123 research outputs found

    Detection of a Cis eQTL Controlling BMCO1 Gene Expression Leads to the Identification of a QTG for Chicken Breast Meat Color

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    Classical quantitative trait loci (QTL) analysis and gene expression QTL (eQTL) were combined to identify the causal gene (or QTG) underlying a highly significant QTL controlling the variation of breast meat color in a F2 cross between divergent high-growth (HG) and low-growth (LG) chicken lines. Within this meat quality QTL, BCMO1 (Accession number GenBank: AJ271386), encoding the β-carotene 15, 15′-monooxygenase, a key enzyme in the conversion of β-carotene into colorless retinal, was a good functional candidate. Analysis of the abundance of BCMO1 mRNA in breast muscle of the HG x LG F2 population allowed for the identification of a strong cis eQTL. Moreover, reevaluation of the color QTL taking BCMO1 mRNA levels as a covariate indicated that BCMO1 mRNA levels entirely explained the variations in meat color. Two fully-linked single nucleotide polymorphisms (SNP) located within the proximal promoter of BCMO1 gene were identified. Haplotype substitution resulted in a marked difference in BCMO1 promoter activity in vitro. The association study in the F2 population revealed a three-fold difference in BCMO1 expression leading to a difference of 1 standard deviation in yellow color between the homozygous birds at this haplotype. This difference in meat yellow color was fully consistent with the difference in carotenoid content (i.e. lutein and zeaxanthin) evidenced between the two alternative haplotypes. A significant association between the haplotype, the level of BCMO1 expression and the yellow color of the meat was also recovered in an unrelated commercial broiler population. The mutation could be of economic importance for poultry production by making possible a gene-assisted selection for color, a determining aspect of meat quality. Moreover, this natural genetic diversity constitutes a new model for the study of β-carotene metabolism which may act upon diverse biological processes as precursor of the vitamin A

    In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

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    Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields in vivo that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured in vivo as a greaterâ thanâ normal 1/T1 that is quenchable with antioxidant as measured by quenchâ assisted (Quest) MRI. Here, we further test this approach in phantoms, and we present proofâ ofâ concept data in models of ADâ like and AS hippocampus oxidative stress that also exhibit impaired spatial learning and memory. ADâ like models showed an abnormal gradient along the CA1 dorsalâ ventral axis of excessive free radical production as measured by Quest MRI, and redoxâ sensitive calcium dysregulation as measured by manganeseâ enhanced MRI and electrophysiology. In the AS model, abnormally high free radical levels were observed in dorsal and ventral CA1. Quest MRI is a promising in vivo paradigm for bridging brain subâ field oxidative stress and behavior in animal models and in human patients to better manage antioxidant therapy in devastating neurodegenerative and neurodevelopmental diseases.â Berkowitz, B. A., Lenning J., Khetarpal, N., Tran, C., Wu, J. Y., Berri, A. M., Dernay, K., Haacke, E. M., Shafieâ Khorassani, F., Podolsky, R. H., Gant, J. C., Maimaiti, S., Thibault, O., Murphy, G. G., Bennett, B. M., Roberts, R. In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome. FASEB J. 31, 4179â 4186 (2017). www.fasebj.orgâ Berkowitz, Bruce A., Lenning, Jacob, Khetarpal, Nikita, Tran, Catherine, Wu, Johnny Y., Berri, Ali M., Dernay, Kristin, Haacke, E. Mark, Shafieâ Khorassani, Fatema, Podolsky, Robert H., Gant, John C., Maimaiti, Shaniya, Thibault, Olivier, Murphy, Geoffrey G., Bennett, Brian M., Roberts, Robin, In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome. FASEB J. 31, 4179â 4186 (2017)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154241/1/fsb2fj201700229r.pd

    Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic review

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    Background: Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a “One Health” perspective to synthesize the published data and identify knowledge gaps.<p></p> Methods/Principal Findings: We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (≤13%) among cattle except for studies in Western and Middle Africa (18–55%). Small ruminant seroprevalence ranged from 11–33%. Human seroprevalence was <8% with the exception of studies among children and in Egypt (10–32%). Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2–9% of febrile illness hospitalizations and 1–3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts.<p></p> Conclusions/Significance: C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real yet underappreciated threat to human and animal health throughout Africa.<p></p&gt

