249 research outputs found

    Facilitation of Male Sexual Behavior in Syrian Hamsters by the Combined Action of Dihydrotestosterone and Testosterone

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    Testosterone (T) controls male Syrian hamster sexual behavior, however, neither of T's primary metabolites, dihydrotestosterone (DHT) and estradiol (E(2)), even in highly supraphysiological doses, fully restores sexual behavior in castrated hamsters. DHT and T apparently interact with androgen receptors differentially to control male sexual behavior (MSB), but whether these two hormones act synergistically or antagonistically to control MSB has received scant experimental attention and is addressed in the present study.Sexually experienced male Syrian hamsters were gonadectomized and monitored 5 weeks later to confirm elimination of the ejaculatory reflex (week 0), at which time they received subcutaneous DHT-filled or empty capsules that remained in situ for the duration of the experiment. Daily injections of a physiological dose of 25 Β΅g T or vehicle commenced two weeks after capsule implantation. MSB was tested 2, 4 and 5 weeks after T treatment began. DHT capsules were no more effective than control treatment for long-term restoration of ejaculation. Combined DHT + T treatment, however, restored the ejaculatory reflex more effectively than T alone, as evidenced by more rapid recovery of ejaculatory behavior, shorter ejaculation latencies, and a greater number of ejaculations in 30 minute tests.DHT and T administered together restored sexual behavior to pre-castration levels more rapidly than did T alone, whereas DHT and vehicle were largely ineffective. The additive actions of DHT and T on MSB are discussed in relation to different effects of these androgens on androgen receptors in the male hamster brain mating circuit

    MUC1 Limits Helicobacter pylori Infection both by Steric Hindrance and by Acting as a Releasable Decoy

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    The bacterium Helicobacter pylori can cause peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. The cell-surface mucin MUC1 is a large glycoprotein which is highly expressed on the mucosal surface and limits the density of H. pylori in a murine infection model. We now demonstrate that by using the BabA and SabA adhesins, H. pylori bind MUC1 isolated from human gastric cells and MUC1 shed into gastric juice. Both H. pylori carrying these adhesins, and beads coated with MUC1 antibodies, induced shedding of MUC1 from MKN7 human gastric epithelial cells, and shed MUC1 was found bound to H. pylori. Shedding of MUC1 from non-infected cells was not mediated by the known MUC1 sheddases ADAM17 and MMP-14. However, knockdown of MMP-14 partially affected MUC1 release early in infection, whereas ADAM17 had no effect. Thus, it is likely that shedding is mediated both by proteases and by disassociation of the non-covalent interaction between the Ξ±- and Ξ²-subunits. H. pylori bound more readily to MUC1 depleted cells even when the bacteria lacked the BabA and SabA adhesins, showing that MUC1 inhibits attachment even when bacteria cannot bind to the mucin. Bacteria lacking both the BabA and SabA adhesins caused less apoptosis in MKN7 cells than wild-type bacteria, having a greater effect than deletion of the CagA pathogenicity gene. Deficiency of MUC1/Muc1 resulted in increased epithelial cell apoptosis, both in MKN7 cells in vitro, and in H. pylori infected mice. Thus, MUC1 protects the epithelium from non-MUC1 binding bacteria by inhibiting adhesion to the cell surface by steric hindrance, and from MUC1-binding bacteria by acting as a releasable decoy

    DNA End Resection Controls the Balance between Homologous and Illegitimate Recombination in Escherichia coli

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    Even a partial loss of function of human RecQ helicase analogs causes adverse effects such as a cancer-prone Werner, Bloom or Rothmund-Thompson syndrome, whereas a complete RecQ deficiency in Escherichia coli is not deleterious for a cell. We show that this puzzling difference is due to different mechanisms of DNA double strand break (DSB) resection in E. coli and humans. Coupled helicase and RecA loading activities of RecBCD enzyme, which is found exclusively in bacteria, are shown to be responsible for channeling recombinogenic 3β€² ending tails toward productive, homologous and away from nonproductive, aberrant recombination events. On the other hand, in recB1080/recB1067 mutants, lacking RecBCD’s RecA loading activity while preserving its helicase activity, DSB resection is mechanistically more alike that in eukaryotes (by its uncoupling from a recombinase polymerization step), and remarkably, the role of RecQ also becomes akin of its eukaryotic counterparts in a way of promoting homologous and suppressing illegitimate recombination. The sickly phenotype of recB1080 recQ mutant was further exacerbated by inactivation of an exonuclease I, which degrades the unwound 3β€² tail. The respective recB1080 recQ xonA mutant showed poor viability, DNA repair and homologous recombination deficiency, and very increased illegitimate recombination. These findings demonstrate that the metabolism of the 3β€² ending overhang is a decisive factor in tuning the balance of homologous and illegitimate recombination in E. coli, thus highlighting the importance of regulating DSB resection for preserving genome integrity. recB mutants used in this study, showing pronounced RecQ helicase and exonuclease I dependence, make up a suitable model system for studying mechanisms of DSB resection in bacteria. Also, these mutants might be useful for investigating functions of the conserved RecQ helicase family members, and congruently serve as a simpler, more defined model system for human oncogenesis

