WorldWideScience

Sample records for hu ril-1 beta

  1. HuB localizes to polysomes and alters C/EBP-beta expression in 3T3-L1 adipocytes.

    Science.gov (United States)

    Gantt, Kira R; Jain, Renu G; Dudek, Ronald W; Pekala, Phillip H

    2004-01-16

    The RNA binding protein HuB was ectopically expressed in 3T3-L1 preadipocytes and localized primarily to the nucleus, as the cells differentiated HuB redistributed to the cytosol and on analysis localized to the dense polysomes. Electron micrographs confirm association of HuB with the ribosomes in the adipocytes consistent with a proposed role in control of translation and mRNA stability. Examination of the expression of C/EBP-beta in the cells expressing HuB relative to the parental 3T3-L1 adipocytes demonstrated an alteration in the LAP to LIP ratio. The data support a role for endogenous Hu proteins in the differentiation process, potentially affecting the rate of differentiation by controlling the concentration of the dominant negative transcription inhibitor, LIP.

  2. Multiple defects in Escherichia coli mutants lacking HU protein.

    OpenAIRE

    Huisman, O; Faelen, M; Girard, D; Jaffé, A; Toussaint, A; Rouvière-Yaniv, J

    1989-01-01

    The HU protein isolated from Escherichia coli, composed of two partially homologous subunits, alpha and beta, shares some of the properties of eucaryotic histones and is a major constituent of the bacterial nucleoid. We report here the construction of double mutants totally lacking both subunits of HU protein. These mutants exhibited poor growth and a perturbation of cell division, resulting in the formation of anucleate cells. In the absence of HU, phage Mu was unable to grow, to lysogenize,...

  3. Repeated intraperitoneal injections of interleukin 1 beta induce glucose intolerance in normal rats

    DEFF Research Database (Denmark)

    Wogensen, L; Reimers, J; Mandrup-Poulsen, T

    1991-01-01

    . An ip glucose tolerance test (0.2 g D-glucose/100 g) was performed 2 h after injection of rIL-1 beta. A single injection of rIL-1 beta caused a mild depression in blood glucose and an improved glucose tolerance. Multiple injections of rIL-1 beta induced a diminished weight gain, a 24-28% reduction......Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1 beta on blood glucose and glucose tolerance...... in vivo. Normal Wistar Kyoto rats were injected ip with a single injection of 4 micrograms/kg of the mature form of recombinant IL-1 beta (amino acids 117-269) or once daily on 5 consecutive days. Control rats were given vehicle and were fed ad libitum or pair-fed together with the rIL-1 beta treated rats...

  4. HuR contributes to Hepatic Stellate Cell activation and liver fibrosis

    Science.gov (United States)

    Woodhoo, A.; Iruarrizaga-Lejarreta, M.; Beraza, N.; García-Rodríguez, J.L.; Embade, N.; Fernández-Ramos, D.; Matinez-Lopez, N.; Gutiérrez, Virginia; Arteta, B.; Caballeria, J.; Lu, S.C.; Mato, J.M.; Varela-Rey, M.; Martinez-Chantar, M.L.

    2012-01-01

    RNA-binding proteins (RBPs) play a major role in control of mRNA turnover and translation rates. We examined the role of the RBP human antigen R (HuR) during cholestatic liver injury and hepatic stellate cells (HSC) activation. HuR silencing attenuated fibrosis development in vivo after BDL, reducing liver damage, oxidative stress, inflammation, and collagen and α-SMA (α-smooth muscle actin) expression. HuR expression increased in activated HSC from BDL mice and during HSC activation in vitro, and HuR silencing markedly reduced HSC activation. HuR regulated platelet-derived growth factor (PDGF)-induced proliferation and migration, and controlled expression of several mRNAs involved in these processes (Actin, MMP9, Cyclin D1 and B1). These functions of HuR were linked to its abundance and cytoplasmic localisation, controlled by PDGF, via ERK and PI3K activation, and ERK-LKB1 activation respectively. More importantly, we identified the tumor suppressor LKB1 as a novel downstream target of PDGF-induced ERK activation in HSC. HuR also controlled transforming growth factor beta (TGF-β-induced profibrogenic actions by regulating expression of TGF-β, α-SMA, and p21. This was likely due to an increased cytoplasmic localisation of HuR, controlled by TGF-β-induced p38 MAPK activation. Finally, we found that HuR and LKB1 (Ser428) levels were highly expressed in activated HSC in human cirrhotic samples. Conclusion: Our results show that HuR is important for pathogenesis of liver fibrosis development in the cholestatic injury model, for HSC activation, and for the response of activated HSC to PDGF and TGF-β. PMID:22576182

  5. Main: 1HU9 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1HU9 大豆 Soybean Glycine max (L.) Merrill Seed Lipoxygenase-3 Name=Lox1.3; Synonyms=...2; CAA31664.1; ALT_SEQ.|EMBL; U50081; AAB41272.1; -.|PDB; 1HU9; X-ray; A=1-857.|PDB; 1IK3; X-ray; A=1-857.|P...WTSDTRALEAFKRFGNKLAQIENKLSERNNDEKLRNRCGPVQMPYTLLLPSSKEGLTFRGIPNSISI soybean_1HU9.jpg ...

  6. Immunostimulatory effects of natural human interferon-alpha (huIFN-alpha) on carps Cyprinus carpio L.

    Science.gov (United States)

    Watanuki, Hironobu; Chakraborty, Gunimala; Korenaga, Hiroki; Kono, Tomoya; Shivappa, R B; Sakai, Masahiro

    2009-10-15

    Human interferon-alpha (huIFN-alpha) is an important immunomodulatory substance used in the treatment and prevention of numerous infectious and immune-related diseases in animals. However, the immunostimulatory effects of huIFN-alpha in fish remain to be investigated. In the current study, the immune responses of the carp species Cyprinus carpio L. to treatment with huIFN-alpha were analyzed via measurement of superoxide anion production, phagocytic activity and the expression of cytokine genes including interleukin-1beta, tumor necrosis factor-alpha and interleukin 10. Low doses of huIFN-alpha were administered orally once a day for 3 days, and sampling was carried out at 1, 3 and 5 days post-treatment. Our results indicate that a low dose of huIFN-alpha significantly increased phagocytic activity and superoxide anion production in the carp kidney. The huIFN-alpha-treated fish also displayed a significant upregulation in cytokine gene expression. The current study demonstrates the stimulatory effects of huIFN-alpha on the carp immune system and highlights the immunomodulatory role of huIFN-alpha in fish.

  7. Infecciones en huéspedes inmunocomprometidos

    OpenAIRE

    Cuéllar Ponce de León, Luis Ernesto; Médico-Cirujano. Especialista en Enfermedades Infecciosas y Tropicales. Jefe del Servicio de Infectología. Instituto Nacional de Enfermedades Neoplásicas. Coordinador del Programa VIH/SIDA/TARGA-INEN. Profesor Asociado de Medicina de la Universidad Nacional Federico Villarreal. Lima.

    2013-01-01

    Las infecciones son causa frecuente de morbimortalidad en huéspedes inmunocomprometidos. La frecuencia y diversidad de infecciones en esta población dependerá del tipo de inmunocompromiso, tratamiento recibido y aspecto epidemiológico. Los huéspedes con neutropenia desarrollan infecciones por bacterias extracelulares no encapsuladas y hongos levaduriformes y filamentosos; el diagnóstico precoz y tratamiento oportuno de las mismas son considerados una emergencia por su severidad y gran mortali...

  8. Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta.

    Science.gov (United States)

    Eizirik, D L; Sandler, S; Hallberg, A; Bendtzen, K; Sener, A; Malaisse, W J

    1989-08-01

    The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of

  9. A probabilistic Hu-Washizu variational principle

    Science.gov (United States)

    Liu, W. K.; Belytschko, T.; Besterfield, G. H.

    1987-01-01

    A Probabilistic Hu-Washizu Variational Principle (PHWVP) for the Probabilistic Finite Element Method (PFEM) is presented. This formulation is developed for both linear and nonlinear elasticity. The PHWVP allows incorporation of the probabilistic distributions for the constitutive law, compatibility condition, equilibrium, domain and boundary conditions into the PFEM. Thus, a complete probabilistic analysis can be performed where all aspects of the problem are treated as random variables and/or fields. The Hu-Washizu variational formulation is available in many conventional finite element codes thereby enabling the straightforward inclusion of the probabilistic features into present codes.

  10. For Hu Zhuanglin: A Prefatory Note

    Institute of Scientific and Technical Information of China (English)

    M. A. K. Halliday

    2012-01-01

    It is a very great pleasure to be able to congratulate Professor Hu Zhuanglin on the occasion of his eightieth birthday. It is also a time to remember that Professor Hu and I have known each other for 33 years, since the moment he arrived in Sydney, together with eight other Chinese scholars, to take part in a programme of studies arranged jointly by the Department of English and the Department of Linguistics at Sydney University. These first arrivals from China were people of some seniority,

  11. Hu on poolel teel / James Miles

    Index Scriptorium Estoniae

    Miles, James

    2006-01-01

    2007. aastal toimuv kommunistliku partei 17. kongress tähistab Hiina presidendi Hu Jintao jaoks oma võimuaja poole peale jõudmist, ees ootavad sellised väljakutsed nagu olümpiamängude korraldamine, valimiskeeris Taiwanis ning hullunud majanduse stabiliseerimine. Vt samas: Hiina avanemise pidu

  12. Hu on poolel teel / James Miles

    Index Scriptorium Estoniae

    Miles, James

    2006-01-01

    2007. aastal toimuv kommunistliku partei 17. kongress tähistab Hiina presidendi Hu Jintao jaoks oma võimuaja poole peale jõudmist, ees ootavad sellised väljakutsed nagu olümpiamängude korraldamine, valimiskeeris Taiwanis ning hullunud majanduse stabiliseerimine. Vt samas: Hiina avanemise pidu

  13. Hu Xiaoyu—an Outstanding Pupil

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    HU Xiaoyu, 11, is a fifth grader at the Beijing Hepingli No. 4 Primary School. She is talkative, cheerful, active and likes to laugh. Her teachers say she is well-behaved and excels in her studies. She is intelligent and always asks many questions both in and outside the classroom. She has been elected a "Three Good" student every year since she started school.

  14. Hu Qiaomu and Hu Feng Event%胡乔木与胡风案

    Institute of Scientific and Technical Information of China (English)

    张成洁

    2015-01-01

    It had a gradual upgrade process on a critique of Hu Feng's literary thoughts and a political settlement to Hu Feng.As the senior vice minister of the Propaganda Department of the Central Committee of the CPC,Hu Qiaomu played an important role on it.In October 1945,Hu Qiaomu still stayed in Chungking after Chungking Negotiations and counter-acted the effects of Hu Feng's literary thoughts by criticizing"subjectiveness".Public criticism to Hufeng launched by"popular literature series" was supported by Hu Qiaomuin in Hongkong in 1948.The first two years of the founding of new China,Hu Qiaomu talked with Hufeng for many times to solve his ideological problems.Hu Qiaomu also organized criticism of Hu Feng's literary thoughts throught the opportunity of Shuwu self-criticism;Hu Qiaomu first mentioned publicly"a small cabal of literary headed by Hufeng"In his giving editorial notes of Shuwu's article.Hu Feng's private let-ters to Shuwu were disclosed which directly led to Hu Feng event upgrading to"anti-party and anti-revolution"problems in the process of the great criticism of Hu Feng.After 1954,this matter had an indirect relationship with Hu Qiaomu's suggest of writing Hu Feng sectarianism.However,Hu Qiaomu disapproved to determine Hu Feng and the people impli-cating with Hu Feng as"Hufeng Anti-Party Clique".He gave a claim in this connection before Mao Zedong.In the past, people very paid attention to Zhouyang who had deep historical grievances with Hu Feng and ignored the role of Hu Qiao-mu in Hu Feng event.%对胡风文艺思想的批判和对胡风的政治清算有一个渐次升级的过程。其中,在对胡风文艺思想的批判中,胡乔木起了重要作用。1945年10月,胡乔木随毛泽东去重庆谈判后逗留重庆,借批《论主观》来清除胡风文艺思想的影响;1948年香港的《大众文艺丛刊》对胡风发起的公开批评,也得到了胡乔木的支持;新中国成立头两年,胡乔木多次奉命找胡风谈话

  15. Regulation of HuR by DNA Damage Response Kinases

    Directory of Open Access Journals (Sweden)

    Hyeon Ho Kim

    2010-01-01

    Full Text Available As many DNA-damaging conditions repress transcription, posttranscriptional processes critically influence gene expression during the genotoxic stress response. The RNA-binding protein HuR robustly influences gene expression following DNA damage. HuR function is controlled in two principal ways: (1 by mobilizing HuR from the nucleus to the cytoplasm, where it modulates the stability and translation of target mRNAs and (2 by altering its association with target mRNAs. Here, we review evidence that two main effectors of ataxia-telangiectasia-mutated/ATM- and Rad3-related (ATM/ATR, the checkpoint kinases Chk1 and Chk2, jointly influence HuR function. Chk1 affects HuR localization by phosphorylating (hence inactivating Cdk1, a kinase that phosphorylates HuR and thereby blocks HuR's cytoplasmic export. Chk2 modulates HuR binding to target mRNAs by phosphorylating HuR's RNA-recognition motifs (RRM1 and RRM2. We discuss how HuR phosphorylation by kinases including Chk1/Cdk1 and Chk2 impacts upon gene expression patterns, cell proliferation, and survival following genotoxic injury.

  16. Flexible DNA bending in HU-DNA cocrystal structures.

    Science.gov (United States)

    Swinger, Kerren K; Lemberg, Kathryn M; Zhang, Ying; Rice, Phoebe A

    2003-07-15

    HU and IHF are members of a family of prokaryotic proteins that interact with the DNA minor groove in a sequence-specific (IHF) or non-specific (HU) manner to induce and/or stabilize DNA bending. HU plays architectural roles in replication initiation, transcription regulation and site-specific recombination, and is associated with bacterial nucleoids. Cocrystal structures of Anabaena HU bound to DNA (1P71, 1P78, 1P51) reveal that while underlying proline intercalation and asymmetric charge neutralization mechanisms of DNA bending are similar for IHF and HU, HU stabilizes different DNA bend angles ( approximately 105-140 degrees ). The two bend angles within a single HU complex are not coplanar, and the resulting dihedral angle is consistent with negative supercoiling. Comparison of HU-DNA and IHF-DNA structures suggests that sharper bending is correlated with longer DNA binding sites and smaller dihedral angles. An HU-induced bend may be better modeled as a hinge, not a rigid bend. The ability to induce or stabilize varying bend angles is consistent with HU's role as an architectural cofactor in many different systems that may require differing geometries.

  17. HU-446 and HU-465, Derivatives of the Non-psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells.

    Science.gov (United States)

    Kozela, Ewa; Haj, Christeene; Hanuš, Lumir; Chourasia, Mukesh; Shurki, Avital; Juknat, Ana; Kaushansky, Nathali; Mechoulam, Raphael; Vogel, Zvi

    2016-01-01

    Cannabidiol (CBD), the non-psychoactive cannabinoid, has been previously shown by us to decrease peripheral inflammation and neuroinflammation in mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Here we have studied the anti-inflammatory effects of newly synthesized derivatives of natural (-)-CBD ((-)-8,9-dihydro-7-hydroxy-CBD; HU-446) and of synthetic (+)-CBD ((+)-8,9-dihydro-7-hydroxy-CBD; HU-465) on activated myelin oligodendrocyte glycoprotein (MOG)35-55-specific mouse encephalitogenic T cells (T(MOG) ) driving EAE/MS-like pathologies. Binding assays followed by molecular modeling revealed that HU-446 has negligible affinity toward the cannabinoid CB1 and CB2 receptors while HU-465 binds to both CB1 and CB2 receptors at the high nanomolar concentrations (Ki = 76.7 ± 5.8 nm and 12.1 ± 2.3 nm, respectively). Both, HU-446 and HU-465, at 5 and 10 μm (but not at 0.1 and 1 μm), inhibited the MOG35-55-induced proliferation of autoreactive T(MOG) cells via CB1/CB2 receptor independent mechanisms. Moreover, both HU-446 and HU-465, at 5 and 10 μm, inhibited the release of IL-17, a key autoimmune cytokine, from MOG35-55-stimulated T(MOG) cells. These results suggest that HU-446 and HU-465 have anti-inflammatory potential in inflammatory and autoimmune diseases.

  18. A Working Day of Professor Hu Yamei

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    Professor Hu Yamei is a well-known pediatrician and one of the first group of academicians to the Institute of Medical Science attached to the Chinese Academy of Engineering. At the start of her career in the 1950s, she focused on nutritional anemia that afflicts children, developing treatment and methods of prevention. Later she researched etiology, pathology and physiology of pediatric toxic indigestion, helping to reduce the child death rate from 20 percent to 1 percent. Over the past 20 years, she has concentrated on pediatric acute lymphoblastic leukemia. As a result, the five-years living rate of the disease treated by Hu’s group has reached 74 percent, approaching the highest level in the world.

  19. Notas sobre el paisaje de Huánuco Pampa

    OpenAIRE

    Román Godines, Oscar; Ministerio de Cultura

    2013-01-01

    El complejo arqueológico Huánuco Pampa se encuentra ubicado en la provincia Dos de Mayo en el departamento de Huánuco y en la actualidad es quizás el principal vestigio de la cosmovisión y la planificación urbana inca.

  20. Rapid purification of HU protein from Halobacillus karajensis

    Directory of Open Access Journals (Sweden)

    Parinaz Ghadam

    2014-03-01

    Full Text Available The histone-like protein HU is the most-abundant DNA-binding protein in bacteria. The HU protein non-specifically binds and bends DNA as a hetero- or homodimer, and can participate in DNA supercoiling and DNA condensation. It also takes part in DNA functions such as replication, recombination, and repair. HU does not recognize any specific sequences but shows a certain degree of specificity to cruciform DNA and repair intermediates such as nick, gap, bulge, etc. To understand the features of HU binding to DNA and repair intermediates, a fast and easy HU protein purification method is required. Here we report a two-step purification procedure of HU from Halobacillus karajensis (the gram positive and moderately halophilic bacteria isolated from Karaj surface soil. The method of HU purification allows obtaining a pure non-tagged protein. Salting out and ion exchange chromatography were applied for purification, and the purified protein was identified by immunoblotting. Results showed that the molecular weight of the purified protein was approximately 11 kDa which is immunologically similar to the Bacillus subtilis HU protein (HBsu.

  1. Sparks sädeleb Rabarocki öös. Ettevaatust! Eliidi rünnak. Hu? Hu da hell?

    Index Scriptorium Estoniae

    2007-01-01

    Ameerika ansamblist Sparks. Vaiko Eplik & Eliit heliplaatidest "1: Aastaajad", "2: Aastaajad" ja "3: Kosmoseodüsseia", esinemisest festivalil Rabarock. Hannaliisa Uusma, Leslie Da Bassi ja DJ Criticali projektist HU?, singlitest "Kosmos" ja "Absoluutselt" (Rabarockil esitusel materjal HU? debüütalbumilt "Film")

  2. Sparks sädeleb Rabarocki öös. Ettevaatust! Eliidi rünnak. Hu? Hu da hell?

    Index Scriptorium Estoniae

    2007-01-01

    Ameerika ansamblist Sparks. Vaiko Eplik & Eliit heliplaatidest "1: Aastaajad", "2: Aastaajad" ja "3: Kosmoseodüsseia", esinemisest festivalil Rabarock. Hannaliisa Uusma, Leslie Da Bassi ja DJ Criticali projektist HU?, singlitest "Kosmos" ja "Absoluutselt" (Rabarockil esitusel materjal HU? debüütalbumilt "Film")

  3. Testing the planetary models of HU Aquarii

    CERN Document Server

    Bours, M; Breedt, E; Copperwheat, C; Dhillon, V; Leckngam, A; Littlefair, S; Parsons, S; Prasit, A

    2014-01-01

    We present new eclipse observations of the polar (i.e. semi-detached magnetic white dwarf + M-dwarf binary) HU Aqr, and mid-egress times for each eclipse, which continue to be observed increasingly early. Recent eclipses occurred more than 70 seconds earlier than the prediction from the latest model that invoked a single circumbinary planet to explain the observed orbital period variations, thereby conclusively proving this model to be incorrect. Using ULTRACAM data, we show that mid-egress times determined for simultaneous data taken at different wavelengths agree with each other. The large variations in the observed eclipse times cannot be explained by planetary models containing up to three planets, because of poor fits to the data as well as orbital instability on short time scales. The peak-to-peak amplitude of the O-C diagram of almost 140 seconds is also too great to be caused by Applegate's mechanism, movement of the accretion spot on the surface of the white dwarf, or by asynchronous rotation of the ...

  4. PKCε promotes HuD-mediated neprilysin mRNA stability and enhances neprilysin-induced Aβ degradation in brain neurons.

    Directory of Open Access Journals (Sweden)

    Chol Seung Lim

    Full Text Available Amyloid-beta (Aβ peptide accumulation in the brain is a pathological hallmark of all forms of Alzheimer's disease. An imbalance between Aβ production and clearance from the brain may contribute to accumulation of neurotoxic Aβ and subsequent synaptic loss, which is the strongest correlate of the extent of memory loss in AD. The activity of neprilysin (NEP, a potent Aβ-degrading enzyme, is decreased in the AD brain. Expression of HuD, an mRNA-binding protein important for synaptogenesis and neuronal plasticity, is also decreased in the AD brain. HuD is regulated by protein kinase Cε (PKCε, and we previously demonstrated that PKCε activation decreases Aβ levels. We hypothesized that PKCε acts through HuD to stabilize NEP mRNA, modulate its localization, and support NEP activity. Conversely, loss of PKCε-activated HuD in AD leads to decreased NEP activity and accumulation of Aβ. Here we show that HuD is associated with NEP mRNA in cultures of human SK-N-SH cells. Treatment with bryostatin, a PKCε-selective activator, enhanced NEP association with HuD and increased NEP mRNA stability. Activation of PKCε also increased NEP protein levels, increased NEP phosphorylation, and induced cell surface expression. In addition, specific PKCε activation directly stimulated NEP activity, leading to degradation of a monomeric form of Aβ peptide and decreased Aβ neuronal toxicity, as measured by cell viability. Bryostatin treatment also rescued Aβ-mediated inhibition of HuD-NEP mRNA binding, NEP protein expression, and NEP cell membrane translocation. These results suggest that PKCε activation reduces Aβ by up-regulating, via the mRNA-binding protein HuD, Aβ-degrading enzymes such as NEP. Thus, PKCε activation may have therapeutic efficacy for AD by reducing neurotoxic Aβ accumulation as well as having direct anti-apoptotic and synaptogenic effects.

  5. CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency.

    Science.gov (United States)

    Smoum, Reem; Baraghithy, Saja; Chourasia, Mukesh; Breuer, Aviva; Mussai, Naama; Attar-Namdar, Malka; Kogan, Natalya M; Raphael, Bitya; Bolognini, Daniele; Cascio, Maria G; Marini, Pietro; Pertwee, Roger G; Shurki, Avital; Mechoulam, Raphael; Bab, Itai

    2015-07-14

    Activation of the CB2 receptor is apparently an endogenous protective mechanism. Thus, it restrains inflammation and protects the skeleton against age-related bone loss. However, the endogenous cannabinoids, as well as Δ(9)-tetrahydrocannabinol, the main plant psychoactive constituent, activate both cannabinoid receptors, CB1 and CB2. HU-308 was among the first synthetic, selective CB2 agonists. HU-308 is antiosteoporotic and antiinflammatory. Here we show that the HU-308 enantiomer, designated HU-433, is 3-4 orders of magnitude more potent in osteoblast proliferation and osteoclast differentiation culture systems, as well as in mouse models, for the rescue of ovariectomy-induced bone loss and ear inflammation. HU-433 retains the HU-308 specificity for CB2, as shown by its failure to bind to the CB1 cannabinoid receptor, and has no activity in CB2-deficient cells and animals. Surprisingly, the CB2 binding affinity of HU-433 in terms of [(3)H]CP55,940 displacement and its effect on [(35)S]GTPγS accumulation is substantially lower compared with HU-308. A molecular-modeling analysis suggests that HU-433 and -308 have two different binding conformations within CB2, with one of them possibly responsible for the affinity difference, involving [(35)S]GTPγS and cAMP synthesis. Hence, different ligands may have different orientations relative to the same binding site. This situation questions the usefulness of universal radioligands for comparative binding studies. Moreover, orientation-targeted ligands have promising potential for the pharmacological activation of distinct processes.

  6. On the HU Aquarii planetary system hypothesis

    Science.gov (United States)

    Goździewski, Krzysztof; Nasiroglu, Ilham; Słowikowska, Aga; Beuermann, Klaus; Kanbach, Gottfried; Gauza, Bartosz; Maciejewski, Andrzej J.; Schwarz, Robert; Schwope, Axel D.; Hinse, Tobias C.; Haghighipour, Nader; Burwitz, Vadim; Słonina, Mariusz; Rau, Arne

    2012-09-01

    In this paper, we investigate the eclipse timing of the polar binary HU Aquarii that has been observed for almost two decades. Recently, Qian et al. attributed large (O-C) deviations between the eclipse ephemeris and observations to a compact system of two massive Jovian companions. We improve the Keplerian, kinematic model of the light travel time effect and re-analyse the whole currently available data set. We add almost 60 new, yet unpublished, mostly precision light curves obtained using the time high-resolution photopolarimeter Optical Timing Analyzer (OPTIMA), as well as photometric observations performed at the Monitoring Network of Telescopes/North, Physics Innovations Robotic Astronomical Telescope Explorer and Carlos Sánchez Telescope. We determine new mid-egress times with a mean uncertainty at the level of 1 s or better. We claim that because the observations that currently exist in the literature are non-homogeneous with respect to spectral windows (ultraviolet, X-ray, visual and polarimetric mode) and the reported mid-egress measurements errors, they may introduce systematics that affect orbital fits. Indeed, we find that the published data, when taken literally, cannot be explained by any unique solution. Many qualitatively different and best-fit two-planet configurations, including self-consistent, Newtonian N-body solutions may be able to explain the data. However, using high-resolution, precision OPTIMA light curves, we find that the (O-C) deviations are best explained by the presence of a single circumbinary companion orbiting at a distance of ˜4.5 au with a small eccentricity and having ˜7 Jupiter masses. This object could be the next circumbinary planet detected from the ground, similar to the announced companions around close binaries HW Vir, NN Ser, UZ For, DP Leo, FS Aur or SZ Her, and planets of this type around Kepler-16, Kepler-34 and Kepler-35.