    Calcineurin and Protein kinase G regulate C. elegans behavioral quiescence during locomotion in liquid

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    <p>Abstract</p> <p>Background</p> <p>Most rhythmic motor behaviors in nature are episodic i.e. they alternate between different behavioral states, including quiescence. Electrophysiological studies in invertebrate behavioral switching, maintenance and quiescence have elucidated several neuronal mechanisms that generate a temporal pattern in behavior. However, the genetic bases of these processes are less well studied. We have previously uncovered a novel episodic behavior exhibited by <it>C. elegans </it>in liquid media where they alternate between distinct phases of rhythmic swimming and quiescence. Here, we have investigated the effect of several genes and their site of action on the behavioral quiescence exhibited in liquid by the nematode <it>C. elegans</it>.</p> <p>Results</p> <p>We have previously reported that high cholinergic signaling promotes quiescence and command interneurons are critical for timing the quiescence bout durations. We have found that in addition to command interneurons, sensory neurons are also critical for quiescence. We show that the protein phosphatase calcineurin homolog <it>tax-6 </it>promotes swimming whereas the protein kinase G homolog <it>egl-4 </it>promotes quiescence. <it>tax-6 </it>expression in the sensory neurons is sufficient to account for its effect. <it>egl-4 </it>also acts in multiple sensory neurons to mediate its effect on quiescence. In addition our data is consistent with regulation of quiescence by <it>egl-4 </it>acting functionally downstream of release of acetylcholine (ACh) by motor neurons.</p> <p>Conclusions</p> <p>Our study provides genetic evidence for mechanisms underlying the maintenance of a behavioral state operating at multiple neuronal levels through the activities of a kinase and a phosphatase. These results in a genetically tractable organism establish a framework for further dissection of the mechanism of quiescence during episodic behaviors.</p

    OsWRKY IIa Transcription Factors Modulate Rice Innate Immunity

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    WRKY transcription factors regulate diverse plant processes including responses to biotic stresses. Our previous studies indicate that OsWRKY62, an OsWRKY IIa subfamily member, functions as a negative regulator of the rice defense against Xanthomonas oryzae pv. oryzae. Here, we report that a large inverted repeat construct designed to knock down the expression of the four OsWRKY IIa subfamily members (OsWRKY62, OsWRKY28, OsWRKY71, and OsWRKY76) leads to overexpression of all four genes and disease resistance in some transgenic plants. These phenotypes are stably inherited as reflected by progeny analysis. A pathogenesis-related gene, PR10, is up-regulated in plants overexpressing the OsWRKY IIa genes. These results suggest that OsWRKY IIa proteins interact functionally to modulate plant innate immunity

    Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

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    <p>Abstract</p> <p>Background</p> <p>Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer.</p> <p>Methods</p> <p>Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice.</p> <p>Results</p> <p>Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg) for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression.</p> <p>Conclusion</p> <p>Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment.</p

    Genome-wide analysis of WRKY gene family in Cucumis sativus

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    <p>Abstract</p> <p>Background</p> <p>WRKY proteins are a large family of transcriptional regulators in higher plant. They are involved in many biological processes, such as plant development, metabolism, and responses to biotic and abiotic stresses. Prior to the present study, only one full-length cucumber WRKY protein had been reported. The recent publication of the draft genome sequence of cucumber allowed us to conduct a genome-wide search for cucumber WRKY proteins, and to compare these positively identified proteins with their homologs in model plants, such as <it>Arabidopsis</it>.</p> <p>Results</p> <p>We identified a total of 55 WRKY genes in the cucumber genome. According to structural features of their encoded proteins, the cucumber WRKY (<it>CsWRKY</it>) genes were classified into three groups (group 1-3). Analysis of expression profiles of <it>CsWRKY </it>genes indicated that 48 WRKY genes display differential expression either in their transcript abundance or in their expression patterns under normal growth conditions, and 23 WRKY genes were differentially expressed in response to at least one abiotic stresses (cold, drought or salinity). The expression profile of stress-inducible <it>CsWRKY </it>genes were correlated with those of their putative <it>Arabidopsis WRKY (AtWRKY) </it>orthologs, except for the group 3 WRKY genes. Interestingly, duplicated group 3 <it>AtWRKY </it>genes appear to have been under positive selection pressure during evolution. In contrast, there was no evidence of recent gene duplication or positive selection pressure among <it>CsWRKY </it>group 3 genes, which may have led to the expressional divergence of group 3 orthologs.</p> <p>Conclusions</p> <p>Fifty-five WRKY genes were identified in cucumber and the structure of their encoded proteins, their expression, and their evolution were examined. Considering that there has been extensive expansion of group 3 WRKY genes in angiosperms, the occurrence of different evolutionary events could explain the functional divergence of these genes.</p

