cell metabolism. We identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a protein with multiple roles in mRNA metabolism, as a LIN28-interacting partner. Subsequently, we used a custom computational method to identify differentially spliced gene isoforms in LIN28 and hnRNP A1 small interfering RNA (siRNA)-treated cells. The results reveal that these proteins regulate alternative splicing and steady-state mRNA expression of genes implicated in aspects of breast cancer biology. Notably, cells lacking LIN28 undergo significant isoform switching of the ENAH gene, resulting in a decrease in the expression of the ENAH exon 11a isoform. The expression of ENAH isoform 11a has been shown to be elevated in breast cancers that express HER2. Intriguingly, analysis of publicly available array data from the Cancer Genome Atlas (TCGA) reveals that LIN28 expression in the HER2 subtype is significantly different from that in other breast cancer subtypes. Collectively, our data suggest that LIN28 may regulate splicing and gene expression programs that drive breast cancer subtype phenotypes. PMID:26149387

  5. The Influence of Major Life Events on Economic Attitudes in a World of Gene-Environment Interplay.

    PubMed

    Hatemi, Peter K

    2013-10-01

    The role of "genes" on political attitudes has gained attention across disciplines. However, person-specific experiences have yet to be incorporated into models that consider genetic influences. Relying on a gene-environment interplay approach, this study explicates how life-events, such as losing one's job or suffering a financial loss, influence economic policy attitudes. The results indicate genetic and environmental variance on support for unions, immigration, capitalism, socialism and property tax is moderated by financial risks. Changes in the magnitude of genetic influences, however, are temporary. After two years, the phenotypic effects of the life events remain on most attitudes, but changes in the sources of individual differences do not. Univariate twin models that estimate the independent contributions of genes and environment on the variation of attitudes appear to provide robust baseline indicators of sources of individual differences. These estimates, however, are not event or day specific. In this way, genetic influences add stability, while environment cues change, and this process is continually updated. PMID:24860199

  6. An orchestrated gene expression component of neuronal programmed cell death revealed by cDNA array analysis

    PubMed Central

    Chiang, Lillian W.; Grenier, Jill M.; Ettwiller, Laurence; Jenkins, Lorayne P.; Ficenec, Dave; Martin, John; Jin, Fenyu; DiStefano, Peter S.; Wood, Andrew

    2001-01-01

    Programmed cell death (PCD) during neuronal development and disease has been shown to require de novo RNA synthesis. However, the time course and regulation of target genes is poorly understood. By using a brain-biased array of over 7,500 cDNAs, we profiled this gene expression component of PCD in cerebellar granule neurons challenged separately by potassium withdrawal, combined potassium and serum withdrawal, and kainic acid administration. We found that hundreds of genes were significantly regulated in discreet waves including known genes whose protein products are involved in PCD. A restricted set of genes was regulated by all models, providing evidence that signals inducing PCD can regulate large assemblages of genes (of which a restricted subset may be shared in multiple pathways). PMID:11226323

  7. Myosin Light Chain Kinase (MLCK) Gene Influences Exercise Induced Muscle Damage during a Competitive Marathon.

    PubMed

    Del Coso, Juan; Valero, Marjorie; Lara, Beatriz; Salinero, Juan José; Gallo-Salazar, César; Areces, Francisco

    2016-01-01

    Myosin light chain kinase (MLCK) phosphorylates the regulatory light chain (RLC) of myosin producing increases in force development during skeletal muscle contraction. It has been suggested that MLCK gene polymorphisms might alter RLC phosphorylation thereby decreasing the ability to produce force and to resist strain during voluntary muscle contractions. Thus, the genetic variations in the MLCK gene might predispose some individuals to higher values of muscle damage during exercise, especially during endurance competitions. The aim of this investigation was to determine the influence of MLCK genetic variants on exercise-induced muscle damage produced during a marathon. Sixty-seven experienced runners competed in a marathon race. The MLCK genotype (C37885A) of these marathoners was determined. Before and after the race, a sample of venous blood was obtained to assess changes in serum myoglobin concentrations and leg muscle power changes were measured during a countermovement jump. Self-reported leg muscle pain and fatigue were determined by questionnaires. A total of 59 marathoners (88.1%) were CC homozygotes and 8 marathoners (11.9%) were CA heterozygotes. The two groups of participants completed the race with a similar time (228 ± 33 vs 234 ± 39 min; P = 0.30) and similar self-reported values for fatigue (15 ± 2 vs 16 ± 2 A.U.; P = 0.21) and lower-limb muscle pain (6.2 ± 1.7 vs 6.6 ± 1.8 cm; P = 0.29). However, CC marathoners presented higher serum myoglobin concentrations (739 ± 792 vs 348 ± 144 μg·mL-1; P = 0.03) and greater pre-to-post- race leg muscle power reduction (-32.7 ± 15.7 vs -21.2 ± 21.6%; P = 0.05) than CA marathoners. CA heterozygotes for MLCK C37885A might present higher exercise-induced muscle damage after a marathon competition than CC counterparts. PMID:27483374

  8. The influence of dopaminergic gene variants on decision making in the ultimatum game

    PubMed Central

    Reuter, Martin; Felten, Andrea; Penz, Sabrina; Mainzer, Anna; Markett, Sebastian; Montag, Christian