  7. Bad Beta, Good Beta

    OpenAIRE

    Campbell, John; Vuolteenaho, Tuomo

    2003-01-01

    This paper explains the size and value "anomalies" in stock returns using an economically motivated two-beta model. We break the beta of a stock with the market portfolio into two components, one reflecting news about the market's future cash flows and one reflecting news about the market's discount rates. Intertemporal asset pricing theory suggests that the former should have a higher price of risk; thus beta, like cholesterol, comes in "had" and "good" varieties. Empirically, we find that v...

  8. Hu Shi's Study of Chinese Medieval intellectual History

    Institute of Scientific and Technical Information of China (English)

    Lou Yulie

    2006-01-01

    Hu Shi frequently gave lectures on the history of Chinese philosophy,especially the history of ancient Chinese philosophy,from the year 1919 to 1937.A large number of papers and dissertations published during this period are related to his research on this topic.In his opinion,there are three characteristics of the history of ancient Chinese philosophy:" religionalization of thought," "Indianization of philosophy," and "conflict between Chinese thought and Indian thought." In this paper,I explore Hu Shi's deep insight into the religionalization of Confucianism in Han dynasty and into the thought of Taoism in the medieval times.

  9. The pharmacokinetics, distribution and degradation of human recombinant interleukin 1 beta in normal rats

    DEFF Research Database (Denmark)

    Reimers, J; Wogensen, L D; Welinder, B

    1991-01-01

    Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half-lives of distribut......Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half......-lives of distribution (T1/2 alpha) and elimination phases (T1/2 beta) of human recombinant interleukin 1 beta (rIL-1 beta), and its tissue distribution and cellular localization by means of mono-labelled, biologically active 125I-rIL-1 beta. After intravenous (i.v.) injection, 125I-rIL-1 beta was eliminated from...

  10. The pharmacokinetics, distribution and degradation of human recombinant interleukin 1 beta in normal rats

    DEFF Research Database (Denmark)

    Wogensen, L D; Welinder, B; Hejnaes, K R

    1991-01-01

    -lives of distribution (T1/2 alpha) and elimination phases (T1/2 beta) of human recombinant interleukin 1 beta (rIL-1 beta), and its tissue distribution and cellular localization by means of mono-labelled, biologically active 125I-rIL-1 beta. After intravenous (i.v.) injection, 125I-rIL-1 beta was eliminated from......Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half...... the circulation with a T1/2 alpha of 2.9 min and a T1/2 beta of 41.1 min. The central and peripheral volume of distribution was 20.7 and 19.1 ml/rat, respectively, and the metabolic clearance rate was 16.9 ml/min/kg. The kidney and liver showed the highest accumulation of tracer, and autoradiography demonstrated...

  11. Treatment of β-Thalassemia With Hydroxyurea (HU)——Effects of HU on Globin Gene Expression

    Institute of Scientific and Technical Information of China (English)

    黄淑帧; 任兆瑞; 陈美珏; 许洪平; 曾溢滔; G.P.Rodgers; 曾凡一; A.N.Schechter

    1994-01-01

    A newly developed method of RT-PCR/competitive PCR for measuring the relative and ab-solute content of globin mRNAs as well as micro-globin chain biosynthetic assay have been used to study thealterations of globin gene expressions in the patients with β-thalassemia pre-and post-hydroxyurea(HU)treatment.It was found for the first time that HU had the effect of enhancing β-globin gene expression insome patients.Two cases with β-thalassemia who were subjected to HU treatment for over two years showeda marked increase in β-globin mRNA level and β-globin chain synthesis,resulting in more effective erythro-poiesis and the alleviation of clinical symptoms.

  12. HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid.

    Science.gov (United States)

    Haj, Christeene G; Sumariwalla, Percy F; Hanuš, Lumír; Kogan, Natalya M; Yektin, Zhana; Mechoulam, Raphael; Feldmann, Mark; Gallily, Ruth

    2015-10-01

    Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ(9)-tetrahydrocannabinol (Δ(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases.

  13. HuR in pheochromocytomas and paragangliomas - overexpression in verified malignant tumors.

    Science.gov (United States)

    Leijon, Helena; Salmenkivi, Kaisa; Heiskanen, Ilkka; Hagström, Jaana; Louhimo, Johanna; Heikkilä, Päivi; Ristimäki, Ari; Paavonen, Timo; Metso, Saara; Mäenpää, Hanna; Haglund, Caj; Arola, Johanna

    2016-09-01

    Pheochromocytomas and paragangliomas are rare, neural crest-originating, neuroendocrine tumors. HuR is an mRNA-binding protein of the ELAV/Hu-protein family, which participates in posttranscriptional regulation of many cancer-associated genes. HuR expression has been connected with aggressive behavior of several malignancies. Cyclooxygenase-2 (COX-2) is also expressed in several malignant tumors, and its expression is regulated by HuR. Tissue microarray of 153 primary pheochromocytomas and paragangliomas was investigated for the expression of HuR and COX-2 proteins by immunohistochemistry using two different HuR antibodies (HuR19F12 and HuR3A). In these tumors, the expression of both intranuclear and cytoplasmic HuR was detectable. Increased cytoplasmic HuR expression was significantly associated with metastatic tumors. Increased COX-2 and MIB-1 expression also was associated with metastatic potential, and moreover, HuR and COX-2 expression correlated with each other. Our data suggest that increased expression of HuR protein is associated with metastatic potential of paragangliomas and pheochromocytomas, and COX-2 seems to be a target of HuR.

  14. Structure-based analysis of HU-DNA binding.

    Science.gov (United States)

    Swinger, Kerren K; Rice, Phoebe A

    2007-01-26

    HU and IHF are prokaryotic proteins that induce very large bends in DNA. They are present in high concentrations in the bacterial nucleoid and aid in chromosomal compaction. They also function as regulatory cofactors in many processes, such as site-specific recombination and the initiation of replication and transcription. HU and IHF have become paradigms for understanding DNA bending and indirect readout of sequence. While IHF shows significant sequence specificity, HU binds preferentially to certain damaged or distorted DNAs. However, none of the structurally diverse HU substrates previously studied in vitro is identical with the distorted substrates in the recently published Anabaena HU(AHU)-DNA cocrystal structures. Here, we report binding affinities for AHU and the DNA in the cocrystal structures. The binding free energies for formation of these AHU-DNA complexes range from approximately 10-14.5 kcal/mol, representing K(d) values in the nanomolar to low picomolar range, and a maximum stabilization of at least approximately 6.3 kcal/mol relative to complexes with undistorted, non-specific DNA. We investigated IHF binding and found that appropriate structural distortions can greatly enhance its affinity. On the basis of the coupling of structural and relevant binding data, we estimate the amount of conformational strain in an IHF-mediated DNA kink that is relieved by a nick (at least 0.76 kcal/mol) and pinpoint the location of the strain. We show that AHU has a sequence preference for an A+T-rich region in the center of its DNA-binding site, correlating with an unusually narrow minor groove. This is similar to sequence preferences shown by the eukaryotic nucleosome.

  15. Structure-based Analysis to Hu-DNA Binding

    Energy Technology Data Exchange (ETDEWEB)

    Swinger,K.; Rice, P.

    2007-01-01

    HU and IHF are prokaryotic proteins that induce very large bends in DNA. They are present in high concentrations in the bacterial nucleoid and aid in chromosomal compaction. They also function as regulatory cofactors in many processes, such as site-specific recombination and the initiation of replication and transcription. HU and IHF have become paradigms for understanding DNA bending and indirect readout of sequence. While IHF shows significant sequence specificity, HU binds preferentially to certain damaged or distorted DNAs. However, none of the structurally diverse HU substrates previously studied in vitro is identical with the distorted substrates in the recently published Anabaena HU(AHU)-DNA cocrystal structures. Here, we report binding affinities for AHU and the DNA in the cocrystal structures. The binding free energies for formation of these AHU-DNA complexes range from 10-14.5 kcal/mol, representing K{sub d} values in the nanomolar to low picomolar range, and a maximum stabilization of at least 6.3 kcal/mol relative to complexes with undistorted, non-specific DNA. We investigated IHF binding and found that appropriate structural distortions can greatly enhance its affinity. On the basis of the coupling of structural and relevant binding data, we estimate the amount of conformational strain in an IHF-mediated DNA kink that is relieved by a nick (at least 0.76 kcal/mol) and pinpoint the location of the strain. We show that AHU has a sequence preference for an A+T-rich region in the center of its DNA-binding site, correlating with an unusually narrow minor groove. This is similar to sequence preferences shown by the eukaryotic nucleosome.

  16. HU-GFP and DAPI co-localize on the Escherichia coli nucleoid.

    Science.gov (United States)

    Wery, M; Woldringh, C L; Rouviere-Yaniv, J

    2001-02-01

    The heterodimeric HU protein, one of the most abundant DNA binding proteins, plays a pleiotropic role in bacteria. Among others, HU was shown to contribute to the maintenance of DNA superhelical density in Escherichia coli. By its properties HU shares some traits with histones and HMG proteins. More recently, its specific binding to DNA recombination and repair intermediates suggests that HU should be considered as a DNA damage sensor. For all these reasons, it will be of interest to follow the localization of HU within the living bacterial cells. To this end, we constructed HU-GFP fusion proteins and compared by microscopy the GFP green fluorescence with images of the nucleoid after DAPI staining. We show that DAPI and HU-GFP colocalize on the E. coli nucleoid. HU, therefore, can be considered as a natural tracer of DNA in the living bacterial cell.

  17. Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors

    Science.gov (United States)

    Bhowmick, Tuhin; Ghosh, Soumitra; Dixit, Karuna; Ganesan, Varsha; Ramagopal, Udupi A.; Dey, Debayan; Sarma, Siddhartha P.; Ramakumar, Suryanarayanarao; Nagaraja, Valakunja

    2014-06-01

    The nucleoid-associated protein HU plays an important role in maintenance of chromosomal architecture and in global regulation of DNA transactions in bacteria. Although HU is essential for growth in Mycobacterium tuberculosis (Mtb), there have been no reported attempts to perturb HU function with small molecules. Here we report the crystal structure of the N-terminal domain of HU from Mtb. We identify a core region within the HU-DNA interface that can be targeted using stilbene derivatives. These small molecules specifically inhibit HU-DNA binding, disrupt nucleoid architecture and reduce Mtb growth. The stilbene inhibitors induce gene expression changes in Mtb that resemble those induced by HU deficiency. Our results indicate that HU is a potential target for the development of therapies against tuberculosis.

  18. Beta Thalassemia

    Science.gov (United States)

    Beta thalassemia is found in people of Mediterranean, Middle Eastern, African, South Asian (Indian, Pakistani, etc.), Southeast Asian and Chinese descent. 1 Beta Thalassemia ßß Normal beta globin genes found on chromosomes ...

  19. Genesis Research与Morphosys扩展HuCAL抗体协议

    Institute of Scientific and Technical Information of China (English)

    黄晓燕(摘)

    2008-01-01

    Genesis Research与Morphosys扩展协议后,靶向FGFR5蛋白的抗体将继续作为其研究的焦点。Genesis将利用Morphosys分公司Serotec开发的人组织抗体库(HuCAL)继续开发成纤维细胞生长因子受体5(FGFR5)靶点。

  20. HuCOP1 contributes to the regulation of DNA repair in keratinocytes.

    Science.gov (United States)

    Fazekas, B; Carty, M P; Németh, I; Kemény, L; Széll, M; Ádám, É

    2017-03-01

    We have previously demonstrated that the E3 ligase Human Constitutive Photomorphogenic Protein (huCOP1) is expressed in human keratinocytes and negatively regulates p53. The MutS homolog 2 (MSH2) protein plays a central role in DNA MMR mechanism and is implicated in the cellular response to anticancer agents, such as cisplatin. Our aim was to clarify whether huCOP1 plays a role in DNA MMR by affecting MSH2 protein level in human keratinocytes. To define the role of huCOP1 in DNA mismatch repair, we determined whether huCOP1 affects MSH2 abundance. MSH2 protein level was detected by immunocytochemical staining using a keratinocyte cell line in which the expression level of huCOP1 was stably decreased (siCOP1). To investigate whether huCOP1 silencing influences cisplatin-induced cell death, control and siCOP1 keratinocyte cells were treated with increasing concentrations of cisplatin and cell viability was recorded after 48 and 96 h. Stable silencing of huCOP1 in human keratinocytes resulted in a reduced level of MSH2 protein. huCOP1 silencing also sensitized keratinocytes to the interstrand crosslinking inducer cisplatin. Our results indicate that decreased huCOP1 correlates with lower MSH2 levels. These protein level changes lead to increased sensitivity toward cisplatin treatment, implicating that huCOP1 plays a positive role in maintaining genome integrity in human keratinocytes.

  1. Low level anti-Hu reactivity: a risk marker for small cell lung cancer?

    Science.gov (United States)

    Tsou, Jeffrey A.; Kazarian, Meleeneh; Patel, Ankur; Galler, Janice S.; Laird-Offringa, Ite A.; Carpenter, Catherine L.; London, Stephanie J.

    2010-01-01

    Background Previous experimental and laboratory studies have implicated antibodies against Hu proteins (anti-Hu) as a potential marker for small cell lung cancer (SCLC); there are no estimates of the association between anti-Hu and SCLC using a population-based design. Methods We used stored plasma specimens to evaluate anti-Hu reactivity in relationship to small cell lung cancer in a population-based case-control study. Using Western Blot analysis, we measured anti-Hu reactivity against recombinant Hu family member, HuD, in plasma samples from forty-one (41) SCLC cases and seventy-nine (79) controls individually matched for age, race, sex, and smoking status (never, past, current). We analyzed the association between anti-Hu reactivity and SCLC using conditional logistic regression. Results Anti-Hu reactivity was associated with SCLC, both before and after adjustment for amount of smoking. We observed a smoking-adjusted odds ratio of 3.2 (95 % confidence interval from 0.98 to 13.4) comparing subjects above 1800 units (the lower limit of the second tertile of the distribution among antibody positive controls) to subjects with lower reactivity. We also found suggestive evidence in follow-up of our cases that anti-Hu above 1800 units was related to longer-term survival from SCLC. The present research is the first report of anti-Hu reactivity and SCLC in a population-based study. Conclusions Given the suggestive evidence in this study, prospective analyses to examine whether anti-Hu reactivity might predict risk of developing SCLC, or whether anti-Hu reactivity could serve as an early marker for SCLC, may be warranted. PMID:19070439

  2. IHF and HU: flexible architects of bent DNA.

    Science.gov (United States)

    Swinger, Kerren K; Rice, Phoebe A

    2004-02-01

    The energetic cost of bending short segments of DNA is very high. This bending is critical for the packaging of DNA and is exploited to regulate many cellular processes. In prokaryotes, IHF and HU are key architectural proteins present at high concentrations. New protein-DNA co-crystal structures, and the adaptation of advanced biophysical and biochemical techniques have led to an improved understanding of how these proteins interact with DNA. These techniques include time-resolved synchrotron X-ray footprinting, differential scanning calorimetry, isothermal titration calorimetry and single-molecule experiments.

  3. HuPSON: the human physiology simulation ontology.

    Science.gov (United States)

    Gündel, Michaela; Younesi, Erfan; Malhotra, Ashutosh; Wang, Jiali; Li, Hui; Zhang, Bijun; de Bono, Bernard; Mevissen, Heinz-Theodor; Hofmann-Apitius, Martin

    2013-11-22

    Large biomedical simulation initiatives, such as the Virtual Physiological Human (VPH), are substantially dependent on controlled vocabularies to facilitate the exchange of information, of data and of models. Hindering these initiatives is a lack of a comprehensive ontology that covers the essential concepts of the simulation domain. We propose a first version of a newly constructed ontology, HuPSON, as a basis for shared semantics and interoperability of simulations, of models, of algorithms and of other resources in this domain. The ontology is based on the Basic Formal Ontology, and adheres to the MIREOT principles; the constructed ontology has been evaluated via structural features, competency questions and use case scenarios.The ontology is freely available at: http://www.scai.fraunhofer.de/en/business-research-areas/bioinformatics/downloads.html (owl files) and http://bishop.scai.fraunhofer.de/scaiview/ (browser). HuPSON provides a framework for a) annotating simulation experiments, b) retrieving relevant information that are required for modelling, c) enabling interoperability of algorithmic approaches used in biomedical simulation, d) comparing simulation results and e) linking knowledge-based approaches to simulation-based approaches. It is meant to foster a more rapid uptake of semantic technologies in the modelling and simulation domain, with particular focus on the VPH domain.

  4. SUPPORT FOR HU CFRT SUMMER HIGH SCHOOL FUSION WORKSHOP

    Energy Technology Data Exchange (ETDEWEB)

    Punjabi, Alkesh

    2010-02-09

    Nine summer fusion science research workshops for minority and female high school students were conducted at the Hampton University Center for Fusion Research and Training from 1996 to 2005. Each workshop was of the duration of eight weeks. In all 35 high school students were mentored. The students presented 28 contributed papers at the annual meetings of the American Physical Society Division of Plasma Physics. These contributed papers were very well received by the plasma physics and fusion science research community. The students won a number of prestigious local, state, and national honors, awards, prizes, and scholarships. The notable among these are the two regional finalist positions in the 1999 Siemens-Westinghouse Science and Technology Competitions; 1st Place U.S. Army Award, 2006; 1st Place U.S. Naval Science Award, 2006; Yale Science and Engineering Association Best 11th Grade Project, 2006; Society of Physics Students Book Award, 2006; APS Corporate Minority Scholarship and others. This workshop program conducted by the HU CFRT has been an exemplary success, and served the minority and female students exceptionally fruitfully. The Summer High School Fusion Science Workshop is an immensely successful outreach activity conducted by the HU CFRT. In this workshop, we train, motivate, and provide high quality research experiences to young and talented high school scholars with emphasis on under-represented minorities and female students in fusion science and related areas. The purpose of this workshop is to expose minority and female students to the excitement of research in science at an early stage in their academic lives. It is our hope that this may lead the high school students to pursue higher education and careers in physical sciences, mathematics, and perhaps in fusion science. To our knowledge, this workshop is the first and only one to date, of fusion science for under-represented minorities and female high school students at an HBCU. The faculty

  5. Adaptive and maladaptive expression of the mRNA regulatory protein HuR

    Institute of Scientific and Technical Information of China (English)

    Suman; Govindaraju; Beth; S; Lee

    2013-01-01

    The RNA-binding proteins involved in regulation of mRNA post-transcriptional processing and translation control the fates of thousands of mRNA transcripts and basic cellular processes. The best studied of these, HuR, is well characterized as a mediator of mRNA stability and translation, and more recently, as a factor in nuclear functions such as pre-mRNA splicing. Due to HuR’s role in regulating thousands of mRNA transcripts, including those for other RNA-binding proteins, HuR can act as a master regulator of cell survival and proliferation. HuR itself is subject to multiple post-translationa modifications including regulation of its nucleocytoplasmic distribution. However, the mechanisms that govern HuR levels in the cell have only recently begun to be defined. These mechanisms are critical to cell health, as it has become clear in recent years that aberrant expression of HuR can lead alternately to decreased cell viability or to promotion of pathological proliferation and invasiveness. HuR is expressed as alternate mRNAs that vary in their untranslated regions, leading to differences in transcript stability and translatability. Multiple transcription factors and modulators of mRNA stability that regulate HuR mRNA expression have been identified. In addition, translation of HuR is regulated by numerous microRNAs, several of which have been demonstrated to have anti-tumor properties due to their suppression of HuR expression. This review summarizes the current state of knowledge of the factors that regulate HuR expression, along with the circumstances under which these factors contribute to cancer and inflammation.

  6. Fingerprint Recognition Using Local Features and Hu Moments

    Directory of Open Access Journals (Sweden)

    G. Aguilar-Torres

    2012-10-01

    Full Text Available Person identification systems based on fingerprint patterns called Automatic Fingerprint Identification Systems, AFIS,are some of the most widely used biometric methods since they provide a high degree of success. The accuracy ofAFIS is mainly due to some unique characteristics called minutiae, which are points where a curve track finishes,intersects with another curve track, or branches off. During past decades several efficient minutia-based fingerprintrecognition algorithms have been proposed which achieve false recognition rates close to 1%, however, theirrecognition rate may be still improved. To this end, this paper presents a fingerprint recognition method using acombination of the Fast Fourier Transform (FFT with Gabor filters for image enhancement. Next, fingerprintrecognition is carried out using a novel recognition stage based on Local Features and Hu invariant moments forverification.

  7. SUPPORT FOR HU CFRT SUMMER HIGH SCHOOL FUSION WORKSHOP

    Energy Technology Data Exchange (ETDEWEB)

    Punjabi, Alkesh

    2010-02-09

    Nine summer fusion science research workshops for minority and female high school students were conducted at the Hampton University Center for Fusion Research and Training from 1996 to 2005. Each workshop was of the duration of eight weeks. In all 35 high school students were mentored. The students presented 28 contributed papers at the annual meetings of the American Physical Society Division of Plasma Physics. These contributed papers were very well received by the plasma physics and fusion science research community. The students won a number of prestigious local, state, and national honors, awards, prizes, and scholarships. The notable among these are the two regional finalist positions in the 1999 Siemens-Westinghouse Science and Technology Competitions; 1st Place U.S. Army Award, 2006; 1st Place U.S. Naval Science Award, 2006; Yale Science and Engineering Association Best 11th Grade Project, 2006; Society of Physics Students Book Award, 2006; APS Corporate Minority Scholarship and others. This workshop program conducted by the HU CFRT has been an exemplary success, and served the minority and female students exceptionally fruitfully. The Summer High School Fusion Science Workshop is an immensely successful outreach activity conducted by the HU CFRT. In this workshop, we train, motivate, and provide high quality research experiences to young and talented high school scholars with emphasis on under-represented minorities and female students in fusion science and related areas. The purpose of this workshop is to expose minority and female students to the excitement of research in science at an early stage in their academic lives. It is our hope that this may lead the high school students to pursue higher education and careers in physical sciences, mathematics, and perhaps in fusion science. To our knowledge, this workshop is the first and only one to date, of fusion science for under-represented minorities and female high school students at an HBCU. The faculty

  8. “Meticulous Crafting” and “Plain Style”: Hu Shi's Prose

    Institute of Scientific and Technical Information of China (English)

    ChenPingyuan; ZhuShida; DavidKelly

    2004-01-01

    Hu Shi's Outline History of Chinese Philosophy, despite a number of shortcomings, opened a new era for an academic prose in vernacular Chinese. Hu set great store by the structural features of a """"work,"""" arguing that it was not enough to assemble quotes,

  9. A Meta Analysis and Hierarchical Classification of HU-Based Atherosclerotic Plaque Characterization Criteria

    NARCIS (Netherlands)

    Kristanto, Wisnumurti; van Ooijen, Peter M. A.; Jansen-van der Weide, Marijke C.; Vliegenthart, Rozemarijn; Oudkerk, Matthijs

    2013-01-01

    Background: Many computed tomography (CT) studies have reported that lipid-rich, presumably rupture-prone atherosclerotic plaques can be characterized according to their Hounsfield Unit (HU) value. However, the published HU-based characterization criteria vary considerably. The present study aims to

  10. HuD Regulates Coding and Noncoding RNA to Induce APP→Aβ Processing

    Directory of Open Access Journals (Sweden)

    Min-Ju Kang

    2014-06-01

    Full Text Available The primarily neuronal RNA-binding protein HuD is implicated in learning and memory. Here, we report the identification of several HuD target transcripts linked to Alzheimer’s disease (AD pathogenesis. HuD interacted with the 3′ UTRs of APP mRNA (encoding amyloid precursor protein and BACE1 mRNA (encoding β-site APP-cleaving enzyme 1 and increased the half-lives of these mRNAs. HuD also associated with and stabilized the long noncoding (lncRNA BACE1AS, which partly complements BACE1 mRNA and enhances BACE1 expression. Consistent with HuD promoting production of APP and APP-cleaving enzyme, the levels of APP, BACE1, BACE1AS, and Aβ were higher in the brain of HuD-overexpressing mice. Importantly, cortex (superior temporal gyrus from patients with AD displayed significantly higher levels of HuD and, accordingly, elevated APP, BACE1, BACE1AS, and Aβ than did cortical tissue from healthy age-matched individuals. We propose that HuD jointly promotes the production of APP and the cleavage of its amyloidogenic fragment, Aβ.

  11. Immune response in lung cancer mouse model mimics human anti-Hu reactivity

    Science.gov (United States)

    Kazarian, Meleeneh; Calbo, Joaquim; Proost, Natalie; Carpenter, Catherine L.; Berns, Anton; Laird-Offringa, Ite A.

    2009-01-01

    Most patients with paraneoplastic encephalomyelitis/sensory neuronopathy PEM/SN have small-cell lung cancer (SCLC) and develop antibodies against neuronal-specific Hu proteins, which are abnormally expressed in the tumor. Anti-Hu reactivity is present in ~16% of SCLC patients without PEM/SN. Here we test the hypothesis that engineered SCLC-prone mice may exhibit anti-Hu reactivity. We show that tumors from SCLC-prone mice misexpress Hu proteins, and 14% of mice harbor anti-Hu antibodies. Mice appear to show reactivity prior to clinical diagnosis of SCLC. This mouse model system will be useful to study SCLC-associated autoimmunity, its diagnostic value, and the potential protective role of oncoantigen-directed autoantibodies. PMID:19765830

  12. HuR knockdown changes the oncogenic potential of oral cancer cells.

    Science.gov (United States)

    Kakuguchi, Wataru; Kitamura, Tetsuya; Kuroshima, Takeshi; Ishikawa, Makoto; Kitagawa, Yoshimasa; Totsuka, Yasunori; Shindoh, Masanobu; Higashino, Fumihiro

    2010-04-01

    HuR binds to AU-rich element-containing mRNA to protect them from rapid degradation. Here, we show that knockdown of HuR changes the oncogenic properties of oral cancer cells. Oral squamous cell carcinoma cell lines, HSC-3 and Ca9.22, which express HuR protein and cytoplasmic AU-rich element mRNA more abundantly than normal cells, were subjected to HuR knockdown. In the HuR-knockdown cancer cells, the cytoplasmic expression of c-fos, c-myc, and COX-2 mRNAs was inhibited compared with those in cells that had been transfected with a control small interfering RNA, and the half-lives of these mRNAs were shorter than those of their counterparts in the control cells. HuR-knockdown cells failed to make colonies in soft agar, suggesting that the cells had lost their ability for anchorage-independent cell growth. Additionally, the motile and invasive activities of the cells decreased remarkably by HuR knockdown. Furthermore, the expression of cell cycle-related proteins, such as cyclin A, cyclin B1, cyclin D1, and cyclin-dependent kinase 1, was reduced in HuR-knockdown cancer cells, and HuR bound to cdk1 mRNA to stabilize it. These findings suggest that HuR knockdown changes the features of oral cancer cells, at least in part, by affecting their cell cycle and shows potential as an effective therapeutic approach.