    Microarray analysis and scale-free gene networks identify candidate regulators in drought-stressed roots of loblolly pine (P. taeda L.)

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    <p>Abstract</p> <p>Background</p> <p>Global transcriptional analysis of loblolly pine (<it>Pinus taeda </it>L.) is challenging due to limited molecular tools. PtGen2, a 26,496 feature cDNA microarray, was fabricated and used to assess drought-induced gene expression in loblolly pine propagule roots. Statistical analysis of differential expression and weighted gene correlation network analysis were used to identify drought-responsive genes and further characterize the molecular basis of drought tolerance in loblolly pine.</p> <p>Results</p> <p>Microarrays were used to interrogate root cDNA populations obtained from 12 genotype × treatment combinations (four genotypes, three watering regimes). Comparison of drought-stressed roots with roots from the control treatment identified 2445 genes displaying at least a 1.5-fold expression difference (false discovery rate = 0.01). Genes commonly associated with drought response in pine and other plant species, as well as a number of abiotic and biotic stress-related genes, were up-regulated in drought-stressed roots. Only 76 genes were identified as differentially expressed in drought-recovered roots, indicating that the transcript population can return to the pre-drought state within 48 hours. Gene correlation analysis predicts a scale-free network topology and identifies eleven co-expression modules that ranged in size from 34 to 938 members. Network topological parameters identified a number of central nodes (hubs) including those with significant homology (E-values ≤ 2 × 10<sup>-30</sup>) to 9-cis-epoxycarotenoid dioxygenase, zeatin O-glucosyltransferase, and ABA-responsive protein. Identified hubs also include genes that have been associated previously with osmotic stress, phytohormones, enzymes that detoxify reactive oxygen species, and several genes of unknown function.</p> <p>Conclusion</p> <p>PtGen2 was used to evaluate transcriptome responses in loblolly pine and was leveraged to identify 2445 differentially expressed genes responding to severe drought stress in roots. Many of the genes identified are known to be up-regulated in response to osmotic stress in pine and other plant species and encode proteins involved in both signal transduction and stress tolerance. Gene expression levels returned to control values within a 48-hour recovery period in all but 76 transcripts. Correlation network analysis indicates a scale-free network topology for the pine root transcriptome and identifies central nodes that may serve as drivers of drought-responsive transcriptome dynamics in the roots of loblolly pine.</p

    Is it really all about money? A study on incentives in elite team sports

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    Research question: A key task for sports managers of elite sports clubs is to create an ideal environment that enables athletes to perform at their best. Therefore, we investigate the relationship among monetary incentives, organizational support, and athletic performance in elite team sports. Research methods: This study is the first in sports management to calculate the relative effects of non-monetary incentives of organizational support and monetary incentives on individual performance through job satisfaction. Furthermore, we apply an innovative measurement approach of player performance by using individual performance ratings of coaches. We collect questionnaires from 315 athletes and 34 coaches of 19 professional football, ice hockey, and handball clubs in Germany. Results and findings: Two variables of organizational support—namely, integration of family and private problem support—show strong positive effects on athletes’ job satisfaction. Whereas prior studies have focused mainly on monetary incentives, this study reveals a strong relevance of organizational support. Furthermore, the results confirm a strong relationship between player satisfaction and individual performance. Implications: Sports managers need to recognize the relevance of non-monetary incentives of organizational support and integrate them into their management repertoire to improve job satisfaction and, consequently, facilitate top performance of their players. Further research should focus on the effects of non-monetary incentives and other aspects of organizational support. In addition, researchers should use individual performance ratings of coaches, rather than other measures, to evaluate player performance because of their expertise and superior background information
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