    2013-01-01

    One of the most prominent paradigms in neuroeconomics is the ultimatum game (UG) that provides a framework for the study of pro-social behavior in two players interacting anonymously with each other: Player 1 has to split an endowment with player 2. Player 2 can either accept or reject the offer from player 1. If player 2 accepts the offer then the money is split as proposed by player 1. In case of rejection both players get nothing. Until now only one twin study investigated the heritability of the behavior in the UG. Results indicated a strong heritability for the decision behavior of player 2 whereas no genetic influence on player 1 behavior could be detected. Further studies are mandatory to validate these heritability estimates. However, a first candidate polymorphism, the DRD4 exon III, constituting the biological basis of the heritability in the responder behavior has already been identified in a Chinese sample (Zhong et al., 2010). Until now genetic studies in Caucasians on the UG are lacking. The present study wants to fill this gap by investigating the UG in a healthy German sample. Moreover, we intend to find candidate genes that are associated with the first-mover-behavior. In a sample of N = 130 healthy participants an online version of the UG was conducted and polymorphisms of the dopamine D2 receptor gene (DRD2) and the DRD4 exon III VNTR were genotyped. We could confirm the DRD4 exon III effect on the responder behavior and the absence of an effect on the proposer behavior reported before. In line with Zhong et al. (2010) carriers of the 4/4 genotype showed a significant higher minimal acceptable offer (p = 0.023) than subjects with any other genotype. Furthermore, a DRD2-haplotype-block containing the single nucleotide polymorphisms rs1800497 and rs2283265 was significantly associated with the amount player1 offered (p = 0.005) but not with the decision of player 2. Results support the importance of the dopaminergic system for pro-social behavior

  9. The influence of dopaminergic gene variants on decision making in the ultimatum game.

    PubMed

    Reuter, Martin; Felten, Andrea; Penz, Sabrina; Mainzer, Anna; Markett, Sebastian; Montag, Christian

    2013-01-01

    One of the most prominent paradigms in neuroeconomics is the ultimatum game (UG) that provides a framework for the study of pro-social behavior in two players interacting anonymously with each other: Player 1 has to split an endowment with player 2. Player 2 can either accept or reject the offer from player 1. If player 2 accepts the offer then the money is split as proposed by player 1. In case of rejection both players get nothing. Until now only one twin study investigated the heritability of the behavior in the UG. Results indicated a strong heritability for the decision behavior of player 2 whereas no genetic influence on player 1 behavior could be detected. Further studies are mandatory to validate these heritability estimates. However, a first candidate polymorphism, the DRD4 exon III, constituting the biological basis of the heritability in the responder behavior has already been identified in a Chinese sample (Zhong et al., 2010). Until now genetic studies in Caucasians on the UG are lacking. The present study wants to fill this gap by investigating the UG in a healthy German sample. Moreover, we intend to find candidate genes that are associated with the first-mover-behavior. In a sample of N = 130 healthy participants an online version of the UG was conducted and polymorphisms of the dopamine D2 receptor gene (DRD2) and the DRD4 exon III VNTR were genotyped. We could confirm the DRD4 exon III effect on the responder behavior and the absence of an effect on the proposer behavior reported before. In line with Zhong et al. (2010) carriers of the 4/4 genotype showed a significant higher minimal acceptable offer (p = 0.023) than subjects with any other genotype. Furthermore, a DRD2-haplotype-block containing the single nucleotide polymorphisms rs1800497 and rs2283265 was significantly associated with the amount player1 offered (p = 0.005) but not with the decision of player 2. Results support the importance of the dopaminergic system for pro-social behavior

  10. Myosin Light Chain Kinase (MLCK) Gene Influences Exercise Induced Muscle Damage during a Competitive Marathon

    PubMed Central

    Valero, Marjorie; Lara, Beatriz; Salinero, Juan José; Gallo-Salazar, César; Areces, Francisco

    2016-01-01

    Myosin light chain kinase (MLCK) phosphorylates the regulatory light chain (RLC) of myosin producing increases in force development during skeletal muscle contraction. It has been suggested that MLCK gene polymorphisms might alter RLC phosphorylation thereby decreasing the ability to produce force and to resist strain during voluntary muscle contractions. Thus, the genetic variations in the MLCK gene might predispose some individuals to higher values of muscle damage during exercise, especially during endurance competitions. The aim of this investigation was to determine the influence of MLCK genetic variants on exercise-induced muscle damage produced during a marathon. Sixty-seven experienced runners competed in a marathon race. The MLCK genotype (C37885A) of these marathoners was determined. Before and after the race, a sample of venous blood was obtained to assess changes in serum myoglobin concentrations and leg muscle power changes were measured during a countermovement jump. Self-reported leg muscle pain and fatigue were determined by questionnaires. A total of 59 marathoners (88.1%) were CC homozygotes and 8 marathoners (11.9%) were CA heterozygotes. The two groups of participants completed the race with a similar time (228 ± 33 vs 234 ± 39 min; P = 0.30) and similar self-reported values for fatigue (15 ± 2 vs 16 ± 2 A.U.; P = 0.21) and lower-limb muscle pain (6.2 ± 1.7 vs 6.6 ± 1.8 cm; P = 0.29). However, CC marathoners presented higher serum myoglobin concentrations (739 ± 792 vs 348 ± 144 μg·mL-1; P = 0.03) and greater pre-to-post- race leg muscle power reduction (-32.7 ± 15.7 vs -21.2 ± 21.6%; P = 0.05) than CA marathoners. CA heterozygotes for MLCK C37885A might present higher exercise-induced muscle damage after a marathon competition than CC counterparts. PMID:27483374