    Prevention of hepatorenal toxicity with Sonchus asper in gentamicin treated rats

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    <p>Abstract</p> <p>Background</p> <p><it>Sonchus asper </it>possesses antioxidant capacity and is used in liver and kidney disorders. We have investigated the preventive effect of methanolic extract of <it>Sonchus asper </it>(SAME) on the gentamicin induced alterations in biochemical and morphological parameters in liver and kidneys of Sprague-Dawley male rat.</p> <p>Methods</p> <p>Acute oral toxicity studies were performed for selecting the therapeutic dose of SAME. 30 Sprague-Dawley male rats were equally divided into five groups with 06 animals in each. Group I received saline (0.5 ml/kg bw; 0.9% NaCl) while Group II administered with gentamicin 0.5 ml (100 mg/kg bw; i.p.) for ten days. Animals of Group III and Group IV received gentamicin and SAME 0.5 ml at a dose of 100 mg/kg bw and 200 mg/kg bw, respectively while Group V received only SAME at a dose of 200 mg/kg bw. Biochemical parameters including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), Ξ³-glutamyltransferase (Ξ³-GT), total cholesterol, triglycerides, total protein, albumin, creatinine, blood urea nitrogen (BUN), total bilirubin and direct bilirubin were determined in serum collected from various groups. Urinary out puts were measured in each group and also assessed for the level of protein and glucose. Lipid peroxides (TBARS), glutathione (GSH), DNA injuries and activities of antioxidant enzymes; catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) were determined in liver and renal samples. Histopathological studies of liver and kidneys were also carried out.</p> <p>Results</p> <p>On the basis of acute oral toxicity studies, 2000 mg/kg bw did not induce any toxicity in rats, 1/10<sup>th </sup>of the dose was selected for preventive treatment. Gentamicin increased the level of serum biomarkers; AST, ALT, ALP, LDH, Ξ³-GT, total cholesterol, triglycerides, total protein, albumin, creatinine, BUN, total and direct bilirubin; as were the urinary level of protein, glucose, and urinary output. Lipid peroxidation (TBARS) and DNA injuries increased while GSH contents and activities of antioxidant enzymes; CAT, POD, SOD decreased with gentamicin in liver and kidney samples. SAME administration, dose dependently, prevented the alteration in biochemical parameters and were supported by low level of tubular and glomerular injuries induced with gentamicin.</p> <p>Conclusion</p> <p>These results suggested the preventive role of SAME for gentamicin induced toxicity that could be attributed by phytochemicals having antioxidant and free radical scavenging properties.</p

    Measurement of CP-Violating Parameters in B→η′KB\to \eta^\prime K Decays

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    We present measurements of CP-violating parameters in B0(BΛ‰0)β†’Ξ·β€²KS0B^0(\bar{B}{}^0) \to \eta^\prime K_S^0 and BΒ±β†’Ξ·β€²KΒ±B^{\pm} \to \eta' K^{\pm} decays based on a 41.8 fbβˆ’1^{-1} data sample collected at the Ξ₯(4S)\Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+eβˆ’e^{+} e^{-} collider. We fully reconstruct one neutral BB meson as a B0(BΛ‰0)β†’Ξ·β€²KS0B^0(\bar{B}{}^0) \to \eta^\prime K_S^0 CP eigenstate and identify the flavor of the accompanying BB from its decay products. From the distribution of time intervals between pairs of BB meson decay points, we obtain the CP-violating asymmetry parameters SΞ·β€²KS0=0.28Β±0.55(stat)βˆ’0.08+0.07(syst){\mathcal S}_{\eta^\prime K_S^0} = 0.28\pm0.55(stat)^{+0.07}_{-0.08}(syst), and AΞ·β€²KS0=0.13Β±0.32(stat)βˆ’0.06+0.09(syst){\mathcal A}_{\eta^\prime K_S^0} = 0.13\pm0.32(stat)^{+0.09}_{-0.06}(syst). We also reconstruct charged BΒ±β†’Ξ·β€²KΒ±B^{\pm} \to \eta^\prime K^{\pm} decays and determine a direct-CP violating asymmetry value of AΞ·β€²KΒ±=(βˆ’1.5Β±7.0(stat)Β±0.9(syst)){\mathcal A}_{\eta^\prime K^\pm}=(-1.5\pm7.0(stat)\pm0.9(syst))%.Comment: Revised version: 16 pages, 3 figures, 1 table submitted to Phys. Lett.