  13. Regulation of the mRNA-binding protein HuR by posttranslational modification: spotlight on phosphorylation.

    Science.gov (United States)

    Eberhardt, Wolfgang; Doller, Anke; Pfeilschifter, Josef

    2012-06-01

    The ubiquitous mRNA-binding protein human antigen R (HuR) and its neuronal relatives (HuB, HuC, HuD) participate in the post-transcriptional regulation of many AU-rich element-bearing mRNAs. In addition to its originally described role in controlling mRNA decay, the binding of HuR to target mRNAs can affect many aspects of mRNA processing including splicing, polyadenylation, intracellular trafficking, translation and modulation of mRNA repression by miRNAs. In accordance to the growing list of signalling events which are involved in regulating these different HuR functions, recent data implicate that posttranslational modification, namely protein kinase-triggered phosphorylation of HuR plays a crucial role in connecting extracellular signal inputs to a specific post-transcriptional program by HuR. Notably, in addition to directly targeting HuR functions, posttranslational modifications of HuR have a major impact on the sequestration and binding to various HuR ligand proteins as has been demonstrated e.g. for the 14-3-3 chaperones. However, the detailed mechanisms of how a specific modification of HuR coordinates different aspects in HuR regulation are currently poorly understood. Due to the fact that most of the described HuR activities are closely related to its subcellular localization and the binding to cargo mRNA, this review will focus on these aspects of HuR functions and their control by posttranslational modification, particularly by HuR phosphorylations by different protein kinases.

  14. Structural characterization of the maytansinoid–monoclonal antibody immunoconjugate, huN901–DM1, by mass spectrometry

    National Research Council Canada - National Science Library

    Wang, Lintao; Amphlett, Godfrey; Blättler, Walter A; Lambert, John M; Zhang, Wei

    2005-01-01

    ...‐specific drug delivery. The immunoconjugate, huN901–DM1, composed of the humanized monoclonal IgG 1 antibody, huN901, and the maytansinoid drug, DM1, is being tested in clinical trials to treat small cell lung carcinoma (SCLC). huN901...

  15. Measurement of hard tissue density of head phantom based on the HU by using CBCT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moon Sun; Kang, Dong Wan; Kim, Jae Duk [School of Dentistry, Chosun University, Gwangju (Korea, Republic of)

    2009-09-15

    The purpose of this study was to determine a conversion coefficient for Hounsfield Units(HU) to material density (g cm{sup -3}) obtained from cone-beam computed tomography (CBMercuRay{sup TM}) data and to measure the hard tissue density based on the Hounsfield scale on dental head phantom. CT Scanner Phantom (AAPM) equipped with CT Number Insert consists of five cylindrical pins of materials with different densities and teflon ring was scanned by using the CBMercuRay{sup TM} (Hitachi, Tokyo, Japan) volume scanner. The raw data were converted into DICOM format and the HU of different areas of CT number insert measured by using CBWorks{sup TM}. Linear regression analysis and Student t-test were performed statistically. There was no significant difference (P>0.54) between real densities and measured densities. A linear regression was performed using the density, {rho} (g cm{sup -3}), as the dependent variable in terms of the HU (H). The regression equation obtained was {rho}=0.00072 H-0.01588 with an R2 value of 0.9968. Density values based on the Hounsfield scale was 1697.1 {+-} 24.9 HU in cortical bone, 526.5 {+-} 44.4 HU in trabecular bone, 2639.1 {+-} 48.7 HU in enamel, 1246.1 {+-} 39.4 HU in dentin of dental head phantom. CBCT provides an effective option for determination of material density expressed as Hounsfield Units.

  16. On the ephemeris of the eclipsing polar HU Aquarii

    CERN Document Server

    Schwope, A D

    2014-01-01

    The magnetic cataclysmic variable HU Aquarii displayed pronounced quasi-periodic modulations of its eclipse timing. These were interpreted in terms of the light-travel time (LTT) effect caused by a circumbinary planet or planetary system. We report new photometric observations that revealed another precise eclipse timing for the October 2013 epoch, the first obtained in a high accretion state after many years in low or intermediate states. The eclipse was observed to occur earlier by 95.3 +- 2.0 s or 62.8 +- 2.0 s than expected for an assumed linear or quadratic ephemeris, respectively. The implied apparent strong evolution of the orbital period calls for a revision of the current planetary model or the planetary parameters. The object deserves further monitoring to uncover the true nature of the observed variability and to constrain the properties of the proposed planet or planetary system. The new observations prove that advanced amateur equipment can successfully be used in the growing field of planet sear...

  17. HuR contributes to Hepatic Stellate Cell activation and liver fibrosis

    OpenAIRE

    Woodhoo, A.; Iruarrizaga-Lejarreta, M.; Beraza, N.; García-Rodríguez, J.L.; Embade, N.; Fernández-Ramos, D.; Matinez-Lopez, N.; Gutiérrez, Virginia; Arteta, B; Caballeria, J.; Lu, S.C. (Shelly C.); Mato, J.M. (José María); Varela-Rey, M.; Martinez-Chantar, M.L.

    2012-01-01

    RNA-binding proteins (RBPs) play a major role in control of mRNA turnover and translation rates. We examined the role of the RBP human antigen R (HuR) during cholestatic liver injury and hepatic stellate cells (HSC) activation. HuR silencing attenuated fibrosis development in vivo after BDL, reducing liver damage, oxidative stress, inflammation, and collagen and α-SMA (α-smooth muscle actin) expression. HuR expression increased in activated HSC from BDL mice and during HSC activation in vitro...

  18. Ms HU Ling-xiang's Experience in Treating Blood Stasis by Acupuncture Balancing Method

    Institute of Scientific and Technical Information of China (English)

    FU Jia; LI Ji; ZHANG Cai-rong

    2005-01-01

    @@ HU Ling-xiang, 60, is a chief doctor and supervisor of postgraduates of master degree. She specializes in the syndrome differentiation and treatment of different kinds of chronic and difficult disorders from the perspective of blood stasis theory.

  19. Zebrafish transgenic line huORFZ is an effective living bioindicator for detecting environmental toxicants.

    Directory of Open Access Journals (Sweden)

    Hung-Chieh Lee

    Full Text Available Reliable animal models are invaluable for monitoring the extent of pollution in the aquatic environment. In this study, we demonstrated the potential of huORFZ, a novel transgenic zebrafish line that harbors a human upstream open reading frame of the chop gene fused with GFP reporter, as an animal model for monitoring environmental pollutants and stress-related cellular processes. When huORFZ embryos were kept under normal condition, no leaked GFP signal could be detected. When treated with hazardous chemicals, including heavy metals and endocrine-disrupting chemicals near their sublethal concentrations (LC50, huORFZ embryos exhibited different tissue-specific GFP expression patterns. For further analysis, copper (Cu2+, cadmium (Cd2+ and Chlorpyrifos were applied. Cu2+ triggered GFP responses in skin and muscle, whereas Cd2+ treatment triggered GFP responses in skin, olfactory epithelium and pronephric ducts. Moreover, fluorescence intensity, as exhibited by huORFZ embryos, was dose-dependent. After surviving treated embryos were returned to normal condition, survival rates, as well as TUNEL signals, returned to pretreatment levels with no significant morphological defects observed. Such results indicated the reversibility of treatment conditions used in this study, as long as embryos survived such conditions. Notably, GFP signals decreased along with recovery, suggesting that GFP signaling of huORFZ embryos likely reflected the overall physiological condition of the individual. To examine the performance of the huORFZ line under real-world conditions, we placed huORFZ embryos in different river water samples. We found that the huORFZ embryos correctly detected the presence of various kinds of pollutants. Based on these findings, we concluded that such uORFchop-based system can be integrated into a first-line water alarm system monitoring the discharge of hazardous pollutants.

  20. Hu'rthle Cell Thyroid Adenoma with an Eggshell Calcification: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Gil; Lee, Sang Kwon; Choe, Mi Sun; Chang, Hyuk Won; Rho, Byung Hak [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2009-09-15

    We report here a case of Hu'rthle cell adenoma with eggshell calcification that presented as a thyroid incidentaloma on ultrasonography (US) in a 58-year-old woman. The mass was hypoechoic with continuous eggshell calcification and intranodular vascularity as seen on gray-scale and power Doppler (PD) US. Hu 'rthle cell adenoma should be considered in the differential diagnosis of a thyroid nodule with eggshell calcification

  1. Neuroprotective effects of the cannabinoid agonist HU210 on retinal degeneration.

    Science.gov (United States)

    Lax, Pedro; Esquiva, Gema; Altavilla, Cesare; Cuenca, Nicolás

    2014-03-01

    Cannabinoids have been demonstrated to exert neuroprotective effects on different types of neuronal insults. Here we have addressed the therapeutic potential of the synthetic cannabinoid HU210 on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model for autosomal dominant retinitis pigmentosa (RP). In P23H rats administered with HU210 (100 μg/kg, i.p.) from P24 to P90, ERG recordings showed an amelioration of vision loss, as compared to vehicle-administered animals. Under scotopic conditions, the maximum a-wave amplitudes recorded at P60 and P90 were higher in HU210-treated animals, as compared to the values obtained in untreated animals. The scotopic b-waves were significantly higher in treated animals than in untreated rats at P30, P60 and P90. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. HU210-treated animals had 40% more photoreceptors than untreated animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were also preserved in HU210-treated P23H rats. These results indicate that HU210 preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in P23H rats. These data suggest that cannabinoids are potentially useful to delay retinal degeneration in RP patients.

  2. Pertussis toxin B-oligomer inhibits HIV infection and replication in hu-PBL-SCID mice.

    Science.gov (United States)

    Lapenta, Caterina; Spada, Massimo; Santini, Stefano M; Racca, Sara; Dorigatti, Fernanda; Poli, Guido; Belardelli, Filippo; Alfano, Massimo

    2005-04-01

    Bordetella pertussis toxin B-oligomer (PTX-B) has been shown to inhibit HIV infection and replication in vitro. The potential anti-viral effect of PTX-B was tested here in an in vivo surrogate model of HIV infection, i.e. SCID mice reconstituted with human peripheral blood leukocytes (PBL) (hu-PBL-SCID) and infected with a CCR5-dependent (R5) HIV-1 strain. SCID mice inoculated intra-peritoneal (i.p.) with PTX-B and then infected with the R5 strain SF-162 were sacrificed 7 days later and analyzed for human PBL (hu-PBL) lymphoid tissue reconstitution, infection of hu-PBL, plasma viremia and viral rescue from ex vivo-cultivated i.p. hu-PBL. Unlike mice treated with 500 ng per animal of PTX-B showing no evidence of viral inhibition, daily administration of PTX-B (50 ng per mouse) strongly inhibited virus infection and replication, as determined by undetectable viremia, absence of infected hu-PBL and lack of rescue of infectious HIV in most animals. Furthermore, PTX-B injection 2 h before and twice after infection prevented HIV-1 infection and replication in all (10/10) tested animals. Thus, PTX-B potently inhibited virus infection and replication in hu-PBL-SCID mice, supporting the hypothesis that it may represent a new pharmacological agent against HIV-1 infection.

  3. Different modes of interaction by TIAR and HuR with target RNA and DNA.

    Science.gov (United States)

    Kim, Henry S; Wilce, Matthew C J; Yoga, Yano M K; Pendini, Nicole R; Gunzburg, Menachem J; Cowieson, Nathan P; Wilson, Gerald M; Williams, Bryan R G; Gorospe, Myriam; Wilce, Jacqueline A

    2011-02-01

    TIAR and HuR are mRNA-binding proteins that play important roles in the regulation of translation. They both possess three RNA recognition motifs (RRMs) and bind to AU-rich elements (AREs), with seemingly overlapping specificity. Here we show using SPR that TIAR and HuR bind to both U-rich and AU-rich RNA in the nanomolar range, with higher overall affinity for U-rich RNA. However, the higher affinity for U-rich sequences is mainly due to faster association with U-rich RNA, which we propose is a reflection of the higher probability of association. Differences between TIAR and HuR are observed in their modes of binding to RNA. TIAR is able to bind deoxy-oligonucleotides with nanomolar affinity, whereas HuR affinity is reduced to a micromolar level. Studies with U-rich DNA reveal that TIAR binding depends less on the 2'-hydroxyl group of RNA than HuR binding. Finally we show that SAXS data, recorded for the first two domains of TIAR in complex with RNA, are more consistent with a flexible, elongated shape and not the compact shape that the first two domains of Hu proteins adopt upon binding to RNA. We thus propose that these triple-RRM proteins, which compete for the same binding sites in cells, interact with their targets in fundamentally different ways.

  4. Functional characterization of the HuR:CD83 mRNA interaction.

    Directory of Open Access Journals (Sweden)

    Dorothea Pieper

    Full Text Available Maturation of dendritic cells (DC is characterized by expression of CD83, a surface protein that appears to be necessary for the effective activation of naïve T-cells and T-helper cells by DC. Lately it was shown that CD83 expression is regulated on the posttranscriptional level by interaction of the shuttle protein HuR with a novel posttranscriptional regulatory RNA element (PRE, which is located in the coding region of the CD83 transcript. Interestingly, this interaction commits the CD83 mRNA to efficient nuclear export via the CRM1 pathway. To date, however, the structural basis of this interaction, which potentially involves three distinct RNA recognition motifs (RRM1-3 in HuR and a complex three-pronged RNA stem-loop element in CD83 mRNA, has not been investigated in detail. In the present work we analyzed this interaction in vitro and in vivo using various HuR- and CD83 mRNA mutants. We are able to demonstrate that both, RRM1 and RRM2 are crucial for binding, whereas RRM3 as well as the HuR hinge region contributed only marginally to this protein:RNA interaction. Furthermore, mutation of uridine rich patches within the PRE did not disturb HuR:CD83 mRNA complex formation while, in contrast, the deletion of specific PRE subfragments from the CD83 mRNA prevented HuR binding in vitro and in vivo. Interestingly, the observed inhibition of HuR binding to CD83 mRNA does not lead to a nuclear trapping of the transcript but rather redirected this transcript from the CRM1- towards the NXF1/TAP-specific nuclear export pathway. Thus, the presence of a functional PRE permits nucleocytoplasmic trafficking of the CD83 transcript via the CRM1 pathway.

  5. Hydroxyurea (HU) for prevention of recurrent stroke in sickle cell anemia (SCA).

    Science.gov (United States)

    Sumoza, Abraham; de Bisotti, Renate; Sumoza, David; Fairbanks, Virgil

    2002-11-01

    Cerebrovascular accident (CVA) is a major cause of morbidity and death in sickle cell anemia (SCA). Transfusion of packed erythrocytes is widely used to prevent this complication. However, chronic transfusion may lead to iron overload, alloimmunization, or infections. Cost and compliance may compromise transfusion therapy. A possible alternative, the prophylactic use of hydroxyurea (HU), has not been tried to determine whether it may prevent recurrent stroke. We used HU in five children with SCA who had suffered stroke, in three of them after a first episode and in the other two after a second CVA. Four had infarctive stroke and one a transient ischemic attack (TIA). Four patients took HU at a dose of 40 mg/kg/d, one patient at 30 mg/kg/d. None of the patients had recurrent stroke during 42-112 months of observation. None experienced pain crises. In all, HbF increased significantly and was maintained above 14.7% during treatment. The total Hb concentration increased 19.5 g/L (median) above the value before treatment. HU was well tolerated. None of the five children had leukopenia or thrombocytopenia during therapy. HU appears to prevent recurrence of stroke in SCA without risk of major toxicity.

  6. dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development.

    Science.gov (United States)

    Guan, Zhen; Wang, Xiuwei; Dong, Yanting; Xu, Lin; Zhu, Zhiqiang; Wang, Jianhua; Zhang, Ting; Niu, Bo

    2015-02-03

    Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225 mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis.

  7. Beta-1 adrenergic agonist treatment mitigates negative changes in cancellous bone microarchitecture and inhibits osteocyte apoptosis during disuse.

    Directory of Open Access Journals (Sweden)

    Joshua M Swift

    Full Text Available The sympathetic nervous system (SNS plays an important role in mediating bone remodeling. However, the exact role that beta-1 adrenergic receptors (beta1AR have in this process has not been elucidated. We have previously demonstrated the ability of dobutamine (DOB, primarily a beta1AR agonist, to inhibit reductions in cancellous bone formation and mitigate disuse-induced loss of bone mass. The purpose of this study was to characterize the independent and combined effects of DOB and hindlimb unloading (HU on cancellous bone microarchitecture, tissue-level bone cell activity, and osteocyte apoptosis. Male Sprague-Dawley rats, aged 6-mos, were assigned to either normal cage activity (CC or HU (n = 18/group for 28 days. Animals were administered either daily DOB (4 mg/kg BW/d or an equal volume of saline (VEH (n = 9/gp. Unloading resulted in significantly lower distal femur cancellous BV/TV (-33%, Tb.Th (-11%, and Tb.N (-25% compared to ambulatory controls (CC-VEH. DOB treatment during HU attenuated these changes in cancellous bone microarchitecture, resulting in greater BV/TV (+29%, Tb.Th (+7%, and Tb.N (+21% vs. HU-VEH. Distal femur cancellous vBMD (+11% and total BMC (+8% were significantly greater in DOB- vs. VEH-treated unloaded rats. Administration of DOB during HU resulted in significantly greater osteoid surface (+158% and osteoblast surface (+110% vs. HU-VEH group. Furthermore, Oc.S/BS was significantly greater in HU-DOB (+55% vs. CC-DOB group. DOB treatment during unloading fully restored bone formation, resulting in significantly greater bone formation rate (+200% than in HU-VEH rats. HU resulted in an increased percentage of apoptotic cancellous osteocytes (+85%, reduced osteocyte number (-16%, lower percentage of occupied osteocytic lacunae (-30% as compared to CC-VEH, these parameters were all normalized with DOB treatment. Altogether, these data indicate that beta1AR agonist treatment during disuse mitigates negative changes

  8. Multiple Functions of the RNA-Binding Protein HuR in Cancer Progression, Treatment Responses and Prognosis

    Directory of Open Access Journals (Sweden)

    Baocheng Wang

    2013-05-01

    Full Text Available The human embryonic lethal abnormal vision-like protein, HuR, is a member of the Hu family of RNA-binding proteins. Over the past decade, this ubiquitously expressed protein has been extensively investigated in cancer research because it is involved in the regulation of mRNA stability and translation in many cell types. HuR activity and function is associated with its subcellular distribution, transcriptional regulation, translational and post-translational modifications. HuR regulation of target mRNAs is based on the interaction between the three specific domains of HuR protein and one or several U- or AU-rich elements (AREs in the untranslated region of target mRNAs. A number of cancer-related transcripts containing AREs, including mRNAs for proto-oncogenes, cytokines, growth factors, and invasion factors, have been characterized as HuR targets. It has been proposed that HuR has a central tumorigenic activity by enabling multiple cancer phenotypes. In this review, we comprehensively survey the existing evidence with regard to the diverse functions of HuR in caner development and progression. The current data also suggest that HuR might be a novel and promising therapeutic target and a marker for treatment response and prognostic evaluation.

  9. Temporally defined neocortical translation and polysome assembly are determined by the RNA-binding protein Hu antigen R.

    Science.gov (United States)

    Kraushar, Matthew L; Thompson, Kevin; Wijeratne, H R Sagara; Viljetic, Barbara; Sakers, Kristina; Marson, Justin W; Kontoyiannis, Dimitris L; Buyske, Steven; Hart, Ronald P; Rasin, Mladen-Roko

    2014-09-09

    Precise spatiotemporal control of mRNA translation machinery is essential to the development of highly complex systems like the neocortex. However, spatiotemporal regulation of translation machinery in the developing neocortex remains poorly understood. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stage-dependent manner in mice. Neocortical absence of HuR alters the phosphorylation states of initiation and elongation factors in the core translation machinery. In addition, HuR regulates the temporally specific positioning of functionally related mRNAs into the active translation sites, the polysomes. HuR also determines the specificity of neocortical polysomes by defining their combinatorial composition of ribosomal proteins and initiation and elongation factors. For some HuR-dependent proteins, the association with polysomes likewise depends on the eukaryotic initiation factor 2 alpha kinase 4, which associates with HuR in prenatal developing neocortices. Finally, we found that deletion of HuR before embryonic day 10 disrupts both neocortical lamination and formation of the main neocortical commissure, the corpus callosum. Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity.

  10. Coordination of genomic structure and transcription by the main bacterial nucleoid-associated protein HU.

    Science.gov (United States)

    Berger, Michael; Farcas, Anca; Geertz, Marcel; Zhelyazkova, Petya; Brix, Klaudia; Travers, Andrew; Muskhelishvili, Georgi

    2010-01-01

    The histone-like protein HU is a highly abundant DNA architectural protein that is involved in compacting the DNA of the bacterial nucleoid and in regulating the main DNA transactions, including gene transcription. However, the coordination of the genomic structure and function by HU is poorly understood. Here, we address this question by comparing transcript patterns and spatial distributions of RNA polymerase in Escherichia coli wild-type and hupA/B mutant cells. We demonstrate that, in mutant cells, upregulated genes are preferentially clustered in a large chromosomal domain comprising the ribosomal RNA operons organized on both sides of OriC. Furthermore, we show that, in parallel to this transcription asymmetry, mutant cells are also impaired in forming the transcription foci-spatially confined aggregations of RNA polymerase molecules transcribing strong ribosomal RNA operons. Our data thus implicate HU in coordinating the global genomic structure and function by regulating the spatial distribution of RNA polymerase in the nucleoid.

  11. Ship Targets Discrimination Algorithm in SAR Images Based on Hu Moment Feature and Texture Feature

    Directory of Open Access Journals (Sweden)

    Liu Lei

    2016-01-01

    Full Text Available To discriminate the ship targets in SAR images, this paper proposed the method based on combination of Hu moment feature and texture feature. Firstly,7 Hu moment features should be extracted, while gray level co-occurrence matrix is then used to extract the features of mean, variance, uniformity, energy, entropy, inertia moment, correlation and differences. Finally the k-neighbour classifier was used to analysis the 15 dimensional feature vectors. The experimental results show that the method of this paper has a good effect.

  12. Neuroprotective effects of the cannabinoid agonist HU210 on retinal degeneration

    OpenAIRE

    Lax Zapata, Pedro; Esquiva Sobrino, Gema; Altavilla, Cesare; Cuenca Navarro, Nicolás

    2014-01-01

    Cannabinoids have been demonstrated to exert neuroprotective effects on different types of neuronal insults. Here we have addressed the therapeutic potential of the synthetic cannabinoid HU210 on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model for autosomal dominant retinitis pigmentosa (RP). In P23H rats administered with HU210 (100 μg/kg, i.p.) from P24 to P90, ERG recordings showed an amelioration of vision...

  13. The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA.

    Science.gov (United States)

    López de Silanes, Isabel; Gorospe, Myriam; Taniguchi, Hiroaki; Abdelmohsen, Kotb; Srikantan, Subramanya; Alaminos, Miguel; Berdasco, María; Urdinguio, Rocío G; Fraga, Mario F; Jacinto, Filipe V; Esteller, Manel

    2009-05-01

    The molecular basis underlying the aberrant DNA-methylation patterns in human cancer is largely unknown. Altered DNA methyltransferase (DNMT) activity is believed to contribute, as DNMT expression levels increase during tumorigenesis. Here, we present evidence that the expression of DNMT3b is post-transcriptionally regulated by HuR, an RNA-binding protein that stabilizes and/or modulates the translation of target mRNAs. The presence of a putative HuR-recognition motif in the DNMT3b 3'UTR prompted studies to investigate if this transcript associated with HuR. The interaction between HuR and DNMT3b mRNA was studied by immunoprecipitation of endogenous HuR ribonucleoprotein complexes followed by RT-qPCR detection of DNMT3b mRNA, and by in vitro pulldown of biotinylated DNMT3b RNAs followed by western blotting detection of HuR. These studies revealed that binding of HuR stabilized the DNMT3b mRNA and increased DNMT3b expression. Unexpectedly, cisplatin treatment triggered the dissociation of the [HuR-DNMT3b mRNA] complex, in turn promoting DNMT3b mRNA decay, decreasing DNMT3b abundance, and lowering the methylation of repeated sequences and global DNA methylation. In summary, our data identify DNMT3b mRNA as a novel HuR target, present evidence that HuR affects DNMT3b expression levels post-transcriptionally, and reveal the functional consequences of the HuR-regulated DNMT3b upon DNA methylation patterns.

  14. Hu Shi and the Continuation of the Revolution of1911——Discussing Intellectuals and Social Revolution%Hu Shi and the Continuation of the Revolution of 1911——Discussing Intellectuals and Social Revolution

    Institute of Scientific and Technical Information of China (English)

    Zhu Cheng

    2011-01-01

    Hu Shi is regarded as one of the most important intellectuals after the Revolution of 1911,and he has a far- reaching influence in 20th century.In the perspective of Hu Shi,the contribution and continuation of the Revolution of 1911 has some inspiration for us to analyze the relationship between Chinese intellectuals and social revolution.

