119 research outputs found
Isomer Spectroscopy of Neutron-rich 165,167Tb
Open Access JournalWe present information on the excited states in the prolate-deformed, neutron-rich nuclei 165;167Tb100;102. The nuclei of interest were synthesized following in-flight fission of a 345 MeV per nucleon 238U primary beam on a 2 mm 9Be target at the Radioactive Ion-Beam Factory (RIBF), RIKEN, Japan. The exotic nuclei were separated and identified event-by-event using the BigRIPS separator, with discrete energy gamma-ray decays from isomeric states with half-lives in the _s regime measured using the EURICA gamma-ray spectrometer. Metastable-state decays are identified in 165Tb and 167Tb and interpreted as arising from hindered E1 decay from the 7/2-[523] single quasi-proton Nilsson configuration to rotational states built on the 3/2-[411] single quasi-proton ground state. These data correspond to the first spectroscopic information in the heaviest, odd-A terbium isotopes reported to date and provide information on proton Nilsson configurations which reside close to the Fermi surface as the 170Dy doubly-midshell nucleus is approached.postprin
Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis
Background
Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult.
Methods
Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays.
Results
The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells.
Conclusions
For the first time this data associates altered CDK5 substrate phosphorylation with oncogenesis in some but not all tumour types, implicating altered CDK5 activity in aspects of pathogenesis. These data identify a novel oncogenic mechanism where CDK5 activation induces CRMP2A phosphorylation in the nuclei of tumour cells
Microbial Fuel Cells and Microbial Ecology: Applications in Ruminant Health and Production Research
Microbial fuel cell (MFC) systems employ the catalytic activity of microbes to produce electricity from the oxidation of organic, and in some cases inorganic, substrates. MFC systems have been primarily explored for their use in bioremediation and bioenergy applications; however, these systems also offer a unique strategy for the cultivation of synergistic microbial communities. It has been hypothesized that the mechanism(s) of microbial electron transfer that enable electricity production in MFCs may be a cooperative strategy within mixed microbial consortia that is associated with, or is an alternative to, interspecies hydrogen (H2) transfer. Microbial fermentation processes and methanogenesis in ruminant animals are highly dependent on the consumption and production of H2in the rumen. Given the crucial role that H2 plays in ruminant digestion, it is desirable to understand the microbial relationships that control H2 partial pressures within the rumen; MFCs may serve as unique tools for studying this complex ecological system. Further, MFC systems offer a novel approach to studying biofilms that form under different redox conditions and may be applied to achieve a greater understanding of how microbial biofilms impact animal health. Here, we present a brief summary of the efforts made towards understanding rumen microbial ecology, microbial biofilms related to animal health, and how MFCs may be further applied in ruminant research
Potential benefit of (-)-epigallocatechin-3-gallate for macrovascular complications in diabetes
Electroacupuncture to treat gastroesophageal reflux disease: study protocol for a randomized controlled trial
The Effect of Intratheeal Morphine Administration on Postoperative Pain Relief in General Anesthesia
Theoretical analysis of flexible strain-gauge sensor with nanofibrillar mechanical interlocking
A flexible, and skin-attachable strain gauge sensor based on interconnected nanofibers was recently reported with discernible gauge factor for a flexible and highly sensitive pressure sensor. Here, we present a simple theory that can explain the observed electrical responses by employing the well-established friction law and electrical circuit analysis. The results are in good agreement with the experimental data obtained under physical loads. (C) 2014 Elsevier B.V. All rights reserved1111sciescopuskc
Gene Transfer of TRPC6DN (Dominant Negative) Restores Erectile Function in Diabetic Rats