    Measurement of Br(Bbar -> D+l-nubar) and Determination of |Vcb|

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    We present a measurement of the branching fraction for the semileptonic B decay Bbar -> D+l-nubar, where l- can be either an electron or a muon. We find Gamma(Bbar -> D+l-nubar)= (13.79+/-0.76+/-2.51) ns^{-1}, and the resulting branching fraction Br(Bbar -> D+l-nubar)= (2.13 +/- 0.12 +/- 0.39)%, where the first error is statistical and the second systematic. We also investigate the Bbar -> D+l-nubar form factor and the implications of the result for |Vcb|. From a fit to the differential decay distribution we obtain the rate normalization |Vcb|F_D(1)= (4.11+/-0.44+/-0.52)x10^{-2}. Using a theoretical calculation of F_D(1), the Cabibbo-Kobayashi-Maskawa matrix element |Vcb|=(4.19+/-0.45+/-0.53+/-0.30)x10^{-2} is obtained, where the last error comes from the theoretical uncertainty of F_D(1). The results are based on a data sample of 10.2 fb^{-1} recorded at the Upsilon(4S)$ resonance with the Belle detector at the KEKB e+e- collider.Comment: 21pages, 5 figures, elsart.cls, to be published in PLB. In this version, the form factor comparison between B->Dlnu and D*lnu is include

    3, 3β€²5 Triiodo L Thyronine Induces Apoptosis in Human Breast Cancer MCF-7cells, Repressing SMP30 Expression through Negative Thyroid Response Elements

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    Thyroid hormones regulate cell proliferation, differentiation as well as apoptosis. However molecular mechanism underlying apoptosis as a result of thyroid hormone signaling is poorly understood. The antiapoptotic role of Senescence Marker Protein-30 (SMP30) has been characterized in response to varieties of stimuli as well as in knock out model. Our earlier data suggest that thyroid hormone 3, 3'5 Triiodo L Thyronine (T(3)), represses SMP30 in rat liver.In highly metastatic MCF-7, human breast cancer cell line T3 treatment repressed SMP30 expression leading to enhanced apoptosis. Analysis by flow cytometry and other techniques revealed that overexpression and silencing of SMP30 in MCF-7 resulted in decelerated and accelerated apoptosis respectively. In order to identify the cis-acting elements involved in this regulation, we have analyzed hormone responsiveness of transiently transfected hSMP30 promoter deletion reporter vectors in MCF-7 cells. As opposed to the expected epigenetic outcome, thyroid hormone down regulated hSMP30 promoter activity despite enhanced recruitment of acetylated H3 on thyroid response elements (TREs). From the stand point of established epigenetic concept we have categorised these two TREs as negative response elements. Our attempt of siRNA mediated silencing of TRΞ², reduced the fold of repression of SMP30 gene expression. In presence of thyroid hormone, Trichostatin- A (TSA), which is a Histone deacetylase (HDAC) inhibitor further inhibited SMP30 promoter activity. The above findings are in support of categorisation of both the thyroid response element as negative response elements as usually TSA should have reversed the repressions.This is the first report of novel mechanistic insights into the remarkable downregulation of SMP30 gene expression by thyroid hormone which in turn induces apoptosis in MCF-7 human breast cancer cells. We believe that our study represents a good ground for future effort to develop new therapeutic approaches to challenge the progression of breast cancer

    The Complete Chloroplast and Mitochondrial Genome Sequences of Boea hygrometrica: Insights into the Evolution of Plant Organellar Genomes

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    The complete nucleotide sequences of the chloroplast (cp) and mitochondrial (mt) genomes of resurrection plant Boea hygrometrica (Bh, Gesneriaceae) have been determined with the lengths of 153,493 bp and 510,519 bp, respectively. The smaller chloroplast genome contains more genes (147) with a 72% coding sequence, and the larger mitochondrial genome have less genes (65) with a coding faction of 12%. Similar to other seed plants, the Bh cp genome has a typical quadripartite organization with a conserved gene in each region. The Bh mt genome has three recombinant sequence repeats of 222 bp, 843 bp, and 1474 bp in length, which divide the genome into a single master circle (MC) and four isomeric molecules. Compared to other angiosperms, one remarkable feature of the Bh mt genome is the frequent transfer of genetic material from the cp genome during recent Bh evolution. We also analyzed organellar genome evolution in general regarding genome features as well as compositional dynamics of sequence and gene structure/organization, providing clues for the understanding of the evolution of organellar genomes in plants. The cp-derived sequences including tRNAs found in angiosperm mt genomes support the conclusion that frequent gene transfer events may have begun early in the land plant lineage
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