  15. The HU Regulon Is Composed of Genes Responding to Anaerobiosis, Acid Stress, High Osmolarity and SOS Induction

    Science.gov (United States)

    Oberto, Jacques; Nabti, Sabrina; Jooste, Valérie; Mignot, Hervé; Rouviere-Yaniv, Josette

    2009-01-01

    Background The Escherichia coli heterodimeric HU protein is a small DNA-bending protein associated with the bacterial nucleoid. It can introduce negative supercoils into closed circular DNA in the presence of topoisomerase I. Cells lacking HU grow very poorly and display many phenotypes. Methodology/Principal Findings We analyzed the transcription profile of every Escherichia coli gene in the absence of one or both HU subunits. This genome-wide in silico transcriptomic approach, performed in parallel with in vivo genetic experimentation, defined the HU regulon. This large regulon, which comprises 8% of the genome, is composed of four biologically relevant gene classes whose regulation responds to anaerobiosis, acid stress, high osmolarity, and SOS induction. Conclusions/Significance The regulation a large number of genes encoding enzymes involved in energy metabolism and catabolism pathways by HU explains the highly pleiotropic phenotype of HU-deficient cells. The uniform chromosomal distribution of the many operons regulated by HU strongly suggests that the transcriptional and nucleoid architectural functions of HU constitute two aspects of a unique protein-DNA interaction mechanism. PMID:19194530

  16. The HU regulon is composed of genes responding to anaerobiosis, acid stress, high osmolarity and SOS induction.

    Directory of Open Access Journals (Sweden)

    Jacques Oberto

    Full Text Available BACKGROUND: The Escherichia coli heterodimeric HU protein is a small DNA-bending protein associated with the bacterial nucleoid. It can introduce negative supercoils into closed circular DNA in the presence of topoisomerase I. Cells lacking HU grow very poorly and display many phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the transcription profile of every Escherichia coli gene in the absence of one or both HU subunits. This genome-wide in silico transcriptomic approach, performed in parallel with in vivo genetic experimentation, defined the HU regulon. This large regulon, which comprises 8% of the genome, is composed of four biologically relevant gene classes whose regulation responds to anaerobiosis, acid stress, high osmolarity, and SOS induction. CONCLUSIONS/SIGNIFICANCE: The regulation a large number of genes encoding enzymes involved in energy metabolism and catabolism pathways by HU explains the highly pleiotropic phenotype of HU-deficient cells. The uniform chromosomal distribution of the many operons regulated by HU strongly suggests that the transcriptional and nucleoid architectural functions of HU constitute two aspects of a unique protein-DNA interaction mechanism.

  17. First International Workshop on Human Factors in Modeling (HuFaMo 2015)

    DEFF Research Database (Denmark)

    Störrle, Harald; Chaudron, Michel R. V.; Amaral, Vasco

    2015-01-01

    and systematic approaches to assert usability in modeling and confirm the claims of productivity. This workshop creates a space for discussion being a get together of both MDE, Usability, Human Interfaces and the Experimental Software engineering community. HuFaMo expressly focuses on human factors, in order...

  18. Rare Association of Anti-Hu Antibody Positive Paraneoplastic Neurological Syndrome and Transitional Cell Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    S. Lukacs

    2012-01-01

    Full Text Available Introduction. Paraneoplastic encephalomyelitis (PEM and subacute sensory neuronopathy (SSN are remote effects of cancer, usually associated with small-cell lung carcinoma and positive anti-Hu antibody. We describe the rare association of bladder transitional cell carcinoma (TCC with anti-Hu antibody positivity resulting in this paraneoplastic neurological syndrome. Patient. A 76-year-old female presented with bilateral muscle weakness and paraesthesia of the upper and lower limbs in a length-dependent “glove and stocking” distribution. Central nervous system symptoms included cognitive problems, personality change, and truncal ataxia. Case notes and the literature were reviewed. Result. Autoantibody screening was positive for anti-Hu antibody (recently renamed antineuronal nuclear antibody 1, ANNA-1. The diagnosis of PEM and SSN was supported by MRI and lumbar puncture results. A superficial bladder TCC was demonstrated on CT and subsequently confirmed on histology. No other primary neoplasm was found on full-body imaging. The neurological symptoms were considered to be an antibody-mediated paraneoplastic neurological syndrome and improved after resection of the tumour. Discussion. The association of anti-Hu positive paraneoplastic neurological syndrome and TCC has not been described in the literature previously. We emphasize the need for detailed clinical examination and the importance of a multidisciplinary thought process and encourage further awareness of this rare association.

  19. Redox behaviors of the neurotoxic portion in human prion protein, HuPrP(106-126)

    Science.gov (United States)

    Yamamoto, Norifumi; Kuwata, Kazuo

    2010-09-01

    A peptide fragment of human prion protein, HuPrP(106-126), has been reported to mimic the pathological features underlying prion diseases. Although the actual neurotoxic mechanism of HuPrP(106-126) has not been elucidated, several hypotheses has been proposed based on the role for copper. In this study, to understand the toxic function of HuPrP(106-126) from a viewpoint of electrochemical competence, we investigated redox properties of copper ion complexes with four different binding motifs of a model of HuPrP(106-126) based on density functional theory calculations. We found that the HuPrP(106-126)-derived models exhibited diverse redox activities that depended on copper-binding conformations.

  20. Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells

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    Elodie Jouan

    2016-12-01

    Full Text Available Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP activity, presumed to reflect expression of various hepatic MRPs, including MRP2. By contrast, they failed to display functional activities of the uptake transporters sodium taurocholate co-transporting polypeptide (NTCP, organic anion-transporting polypeptides (OATPs and organic cation transporter 1 (OCT1, and of the canalicular transporters P-glycoprotein and breast cancer resistance protein (BCRP. Concomitantly, mRNA expressions of various sinusoidal and canalicular hepatic drug transporters were not detected (NTCP, OATP1B1, organic anion transporter 2 (OAT2, OCT1 and bile salt export pump or were found to be lower (OATP1B3, OATP2B1, multidrug and toxin extrusion protein 1, BCRP and MRP3 in hepatoma HuH-7 cells than those found in human hepatocytes, whereas other transporters such as OAT7, MRP4 and MRP5 were up-regulated. HuH-7 cells additionally exhibited farnesoid X receptor (FXR- and nuclear factor erythroid 2-related factor 2 (Nrf2-related up-regulation of some transporters. Such data indicate that HuH-7 cells, although expressing rather poorly some main hepatic drug transporters, may be useful for investigating interactions of drugs with MRPs, notably MRP2, and for studying FXR- or Nrf2-mediated gene regulation.

  1. Discriminating between HuR and TTP binding sites using the k-spectrum kernel method

    Science.gov (United States)

    Goldberg, Debra S.; Dowell, Robin

    2017-01-01

    Background The RNA binding proteins (RBPs) human antigen R (HuR) and Tristetraprolin (TTP) are known to exhibit competitive binding but have opposing effects on the bound messenger RNA (mRNA). How cells discriminate between the two proteins is an interesting problem. Machine learning approaches, such as support vector machines (SVMs), may be useful in the identification of discriminative features. However, this method has yet to be applied to studies of RNA binding protein motifs. Results Applying the k-spectrum kernel to a support vector machine (SVM), we first verified the published binding sites of both HuR and TTP. Additional feature engineering highlighted the U-rich binding preference of HuR and AU-rich binding preference for TTP. Domain adaptation along with multi-task learning was used to predict the common binding sites. Conclusion The distinction between HuR and TTP binding appears to be subtle content features. HuR prefers strongly U-rich sequences whereas TTP prefers AU-rich as with increasing A content, the sequences are more likely to be bound only by TTP. Our model is consistent with competitive binding of the two proteins, particularly at intermediate AU-balanced sequences. This suggests that fine changes in the A/U balance within a untranslated region (UTR) can alter the binding and subsequent stability of the message. Both feature engineering and domain adaptation emphasized the extent to which these proteins recognize similar general sequence features. This work suggests that the k-spectrum kernel method could be useful when studying RNA binding proteins and domain adaptation techniques such as feature augmentation could be employed particularly when examining RBPs with similar binding preferences. PMID:28333956

  2. Transcriptomic-Wide Discovery of Direct and Indirect HuR RNA Targets in Activated CD4+ T Cells.

    Directory of Open Access Journals (Sweden)

    Patsharaporn Techasintana

    Full Text Available Due to poor correlation between steady state mRNA levels and protein product, purely transcriptomic profiling methods may miss genes posttranscriptionally regulated by RNA binding proteins (RBPs and microRNAs (miRNAs. RNA immunoprecipitation (RIP methods developed to identify in vivo targets of RBPs have greatly elucidated those mRNAs which may be regulated via transcript stability and translation. The RBP HuR (ELAVL1 and family members are major stabilizers of mRNA. Many labs have identified HuR mRNA targets; however, many of these analyses have been performed in cell lines and oftentimes are not independent biological replicates. Little is known about how HuR target mRNAs behave in conditional knock-out models. In the present work, we performed HuR RIP-Seq and RNA-Seq to investigate HuR direct and indirect targets using a novel conditional knock-out model of HuR genetic ablation during CD4+ T activation and Th2 differentiation. Using independent biological replicates, we generated a high coverage RIP-Seq data set (>160 million reads that was analyzed using bioinformatics methods specifically designed to find direct mRNA targets in RIP-Seq data. Simultaneously, another set of independent biological replicates were sequenced by RNA-Seq (>425 million reads to identify indirect HuR targets. These direct and indirect targets were combined to determine canonical pathways in CD4+ T cell activation and differentiation for which HuR plays an important role. We show that HuR may regulate genes in multiple canonical pathways involved in T cell activation especially the CD28 family signaling pathway. These data provide insights into potential HuR-regulated genes during T cell activation and immune mechanisms.

  3. Intestinal epithelial HuR modulates distinct pathways of proliferation and apoptosis and attenuates small intestinal and colonic tumor development.

    Science.gov (United States)

    Giammanco, Antonina; Blanc, Valerie; Montenegro, Grace; Klos, Coen; Xie, Yan; Kennedy, Susan; Luo, Jianyang; Chang, Sung-Hee; Hla, Timothy; Nalbantoglu, Ilke; Dharmarajan, Sekhar; Davidson, Nicholas O

    2014-09-15

    HuR is a ubiquitous nucleocytoplasmic RNA-binding protein that exerts pleiotropic effects on cell growth and tumorigenesis. In this study, we explored the impact of conditional, tissue-specific genetic deletion of HuR on intestinal growth and tumorigenesis in mice. Mice lacking intestinal expression of HuR (Hur (IKO) mice) displayed reduced levels of cell proliferation in the small intestine and increased sensitivity to doxorubicin-induced acute intestinal injury, as evidenced by decreased villus height and a compensatory shift in proliferating cells. In the context of Apc(min/+) mice, a transgenic model of intestinal tumorigenesis, intestinal deletion of the HuR gene caused a three-fold decrease in tumor burden characterized by reduced proliferation, increased apoptosis, and decreased expression of transcripts encoding antiapoptotic HuR target RNAs. Similarly, Hur(IKO) mice subjected to an inflammatory colon carcinogenesis protocol [azoxymethane and dextran sodium sulfate (AOM-DSS) administration] exhibited a two-fold decrease in tumor burden. Hur(IKO) mice showed no change in ileal Asbt expression, fecal bile acid excretion, or enterohepatic pool size that might explain the phenotype. Moreover, none of the HuR targets identified in Apc(min/+)Hur(IKO) were altered in AOM-DSS-treated Hur(IKO) mice, the latter of which exhibited increased apoptosis of colonic epithelial cells, where elevation of a unique set of HuR-targeted proapoptotic factors was documented. Taken together, our results promote the concept of epithelial HuR as a contextual modifier of proapoptotic gene expression in intestinal cancers, acting independently of bile acid metabolism to promote cancer. In the small intestine, epithelial HuR promotes expression of prosurvival transcripts that support Wnt-dependent tumorigenesis, whereas in the large intestine epithelial HuR indirectly downregulates certain proapoptotic RNAs to attenuate colitis-associated cancer. Cancer Res; 74(18); 5322-35. ©2014 AACR.

  4. 胞质HuR在卵巢上皮性癌的表达及意义%The expression and significance of cytoplasmic HuR in epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    齐玉明; 石彬; 郭皓; 成艳梅

    2011-01-01

    Objective To investigate the correlation between the expression of HuR in epithelial ovarian cancer and clinicopathological parameters in order to explore the factors that affect the prognosis of patients with epithelial ovarian carcinoma. Methods The expressions of cytoplasmic and nuclear HuR in normal ovary tissues,borderline tissue of ovary tumor and epithelial ovarian carcinoma were detected by SP immunohistochemical technique and RT-PCR. The relationship between cytoplasmic HuR expression and prognostic factors was analyzed.Results The expressions of cytoplasmic and nuclear HuR in epithelial ovarian cancer tissue were significantly higher than those in borderline tissue of epithelial ovarian tumor and normal ovarian tissues,however,there was no significant difference between the borderline tissue of epithelial ovarian tumor and normal ovarian tissue ( P >0.05). The statistical analysis showed that the positive expression rate of cytoplasmic HuR in epithelial ovarian carcinoma was closely correlated with histological grade and FIGO stage, but the positive expression rate of nuclear HuR was not correlated with the clinicopathological parameters. Conclusion The over-expression of HuR may play an important role in the growth and progress of epithelial ovarian carcinoma. To detect the expression of cytoplasmic HuR in epithelial ovarian carcinoma may predict the characteristics of oncobiology behaviour. The expression of cytoplasmic HuR may act as an independent prognostic indicator.%目的 检测HuR在卵巢上皮性癌中的表达及与临床病理参数的关系,寻求卵巢癌的预后因素.方法 采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接(SP)法和逆转录RT-PCR技术,检测胞质和胞核HuR在正常、交界性、恶性卵巢组织中的表达;分析胞质HuR的表达与预后的关系.结果 胞质和胞核HuR在恶性卵巢肿瘤组织的表达明显高于交界性卵巢肿瘤和正常卵巢组织,胞质和胞核HuR在交界性

  5. Beta Thalassemia (For Parents)

    Science.gov (United States)

    ... Kids to Be Smart About Social Media Beta Thalassemia KidsHealth > For Parents > Beta Thalassemia Print A A ... Complications Symptoms Diagnosis Treatment en español Beta talasemia Thalassemias Thalassemias are a group of blood disorders that ...

  6. Reversible HuR-microRNA binding controls extracellular export of miR-122 and augments stress response.

    Science.gov (United States)

    Mukherjee, Kamalika; Ghoshal, Bartika; Ghosh, Souvik; Chakrabarty, Yogaditya; Shwetha, Shivaprasad; Das, Saumitra; Bhattacharyya, Suvendra N

    2016-08-01

    microRNAs (miRNAs), the tiny but stable regulatory RNAs in metazoan cells, can undergo selective turnover in presence of specific internal and external cues to control cellular response against the changing environment. We have observed reduction in cellular miR-122 content, due to their accelerated extracellular export in human hepatic cells starved for small metabolites including amino acids. In this context, a new role of human ELAV protein HuR has been identified. HuR, a negative regulator of miRNA function, accelerates extracellular vesicle (EV)-mediated export of miRNAs in human cells. In stressed cells, HuR replaces miRNPs from target messages and is both necessary and sufficient for the extracellular export of corresponding miRNAs. HuR could reversibly bind miRNAs to replace them from Ago2 and subsequently itself gets freed from bound miRNAs upon ubiquitination. The ubiquitinated form of HuR is predominantly associated with multivesicular bodies (MVB) where HuR-unbound miRNAs also reside. These MVB-associated pool of miRNAs get exported out via EVs thereby delimiting cellular miR-122 level during starvation. Therefore, by modulating extracellular export of miR-122, HuR could control stress response in starved human hepatic cells.

  7. SU-E-T-470: Importance of HU-Mass Density Calibration Technique in Proton Pencil Beam Dose Calculation

    Energy Technology Data Exchange (ETDEWEB)

    Penfold, S; Miller, A [University of Adelaide, Adelaide, SA (Australia)

    2015-06-15

    Purpose: Stoichiometric calibration of Hounsfield Units (HUs) for conversion to proton relative stopping powers (RStPs) is vital for accurate dose calculation in proton therapy. However proton dose distributions are not only dependent on RStP, but also on relative scattering power (RScP) of patient tissues. RScP is approximated from material density but a stoichiometric calibration of HU-density tables is commonly neglected. The purpose of this work was to quantify the difference in calculated dose of a commercial TPS when using HU-density tables based on tissue substitute materials and stoichiometric calibrated ICRU tissues. Methods: Two HU-density calibration tables were generated based on scans of the CIRS electron density phantom. The first table was based directly on measured HU and manufacturer quoted density of tissue substitute materials. The second was based on the same CT scan of the CIRS phantom followed by a stoichiometric calibration of ICRU44 tissue materials. The research version of Pinnacle{sup 3} proton therapy was used to compute dose in a patient CT data set utilizing both HU-density tables. Results: The two HU-density tables showed significant differences for bone tissues; the difference increasing with increasing HU. Differences in density calibration table translated to a difference in calculated RScP of −2.5% for ICRU skeletal muscle and 9.2% for ICRU femur. Dose-volume histogram analysis of a parallel opposed proton therapy prostate plan showed that the difference in calculated dose was negligible when using the two different HU-density calibration tables. Conclusion: The impact of HU-density calibration technique on proton therapy dose calculation was assessed. While differences were found in the calculated RScP of bony tissues, the difference in dose distribution for realistic treatment scenarios was found to be insignificant.

  8. Altered regulation of ELAVL1/HuR in HLA-B27-expressing U937 monocytic cells.

    Directory of Open Access Journals (Sweden)

    Anna S Sahlberg

    Full Text Available OBJECTIVE: To investigate the role of HLA-B27 expression in the regulation of RNA binding protein (RBP Embryonic Lethal Abnormal Vision (ELAV L1/Human antigen R (HuR expression in Salmonella-infected or LPS-stimulated human monocytic cells, since HuR is a critical regulator of the post-transcriptional fate of many genes (e.g. TNFα important in inflammatory response. METHODS: U937 monocytic cells were stably transfected with pSV2neo resistant vector (mock, wild type HLA-B27, or mutated HLA-B27 with amino acid substitutions in the B pocket. Cells were differentiated, infected with Salmonella enteritidis or stimulated with lipopolysaccharide. The expression levels of HuR protein and cleavage products (CP1 and CP2 were detected by Western blotting and flow cytometry. Specific inhibitors were used to study the role of PKR and p38 in HuR expression and generation of CPs. TNFα and IL-10 secretion after p38 and PKR inhibition were measured by ELISA. RESULTS: Full length HuR is overexpressed and HuR cleavage is disturbed in U937 monocytic cells expressing HLA-B27 heavy chains (HC. Increased full length HuR expression, disturbed cleavage and reduced dependence on PKR after infection correlate with the expression of glutamic acid 45 in the B pocket that is linked to the misfolding of HLA-B27. CONCLUSION: Results show that the expression of HLA-B27 HCs modulates the intracellular environment of U937 monocyte/macrophages by altering HuR regulation. This phenomenon is at least partly dependent on the misfolding feature of the B27 molecule. Since HuR is an important regulator of multiple genes involved in inflammatory response observations offer an explanation how HLA-B27 may modulate inflammatory response.

  9. Central hypoventilation as the presenting symptom in Hu associated paraneoplastic encephalomyelitis.

    Science.gov (United States)

    Gómez-Choco, Manuel J; Zarranz, Juan J; Saiz, Albert; Forcadas, María I; Graus, Francesc

    2007-10-01

    Central hypoventilation is usually caused by ischaemic or neoplastic lesions of the medulla and upper cervical spinal cord. An autoimmune disorder is not usually considered in the differential diagnosis of this syndrome. We retrospectively identified 14 patients from our database of 202 patients with Hu antibodies who presented with brainstem symptoms. Three were admitted to hospital because of central hypoventilation. All underwent intubation and mechanical ventilation. They could breathe properly while they were awake but suffered deep apnoeas during sleep. Two died, but one is still alive requiring ventilatory assistance during sleep. Autopsy was performed in one of the patients which showed severe inflammatory infiltrates and neuronal loss in the medulla. All patients had normal brain imaging studies and the cause of central hypoventilation was an unsolved problem until Hu antibodies were determined.

  10. Identification of a Calcium Signalling Pathway of S-[6]-Gingerol in HuH-7 Cells

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Li

    2013-01-01

    Full Text Available Calcium signals in hepatocytes control cell growth, proliferation, and death. Members of the transient receptor potential (TRP cation channel superfamily are candidate calcium influx channels. NFκB activation strictly depends on calcium influx and often induces antiapoptotic genes favouring cell survival. Previously, we reported that S-[6]-gingerol is an efficacious agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1 in neurones. In this study, we tested the effect of S-[6]-gingerol on HuH-7 cells using the Fluo-4 calcium assay, RT-qPCR, transient cell transfection, and luciferase measurements. We found that S-[6]-gingerol induced a transient rise in [Ca2+]i in HuH-7 cells. The increase in [Ca2+]i induced by S-[6]-gingerol was abolished by preincubation with EGTA and was also inhibited by the TRPV1 channel antagonist capsazepine. Expression of TRPV1 in HuH-7 cells was confirmed by mRNA analysis as well as a test for increase of [Ca2+]i by TRPV1 agonist capsaicin and its inhibition by capsazepine. We found that S-[6]-gingerol induced rapid NFκB activation through TRPV1 in HuH-7 cells. Furthermore, S-[6]-gingerol-induced NFκB activation was dependent on the calcium gradient and TRPV1. The rapid NFκB activation by S-[6]-gingerol was associated with an increase in mRNA levels of NFκB-target genes: cIAP-2, XIAP, and Bcl-2 that encode antiapoptotic proteins.

  11. Effects of animal class and genotype on beef muscle nanostructure, pHu, colour and tenderness

    Directory of Open Access Journals (Sweden)

    Amanda Y. Chulayo

    2016-07-01

    Full Text Available The objective of the study was to determine the effects of animal class and genotype of cattle on Muscularis longissimus thoracis et lumborum (LTL nanostructure, ultimate pH (pHu, colour and tenderness of beef. We found significant positive relationships between distance travelled (DT and meat temperature (Tm (p"less than"0.01; lairage duration (LDhr and lightness of colour (L* (p"less than"0.01; ambient temperature (Ta and L* (p"less than"0.05 and LDhr and yellowness (b* (p"less than"0.05 of beef from Bonsmara cattle. Positive linear relationships were observed between DT and Tm (p"less than"0.05 and DT and L* (p"less than"0.01 of the non-descript cattle. There were no significant relationships between pre-slaughter stress and other beef quality parameters (pHu, Warner– Bratzler shear force [WBSF], redness [a*] and b* of Bonsmara, Nguni and non-descript cattle. Muscle fibres differed among class and genotype and had an effect on meat quality. The Bonsmara, non-descript and Nguni cows and heifers had visible skeletal muscle fibres which were thin and long, promising improved tenderness of beef. Genotype and class had significant effects on meat quality parameters (Tm, pHu, L*, a*, b* and WBSF. The first important principal components as they appeared from the analysis were pHu, Tm, L*, a*, b* and WBSF. Therefore, animal class did not affect the nanostructure of beef; instead, meat tenderness was enhanced by the longer and visible muscle fibres. Nguni cattle produced meat of superior quality to that of the Bonsmara and the non-descript cattle.

  12. The outcome of PIE *#Hi- and *#Hu- in Germanic

    DEFF Research Database (Denmark)

    Hansen, Bjarne Simmelkjær Sandgaard

    2015-01-01

    It has been established with a great amount of certainty that PIE *#Hu- > Gr. #Vὐ- and that PIE *#Hi- > Gr. #ἰ-. It still remains to be demonstrated what happens in other Western Indo-European branches, including Germanic. In this article , I reject the statement by Ringe (1988: 433) that PIE *#H...... tentatively propose that PG *#au- > PG *#u- when followed by a labial consonant; a development partially paralleled in Greek and in English....

  13. Sustainable groundwater development and management in the Quaternary Hang-Jia-Hu Plain, China

    Institute of Scientific and Technical Information of China (English)

    朱琰

    2002-01-01

    Based on the results of study on regional water supply system, water quality assessments, Quaternary aquifers investigation, and correlation analysis of groundwater depression resulting from land subsidence in the Hang-Jia-Hu Quaternary Plain, this paper presents the groundwater resources policy and sustainable management methods suitable for this area. Suggestions for controlling land subsidence by implementation of wise groundwater policy and management measures are also given.

  14. The outcome of PIE *#Hi- and *#Hu- in Germanic

    DEFF Research Database (Denmark)

    Hansen, Bjarne Simmelkjær Sandgaard

    2015-01-01

    It has been established with a great amount of certainty that PIE *#Hu- > Gr. #Vὐ- and that PIE *#Hi- > Gr. #ἰ-. It still remains to be demonstrated what happens in other Western Indo-European branches, including Germanic. In this article , I reject the statement by Ringe (1988: 433) that PIE *#H...... tentatively propose that PG *#au- > PG *#u- when followed by a labial consonant; a development partially paralleled in Greek and in English....

