25 research outputs found

    Dissection of chromosome 18 blood pressure and salt-sensitivity quantitative trait loci in the spontaneously hypertensive rat

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    Hypertension in humans and experimental models has a strong hereditary basis, but identification of causative genes remains challenging. Quantitative trait loci (QTLs) for hypertension and salt sensitivity have been reported on rat chromosome 18. We set out to genetically isolate and prioritise genes within the salt sensitivity and hypertension QTLs on the spontaneously hypertensive rat (SHR) chromosome 18, by developing and characterising a series of congenic strains derived from the SHR and normotensive Brown Norway (BN) rat strains. The SHR.BN-D18Rat113/D18Rat82 (SHR-18) congenic strain exhibits significantly lower blood pressure and is salt-resistant compared to SHR. Transplantation of kidneys from SHR-18 donors into SHR recipients is sufficient to attenuate increased blood pressure but not salt sensitivity. Derivation of congenic sublines allowed separation of salt sensitivity from hypertension QTL regions. Renal expression studies with microarray and Solexa-based sequencing in parental and congenic strains identified four differentially expressed genes within the hypertension QTL region, one of which is an unannotated transcript encoding a previously undescribed, small non-coding RNA. Sequencing selected biological candidate genes within the minimal congenic interval revealed a non-synonymous variant in SHR Transcription factor 4. The minimal congenic interval is syntenic to a region of human chromosome 18 where significant linkage to hypertension was observed in family-based linkage studies. These congenic lines provide reagents for identifying causative genes that underlie the chromosome 18 SHR QTLs for hypertension and salt sensitivity. Candidate genes identified in these studies merit further investigation as potentially causative hypertension genes in SHR and human hypertension

    Factors affecting heavy metals accumulation in potato tubers / Czynniki wpływające na akumulację metali ciężkich w bulwach ziemniaka

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    Badano wpływ wybranych czynników agrochemicznych na akumulację metali ciężkich w bulwach ziemniaka. Gleby uprawne mogą być zanieczyszczone metalami ciężkimi. Pierwiastki, które występują w glebach w formach biodostępnych (mobilnych) mogą zostać włączone do obiegu biologicznego, mając tym samym negatywny wpływ na jakość plonów i zdrowie konsumentów/ człowieka. W badanych glebach oznaczono całkowitą zawartość: Zn, Cu, Ni, Pb, Cd oraz udział tych pierwiastków w formach mobilnych. Spośród badanych pierwiastków najbardziej mobilnym metalem był ołów, którego zakres zawartości w formach mobilnych wynosił: 0,100-0,295 mg∙kg-1, przekraczając dopuszczalne wartości dla tego pierwiastka. Zawartość ołowiu w ziemniakach wynosiła: 0.244-0.855 mg∙kg-1 FM. Analiza statystyczna wykazała istotną korelację pomiędzy zawartością pierwiastków w formach mobilnych i ich zawartością w ziemniakach oraz między odczynem badanych gleb, a całkowitą zawartością ołowiu w ziemniakach. Nie zaobserwowano istotnej statystycznie korelacji pomiędzy zawartością próchnicy w glebach a zawartością ołowiu w ziemniakac

    Changes of Polyphenolic Substances in the Anatomical Parts of Buckwheat (Fagopyrum esculentum Moench.) during Its Growth Phases

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    In this study the changes of total polyphenolics in different anatomical parts (stems, leaves, flowers and seeds) of common buckwheat (Fagopyrum esculentum Moench.) during vegetation period were analysed. The content of total polyphenolics was evaluated in growth phase I (formation of buds), phase II (at the beginning of flowering), phase III (full blossoming) and phase IV (full ripeness). In all growth phases (GP) the stems and leaves were evaluated and statistically significant differences in polyphenolics content between the two parts were confirmed. Statistically significant differences (p < 0.01) in polyphenolics content (in GP II and III) between stems and leaves; and between stems and flowers were found. In flowers an average of 13.8 times higher and in leaves 6 times higher concentration of polyphenolics in comparison with stems was measured. In GP III the content of polyphenolics in common buckwheat was following: flowers > leaves > achene > stems. In flowers an average of 11.9 times higher, in leaves 8.3 times higher and in achenes 5.9 times higher contents of polyphenolics compared with stems were found. In GP III and IV (leaves, achenes, stems) the leaves contained in average 20 times higher and achenes 5.6 times higher polyphenolics than stems

    Low HOX gene expression in PML-RARα-positive leukemia results from suppressed histone demethylation

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    Homeobox (HOX) genes are frequently dysregulated in leukemia. Previous studies have shown that aberrant HOX gene expression accompanies leukemogenesis and affects disease progression and leukemia patient survival. Patients with acute myeloid leukemia (AML) bearing PML-RARα fusion gene have distinct HOX gene signature in comparison to other subtypes of AML patients, although the mechanism of transcription regulation is not completely understood. We previously found an association between the mRNA levels of HOX genes and those of the histone demethylases JMJD3 and UTX in PML-RARα- positive leukemia patients. Here, we demonstrate that the release of the PML-RARα-mediated block in PML-RARα-positive myeloid leukemia cells increased both JMJD3 and HOX gene expression, while inhibition of JMJD3 using the specific inhibitor GSK-J4 reversed the effect. This effect was driven specifically through PML-RARα fusion protein since expression changes did not occur in cells with mutated RARα and was independent of differentiation. We confirmed that gene expression levels were inversely correlated with alterations in H3K27me3 histone marks localized at HOX gene promoters. Furthermore, data from chromatin immunoprecipitation followed by sequencing broaden a list of clustered HOX genes regulated by JMJD3 in PML-RARα-positive leukemic cells. Interestingly, the combination of GSK-J4 and all-trans retinoic acid (ATRA) significantly increased PML-RARα-positive cell apoptosis compared with ATRA treatment alone. This effect was also observed in ATRA-resistant NB4 clones, which may provide a new therapeutic opportunity for patients with acute promyelocytic leukemia (APL) resistant to current treatment. The results of our study reveal the mechanism of HOX gene expression regulation and contribute to our understanding of APL pathogenesis

    Prior and posterior distributions of parameters in the BPP Bayesian analysis of the nine nuclear loci.

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    a<p>Priors set with <i>Ne</i> = 225,000 covering Watterson's <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080641#pone.0080641-Watterson1" target="_blank">[91]</a> θ estimate (<i>θ</i><sub>W</sub> = 0.002, <i>Ne = </i>138,889) and from branching event t = 3.31 Mya between European closely related <i>Cobitis</i> species <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080641#pone.0080641-Tang1" target="_blank">[104]</a>. Relatively fast autosomal mutation rate (<i>μ</i>) of 3.6×10<sup>−9</sup> estimated in vertebrates <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080641#pone.0080641-Axelsson1" target="_blank">[105]</a> was used to transform prior expectations of <i>θ</i> and <i>τ</i> from absolute estimates of <i>N<sub>e</sub></i> and t. Both <i>τ</i> and <i>θ</i> are measured as the expected number of mutations per site.</p>b<p>Prior for the node age was generated from the Dirichlet distribution (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080641#pone.0080641-Yang1" target="_blank">[63]</a>: equation 2).</p><p><i>C. tae</i> = <i>C. taenia</i>, <i>C. tan</i> = <i>C. tanaitica</i>, <i>C. elo</i> = <i>C. elongatoides.</i></p
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