Introduction. Transient receptor potential (TRP) channels play an important role in modulating intracellular Ca2+ ([Ca2+](i) ) levels. Aim. We examined the hypothesis that overexpression of TRPC6DN (dominant negative) may contribute to decreased [Ca2+](i) levels in corporal smooth muscle (CSM). We also investigated whether gene transfer of TRPC6DN could restore erectile function in diabetic rats. Methods. For the in vitro study, the K(Ca), K(ATP), and TRPC6DN channel genes were transferred using cDNA, into cultured human CSM cells and human embryonic kidney cells. For the in vivo study, young adult rats were divided into three groups: normal controls; diabetic controls transfected with vector only; and a diabetic group transfected with pcDNA of the TRPC6DN gene. Main Outcome Measures. After gene transfer, the effects of reducing [Ca2+](i) levels were assessed by Fura-2-based imaging analysis. The intracavernosal pressure (ICP) response to cavernosal nerve stimulation was assessed after intracorporal injection of TRPC6DN pcDNA. The transgene expression of the TRPC6DN was examined by reverse transcription polymerase chain reaction (RT-PCR) in rats transfected with TRPC6DN pcDNA. Results. Gene transfer of ion channels effectively reduced [Ca2+](i) . Among these channels, transfer of the TRPC6DN gene resulted in the greatest reduction of [Ca2+](i) in human CSM. The mean (+/- standard error of the mean) ratio of ICP to mean arterial pressure (BP) in the gene-transfer rats was 79.4 +/- 2.4% (N = 8). This was significantly higher than that in control rats (55.6 +/- 3.7% [N = 8]), and similar to that in the young control rats (83 +/- 2.2% [N = 12]). The RT-PCR showed expression of TRPC6DN genes in the transfected rats. Conclusion. Gene transfer of TRPC6DN not only reduced [Ca2+](i) in human CSM but also restored erectile function in diabetic rats. These results suggest that pcDNA transfer of TRPC6DN may represent a promising new form of therapy for the treatment of male erectile dysfunction in the future. Jung JH, Kim BJ, Chae MR, Kam SC, Jeon J-H, So I, Chung KH, and Lee SW. Gene transfer of TRPC6DN (dominant negative) restores erectile function in diabetic rats. J Sex Med 2010;7:1126-1138.Hu GQ, 2009, MOL ENDOCRINOL, V23, P689, DOI 10.1210/me.2008-0350Xie DH, 2008, J SEX MED, V5, P2069, DOI 10.1111/j.1743-6109.2008.00933.xLee M, 2008, J SEX MED, V5, P1355, DOI 10.1111/j.1743-6109.2008.00771.xLiu DY, 2008, ARTERIOSCL THROM VAS, V28, P746, DOI 10.1161/ATVBAHA.108.162222Han DH, 2008, J SEX MED, V5, P822, DOI 10.1111/j.1743-6109.2007.00732.xBivalacqua TJ, 2008, J SEX MED, V5, P268So I, 2007, BJU INT, V100, P1154, DOI 10.1111/j.1464-410X.2007.07050.xDIETRICH A, 2007, HANDB EXP PHARM, V179, P125Lau DHW, 2007, ASIAN J ANDROL, V9, P8, DOI 10.1111/j.1745-7262.2007.00224.xHAN DH, 2007, INT J IMPOT RES, V20, P53So I, 2005, INT J IMPOT RES, V17, P475, DOI 10.1038/sj.ijir.3901356Dietrich A, 2005, MOL CELL BIOL, V25, P6980, DOI 10.1128/MCB.25.16.6980-6989.2005Christ GJ, 2004, AM J PHYSIOL-HEART C, V287, pH1544, DOI 10.1152/ajpheart.00792.2003Bivalacqua TJ, 2004, P NATL ACAD SCI USA, V101, P9121, DOI 10.1073/pnas.0400520101CHRIST GJ, 2004, CURR UROL REP, V5, P52Clapham DE, 2003, NATURE, V426, P517, DOI 10.1038/nature02196Insuk SO, 2003, INT J IMPOT RES, V15, P258, DOI 10.1038/sj.ijir.3901013Bivalacqua TJ, 2003, J UROLOGY, V169, P1911, DOI 10.1097/01.ju.0000051881.14239.4aBIVALACQUA TJ, 2003, AM J PHYSIOL-HEART C, V284, P1408Chitaley K, 2002, BIOCHEM BIOPH RES CO, V298, P427MAGEE TR, 2002, SOC STUDY REPROD, V1, P20Tirney S, 2001, MOL UROL, V5, P37SCHENK G, 2001, CURR UROL REP, V2, P480BIVALACQUA TJ, 2001, SOC STUDY REPROD, V1, P1371INOUE R, 2001, AM HEART ASS, P325Yla-Herttuala S, 2000, LANCET, V355, P213Cellek S, 1999, BRIT J PHARMACOL, V128, P1804Melman A, 1999, J UROLOGY, V161, P5Christ GJ, 1998, AM J PHYSIOL-HEART C, V275, pH600Boulay G, 1997, J BIOL CHEM, V272, P29672Rehman J, 1997, AM J PHYSIOL-HEART C, V272, pH1960BRINK PR, 1996, AM J PHYSIOL-CELL PH, V271, P321CHANG MW, 1995, J CLIN INVEST, V96, P2260ZHAO WX, 1995, J UROLOGY, V154, P1571GARBAN H, 1995, AM J PHYSIOL, V268, P467PALMER LS, 1994, J UROLOGY, V152, P1308CARRIER S, 1993, UROLOGY, V42, P468CHRIST GJ, 1993, INT J IMPOT RES, V5, P77
Genetic identification of species and natural hybridization determination based on mitochondrial DNA and nuclear DNA of genus Zacco
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