  15. Screening candidate microRNAs (miRNAs) in different lambskin hair follicles in Hu sheep.

    Science.gov (United States)

    Gao, Wen; Sun, Wei; Yin, Jinfeng; Lv, Xiaoyang; Bao, Jianjun; Yu, Jiarui; Wang, Lihong; Jin, Chengyan; Hu, Liang

    2017-01-01

    Hu sheep lambskin is a unique white lambskin from China that exhibits three types of flower patterns, including small waves, medium waves, and large waves, with small waves considered the best quality. However, our understanding of the molecular mechanism underlying flower pattern formation in Hu sheep lambskin is limited. The aim of the present study was to further explore the relevance between candidate microRNAs (miRNAs) and developmental characteristics of hair follicles and screen miRNAs for later functional validation. Herein, we employed Illumina Hiseq 2500 to identify differentially expressed miRNAs in hair follicles of different flower patterns with small, medium, and large waves to construct a comprehensive sequence database on the mechanism of hair follicle development. Paraffin sections of lambskin tissue were prepared to assess the structure of different hair follicles. Expression levels of candidate miRNAs in different flower patterns were analyzed by relative quantitation using real-time PCR, combined with histological observation and micro-observation technologies, and the correlation between expression levels of candidate miRNAs and histological properties of hair follicles was analyzed by using SPSS 17.0. A total of 522 differentially expressed miRNAs were identified, and RNA-seq analysis detected 7,266 target genes in different groups of flower patterns. Gene ontological analysis indicated these target genes were mainly involved in cell proliferation, differentiation, growth, apoptosis, and ion transport, and 14 miRNAs, including miR-143, miR-10a, and let-7 were screened as candidate miRNAs in Hu sheep hair follicle growth and development. In the same field of vision, variance analysis showed that the number of secondary follicles in small waves was significantly larger than that in large and medium waves (Phair follicles, highly significant differences in miRNA-143 expression levels between large and small waves were observed (Phair follicle

  16. Downregulation of β-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling through HuR.

    Directory of Open Access Journals (Sweden)

    Qian Yin

    Full Text Available β-adrenergic receptors (β-ARs play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of β-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β1- and β2-AR expression in cardiac remodeling. The rat model of cardiac remodeling was established by subcutaneous injection of isoproterenol(ISO at the dose of 0.25 mg·kg(-1·d(-1 for 7 days. We found that the expression of β1- and β2-ARs decreased in the remodeling heart. The mechanisms may include the inhibition of DNA transcription and the increase of mRNA degradation. cAMP-response element binding protein(CREB is a well-known transcription factor of β-AR. However, the expression and activation of CREB was not changed in the remodeling heart. Further, human Antigen-R (HuR, a RNA binding protein, which binds to the 3'-untranslated region of the β-AR mRNA and promotes RNA degradation, was increased in the remodeling model. And in vitro, HuR deficiency reversed the reduction of β-AR mRNA induced by ISO. Therefore, the present findings indicate that HuR, but not CREB, is responsible for the reduction of β-AR expression in ISO induced cardiac remodeling.

  17. Intraperirhinal cortex administration of the synthetic cannabinoid, HU210, disrupts object recognition memory in rats.

    Science.gov (United States)

    Sticht, Martin A; Jacklin, Derek L; Mechoulam, Raphael; Parker, Linda A; Winters, Boyer D

    2015-03-25

    Cannabinoids disrupt learning and memory in human and nonhuman participants. Object recognition memory, which is particularly susceptible to the impairing effects of cannabinoids, relies critically on the perirhinal cortex (PRh); however, to date, the effects of cannabinoids within PRh have not been assessed. In the present study, we evaluated the effects of localized administration of the synthetic cannabinoid, HU210 (0.01, 1.0 μg/hemisphere), into PRh on spontaneous object recognition in Long-Evans rats. Animals received intra-PRh infusions of HU210 before the sample phase, and object recognition memory was assessed at various delays in a subsequent retention test. We found that presample intra-PRh HU210 dose dependently (1.0 μg but not 0.01 μg) interfered with spontaneous object recognition performance, exerting an apparently more pronounced effect when memory demands were increased. These novel findings show that cannabinoid agonists in PRh disrupt object recognition memory.

  18. 论胡锦涛的人才观%On HuJintao' s View of Talent

    Institute of Scientific and Technical Information of China (English)

    于伟峰; 黄静

    2012-01-01

    胡锦涛的人才观主要体现在:树立人才资源为第一资源、人人皆可成才和以人为本的观念。胡锦涛的人才观的核心内容与前三代领导集体人才观的核心内容既一眯相承又有其独特的创新点,他首次提出了党管人才的原则和将人才观与以人为本的发展观相结合的原则。%Hu Jintao' s view of talents is embodied in 1 ) his view that human resources are paramount to all other resources; 2) his belief that everyone can develop into a man of caliber; and 3) his people-oriented approach to development. The kernel of Hu Jintao' s view of talent is imbued with the same spirit reflected in the general out- look on talent of previous three generations of central collective leadership of the CPC, while boasting unique inno- vations. Hu first puts forward the principle of managing talents by the party and the principle of combining the sci- entific view of talent with the people-oriented approach to development.

  19. Anti-solar differential rotation on the active sub-giant HU Virginis

    CERN Document Server

    Harutyunyan, G; Künstler, A; Carroll, T A; Weber, M

    2016-01-01

    Measuring surface differential rotation (DR) on different types of stars is important when characterizing the underlying stellar dynamo. It has been suggested that anti-solar DR laws can occur when strong meridional flows exist. We aim to investigate the differential surface rotation on the primary star of the RS CVn binary HU Vir by tracking its starspot distribution as a function of time. We also aim to recompute and update the values for several system parameters of the triple system HU Vir (close and wide orbits). Time-series high-resolution spectroscopy for four continuous months was obtained with the 1.2-m robotic STELLA telescope. Nine consecutive Doppler images were reconstructed from these data, using our line-profile inversion code iMap. An image cross-correlation method was applied to derive the surface differential-rotation law for HU Vir. New orbital elements for the close and the wide orbits were computed using our new STELLA radial velocities (RVs) combined with the RV data available in the lit...

  20. CTXφ Replication Depends on the Histone-Like HU Protein and the UvrD Helicase.

    Directory of Open Access Journals (Sweden)

    Eriel Martínez

    2015-05-01

    Full Text Available The Vibrio cholerae bacterium is the agent of cholera. The capacity to produce the cholera toxin, which is responsible for the deadly diarrhea associated with cholera epidemics, is encoded in the genome of a filamentous phage, CTXφ. Rolling-circle replication (RCR is central to the life cycle of CTXφ because amplification of the phage genome permits its efficient integration into the genome and its packaging into new viral particles. A single phage-encoded HUH endonuclease initiates RCR of the proto-typical filamentous phages of enterobacteriaceae by introducing a nick at a specific position of the double stranded DNA form of the phage genome. The rest of the process is driven by host factors that are either essential or crucial for the replication of the host genome, such as the Rep SF1 helicase. In contrast, we show here that the histone-like HU protein of V. cholerae is necessary for the introduction of a nick by the HUH endonuclease of CTXφ. We further show that CTXφ RCR depends on a SF1 helicase normally implicated in DNA repair, UvrD, rather than Rep. In addition to CTXφ, we show that VGJφ, a representative member of a second family of vibrio integrative filamentous phages, requires UvrD and HU for RCR while TLCφ, a satellite phage, depends on Rep and is independent from HU.

  1. Cannabinoids & Stress: impact of HU-210 on behavioral tests of anxiety in acutely stressed mice.

    Science.gov (United States)

    Kinden, Renee; Zhang, Xia

    2015-05-01

    Anxiety disorders are one of the most prevalent classes of mental disorders affecting the general population, but current treatment strategies are restricted by their limited efficacy and side effect profiles. Although the cannabinoid system is speculated to be a key player in the modulation of stress responses and emotionality, the vast majority of current research initiatives had not incorporated stress exposure into their experimental designs. This study was the first to investigate the impact of exogenous cannabinoid administration in an acutely stressed mouse model, where CD1 mice were pre-treated with HU-210, a potent CB1R agonist, prior to acute stress exposure and subsequent behavioral testing. Exogenous cannabinoid administration induced distinct behavioral phenotypes in stressed and unstressed mice. While low doses of HU-210 were anxiolytic in unstressed subjects, this effect was abolished when mice were exposed to an acute stressor. The administration of higher HU-210 doses in combination with acute stress exposure led to severe locomotor deficits that were not previously observed at the same dose in unstressed subjects. These findings suggest that exogenous cannabinoids and acute stress act synergistically in an anxiogenic manner. This study underlies the importance of including stress exposure into future anxiety-cannabinoid research due to the differential impact of cannabinoid administration on stressed and unstressed subjects.

  2. Clinical study on intravitreal injection of cannabinoid HU-211 for optic nerve damage in glaucoma rats

    Directory of Open Access Journals (Sweden)

    Hui-Feng Liu

    2014-09-01

    Full Text Available AIM: To evaluate the protective effects of intravitreal injection of cannabinoid HU-211 for optic nerve in glaucoma rats, providing the experimental evidence in the treatment of glaucoma optic nerve injury.METHODS: Glaucoma rats(18 eyeswere modeled by electric coagulation sclera surface vein and randomized into 3 groups, group A received intravitreal injection of 1mg/0.1mL cannabinoid HU-211 every other day respectively; group B was given intravitreal injection of 0.1mL water every other day, group C was high intraocular pressure(IOPgroup, 6 eyes were randomly selected for blank control group(group D. IOP was observed every day. The rats were sacrificed after treatment 4wk, froze retina section, HE stain. The density fluctuation of retinal ganglion cell(RGCneurons assessment the optic nerve of rat model with chronic high IOP glaucoma were measured.RESULTS: The apoptosis and damage degree of RGC in group B was obviously higher than that in group A, with statistically significant difference(PP >0.05.CONCLUSION: Intravitreal injection of cannabinoid HU-211 shows obvious protective effect on optic nerve in glaucom rat models.

  3. The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Doller, Anke; Badawi, Amel [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Schmid, Tobias; Brauß, Thilo [Institut für Biochemie I (Pathobiochemie), Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pleli, Thomas [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Meyer zu Heringdorf, Dagmar [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Piiper, Albrecht [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Eberhardt, Wolfgang, E-mail: w.eberhardt@em.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany)

    2015-01-01

    The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D{sub 1} encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E{sub 2} synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on

  4. High-level Expression and Purification of Human Zona Pellucida huZP3a22-176 and huZP3b177-348 Peptides in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To try making huZP3a22-176 and huZP3b177-348 polypeptides (representing an intact huZP322-348 protein without its N-terminal signal peptide and C-terminal transmembrane domain ) express in E. coli at a higher levelMethods The cDNAs encoding huZP3a and huZP3b were obtained with PCR method.The pB V221 plasmid was used to construct thermo-inducible recombinant expression vector. Purification of two target expression products employed an improved method of preparative gel polyacrylamide gel electrophoresis.Results Two polypeptides of recombinant huZP3a (rhuZP3a) and recombinant huZP3b(rhuZP3b) were all expressed respectively in an E. coli BL21(DE3)pLysS strain at a higher level, which were recognized by two specific polyclonal antisera in Western blotting test which recognize a linear B cell epitope present in rhuZP3a or rhuZP3b respectively. Using the shake-flask method, approximately 5 mg of rhuZP3a and rhuZP3b with more than 95% relative homogeneity were harvested from 1 L culture respectively.Conclusion The availability of two rhuZP3 polypeptides will help in detecting the immunogenicities of rhuZP3a and rhuZP3b through animal experiments and confirming the function domain of non-glycosylated huZP3 to induce acrosome reaction in vitro.

  5. Isolation, purification, crystallization, and preliminary X-ray diffraction study of the crystals of HU protein from M. gallisepticum

    Science.gov (United States)

    Nikolaeva, A. Yu.; Timofeev, V. I.; Boiko, K. M.; Korzhenevskii, D. A.; Rakitina, T. V.; Dorovatovskii, P. V.; Lipkin, A. V.

    2015-11-01

    HU proteins are involved in bacterial DNA and RNA repair. Since these proteins are absent in cells of higher organisms, inhibitors of HU proteins can be used as effective and safe antibiotics. The crystallization conditions for the M. gallisepticum HU protein were found and optimized by the vapor-diffusion method. The X-ray diffraction data set was collected to 2.91 Å resolution from the crystals grown by the vapor-diffusion method on a synchrotron source. The crystals of the HU protein belong to sp. gr. P41212 and have the following unit-cell parameters: a = b = 97.94 Å, c = 77.92 Å, α = β = γ = 90°.

  6. HuR interacts with human immunodeficiency virus type 1 reverse transcriptase, and modulates reverse transcription in infected cells

    Directory of Open Access Journals (Sweden)

    Ennifar Eric

    2008-06-01

    Full Text Available Abstract Reverse transcription of the genetic material of human immunodeficiency virus type 1 (HIV-1 is a critical step in the replication cycle of this virus. This process, catalyzed by reverse transcriptase (RT, is well characterized at the biochemical level. However, in infected cells, reverse transcription occurs in a multiprotein complex – the reverse transcription complex (RTC – consisting of viral genomic RNA associated with viral proteins (including RT and, presumably, as yet uncharacterized cellular proteins. Very little is known about the cellular proteins interacting with the RTC, and with reverse transcriptase in particular. We report here that HIV-1 reverse transcription is affected by the levels of a nucleocytoplasmic shuttling protein – the RNA-binding protein HuR. A direct protein-protein interaction between RT and HuR was observed in a yeast two-hybrid screen and confirmed in vitro by homogenous time-resolved fluorescence (HTRF. We mapped the domain interacting with HuR to the RNAse H domain of RT, and the binding domain for RT to the C-terminus of HuR, partially overlapping the third RRM RNA-binding domain of HuR. HuR silencing with specific siRNAs greatly impaired early and late steps of reverse transcription, significantly inhibiting HIV-1 infection. Moreover, by mutagenesis and immunoprecipitation studies, we could not detect the binding of HuR to the viral RNA. These results suggest that HuR may be involved in and may modulate the reverse transcription reaction of HIV-1, by an as yet unknown mechanism involving a protein-protein interaction with HIV-1 RT.

  7. Domain-specific phosphomimetic mutation allows dissection of different protein kinase C (PKC) isotype-triggered activities of the RNA binding protein HuR.

    Science.gov (United States)

    Schulz, Sebastian; Doller, Anke; Pendini, Nicole R; Wilce, Jacqueline A; Pfeilschifter, Josef; Eberhardt, Wolfgang

    2013-12-01

    The ubiquitous mRNA binding protein human antigen R (HuR) participates in the post-transcriptional regulation of many AU-rich element (ARE)-bearing mRNAs. Previously, by using in vitro kinase assay, we have identified serines (Ser) 158, 221 and 318 as targets of protein kinase C (PKC)-triggered phosphorylation. In this study, we tested whether GFP- or GST-tagged HuR constructs bearing a phosphomimetic Ser (S)-to-Asp (D) substitution at the different PKC target sites, would affect different HuR functions including HuR nucleo-cytoplasmic redistribution and binding to different types of ARE-containing mRNAs. The phosphomimetic GFP-tagged HuR protein bearing a phosphomimetic substitution in the hinge region of HuR (HuR-S221D) showed an increased cytoplasmic abundance when compared to wild-type HuR. Conversely, data from in vitro kinase assay and electrophoretic mobility shift assay (EMSA), implicates that phosphorylation at Ser 221 is not relevant for mRNA binding of HuR. Quantification of in vitro binding affinities of GST-tagged wild-type HuR and corresponding HuR proteins bearing a phosphomimetic substitution in either RRM2 (HuR-S158D) or in RRM3 (HuR-S318D) by microscale thermophoresis (MST) indicates a specific binding of wild-type HuR to type I, II or type III-ARE-oligonucleotides in the high nanomolar range. Interestingly, phosphomimetic mutation at position 158 or 318 had a negative influence on HuR binding to type I- and type II-ARE-mRNAs whereas it significantly enhanced HuR affinity to a type III-ARE substrate. Our data suggest that differential phosphorylation of HuR by PKCs at different HuR domains coordinates subcellular HuR distribution and leads to a preferential binding to U-rich bearing target mRNA.

  8. A Review of the Pharmacological Effects of the Dried Root of Polygonum cuspidatum (Hu Zhang and Its Constituents

    Directory of Open Access Journals (Sweden)

    Huan Zhang

    2013-01-01

    Full Text Available Traditional Chinese medicine (TCM has been widely used in China for thousands of years to treat and prevent diseases. TCM has been proven safe and effective, and it is being considered as one of the important types of complementary and alternative medicine and receives increasing attention worldwide. The dried root of Polygonum cuspidatum Sieb. et Zucc. (also known as “Hu Zhang” in Chinese is one of the medicinal herbs listed in the Pharmacopoeia of the People's Republic of China. Hu Zhang is widely distributed in the world. It can be found in Asia and North America and is used as folk medicine in countries such as Japan and Korea. In China, Hu Zhang is usually used in combination with other TCM herbs. The therapeutic uses of those Hu Zhang-containing TCM prescriptions or formulations are for treating cough, hepatitis, jaundice, amenorrhea, leucorrhea, arthralgia, burns and snake bites. Recent pharmacological and clinical studies have indicated that Hu Zhang has antiviral, antimicrobial, anti-inflammatory, neuroprotective, and cardioprotective functions. This review gives a summary of the reported therapeutic effects of the active compounds and the different extracts of Hu Zhang.

  9. CONSTRUCTION OF HU-PBL/SCID CHIMERAS AND DEVELOPMENT OF EBV-RELATED LYMPHOMAS

    Institute of Scientific and Technical Information of China (English)

    Run-liang Gan; Ke Lan; Zhi-hua Yin; Li-jiang Wang; Ying Song; Kai-tai Yao

    2005-01-01

    Objective To construct hu-PBL/SCID chimeras and to investigate the development of lymphoma and oncogenicity of the Epstein-Barr virus (EBV).Mtehods Human peripheral blood lymphocytes (PBLs) were isolated from healthy adult donors and transplanted intraperitoneally into severe combined immunodeficient (SCID) mice. Mice with hu-PBL engraftment from healthy EBV seronegative donors were injected intraperitoneally with EBV-containing supematant from suspension culture of B95-8 cell line (active infection), whereas mice receiving lymphocytes from healthy EBV seropositive donors were not re-infected with B95-8 derived EBV (latent infection). Pathological examination and molecular analysis were performed on experimental animals and induced neoplasms.Results In the early stage of this experiment, 12 mice died of acute graft-versus-host disease, mortality was 34.3%(12/35 mice) with an average life span of 17.5 days. In 19 survival hu-PBL/SCID chimeric recipients from 12 healthy donors,tumor incidence was 84.2% (16/19 mice). The average survival time of tumor-bearing mice was 65.5 days. EBV-related neoplasms in SCID mice were nodular tumors with aggressive and fatal features. Histological morphology of tumors exhibited diffuse large cell lymphomas. Immunohistochemistry revealed that LCA (CD45) and L26 (CD20) were positive, but both PS1 (CD3) and UCHL-1 (CD45RO) were negative, and EBV products ZEBRA, LMP1, and EBNA2 were expressed in a small number of tumor cells. EB virus particles were seen in the nuclei of some tumor cells by electron microscopy, and EBV DNA could be amplified in the tumor tissues by PCR. In situ hybridization indicated that the nuclei of tumor cells contained human-specific Alu sequence.Conclusions EBV-induced tumors were human B-cell malignant lymphomas. We obtained direct causative evidence dealing with EBV-associated tumor deriving from normal human cells.

  10. 'Hu Hong' (bad thing): parental perceptions of teenagers' sexuality in urban Vietnam.

    Science.gov (United States)

    Do, Lan Anh Thi; Boonmongkon, Pimpawun; Paek, Seung Chun; Guadamuz, Thomas E

    2017-02-28

    Teenagers under 18 years old in Vietnam are considered as minors who usually lack the autonomy to make decisions. They are also sometimes viewed as contributors to social evils including crime, violence and substance use. Moreover, most Vietnamese teenagers have unsafe sex before marriage. The objective of this study is to explore the parental perceptions relating to their teenagers' sexuality, particularly the social and cultural forces, that may hinder access to sexuality information. Guided by a Community Advisory Board (CAB), this qualitative study uses four focus group discussions (FGDs) consisting of 12 mothers and 12 fathers, as well as twelve individual in-depth interviews (IDIs) with a diverse sample of parents of teens in Ho Chi Minh City (HCMC), Vietnam. Content and discourse analysis were conducted, based on Foucauldian concepts. Four themes emerged: 1) Meanings of sexuality and sexuality education, 2) Early sexual intercourse destroys teenagers' future, 3) Teenagers are not hu hong (spoil/bad thing), are innocent and virgin, and 4) Policing and controlling of sexual intercourse among teens. Parents did not view their teenage children as sexual beings; those who are sexual are considered hu hong. Parents believed that teens need to be policed and controlled to prevent them from becoming hu hong, particularly girls. Controlling of sexuality information by parents was therefore common in HCMC, but differed by gender and educational levels of parents. For example, fathers more than mothers were not comfortable teaching their teenage children about sex and sexuality. Parents with higher education police their teenage children's usage of the Internet and social media, while parents with lower education control who can be friends with their teenage children. Vietnamese parents in general have negative views of sex and sexuality education for their teenage children. Recognizing that many Vietnamese teenagers have unsafe sex before marriage, parents need to

  11. Effects of weaning age on growth, nutrient digestibility and metabolism, and serum parameters in Hu lambs

    Directory of Open Access Journals (Sweden)

    Jianmin Chai

    2015-12-01

    Full Text Available This study was conducted to investigate the effect of weaning age on growth performance, nutrient digestion and metabolism, and serological indicators, and to obtain an optimal weaning age in Hu lambs. Forty-eight newborn Hu lambs (birth weight, 2.53 ± 0.14 kg were randomly divided into 4 groups. The lambs in control group (ER suckled their dams. The lambs in other three experimental groups were weaned on milk replacer at 10, 20, and 30 days of age (EW10, EW20, and EW30 groups, respectively. The results were as follows: 1 lambs in EW10 and EW30 groups had a lower (P  0.05 among groups; however, the apparent digestibility and deposition of calcium in early weaned lambs were lower (P < 0.05 than those in ewe-reared lambs. 4 The albumin content in EW30 group was lower (P < 0.05 than that in ER group; the globulin content in EW30 group was higher (P < 0.05 than that in other groups; the content of serum insulin-like growth factor-Ⅰ in weaned lambs tended to increase compared with lambs in ER group. Finally, the growth rate of lambs decreased within 10 days post-weaning, but early weaning boosted creep feed intake, leading to better growth and health later in life. The Hu lambs can be weaned on milk replacer and creep feed at 10 days of age.

  12. Chemical Constituents from the Seeds of Ziziphus jujuba var. Spinosa (Bunge) Hu

    Institute of Scientific and Technical Information of China (English)

    Li-Mei LI; Xun LIAO; Shu-Lin PENG; Li-Sheng DING

    2005-01-01

    To search for new and bioactive minor components from traditional Chinese medicines, a new compound, named jujuphenoside (1), was isolated from the seeds of Ziziphusjujuba var. spinosa (Bunge)Hu. The structure of jujuphenoside was elucidated by spectral and chemical methods, particularly twodimensional nuclear magnetic resonance analysis. Together with the new compound, 22 known compounds were also isolated and identified from the seeds of Z. jujuba var. spinosa, among which, epiceanothic acid (2) was first obtained from natural resources, whereas compounds 7-16 were first obtained from this plant.

  13. Opsoclonus-myoclonus and anti-Hu positive limbic encephalitis in a patient with neuroblastoma.

    Science.gov (United States)

    Morales La Madrid, Andres; Rubin, Charles M; Kohrman, Michael; Pytel, Peter; Cohn, Susan L

    2012-03-01

    Opsoclonus-myoclonus syndrome (OMS) is seen in 2-3% of children with neuroblastoma and is believed to be caused by an autoimmune process elicited by the tumor. Although long-term neurologic sequelae are common in children with OMS, limbic encephalitis has not previously been reported. We report a child who developed limbic encephalitis associated with anti-Hu antibodies, 6 years after her initial diagnosis of neuroblastoma and OMS. This case demonstrates that patients with neuroblastoma and OMS are at risk for developing new paraneoplastic symptoms years after their original diagnosis and emphasizes the need for careful long-term follow-up.

  14. Micología Lista de Huéspedes Colombianos

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    Obregon Botero Rafael

    1964-12-01

    Full Text Available El presente trabajo es una lista de hongos encontrados en Colombia. Está ordenada por Familias del huésped y cada nombre científico del hongo va seguido por la mención de los lugares donde fue encontrado así como la altura de tales localidades. Luego precede un número que corresponde a la colección existente en el Ministerio de Agricultura de Colombia. No pretendo sino iniciar la labor que han de completar especialistas mejor informados y espero que sea de alguna utilidad para los que se dedican a esta rama de las Ciencias Naturales.

  15. Hybrid Semiloof elements for plates and shells based upon a modified Hu-Washizu principle

    Science.gov (United States)

    Pian, T. H. H.; Sumihara, K.

    1984-01-01

    Hybrid SemiLoof elements for plates and shells are developed based upon modified Hu-Washizu principle. In the new version of the assumed stress hybrid formulation the equilibrium equations are satisfied through the introduction of internal displacement parameters as Lagrange multipliers. The inversion of the resulting H-matrices is simplified particularly when the stresses are expressed in terms of natural coordinates. A 24-DOF triangular element and a 32-DOF quadrilateral element based on shallow shell theory are derived and evaluated.

  16. HuLiS, a program to teach mesomerism and more

    Science.gov (United States)

    Carissan, Yannick; Goudard, Nicolas; Hagebaum-Reignier, Denis; Humbel, Stéphane

    2016-08-01

    The HuLiS program is presented as a tool to decompose a delocalized wave function as a linear combination of localized electronic structures. The principles of the energy based HL-CI and the overlap based schemes HL-P are developed. The results obtained for a set of 10 relevant organic molecules are shown to compare very well with high level quantum chemistry calculations. A trust factort is introduced and its use is shown on the allyl radical case where symmetry must be taken into account.

  17. MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells

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    Xun Guo

    2015-03-01

    Full Text Available RNA binding protein (RBPs and microRNAs (miRNAs or miRs are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC. Despite this, miR-16 and HuR do not affect the other’s expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA.

  18. 可在鱼体内表达hu-IFN-α的基因重组构建及转化%Construction of a Fish Expression hu-IFN-α Recombinant Gene

    Institute of Scientific and Technical Information of China (English)

    张学文; 章怀云; 符少辉; 陈韬; 陈立祥; 肖调义

    2001-01-01

    通过分子重组,将人α-干扰素(hu-IFN-α)基因编码序列克隆到鲤鱼β-肌动蛋白基因启动子下游,构建成能在鱼体内组成型表达hu-IFN-α的基因重组分子。经限制性酶切分析、Southern杂交和序列测定,证明重组分子构建的正确性。采用显微注射法将这一重组基因转化草鱼受精卵,获得了表达人α-干扰素的转基因草鱼。%The coding sequence of hu-IFN-α gene is cloned under the control of Carp β-actin gene promoter. Thus a fish constantly expression of hu-IFN-α gene recombinant is constructed. Southern blot and sequencing results show that the recombinant molecule is correctly constructed. The recombinant gene is transferred into fertilized zygotes of grass carp via microinjection. And hu-IFN-α is detected out in 20% of transgenic fish by ELISA.

  19. Beta-carotene

    Science.gov (United States)

    ... patches on the tongue and mouth called oral leukoplakia. Taking beta-carotene by mouth for up to 12 months seems to decrease symptoms of oral leukoplakia. Osteoarthritis. Beta-carotene taken by mouth may prevent ...

  20. Betting Against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    .S. equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures; (2) A betting-against-beta (BAB) factor, which is long leveraged low beta assets and short high-beta assets, produces significant positive risk-adjusted returns; (3) When funding constraints tighten, the return...

  1. Genetic determination of the enhanced drought resistance of rice maintainer HuHan2B by pedigree breeding.

    Science.gov (United States)

    Wei, Haibin; Feng, Fangjun; Lou, Qiaojun; Xia, Hui; Ma, Xiaosong; Liu, Yunhua; Xu, Kai; Yu, Xinqiao; Mei, Hanwei; Luo, Lijun

    2016-11-17

    The ongoing deficit of fresh water resource in rice growing regions has made the selection of water-saving and drought-resistance rice (WDR) a crucial factor in developing sustainable cultivation. HuHan2B, a new japonica maintainer for WDR breeding, had the same yield potential as recurrent parent HanFengB but showed improved drought resistance in fields. We investigated the genomic content accumulation and candidate genes passed from parent to offspring using the genomic and transcriptomic approaches. The genomic constitution indicated that the genetic similarity was 84% between HuHan2B and HanFengB; additionally, 7,256 genes with specific alleles were inherited by HuHan2B from parents other than HanFengB. The differentially expressed genes (DEGs) under drought stress showed that biological function was significantly enriched for transcript regulation in HuHan2B, while the oxidation-reduction process was primarily enriched in HanFengB. Furthermore, 36 DEGs with specific inherited alleles in HuHan2B were almost involved in the regulatory network of TFs and target genes. These findings suggested that major-effect genes were congregated and transformed into offspring in manner of interacting network by breeding. Thus, exploiting the potential biological function of allelic-influencing DEGs would be of great importance for improving selection efficiency and the overall genetic gain of multiple complex traits.

  2. HuR-Regulated mRNAs Associated with Nuclear hnRNP A1-RNP Complexes

    Directory of Open Access Journals (Sweden)

    Apostolia Guialis

    2013-10-01

    Full Text Available Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding proteins having a major role in mRNA processing events in mammals. We have been interested in the concerted action of the two RNA-binding proteins hnRNP A1 and HuR, both stable components of immunoselected hnRNP complexes and having a major nuclear localization. Specifically, we present here the application of the RNA-immunoprecipitation (RIP-Chip technology to identify a population of nuclear transcripts associated with hnRNP A1-RNPs as isolated from the nuclear extract of either HuR WT or HuR-depleted (KO mouse embryonic fibroblast (MEF cells. The outcome of this analysis was a list of target genes regulated via HuR for their association (either increased or reduced with the nuclear hnRNP A1-RNP complexes. Real time PCR analysis was applied to validate a selected number of nuclear mRNA transcripts, as well as to identify pre-spliced transcripts (in addition to their mature mRNA counterpart within the isolated nuclear hnRNP A1-RNPs. The differentially enriched mRNAs were found to belong to GO categories relevant to biological processes anticipated for hnRNP A1 and HuR (such as transport, transcription, translation, apoptosis and cell cycle indicating their concerted function in mRNA metabolism.

  3. Effects of rHu-EPO on Myocyte Apoptosis and Cardiac Function Follow-ing Acute Myocardial Infarction in Rats

    Institute of Scientific and Technical Information of China (English)

    YE Liang; DU Xinling; XIA Jiahong; JIANG Ping

    2005-01-01

    The mechanisms of rHu-EPO attenuating the apoptosis after myocardial infarction in rats were studied. Thirty-two rats were divided into three groups: sham operation group (Sham), acute myocardial infarction group (MI) and rHu-EPO-treated group (MI+ EPO). Acute myocardial infarction model was made by ligating the anterior descending coronary artery. rHu-EPO was administered i. p. in MI+EPO group at the dose of 5 000 IU/kg body weight immediately after the ligation. Each rat in MI+EPO group received the same dose of rHu-EPO daily the next 6 days. On the 14th day all rats underwent hemodynamic measurements and then killed. The samples were examined with HE stain, immunohistochemistry technique (bcl-2, bax) and TUNEL dyeing. The results showed that hemodynamic function in MI+ EPO group was much better than in MI group.The number of the cells positive for bax and TUNEL in MI+EPO group was less than that in MI group. The number of the cells positive for bcl-2 in MI+EPO group was more than that in MI group. These findings suggested that rHu-EPO could treat myocardial infarction by preventing apoptosis and attenuating post-infarction deterioration in hemodynamic function.

  4. The Use of Soluble Transferrin Receptor in the Detection of rHuEPO Abuse in Sports

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    Lorenzo Gordon

    2010-02-01

    Full Text Available Erythropoietin (EPO increases the number of circulating erythrocytes and muscle oxygenation. The recombinant forms of EPO have indiscriminately been used by athletes, mainly in endurance sports to increase their erythrocytes concentration, thus generating a better delivery of oxygen to the muscle tissue. The administration of recombinant human erythropoietin (rHuEPO except for therapeutic use was prohibited by the International Olympic Committee (IOC and its unauthorized use considered as doping. In the last few years, a number of studies using parameters indicative of accelerated erythropoiesis have investigated a number of indirect methods for the detection of rHuEPO abuse. No single indirect marker has been found that can satisfactorily demonstrated rHuEPO misuse. Soluble transferrin receptor (sTfR is a new marker of iron status and erythropoietic activity. It has been included in multivariable blood testing models for the detection of performance enhancing EPO abuse in sports. Indirect markers of altered erythropoiesis give reliable evidence of current or discontinued rHuEPO usage. This review describes the physical, biological and pharmacokinetic properties of endogenous EPO and its recombinant form. It also discusses the available strategies for the detection of rHuEPO abuse in sports, involving the use of sTfR concentration directly or in mathematical multivariate models.

  5. Potential Risk of Hybridization in Ex Situ Collections of Two Endangered Species of Sinojackia Hu (Styracaceae)

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Spontaneous hybridization in ex situ facilities can undermine the genetic integrity of ex situ collections and potentially contaminate open-pollinated seeds or seedlings destined for the reintroduction of endangered plant species into the wild. In the present study, the potential risk of hybridization between two endangered Chinese endemic species, namely Sinojackia xylocarpa Hu and S. rehderiana Hu, which are naturally allopatric species but were conserved ex situ in Wuhan Botanical Garden (WBG), Wuhan, China, were investigated over three consecutive years from 2003 to 2005. The entire overlapping flowering period of the two species was 14-20 d and the two species shared the same pollinator insects during the entire flowering season in WBG. The floral isolation between the two species was not an issue in the ex situ collection at WBG. The results suggest an opportunity for pollen transfer between species and a potential risk of genetic introgression and loss of genetic identity of open-pollinated seeds produced in the ex situ collection of these two endangered species. An artificial reciprocal cross between S. xylocarpa and S. rehderiana confirmed that the two congener species could readily set seeds, indicating no post-pollination barriers to hybridization and the importance of spatial isolation as a barrier to inter-specific crossing. Therefore, to manage these crossable species with overlapping flowering times and shared pollination vectors in ex situ facilities, spatial isolation should be carefully considered to minimize the possibility of spontaneous hybridization.

  6. Combining wavelets transform and Hu moments with self-organizing maps for medical image categorization

    Science.gov (United States)

    Silva, Leandro A.; Del-Moral-Hernandez, Emilio; Moreno, Ramon A.; Furuie, Sérgio S.

    2011-10-01

    Images are fundamental sources of information in modern medicine. The images stored in a database and divided in categories are an important step for image retrieval. For an automatic categorization process, detailed analysis is done regarding image representation and generalization method. The baseline method for this process, in the medical image context, is using thumbnails and K-nearest neighbor (KNN), which is easily implemented and has had satisfactory results in literature. This work addresses an alternative method for automatic categorization, which jointly uses discrete wavelet transform with Hu's moments for image representation and self-organizing maps (SOM) neural networks combined with the KNN classifier (SOM-KNN), for medical image categorization. Furthermore, extensive experiments are conducted, to define the best wavelet family and to select the best coefficients set, to consider the remaining wavelet coefficients set (not selected as the best ones) through their Hu's moments, and to carry out a contrastive study with other successful approaches for categorization. The categorization result from a database with 10,000 images in 116 categories yielded 81.8% of correct rate, which is much better than the 67.9% obtained by the baseline method; and the time consumed in classification processing with SOM-KNN is 100 times shorter than KNN.

  7. Hu1-2: a metal-poor bipolar planetary nebula with fast collimated outflows

    CERN Document Server

    Fang, Xuan; Miranda, Luis F; Riera, Angels; Velazquez, Pablo F; Raga, Alejandro C

    2015-01-01

    We present narrow-band optical and near-IR imaging and optical long-slit spectroscopic observations of Hu1-2, a Galactic planetary nebula (PN) with a pair of [N II]-bright, fast-moving (> 340 km/s) bipolar knots. Intermediate-dispersion spectra are used to derive physical conditions and abundances across the nebula, and high-dispersion spectra to study the spatio-kinematical structure. Generally Hu1-2 has high He/H (~0.14) and N/O ratios (~0.9), typical of Type I PNe. On the other hand, its abundances of O, Ne, S, and Ar are low as compared with the average abundances of Galactic bulge and disc PNe. The position-velocity maps can be generally described as an hour-glass shaped nebula with bipolar expansion, although the morphology and kinematics of the innermost regions cannot be satisfactorily explained with a simple, tilted equatorial torus. The spatio-kinematical study confines the inclination angle of its major axis to be within 10 degrees of the plane of sky. As in the irradiated bow-shocks of IC4634 and ...

  8. Revisiting the proposed planetary system orbiting the eclipsing polar HU Aquarii

    CERN Document Server

    Wittenmyer, Robert A; Marshall, J P; Butters, O W; Tinney, C G

    2011-01-01

    It has recently been proposed, on the basis of eclipse-timing data, that the eclipsing polar cataclysmic variable HU Aquarii is host to at least two giant planets. However, that result has been called into question based upon the dynamical stability of the proposed planets. In this work, we present a detailed re-analysis of all eclipse timing data available for the HU Aquarii system, making use of standard techniques used to fit orbits to radial-velocity data. We find that the eclipse timings can be used to obtain a two-planet solution that does not require the presence of additional bodies within the system. We then perform a highly detailed dynamical analysis of the proposed planetary system. We show that the improved orbital parameters we have derived correspond to planets that are dynamically unstable on unfeasibly short timescales (of order 10^4 years or less). Given these results, we discuss briefly how the observed signal might in fact be the result of the intrinsic properties of the eclipsing polar, r...

  9. ReHuNa- La Red por la Humanización del Parto y Nacimiento

    Directory of Open Access Journals (Sweden)

    Daphne RATTNER

    2010-12-01

    Full Text Available La ReHuNa - Red por la Humanización del Parto y Nacimiento - es una organización de la sociedad civil que actúa desde 1993 en forma de red de asociados en el Brasil. Su principal objetivo es la divulgación de la asistencia y cuidados perinatales con base en evidencias científicas y de acuerdo a las recomendaciones de la Organización Mundial de la Salud. Esta red tuvo un papel fundamental en la estructura de un movimiento que hoy se denomina “humanización de la asistencia al parto y nacimiento”, que pretende disminuir las intervenciones innecesarias y promover cuidados al proceso del embarazo-parto-nacimiento-lactancia comprendido como un proceso natural y fisiológico basado en conocimientos científicos. Este artículo relata la historia de la ReHuNa y sus principales realizaciones y señala sus caminos futuros.

  10. The impact of the vaccination program for hemorrhagic fever with renal syndrome in Hu County, China.

    Science.gov (United States)

    Xiao, Dan; Wu, Kejian; Tan, Xin; Yan, Tiecheng; Li, Haitao; Yan, Yongping

    2014-02-03

    The incidence of hemorrhagic fever with renal syndrome (HFRS) in Hu County ranked third of all counties in China in 2010. Although this county has provided a HFRS vaccination program freely since 1994, the impact of HFRS remains quite substantial. In order to continue the vaccination program effectively and control HFRS, a detailed understanding of the effect of the vaccination program should be undertaken. The Cochran-Armitage trend test was employed to examine the temporal trends of HFRS incidences, mortality rate and vaccination compliance. Temporal cluster analysis was performed to detect time periods of high HFRS risk. Cross correlation analysis was conducted to detect the correlation between HFRS incidence and vaccination compliance. Wavelet analysis was employed to detect the shift of the periodicity of HFRS. Between 1971 and 2011, the HFRS incidence and mortality rate ranged from 9.53/100,000 to 300.57/100,000 and 0 to 24.91/100,000, respectively, with a fluctuating but distinctly declining trend (incidence: Z=-34.38, P1994. In conclusion, the increase in vaccination compliance may play an important role in HFRS control and prevention in Hu County, China.

  11. The SCID-hu mouse as a model for HIV-1 infection.

    Science.gov (United States)

    Aldrovandi, G M; Feuer, G; Gao, L; Jamieson, B; Kristeva, M; Chen, I S; Zack, J A

    1993-06-24

    During normal fetal ontogeny, one of the first organs to harbour CD4-positive cells is the thymus. This organ could therefore be one of the earliest targets infected by human immunodeficiency virus type 1 (HIV-1) in utero. HIV-1-infected cells and pathological abnormalities of the thymus have been seen in HIV-1-infected adults and children, and in some fetuses aborted from infected women. Studies of HIV-1 pathogenesis have been hampered by lack of a suitable animal model system. Here we use the SCID-hu mouse as a model to investigate the effect of virus infection on human tissue. The mouse is homozygous for the severe combined immunodeficiency (SCID) defect. The model is constructed by implanting human fetal liver and thymus under the mouse kidney capsule. A conjoint human organ develops, which allows normal maturation of human thymocytes. After direct inoculation of HIV-1 into these implants, we observed severe depletion of human CD4-bearing cells within a few weeks of infection. This correlated with increasing virus load in the implants. Thus the SCID-hu mouse may be a useful in vivo system for the study of HIV-1-induced pathology.

  12. RNA-binding protein HuD reduces triglyceride production in pancreatic β cells by enhancing the expression of insulin-induced gene 1.

    Science.gov (United States)

    Kim, Chongtae; Lee, Heejin; Kang, Hoin; Shin, Jung Jae; Tak, Hyosun; Kim, Wook; Gorospe, Myriam; Lee, Eun Kyung

    2016-04-01

    Although triglyceride (TG) accumulation in the pancreas leads to β-cell dysfunction and raises the chance to develop metabolic disorders such as type 2 diabetes (T2DM), the molecular mechanisms whereby intracellular TG levels are regulated in pancreatic β cells have not been fully elucidated. Here, we present evidence that the RNA-binding protein HuD regulates TG production in pancreatic β cells. Mouse insulinoma βTC6 cells stably expressing a small hairpin RNA targeting HuD (shHuD) (βTC6-shHuD) contained higher TG levels compared to control cells. Moreover, downregulation of HuD resulted in a decrease in insulin-induced gene 1 (INSIG1) levels but not in the levels of sterol regulatory element-binding protein 1c (SREBP1c), a key transcription factor for lipid production. We identified Insig1 mRNA as a direct target of HuD by using ribonucleoprotein immunoprecipitation (RIP) and biotin pulldown analyses. By associating with the 3'-untranslated region (3'UTR) of Insig1 mRNA, HuD promoted INSIG1 translation; accordingly, HuD downregulation reduced while ectopic HuD expression increased INSIG1 levels. We further observed that HuD downregulation facilitated the nuclear localization of SREBP1c, thereby increasing the transcriptional activity of SREBP1c and the expression of target genes involved in lipogenesis; likewise, we observed lower INSIG1 levels in the pancreatic islets of HuD-null mice. Taken together, our results indicate that HuD functions as a novel repressor of lipid synthesis in pancreatic β cells.

  13. Forward-Looking Betas

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Vainberg, Gregory

    Few issues are more important for finance practice than the computation of market betas. Existing approaches compute market betas using historical data. While these approaches differ in terms of statistical sophistication and the modeling of the time-variation in the betas, they are all backward......-looking. This paper introduces a radically different approach to estimating market betas. Using the tools in Bakshi and Madan (2000) and Bakshi, Kapadia and Madan (2003) we employ the information embedded in the prices of individual stock options and index options to compute our forward-looking market beta...

  14. HuR-targeted nanotherapy in combination with AMD3100 suppresses CXCR4 expression, cell growth, migration, and invasion in lung cancer

    Science.gov (United States)

    Muralidharan, Ranganayaki; Panneerselvam, Janani; Chen, Allshine; Zhao, Yan Daniel; Munshi, Anupama; Ramesh, Rajagopal

    2015-01-01

    The CXCR4 chemokine receptor plays an important role in cancer cell metastasis. The CXCR4 antagonist, AMD3100, has limited efficacy in controlling metastasis. HuR, an RNA-binding protein, regulates CXCR4 in cancer cells. We therefore investigated whether targeting HuR using a siRNA-based nanoparticle plus AMD3100 would suppress CXCR4 and inhibit lung cancer metastasis. We treated human H1299 lung cancer cell with HuR-specific siRNA contained in a folate-targeted lipid nanoparticle (HuR-FNP) plus AMD3100, and compared this with AMD3100 alone, HuR-FNP alone and no treatment. HuR-FNP plus AMD3100 treatment produced a G1 phase cell-cycle arrest and reduced cell viability above and beyond the effects of AMD3100 alone. HuR and CXCR4 mRNA and protein expression levels were markedly reduced in all treatment groups. Phosphorylated (p) AKTS473 protein was also reduced. P27 protein expression increased with HuR-FNP and combination treatment. Promoter-based reporter studies showed that the combination inhibited CXCR4 promoter activity more than did either treatment alone. Cell migration and invasion was significantly reduced with all treatment; the combination provided the most inhibition. Reduced matrix metalloprotease (MMP) -2 and -9 expression was associated with reduced invasion in all treatment groups. Thus, we found that combined HuR and CXCR4 targeting effectively controlled lung cancer metastasis. PMID:26494555

  15. HuR-targeted nanotherapy in combination with AMD3100 suppresses CXCR4 expression, cell growth, migration and invasion in lung cancer.

    Science.gov (United States)

    Muralidharan, R; Panneerselvam, J; Chen, A; Zhao, Y D; Munshi, A; Ramesh, R

    2015-12-01

    The CXCR4 chemokine receptor has an important role in cancer cell metastasis. The CXCR4 antagonist, AMD3100, has limited efficacy in controlling metastasis. HuR, an RNA-binding protein, regulates CXCR4 in cancer cells. We therefore investigated whether targeting HuR using a siRNA-based nanoparticle plus AMD3100 would suppress CXCR4 and inhibit lung cancer metastasis. We treated human H1299 lung cancer cells with HuR-specific siRNA contained in a folate-targeted lipid nanoparticle (HuR-FNP) plus AMD3100, and compared this with AMD3100 alone, HuR-FNP alone and no treatment. HuR-FNP plus AMD3100 treatment produced a G1 phase cell cycle arrest and reduced cell viability above and beyond the effects of AMD3100 alone. HuR and CXCR4 mRNA and protein expression levels were markedly reduced in all treatment groups. Phosphorylated (p) AKT(S473) protein was also reduced. P27 protein expression increased with HuR-FNP and combination treatment. Promoter-based reporter studies showed that the combination inhibited CXCR4 promoter activity more than did either treatment alone. Cell migration and invasion was significantly reduced with all treatments; the combination provided the most inhibition. Reduced matrix metalloprotease (MMP)-2 and -9 expression was associated with reduced invasion in all treatment groups. Thus, we found that combined HuR and CXCR4 targeting effectively controlled lung cancer metastasis.

  16. Expression of ARE-binding proteins AUF1 and HuR in follicular adenoma and carcinoma of thyroid gland.

    Science.gov (United States)

    Trojanowicz, B; Sekulla, C; Dralle, H; Hoang-Vu, C

    2016-01-01

    Both adenylate-uridylate rich elements binding proteins AUF1 and HuR may participate in thyroid carcinoma progression. In this study we investigated the expression of both factors on a protein level with a special focus on follicular adenoma and follicular thyroid carcinoma. By employment of immunofluorescence and western blot on 68 thyroid tissues including 7 goiter, 16 follicular adenoma (4 adenomatous hyperplasia), 19 follicular thyroid carcinomas, 13 papillary thyroid carcinomas and 14 undifferentiated thyroid carcinomas we investigated protein expression of AUF1 and HuR. In addition to previous results we demonstrated that AUF1 and HuR are significantly up-regulated in carcinoma tissues as compared with follicular adenoma or goiter tissues. Furthermore, by evaluation of AUF1 or HuR expression, or combination of both proteins on total tissue lysates, we were able to demonstrate a significant difference between follicular adenoma and follicular thyroid carcinoma. Overexpression of AUF1 and HuR is a common finding observed in thyroid malignancy. Analysis of the tissues obtained by surgical resection as demonstrated in this study is comparable to a fine needle aspiration and in combination with AUF1/HuR immuno-analysis may support the conventional immunohistological investigations. The promising results of this study were performed on relatively small collective, but justify future development of a quick thyroid diagnostic test on larger cohort of the patients, especially for thyroid samples which are inadequate for histological examinations.

  17. Antonio Rodríguez Huéscar y José Ortega y Gasset: Tres cartas

    OpenAIRE

    Esteban Enguita, José Emilio; Lasaga Medina, José

    2015-01-01

    El objetivo principal de este artículo es comentar las cartas que se enviaron Antonio Rodríguez Huéscar y José Ortega y Gasset entre 1942 y 1943. Dichas cartas se incluyen en el artículo. The principal aim of this paper is to comment on the letters which Antonio Rodríguez Huéscar and José Ortega y Gasset sent each other between 1942 and 1943. The above said letters are included in the paper

  18. The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA

    OpenAIRE

    Lopez de Silanes, I.; Gorospe, M.; Taniguchi, H; Abdelmohsen, K; Srikantan, S.; Alaminos, M.; Berdasco, M.; Urdinguio, R. G.; Fraga, M. F.; Jacinto, F. V.; Esteller, M.

    2009-01-01

    The molecular basis underlying the aberrant DNA-methylation patterns in human cancer is largely unknown. Altered DNA methyltransferase (DNMT) activity is believed to contribute, as DNMT expression levels increase during tumorigenesis. Here, we present evidence that the expression of DNMT3b is post-transcriptionally regulated by HuR, an RNA-binding protein that stabilizes and/or modulates the translation of target mRNAs. The presence of a putative HuR-recognition motif in the DNMT3b 3???UTR pr...

  19. Comparison of the Debye–Hückel and the Mean Spherical Approximation Theories for Electrolyte Solutions

    DEFF Research Database (Denmark)

    Maribo-Mogensen, Bjørn; Kontogeorgis, Georgios M.; Thomsen, Kaj

    2012-01-01

    The thermodynamics of electrolyte solutions has been investigated by many scientists throughout the last century. While several theories have been presented, the most popular models for the electrostatic interactions are based on the Debye–Hückel and mean spherical approximation (MSA) theories....... In this paper we investigate the differences between the Debye–Hückel and the MSA theories, and comparisons of the numerical results for the Helmholtz energy and its derivatives with respect to temperature, volume and composition are presented. The investigation shows that the nonrestricted primitive MSA...

  20. Anti-solar differential rotation on the active sub-giant HU Virginis

    Science.gov (United States)

    Harutyunyan, G.; Strassmeier, K. G.; Künstler, A.; Carroll, T. A.; Weber, M.

    2016-08-01

    Context. Measuring surface differential rotation (DR) on different types of stars is important when characterizing the underlying stellar dynamo. It has been suggested that anti-solar DR laws can occur when strong meridional flows exist. Aims: We aim to investigate the differential surface rotation on the primary star of the RS CVn binary, HU Vir, by tracking its starspot distribution as a function of time. We also aim to recompute and update the values for several system parameters of the triple system HU Vir (close and wide orbits). Methods: Time-series high-resolution spectroscopy for four continuous months was obtained with the 1.2-m robotic STELLA telescope. Nine consecutive Doppler images were reconstructed from these data, using our line-profile inversion code iMap. An image cross-correlation method was applied to derive the surface differential-rotation law for HU Vir. New orbital elements for the close and the wide orbits were computed using our new STELLA radial velocities (RVs) combined with the RV data available in the literature. Photometric observations were performed with the Amadeus Automatic Photoelectric Telescope (APT), providing contemporaneous Johnson-Cousins V and I data for approximately 20 yrs. This data was used to determine the stellar rotation period and the active longitudes. Results: We confirm anti-solar DR with a surface shear parameter α of -0.029 ± 0.005 and -0.026 ± 0.009, using single-term and double-term differential rotation laws, respectively. These values are in good agreement with previously claimed results. The best fit is achieved assuming a solar-like double-term law with a lap time of ≈400 d. Our orbital solutions result in a period of 10.387678 ± 0.000003 days for the close orbit and 2726 ± 7 d (≈7.5 yr) for the wide orbit. A Lomb-Scarge (L-S) periodogram of the pre-whitened V-band data reveals a strong single peak providing a rotation period of 10.391 ± 0.008 d, well synchronized to the short orbit. Based on

  1. CRM 1-mediated degradation and agonist-induced down-regulation of beta-adrenergic receptor mRNAs.

    Science.gov (United States)

    Bai, Ying; Lu, Huafei; Machida, Curtis A

    2006-10-01

    The beta1-adrenergic receptor (beta1-AR) mRNAs are post-transcriptionally regulated at the level of mRNA stability and undergo accelerated agonist-mediated degradation via interaction of its 3' untranslated region (UTR) with RNA binding proteins, including the HuR nuclear protein. In a previous report [Kirigiti et al. (2001). Mol. Pharmacol. 60:1308-1324], we examined the agonist-mediated down-regulation of the rat beta1-AR mRNAs, endogenously expressed in the rat C6 cell line and ectopically expressed in transfectant hamster DDT1MF2 and rat L6 cells. In this report, we determined that isoproterenol treatment of neonatal rat cortical neurons, an important cell type expressing beta1-ARs in the brain, results in significant decreases in beta1-AR mRNA stability, while treatment with leptomycin B, an inhibitor of the nuclear export receptor CRM 1, results in significant increases in beta1-AR mRNA stability and nuclear retention. UV-crosslinking/immunoprecipitation and glycerol gradient fractionation analyses indicate that the beta1-AR 3' UTR recognize complexes composed of HuR and multiple proteins, including CRM 1. Cell-permeable peptides containing the leucine-rich nuclear export signal (NES) were used as inhibitors of CRM 1-mediated nuclear export. When DDT1MF2 transfectants were treated with isoproterenol and peptide inhibitors, only the co-addition of the NES inhibitor reversed the isoproterenol-induced reduction of beta1-AR mRNA levels. Our results suggest that CRM 1-dependent NES-mediated mechanisms influence the degradation and agonist-mediated down-regulation of the beta1-AR mRNAs.

  2. Isolation and characterization of a catalase gene "HuCAT3" from pitaya (Hylocereus undatus) and its expression under abiotic stress.

    Science.gov (United States)

    Nie, Qiong; Gao, Guo-Li; Fan, Qing-jie; Qiao, Guang; Wen, Xiao-Peng; Liu, Tao; Peng, Zhi-Jun; Cai, Yong-Qiang

    2015-05-25

    Abiotic stresses usually cause H2O2 accumulation, with harmful effects, in plants. Catalase may play a key protective role in plant cells by detoxifying this excess H2O2. Pitaya (Hylocereus undatus) shows broad ecological adaptation due to its high tolerance to abiotic stresses, e.g. drought, heat and poor soil. However, involvement of the pitaya catalase gene (HuCAT) in tolerance to abiotic stresses is unknown. In the present study, a full-length HuCAT3 cDNA (1870 bp) was isolated from pitaya based on our previous microarray data and RACE method. The cDNA sequence and deduced amino acid sequence shared 73-77% and 75-80% identity with other plant catalases, respectively. HuCAT3 contains conserved catalase family domain and catalytic sites. Pairwise comparison and phylogenetic analysis indicated that HuCAT3 is most similar to Eriobotrya japonica CAT, followed by Dimocarpus longan CAT and Nicotiana tabacum CAT1. Expression profile analysis demonstrated that HuCAT3 is mainly expressed in green cotyledons and mature stems, and was regulated by H2O2, drought, cold and salt stress, whereas, its expression patterns and maximum expression levels varied with stress types. HuCAT activity increased as exposure to the tested stresses, and the fluctuation of HuCAT activity was consistent with HuCAT3 mRNA abundance (except for 0.5 days upon drought stress). HuCAT3 mRNA elevations and HuCAT activities changes under cold stress were also in conformity with the cold tolerances among the four genotypes. The obtained results confirmed a major role of HuCAT3 in abiotic stress response of pitaya. This may prove useful in understanding pitaya's high tolerance to abiotic stresses at molecular level.

  3. Energy restriction affect liver development in Hu sheep ram lambs through Hippo signaling pathway.

    Science.gov (United States)

    Zhang, Ting-Ting; Zhang, Guo-Min; Jin, Yu-Hang; Guo, Yi-Xuan; Wang, Zhen; Fan, Yi-Xuan; El-Samahy, M A; Wang, Feng

    2017-09-02

    This study aimed to evaluate the effects of dietary energy restriction on postnatal liver development in Hu sheep ram lambs. A total of 16 ram lambs were randomly divided into two groups: 100% energy requirements diet and 55% energy requirements diet, which were fed for 75 d. Results showed that the final body and liver weights decreased with energy restriction (p Energy restriction caused a significant decrease in the levels of circulating insulin-like growth factor 1 (IGF1) and an increase in growth hormone secretion (p energy restriction, respectively (p energy restriction group (p energy restriction group (p energy restriction in ram lambs impairs liver development by increasing apoptosis, which may occur via the Hippo signaling pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Flight Testing Surfaces Engineered for Mitigating Insect Adhesion on a Falcon HU-25C

    Science.gov (United States)

    Shanahan, Michelle; Wohl, Chris J.; Smith, Joseph G., Jr.; Connell, John W.; Siochi, Emilie J.; Doss, Jereme R.; Penner, Ronald K.

    2015-01-01

    Insect residue contamination on aircraft wings can decrease fuel efficiency in aircraft designed for natural laminar flow. Insect residues can cause a premature transition to turbulent flow, increasing fuel burn and making the aircraft less environmentally friendly. Surfaces, designed to minimize insect residue adhesion, were evaluated through flight testing on a Falcon HU-25C aircraft flown along the coast of Virginia and North Carolina. The surfaces were affixed to the wing leading edge and the aircraft remained at altitudes lower than 1000 feet throughout the flight to assure high insect density. The number of strikes on the engineered surfaces was compared to, and found to be lower than, untreated aluminum control surfaces flown concurrently. Optical profilometry was used to determine insect residue height and areal coverage. Differences in results between flight and laboratory tests suggest the importance of testing in realistic use environments to evaluate the effectiveness of engineered surface designs.

  5. The Curious Case of HU Aquarii - Dynamically Testing Proposed Planetary Systems

    CERN Document Server

    Horner, Jonathan; Marshall, Jonathan P; Tinney, Chris G; Butters, Oliver W

    2012-01-01

    In early 2011, the discovery of two planets moving on surprisingly extreme orbits around the eclipsing polar cataclysmic variable system HU Aquraii was announced based on variations in the timing of mutual eclipses between the two central stars. We perform a detailed dynamical analysis of the stability of the exoplanet system as proposed in that work, revealing that it is simply dynamically unfeasible. We then apply the latest rigorous methods used by the Anglo-Australian Planet Search to analyse radial velocity data to re-examine the data used to make the initial claim. Using that data, we arrive at a significantly different orbital solution for the proposed planets, which we then show through dynamical analysis to be equally unfeasible. Finally, we discuss the need for caution in linking eclipse-timing data for cataclysmic variables to the presence of planets, and suggest a more likely explanation for the observed signal.

  6. Congenital Pelger-Huët anomaly in a Danish/Swedish Farmdog: Case Report

    Directory of Open Access Journals (Sweden)

    Allison Robin W

    2011-03-01

    Full Text Available Abstract A 13 year old Danish/Swedish Farmdog from Denmark was evaluated in a veterinary clinic in Warsaw, Poland for evaluation of an orthopedic problem. Radiographs revealed spondylosis and degenerative vertebral disease, which responded to treatment with anti-inflammatory medications. A predominance of hyposegmented neutrophils and eosinophils containing condensed chromatin and normal cytoplasm were identified on a routine CBC. Follow-up blood film evaluations over the course of 12 months confirmed that the hyposegmented granulocytes persisted. The majority of neutrophils contained Grade 2 nuclei (slightly indented, and the mean nuclear score varied from 1.9 to 2.3. Pelger-Huët anomaly (PHA, presumably congenital, was diagnosed based on persistent hyposegmented granulocytes in the absence of an underlying cause for acquired PHA; genetically related dogs were unavailable for testing to confirm vertical transmission. To the authors' knowledge this is the first report of PHA in a Danish/Swedish Farmdog.

  7. Potential therapeutic use of antibodies directed towards HuIFN-gamma.

    Science.gov (United States)

    Froyen, G; Billiau, A

    1997-01-01

    IFN-gamma is an important regulator of immune responses and inflammation. Studies in animal models of inflammation, autoimmunity, cancer, transplant rejection and delayed-type hypersensitivity have indicated that administration of antibodies against IFN-gamma can prevent the occurrence of diseases or alleviate disease manifestations. Therefore, it is speculated that such antibodies may have therapeutical efficacy in human diseases. Since animal-derived antibodies are immunogenic in patients several strategies are being developed in order to reduce or abolish this human anti-mouse antibody (HAMA) response. In our laboratory, we have constructed a single-chain variable fragment (scFv) derived from a mouse antibody with neutralizing potential for human IFN-gamma. A scFv consists of only variable domains tethered together by a flexible linker. The scFv was demonstrated to neutralize the antiviral activity of HuIFN-gamma in vitro and therefore might be considered as a candidate for human therapy.

  8. La voz y la letra en "Un huésped", de Yoko Tawada

    Directory of Open Access Journals (Sweden)

    María Lucía Correa

    2009-05-01

    Full Text Available Los textos de Yoko Tawada, escritorajaponesa residente en Alemania,hacen presente el desgarramientode quien vive fuera de la lenguamaterna. Es una obra que se balanceasobre el límite entre loscódigos, donde nada hay evidente,donde la palabra parece tener vidapropia. Entre los textos que tomanesta extrañeza del lenguaje comosustrato, se encuentra el relato"Un huésped", cuya particular referenciaa la voz y a la letra comodos registros que se entrelazan yse repelen alternativamente, loconvierte en una valiosa fuente dereflexiones sobre lo oral, la voz, laletra, la lectura y la escritura.Palabras clave: Yoko Tawada, literaturajaponesa contemporánea, voz,letra, escritura.

  9. The SCID-hu mouse as a tool in immunotoxicological risk assessment: Effects of 2-acetyl-4(5)-tetrahydroxybutyl-imidazole (THI) and di-n-butyltin dichloride (DBTC) on the human thymus in SCID-hu mice

    NARCIS (Netherlands)

    Heer, C. de; Schuurman, H.J.; Houben, G.F.; Pieters, R.H.H.; Penninks, A.H.; Loveren, H. van

    1995-01-01

    SCID mice engrafted with human fetal thymus and liver tissue fragments (SCID-hu mice) are currently considered as a new tool in human immunotoxicological risk assessment. Testing of various immunotoxicants exerting thymotoxicity via different intrathymic target cell types is necessary for validation

  10. The complete chloroplast genome sequence of the relict woody plant Metasequoia glyptostroboides Hu et Cheng.

    Science.gov (United States)

    Chen, Jinhui; Hao, Zhaodong; Xu, Haibin; Yang, Liming; Liu, Guangxin; Sheng, Yu; Zheng, Chen; Zheng, Weiwei; Cheng, Tielong; Shi, Jisen

    2015-01-01

    Metasequoia glyptostroboides Hu et Cheng is the only species in the genus Metasequoia Miki ex Hu et Cheng, which belongs to the Cupressaceae family. There were around 10 species in the Metasequoia genus, which were widely spread across the Northern Hemisphere during the Cretaceous of the Mesozoic and in the Cenozoic. M. glyptostroboides is the only remaining representative of this genus. Here, we report the complete chloroplast (cp) genome sequence and the cp genomic features of M. glyptostroboides. The M. glyptostroboides cp genome is 131,887 bp in length, with a total of 117 genes comprised of 82 protein-coding genes, 31 tRNA genes and four rRNA genes. In this genome, 11 forward repeats, nine palindromic repeats, and 15 tandem repeats were detected. A total of 188 perfect microsatellites were detected through simple sequence repeat (SSR) analysis and these were distributed unevenly within the cp genome. Comparison of the cp genome structure and gene order to those of several other land plants indicated that a copy of the inverted repeat (IR) region, which was found to be IR region A (IRA), was lost in the M. glyptostroboides cp genome. The five most divergent and five most conserved genes were determined and further phylogenetic analysis was performed among plant species, especially for related species in conifers. Finally, phylogenetic analysis demonstrated that M. glyptostroboides is a sister species to Cryptomeria japonica (L. F.) D. Don and to Taiwania cryptomerioides Hayata. The complete cp genome sequence information of M. glyptostroboides will be great helpful for further investigations of this endemic relict woody plant and for in-depth understanding of the evolutionary history of the coniferous cp genomes, especially for the position of M. glyptostroboides in plant systematics and evolution.

  11. Forward-Looking Betas

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Vainberg, Gregory

    -looking. This paper introduces a radically different approach to estimating market betas. Using the tools in Bakshi and Madan (2000) and Bakshi, Kapadia and Madan (2003) we employ the information embedded in the prices of individual stock options and index options to compute our forward-looking market beta......Few issues are more important for finance practice than the computation of market betas. Existing approaches compute market betas using historical data. While these approaches differ in terms of statistical sophistication and the modeling of the time-variation in the betas, they are all backward...... at the daily frequency. This beta can be computed using option data for a single day, and is able to reflect sudden changes in the structure of the underlying company. Based on an empirical investigation of daily cross-sections of option contracts on thirty underlying companies, we conclude that these forward...

  12. Betting against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    2014-01-01

    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model's five central predictions: (1) Because constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for......, the return of the BAB factor is low. (4) Increased funding liquidity risk compresses betas toward one. (5) More constrained investors hold riskier assets....... for US equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures. (2) A betting against beta (BAB) factor, which is long leveraged low-beta assets and short high-beta assets, produces significant positive risk-adjusted returns. (3) When funding constraints tighten...

  13. Betting Against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model’s five central predictions: (1) Since constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for U...... of the BAB factor is low; (4) Increased funding liquidity risk compresses betas toward one; (5) More constrained investors hold riskier assets........S. equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures; (2) A betting-against-beta (BAB) factor, which is long leveraged low beta assets and short high-beta assets, produces significant positive risk-adjusted returns; (3) When funding constraints tighten, the return...

  14. Imperfect World of $\\beta\\beta$-decay Nuclear Data Sets

    CERN Document Server

    Pritychenko, B

    2015-01-01

    The precision of double-beta ($\\beta\\beta$) decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for $\\beta\\beta$-decay T$_{1/2}^{2\

  15. Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression

    Science.gov (United States)

    He, Xiaolie; Zhu, Yanjing; Wang, Mei; Jing, Guoxin; Zhu, Rongrong; Wang, Shilong

    2016-01-01

    Major depression is a complex neuropsychiatric disorder with few treatment approaches. The use of nontargeted antidepressants induced many side effects with their low efficacy. A more precise targeting strategy is to develop nanotechnology-based drug delivery systems; hence, we employed solid lipid nanoparticles (SLNs) to encapsulate HU-211 and curcumin (Cur). The antidepressant effects of the dual-drug nanoparticles (Cur/SLNs-HU-211) for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depression. Cur/SLNs-HU-211 can effectively protect PC12 cells from corticosterone-induced apoptosis and can release more dopamine, which may be associated with the higher uptake of Cur/SLNs-HU-211 shown by cellular uptake behavior analysis. Additionally, Cur/SLNs-HU-211 significantly reduced the immobility time in forced swim test, enhanced fall latency in rotarod test, and improved the level of dopamine in mice blood. Cur/SLNs-HU-211 can deliver more Cur to the brain and thus produce a significant increase in neurotransmitters level in brain tissue, especially in the hippocampus and striatum. The results of Western blot and immunofluorescence revealed that Cur/SLNs-HU-211 can significantly enhance the expression of CB1, p-MEK1, and p-ERK1/2. Our study suggests that Cur/SLNs-HU-211 may have great potential for major depression treatment. PMID:27757031

  16. HuD interacts with Bdnf mRNA and is essential for activity-induced BDNF synthesis in dendrites.

    Directory of Open Access Journals (Sweden)

    Filip Vanevski

    Full Text Available Highly specific activity-dependent neuronal responses are necessary for modulating synapses to facilitate learning and memory. We present evidence linking a number of important processes involved in regulating synaptic plasticity, suggesting a mechanistic pathway whereby activity-dependent signaling, likely through protein kinase C (PKC-mediated phosphorylation of HuD, can relieve basal repression of Bdnf mRNA translation in dendrites, allowing for increased TrkB signaling and synaptic remodeling. We demonstrate that the neuronal ELAV family of RNA binding proteins associates in vivo with several Bdnf mRNA isoforms present in the adult brain in an activity-dependent manner, and that one member, HuD, interacts directly with sequences in the long Bdnf 3' untranslated region (3'UTR and co-localizes with Bdnf mRNA in dendrites of hippocampal neurons. Activation of PKC leads to increased dendritic translation of mRNAs containing the long Bdnf 3'UTR, a process that is dependent on the presence of HuD and its phosphorylation at threonine residues 149 and/or 165. Thus, we found a direct effect of HuD on regulating translation of dendritic Bdnf mRNAs to mediate local and activity-dependent increases in dendritic BDNF synthesis.

  17. Genetic diversity and population structure in the narrow endemic Chinese walnut Juglans hopeiensis Hu: implications for conservation

    Science.gov (United States)

    Yiheng Hu; Meng Dang; Xiaojia Feng; Keith Woeste; Peng Zhao

    2017-01-01

    The conservation of narrow endemic species relies on accurate information regarding their population structure. Juglans hopeiensis Hu (Ma walnut), found only in Hebei province, Beijing, and Tianjin, China, is a threatened tree species valued commercially for its nut and wood. Sequences of two maternally inherited mitochondrial markers and two...

  18. The Preliminary Research on Rupture and Factors Affecting Rupturing of the Hoh Sai Hu Segment in Eastern Kunlun

    Institute of Scientific and Technical Information of China (English)

    Bai Yuzhu; Xu Jie; Zhou Qing; Zhou Bengang

    2012-01-01

    On November 14, 2001, an extraordinarily large earthquake (Ms8. 1) occurred on the Hoh Sai Hu segment of the Eastern Kunlun Fault, in the northern Qinghai-Tibetan Plateau. The seismogenic fault, the Hoh Sai Hu segment, is a left-lateral fault with a high slip rate in geological history, with the average slip rate reaching( 14. 8± 2. 8)mm/a since the late Pleistocene. Different slip rates of the Hoh Sai Hu segment can affect fault motion in the future. Therefore, this paper analyzes the effect of different slip rates and different initial friction coefficients on the fault plane of the Hoh Sai Hu segment of the eastern Kunlun Fault on the rupture behaviors of the fault. In this research, we apply the single degree of spring block model controlled by the rate- and state-dependent frictional constitutive laws. Using the fault dislocation model and based on ancient earthquake research, historical earthquakes data and the achievements of previous researchers, we obtained the parameters of this model. Through numerical simulation of the rupturing motion of the Hoh Sai Hu segment in the next 6500 years under different slip rates, we find that a faster annual slip rate will shorten the recurrence interval of the earthquake. For example, the earthquake recurrence interval is 2100a at a slip rate of 0. 014m/a, which agrees with previous research, but, the recurrence interval will be 1000 - 1500a and 2100 - 2500a, corresponding to the slip rates of 0. 018m/a and 0. 008m/a, respectively. The fault slip rate has no regular effect on the coseismic slip rate and fault displacement in an earthquake. The initial friction coefficient on the fault surface has an effect on the earthquake recurrence interval. A smaller initial friction coefficient will lengthen the earthquake recurrence interval. At the same time, the smaller initial friction coefficient will lead to larger slip rates and fault displacement when earthquakes occur.

  19. Striatal synaptic dysfunction and hippocampal plasticity deficits in the Hu97/18 mouse model of Huntington disease.

    Directory of Open Access Journals (Sweden)

    Karolina Kolodziejczyk

    Full Text Available Huntington disease (HD is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the gene (HTT encoding the huntingtin protein (HTT. This mutation leads to multiple cellular and synaptic alterations that are mimicked in many current HD animal models. However, the most commonly used, well-characterized HD models do not accurately reproduce the genetics of human disease. Recently, a new 'humanized' mouse model, termed Hu97/18, has been developed that genetically recapitulates human HD, including two human HTT alleles, no mouse Hdh alleles and heterozygosity of the HD mutation. Previously, behavioral and neuropathological testing in Hu97/18 mice revealed many features of HD, yet no electrophysiological measures were employed to investigate possible synaptic alterations. Here, we describe electrophysiological changes in the striatum and hippocampus of the Hu97/18 mice. At 9 months of age, a stage when cognitive deficits are fully developed and motor dysfunction is also evident, Hu97/18 striatal spiny projection neurons (SPNs exhibited small changes in membrane properties and lower amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs; however, release probability from presynaptic terminals was unaltered. Strikingly, these mice also exhibited a profound deficiency in long-term potentiation (LTP at CA3-to-CA1 synapses. In contrast, at 6 months of age we found only subtle alterations in SPN synaptic transmission, while 3-month old animals did not display any electrophysiologically detectable changes in the striatum and CA1 LTP was intact. Together, these data reveal robust, progressive deficits in synaptic function and plasticity in Hu97/18 mice, consistent with previously reported behavioral abnormalities, and suggest an optimal age (9 months for future electrophysiological assessment in preclinical studies of HD.

  20. Alternativa terapeutica en la isquemia cerebral empleando la Eritropoyetina humana recombinante (rHu-EPO CIM como neuroprotector.

    Directory of Open Access Journals (Sweden)

    Iliana Sosa Testé

    2005-01-01

    Full Text Available Las enfermedades vasculares constituyen las terceras causas de muerte en Cuba. Su variante isquémica es causa de invalidez y perdida de la calidad de la vida. La búsqueda de agentes neuroprotectores es muy importante sí tenemos en cuenta que nuestra población está envejecida. Muchos son las razones por la que una molécula con propiedades neuroprotectoras en los modelos animales no tenga los resultados en ensayos clínicos en humanos. Este trabajo analiza y discute como mejorar estos aspectos. La Eritropoyetina humana recombinante (rHu EPO, conocido por su papel en la diferenciación del eritrocito, ha mostrado ser neuroprotector durante la isquemia cerebral en los modelos de animales adultos. De esta molécula se exponen los mecanismos de acción, que son las bases de los resultados positivos alcanzaron en las investigaciones preclínicas y los ensayos clínicos, que lo proponen como el neuroprotector ideal. Finalmente se comparan los resultados alcanzados por los autores en las investigaciones con la rHu EPO producida por el Centro Molecular de Inmunología de Cuba (CIM. El efecto de la aplicación de rHu EPO se evidenció por la disminución del edema cerebral, preservación de la conducta exploratoria y la disminución de la incidencia de señales clínicas de infarto cerebral y alteraciones patológicas. El grupo de resultados demostró las diferencias significantes entre los animales controles y tratados con el rHu EPO con los no tratados que sugieren que el rHu EPO debe ser considerado como una alternativa terapéutica contra el infarto cerebral en su fase aguda.

  1. A novel high throughput biochemical assay to evaluate the HuR protein-RNA complex formation.

    Directory of Open Access Journals (Sweden)

    Vito G D'Agostino

    Full Text Available The RNA binding protein HuR/ELAVL1 binds to AU-rich elements (AREs promoting the stabilization and translation of a number of mRNAs into the cytoplasm, dictating their fate. We applied the AlphaScreen technology using purified human HuR protein, expressed in a mammalian cell-based system, to characterize in vitro its binding performance towards a ssRNA probe whose sequence corresponds to the are present in TNFα 3' untranslated region. We optimized the method to titrate ligands and analyzed the kinetic in saturation binding and time course experiments, including competition assays. The method revealed to be a successful tool for determination of HuR binding kinetic parameters in the nanomolar range, with calculated Kd of 2.5±0.60 nM, k on of 2.76±0.56*10(6 M(-1 min(-1, and k off of 0.007±0.005 min(-1. We also tested the HuR-RNA complex formation by fluorescent probe-based RNA-EMSA. Moreover, in a 384-well plate format we obtained a Z-factor of 0.84 and an averaged coefficient of variation between controls of 8%, indicating that this biochemical assay fulfills criteria of robustness for a targeted screening approach. After a screening with 2000 small molecules and secondary verification with RNA-EMSA we identified mitoxantrone as an interfering compound with rHuR and TNFα probe complex formation. Notably, this tool has a large versatility and could be applied to other RNA Binding Proteins recognizing different RNA, DNA, or protein species. In addition, it opens new perspectives in the identification of small-molecule modulators of RNA binding proteins activity.

  2. Negative Beta Encoder

    CERN Document Server

    Kohda, Tohru; Aihara, Kazuyuki

    2008-01-01

    A new class of analog-digital (A/D), digital-analog (D/A) converters as an alternative to conventional ones, called $\\beta$-encoder, has been shown to have exponential accuracy in the bit rates while possessing self-correction property for fluctuations of amplifier factor $\\beta$ and quantizer threshold $\

  3. Double beta decay experiments

    CERN Document Server

    Barabash, A S

    2011-01-01

    The present status of double beta decay experiments is reviewed. The results of the most sensitive experiments are discussed. Proposals for future double beta decay experiments with a sensitivity to the $$ at the level of (0.01--0.1) eV are considered.

  4. Sorting out Downside Beta

    NARCIS (Netherlands)

    G.T. Post (Thierry); P. van Vliet (Pim); S.D. Lansdorp (Simon)

    2009-01-01

    textabstractDownside risk, when properly defined and estimated, helps to explain the cross-section of US stock returns. Sorting stocks by a proper estimate of downside market beta leads to a substantially larger cross-sectional spread in average returns than sorting on regular market beta. This

  5. Genetics Home Reference: beta thalassemia

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions beta thalassemia beta thalassemia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Beta thalassemia is a blood disorder that reduces the production ...

  6. Rapid synthesis of beta zeolites

    Science.gov (United States)

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  7. A new phantom for image quality, geometric destortion, and HU calibration in MSCT and CBCT

    Science.gov (United States)

    Voigt, Johannes M.; Blendl, Christian; Selbach, Markus; Uphoff, Clemens; Fiebich, Martin

    2012-03-01

    Flat panel cone-beam computed tomography (CBCT) is developing to the state-of-the-art technique in several medical disciplines such as dental and otorhinolaryngological imaging. Dental and otorhinolaryngological CBCT systems offer a variety of different field-of-view sizes from 6.0 to 17.0 cm. Standard phantoms are only designed for the use in multi-slices CT (MSCT) and there is no phantom which provides detail structures for all common characteristic values and Hounsfield calibration. In this study we present a new phantom specially designed for use with MSCT and CBCT systems providing detail structures for MTF, 3D MTF, NPS, SNR, geometric distortion and HU calibration. With this phantom you'll only need one acquisition for image quality investigation and assurance. Materials and methods: The phantom design is shown in figure 1. To investigate the practicability, the phantom was scanned using dedicated MSCT-scanners, 3D C-arms und digital volume tomographs. The acquired axial image stacks were analyzed using a dedicated computer program, which is provided as an ImageJ plugin. The MTF was compared to other methodologies such as a thin wire, a sphere or noise response [10, 13, 14]. The HU values were also computed using other common methods. Results: These results are similar to the results of others studies [10, 13, 14]. The method has proven to be stable and delivers comparable results to other methodologies such as using a thin wire. The NPS was calculated for all materials. Furthermore, CT numbers for all materials were computed and compared to the desired values. The measurement of geometric deformation has proven to be accurate. Conclusion: A unique feature of this phantom is to compute the geometric deformation of the 3D-volume image. This offers the chance to improve accuracy, e.g. in dental implant planning. Another convenient feature is that the phantom needs to be scanned only once with otorhinolaryngological volume tomographs to be fully displayed. It is

  8. {sup 89}Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pandit-Taskar, Neeta; Solomon, Stephen B.; Durack, Jeremy C.; Carrasquillo, Jorge A.; Lefkowitz, Robert A.; Osborne, Joseph R. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); O' Donoghue, Joseph A. [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Beylergil, Volkan; Ruan, Shutian; Cheal, Sarah M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Lyashchenko, Serge [Memorial Sloan Kettering Cancer Center, Department of Radiochemistry and Molecular Imaging Probes Core, New York, NY (United States); Gonen, Mithat [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Lewis, Jason S. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Radiochemistry and Molecular Imaging Probes Core, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Holland, Jason P. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Harvard Medical School, Department of Radiology of Massachusetts General Hospital, Boston, MA (United States); Reuter, Victor E. [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Weill Cornell Medical College, Department of Pathology, New York, NY (United States); Loda, Massimo F. [Dana-Farber Cancer Institute, Boston, MA (United States); Broad Institute of Harvard and MIT, Cambridge, MA (United States); Smith-Jones, Peter M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Department of Psychiatry and Behavioral Science of Stony Brook University, Stony Brook, NY (United States); Weber, Wolfgang A.; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Bander, Neil H. [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States); Weill Cornell Medical College, Department of Urology, New York, NY (United States); Scher, Howard I.; Morris, Michael J. [Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY (United States); Weill Cornell Medical College, Department of Medicine, New York, NY (United States)

    2014-11-15

    Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. {sup 89}Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection. Ten patients with metastatic prostate cancer received 5 mCi of {sup 89}Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by {sup 89}Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of {sup 89}Zr-huJ591 was done. Optimal time for imaging post-injection was determined. The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of {sup 89}Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1-14 h) and 62 ± 13 h (range 51-89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153-317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on {sup 89}Zr-huJ591, while the remaining 11 lesions were {sup 89}Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on

  9. Mechanism of RNA binding protein HuR in regulating the activity of prostate cancer cells%RNA结合蛋白HuR调控前列腺癌细胞活力机制的研究

    Institute of Scientific and Technical Information of China (English)

    周宁; 程娟; 钟毅; 冉新建; 于文燕; 马琪

    2016-01-01

    目的 前列腺癌在我国的发病率及病死率逐年上升,但其发病机制尚未明确,本研究从转录后水平初步探讨RNA结合蛋白HuR参与调控前列腺癌细胞活力的机制.方法 免疫荧光检测前列腺增生细胞(BPH)及前列腺癌细胞(PC3)中HuR蛋白的定位,蛋白质印迹法检测HuR及环氧合酶-2(cyclooxygenase,COX-2)蛋白在细胞内的表达,MTT法检测细胞活力,脂质体转染法转染质粒及干扰片段,qPCR检测干扰效率,RNA-pull down实验验证HuR对COX-2的调控.结果 HuR在BPH细胞主要定位于细胞核,在PC3细胞中主要定位于胞质.PC3细胞中HuR表达水平为1.699±0.011,高于BPH细胞的0.654±0.028,差异有统计学意义,t=58.67,P<0.001.PC3细胞中过表达HuR后,转染空质粒组细胞活力为1.038±0.117,转染HuR表达质粒后细胞活力为1.838±0.057,差异有统计学意义,t=10.656,P<0.001.干扰HuR表达后,转染siNC组细胞活力为1.254±0.095,转染siHuR干扰片段组细胞活力为0.66±0.102,t=7.383,P=0.002;BPH组和PC3组COX-2表达水平分别为0.449±0.055和1.066±0.068,t=12.147,P<0.001;过表达COX-2后PC3细胞活力明显增加,转染空质粒组细胞活力为1.296±0.114,转染COX-2表达质粒后细胞活力为1.954±0.062,t=18.062,P<0.001.干扰COX-2表达后,PC3细胞活力明显降低,转染siNC组细胞活力为1.233±0.145,转染siCOX-2干扰片段后细胞活力为0.661±0.096,t=5.688,P=0.005.HuR可以结合于COX-2的3′-UTR并上调COX-2蛋白表达,转染空质粒组COX-2蛋白表达水平为0.638±0.067,转染HuR表达质粒组为1.703±0.022,t=26.26,P<0.001.结论 HuR参与调控前列腺癌细胞活力可能是通过上调COX-2表达而实现.

  10. Detection of neutralizing antibodies to erythropoietin by inhibition of rHuEPO-stimulated EGR1 gene expression in the UT-7/EPO cell line.

    Science.gov (United States)

    Ferguson, Jackie; Bird, Chris; Wadhwa, Meenu; Burns, Chris

    2013-01-31

    Recombinant erythropoietin (rHuEPO) is used extensively to treat anaemia associated with chronic kidney disease. However, the development of neutralizing antibodies (NAbs) to rHuEPO can result in the development of antibody-mediated pure red cell aplasia (PRCA). The detection of NAb in patient sera by in vitro bioassay relies on the inhibition of a cellular response to rHuEPO. Current bioassays for rHuEPO measure proliferation in responsive cell lines such as the erythroleukaemic cell lines, UT-7 and UT-7/EPO, the latter sensitized to EPO. Using these cell lines, we show the dose-responsive induction of both PIM1 and EGR1 gene expression in UT-7 cells and of EGR1 in UT-7/EPO cells. The expression of EGR1 in UT-7/EPO cells in response to rHuEPO was comparable to the proliferative response measured by (3)H-thymidine incorporation and could be inhibited by serum from a patient with NAb-mediated PRCA in a dilution-dependent manner. Bioassays based on the induction of endogenous gene expression are comparable to current bioassays but are considerably quicker given that incubation time is decreased from 2-3 days to 50 min. Measurement of EGR1 gene expression in response to rHuEPO in UT-7/EPO cells offers a rapid, non-radioactive and automatable alternative to current assays for the detection of rHuEPO NAbs.

  11. Testing Hu-Sawicki f(R) gravity with the Effective Field Theory approach

    CERN Document Server

    Hu, Bin; Rizzato, Matteo; Silvestri, Alessandra

    2016-01-01

    We show how to fully map a specific model of modified gravity into the Einstein-Boltzmann solver EFTCAMB. This approach consists in few steps and allows to obtain the cosmological phenomenology of a model with minimal effort. We discuss all these steps, from the solution of the dynamical equations for the cosmological background of the model to the use of the mapping relations to cast the model into the effective field theory language and use the latter to solve for perturbations. We choose the Hu-Sawicki f(R) model of gravity as our working example. After solving the background and performing the mapping, we interface the algorithm with EFTCAMB and take advantage of the effective field theory framework to integrate the full dynamics of linear perturbations, returning all quantities needed to accurately compare the model with observations. We discuss some observational signatures of this model, focusing on the linear growth of cosmic structures. In particular we present the behavior of $f\\sigma_8$ and $E_G$ t...

  12. La huída en la obra de Mario Vargas Llosa

    Directory of Open Access Journals (Sweden)

    German Arce Ross

    Full Text Available Se trata de poner en perspectiva la mayor parte de novelas de Mario Vargas Llosa en función del tema de la huída, partiendo del hecho que é1 solicitó la nacionalidad Española inmediatamente después de haber perdido las elecciones para la Presidencia del Perú y de haber escrito El pez en el agua. Nuestro análisis intenta demostrar la importancia de la figura paterna – principalmente en el sentido de su ausencia y de sus bruscas reapariciones – en la cristalización sintomática del tema de la fuga. Es por eso que una analogía con la posición fóbica, en relación al padre o a sus substitutos, nos ha parecido pertinente. Teniendo como pivot el análisis de la forma, del contexto y del contenido de su libro de memorias, este trabajo definiría así las bases de una contribución literaria de la obra de Vargas Llosa a la clinica de la fobia.

  13. Systematics of a kleptoplastidal dinoflagellate, Gymnodinium eucyaneum Hu (Dinophyceae, and its cryptomonad endosymbiont.

    Directory of Open Access Journals (Sweden)

    Shuang Xia

    Full Text Available New specimens of the kleptoplastidal dinoflagellate Gymnodinium eucyaneum Hu were collected in China. We investigated the systematics of the dinoflagellate and the origin of its endosymbiont based on light morphology and phylogenetic analyses using multiple DNA sequences. Cells were dorsoventrally flattened with a sharply acute hypocone and a hemispherical epicone. The confusion between G. eucyaneum and G. acidotum Nygaard still needs to be resolved. We found that the hypocone was conspicuously larger than the epicone in most G. eucyaneum cells, which differed from G. acidotum, but there were a few cells whose hypocone and epicone were of nearly the same size. In addition, there was only one site difference in the partial nuclear LSU rDNA sequences of a sample from Japan given the name G. acidotum and G. eucyaneum in the present study, which suggest that G. eucyaneum may be a synonym of G. acidotum. Spectroscopic analyses and phylogenetic analyses based on nucleomorph SSU rDNA sequences and chloroplast 23 s rDNA sequences suggested that the endosymbiont of G. eucyaneum was derived from Chroomonas (Cryptophyta, and that it was most closely related to C. coerulea Skuja. Moreover, the newly reported kleptoplastidal dinoflagellates G. myriopyrenoides and G. eucyaneum in our study were very similar, and the taxonomy of kleptoplastidal dinoflagellates was discussed.

  14. Screening of a xylanase clone from a fosmid library of rumen microbiota in Hu sheep.

    Science.gov (United States)

    Wang, Jiakun; Sun, Zhongyuan; Zhou, Yan; Wang, Qian; Ye, Jun'an; Chen, Zhenming; Liu, Jianxin

    2012-01-01

    The glycosyl hydrolase family 11, which is responsible for carbohydrate metabolism, was identified in the open reading frame (ORF) 6 of a xylanase positive clone from a fosmid library of rumen microbiota of Hu sheep. A BLASTP search of GenBank revealed that ORF6 encoded a 355-amino acid putative endoxylanase, having 61% similarity (e(-73)) to endo-1,4-β-xylanase of Fibrobacter succinogenes S85 (YP_003250510.1). Predicted with the SWISS-MODEL, there were two separate β-sandwich clusters linked with a high serine containing linker in ORF6. The N-terminal β-sandwich is a novel endoxylanase of the glycosyl hydrolase family 11 with a specific activity of 1150.00 U/mg. The optimal pH and temperature for this enzyme were shown to be pH 5.0 and 50°C, respectively. The C-terminal helped increase the stability of the xylanase but decreased the activity to some degree. The C-terminal β-sandwich could bind avicel, but no conserved domain could be found. It may be a novel carbohydrate-binding module.

  15. Managing Stability in the Taiwan Strait: Non-Military Policy towards Taiwan under Hu Jintao

    Directory of Open Access Journals (Sweden)

    Wu-ueh Chang

    2009-10-01

    Full Text Available China’s Taiwan policy has been one of coupling intimidation (the “stick” approach with coercion (the “carrot” approach, a policy mix which, in the near term, is not likely to change, as is evidenced by the passage of the “Anti-Secession Law” in March, 2005. However, under Hu Jintao, the focus has been on pragmatism. The warm atmosphere that presently reigns in the Taiwan Strait area is unprecedented. Further talks are expected before the two cross-Strait leaders are slated to step down, simultaneously, in 2012. An era of reconciliation and negotiations has dawned. For the first time there is consensus regarding norms of interaction between the two sides. Cross-Strait relations have stabilized after years of tumult. More open, stable and predictable cross-Strait relations are in the interests of both sides. Difficulties surely lie ahead, but they will be dealt with in a different manner than what has been witnessed in the past.

  16. Detection of a planetary system orbiting the eclipsing polar HU Aqr

    CERN Document Server

    Qian, S -B; Liao, W -P; Li, L -J; Zhu, L -Y; Dai, Z -B; He, J -J; Zhao, E -G; Zhang, J; Li, K

    2011-01-01

    Using the precise times of mid-egress of the eclipsing polar HU Aqr, we discovered that this polar is orbited by two or more giant planets. The two planets detected so far have masses of at least 5.9 and 4.5\\,M_{Jup}. Their respective distances from the polar are 3.6 AU and 5.4 AU with periods of 6.54 and 11.96 years, respectively. The observed rate of period decrease derived from the downward parabolic change in O-C curve is a factor 15 larger than the value expected for gravitational radiation. This indicates that it may be only a part of a long-period cyclic variation, revealing the presence of one more planet. It is interesting to note that the two detected circumbinary planets follow the Titus-Bode law of solar planets with n=5 and 6. We estimate that another 10 years of observations will reveal the presence of the predicted third planet.

  17. Construction of a eukaryotic expression plasmid pcDNA3.1-HuR-FLAG and its transient expression in NIH3T3 cells

    Directory of Open Access Journals (Sweden)

    Tao LI

    2011-04-01

    Full Text Available Objective To construct a eukaryotic expression vector for HuR and analyze its expression and biological function in NIH3T3 cells.Methods The total RNA was extracted from NIH3T3 cells and reverse transcribed to cDNAs.The coding region sequence of mouse HuR was then amplified by PCR and subcloned into the pcDNA3.1-FLAG plasmid.The recombinant plasmid pcDNA3.1-HuR-FLAG was verified by PCR and restriction endonuclease analysis,confirmed by DNA sequence analysis,and then transiently transfected into NIH3T3 cells with Lipofectamine LTX.The expression of HuR protein was determined by Western blotting,and the mRNA level of HuR and DUSP1 were analyzed by using real-time PCR.Result The recombinant plasmid pcDNA3.1-HuR-FLAG was correctly constructed.Twenty-four hours after transfection of the recombinant plasmid into NIH3T3 cells,the fusion protein was found to have highly expressed in the cells as revealed by Western blotting.Real-time PCR results detected that the over-expression of HuR could up-regulate the expression of DUSP1.Conclusion The eukaryotic expression vector for HuR-FLAG fusion protein has been successfully constructed and transiently expressed in NIH3T3 cells.It can be used in further analysis of the posttranscriptional regulation of DUSP1 by HuR in cancer cells.

  18. Massive parallel analysis of the binding specificity of histone-like protein HU to single- and double-stranded DNA with generic oligodeoxyribonucleotide microchips.

    Energy Technology Data Exchange (ETDEWEB)

    Krylov, A. S.; Zasedateleva, O. A.; Prokopenko, D. V.; Rouviere-Yaniv, J.; Mirzabekov, A. D.; Biochip Technology Center; Engelhardt Inst. of Molecular Biology; Inst. de Biologie Physico-Chimique

    2001-06-15

    A generic hexadeoxyribonucleotide microchip has been applied to test the DNA-binding properties of HU histone-like bacterial protein, which is known to have a low sequence specificity. All 4096 hexamers flanked within 8mers by degenerate bases at both the 3'- and 5'-ends were immobilized within the 100 x 100 x 20 mm polyacrylamide gel pads of the microchip. Single-stranded immobilized oligonucleotides were converted in some experiments to the double-stranded form by hybridization with a specified mixture of 8mers. The DNA interaction with HU was characterized by three type of measurements: (i) binding of FITC-labeled HU to microchip oligonucleotides; (ii) melting curves of complexes of labeled HU with single-stranded microchip oligonucleotides; (iii) the effect of HU binding on melting curves of microchip double-stranded DNA labeled with another fluorescent dye, Texas Red. Large numbers of measurements of these parameters were carried out in parallel for all or many generic microchip elements in real time with a multi-wavelength fluorescence microscope. Statistical analysis of these data suggests some preference for HU binding to G/C-rich single-stranded oligonucleotides. HU complexes with double-stranded microchip 8mers can be divided into two groups in which HU binding either increased the melting temperature (T{sub m}) of duplexes or decreased it. The stabilized duplexes showed some preference for presence of the sequence motifs AAG, AGA and AAGA. In the second type of complex, enriched with A/T base pairs, the destabilization effect was higher for longer stretches of A/T duplexes. Binding of HU to labeled duplexes in the second type of complex caused some decrease in fluorescence. This decrease also correlates with the higher A/T content and lower T{sub m}. The results demonstrate that generic microchips could be an efficient approach in analysis of sequence specificity of proteins.

  19. Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression

    Directory of Open Access Journals (Sweden)

    He XL

    2016-10-01

    Full Text Available Xiaolie He,* Yanjing Zhu,* Mei Wang, Guoxin Jing, Rongrong Zhu, Shilong Wang Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Major depression is a complex neuropsychiatric disorder with few treatment approaches. The use of nontargeted antidepressants induced many side effects with their low efficacy. A more precise targeting strategy is to develop nanotechnology-based drug delivery systems; hence, we employed solid lipid nanoparticles (SLNs to encapsulate HU-211 and curcumin (Cur. The antidepressant effects of the dual-drug nanoparticles (Cur/SLNs-HU-211 for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depression. Cur/SLNs-HU-211 can effectively protect PC12 cells from corticosterone-induced apoptosis and can release more dopamine, which may be associated with the higher uptake of Cur/SLNs-HU-211 shown by cellular uptake behavior analysis. Additionally, Cur/SLNs-HU-211 significantly reduced the immobility time in forced swim test, enhanced fall latency in rotarod test, and improved the level of dopamine in mice blood. Cur/SLNs-HU-211 can deliver more Cur to the brain and thus produce a significant increase in neurotransmitters level in brain tissue, especially in the hippocampus and striatum. The results of Western blot and immunofluorescence revealed that Cur/SLNs-HU-211 can significantly enhance the expression of CB1, p-MEK1, and p-ERK1/2. Our study suggests that Cur/SLNs-HU-211 may have great potential for major depression treatment. Keywords: major depression, curcumin, HU-211, solid lipid nanoparticles, dopamine

  20. Effect of various factors and substrates on the growth of a human hepatoblastoma cell line, HuH-6 in a serum-free medium.

    Directory of Open Access Journals (Sweden)

    Tokiwa,Takayoshi

    1989-12-01

    Full Text Available The effect of various factors and substrates on the growth of a human hepatoblastoma cell line, HuH-6, which was inoculated at low density in a serum-free medium was examined. Several supplements were required to enhance cell growth of HuH-6. These included cholera toxin (CT, glucagon (Glu and selenium (Se. Type IV collagen (C-IV provided the most conductive environment tested for cell growth. These results suggest that CT, Glu, Se, and C-IV are important stimulators for the continuous growth of HuH-6 in a serum-free medium at low density.

  1. Neutrinoless double beta decay

    Indian Academy of Sciences (India)

    Kai Zuber

    2012-10-01

    The physics potential of neutrinoless double beta decay is discussed. Furthermore, experimental considerations as well as the current status of experiments are presented. Finally, an outlook towards the future, work on nuclear matrix elements and alternative processes is given.

  2. Identification of flavonoid diglycosides in several genotypes of asparagus from the Huétor-Tájar population variety.

    Science.gov (United States)

    Fuentes-Alventosa, José María; Rodríguez, Guillermo; Cermeño, Pedro; Jiménez, Ana; Guillén, Rafael; Fernández-Bolaños, Juan; Rodríguez-Arcos, Rocío

    2007-11-28

    The qualitative and quantitative composition of flavonoids from the Huétor-Tájar population variety of asparagus (commonly known as " triguero") was investigated. Flavonoids were analyzed by reversed-phase high-performance liquid chromatography-diode array detection (HPLC-DAD). Liquid chromatography-mass spectrometry (LC-MS) under identical HPLC conditions was used to verify the identities of the flavonoid glycosides from triguero asparagus. The quantities of asparagus flavonoids were calculated according to concentration curves constructed with authentic standards. Total flavonoid contents, calculated as the sum of individual compounds, were determined and ranged from 400 to 700 mg/kg fresh weight. The most abundant was rutin, which represented 55-98% of the total flavonoid complement. Triguero asparagus were revealed to be an important source of not only quercetin derivatives but also kaempferol and isorhamnetin glycosides. Significant differences (p asparagus genotypes from the Huétor-Tájar population variety.

  3. Beta-thalassemia

    OpenAIRE

    Origa Raffaella; Galanello Renzo

    2010-01-01

    Abstract Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor...

  4. Alpha and Beta Determinations

    CERN Document Server

    Dunietz, Isard

    1999-01-01

    Because the Bd -> J/psi Ks asymmetry determines only sin(2 beta), a discrete ambiguity in the true value of beta remains. This note reviews how the ambiguity can be removed. Extractions of the CKM angle alpha are discussed next. Some of the methods require very large data samples and will not be feasible in the near future. In the near future, semi-inclusive CP-violating searches could be undertaken, which are reviewed last.

  5. HTLV-1 Infection and Neuropathogenesis in the Context of Rag1(-/-)γc(-/-) (RAG1-Hu) and BLT Mice.

    Science.gov (United States)

    Ginwala, Rashida; Caruso, Breanna; Khan, Zafar K; Pattekar, Ajinkya; Chew, Glen M; Corley, Michael J; Loonawat, Ronak; Jacobson, Steven; Sreedhar, Sreesha; Ndhlovu, Lishomwa C; Jain, Pooja

    2017-09-01

    To date, the lack of a suitable small animal model has hindered our understanding of Human T-cell lymphotropic virus (HTLV)-1 chronic infection and associated neuropathogenesis defined as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The host immune response plays a critical role in the outcome of HTLV-1 infection, which could be better tested in the context of humanized (hu) mice. Thus, we employ here the Balb/c-Rag1(-/-)γc(-/-) or Rag1 as well as Bone marrow-Liver-Thymic (BLT) mouse models for engraftment of human CD34(+) hematopoietic stem cells. Flow cytometry and histological analyses confirmed reconstitution of Rag1 and BLT mice with human immune cells. Following HTLV-1 infection, proviral load (PVL) was detected in the blood of Rag-1 and BLT hu-mice as early as 2 weeks post-infection (wpi) with sustained elevation in the subsequent weeks followed by Tax expression. Additionally, infection was compared between adult and neonatal Rag1 mice with both PVL and Tax expression considerably higher in the adult Rag1 mice as compared to the neonates. Establishment of peripheral infection led to lymphocytic infiltration with concomitant Tax expression and resulting myelin disruption within the central nervous system of infected mice. In addition, up-regulation in the expression of several immune checkpoint mediators such as programmed cell death-1 (PD-1), T-cell Ig and ITIM domain (TIGIT), and T cell Ig and mucin domain-3 protein (Tim-3) were observed on CD8(+) T cells in various organs including the CNS of infected hu-mice. Collectively, these studies represent the first attempt to establish HTLV-1 neuropathogenesis in the context of Rag-1 and BLT hu-mice as potential novel tools for understanding HTLV-1 neuropathogenesis and testing of novel therapies such as immune checkpoint blockade in the amelioration of chronic HTLV-1 infection.

  6. {beta} - amyloid imaging probes

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Imaging distribution of {beta} - amyloid plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the {beta} -amyloid plaques includes using radiolabeled peptides which can be only applied for peripheral {beta} - amyloid plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging {beta} - amyloid plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for {beta} - amyloid imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for {beta} - amyloid imaging agent.

  7. Beta cell dynamics: beta cell replenishment, beta cell compensation and diabetes.

    Science.gov (United States)

    Cerf, Marlon E

    2013-10-01

    Type 2 diabetes, characterized by persistent hyperglycemia, arises mostly from beta cell dysfunction and insulin resistance and remains a highly complex metabolic disease due to various stages in its pathogenesis. Glucose homeostasis is primarily regulated by insulin secretion from the beta cells in response to prevailing glycemia. Beta cell populations are dynamic as they respond to fluctuating insulin demand. Beta cell replenishment and death primarily regulate beta cell populations. Beta cells, pancreatic cells, and extra-pancreatic cells represent the three tiers for replenishing beta cells. In rodents, beta cell self-replenishment appears to be the dominant source for new beta cells supported by pancreatic cells (non-beta islet cells, acinar cells, and duct cells) and extra-pancreatic cells (liver, neural, and stem/progenitor cells). In humans, beta cell neogenesis from non-beta cells appears to be the dominant source of beta cell replenishment as limited beta cell self-replenishment occurs particularly in adulthood. Metabolic states of increased insulin demand trigger increased insulin synthesis and secretion from beta cells. Beta cells, therefore, adapt to support their physiology. Maintaining physiological beta cell populations is a strategy for targeting metabolic states of persistently increased insulin demand as in diabetes.

  8. Comment on "Tropospheric temperature response to stratospheric ozone recovery in the 21st century" by Hu et al. (2011

    Directory of Open Access Journals (Sweden)

    C. McLandress

    2012-03-01

    Full Text Available In a recent paper Hu et al. (2011 suggest that the recovery of stratospheric ozone during the first half of this century will significantly enhance free tropospheric and surface warming caused by the anthropogenic increase of greenhouse gases, with the effects being most pronounced in Northern Hemisphere middle and high latitudes. These surprising results are based on a multi-model analysis of CMIP3 model simulations with and without prescribed stratospheric ozone recovery. Hu et al. suggest that in order to properly quantify the tropospheric and surface temperature response to stratospheric ozone recovery, it is necessary to run coupled atmosphere-ocean climate models with stratospheric ozone chemistry. The results of such an experiment are presented here, using a state-of-the-art chemistry-climate model coupled to a three-dimensional ocean model. In contrast to Hu et al., we find a much smaller Northern Hemisphere tropospheric temperature response to ozone recovery, which is of opposite sign. We suggest that their result is an artifact of the incomplete removal of the large effect of greenhouse gas warming between the two different sets of models.

  9. Cannabinoid HU210 protects isolated rat stomach against impairment caused by serum of rats with experimental acute pancreatitis.

    Directory of Open Access Journals (Sweden)

    Ming-hua Cao

    Full Text Available Acute pancreatitis (AP, especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS, proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis.

  10. Alginate hydrogel protects encapsulated hepatic HuH-7 cells against hepatitis C virus and other viral infections.

    Directory of Open Access Journals (Sweden)

    Nhu-Mai Tran

    Full Text Available Cell microencapsulation in alginate hydrogel has shown interesting applications in regenerative medicine and the biomedical field through implantation of encapsulated tissue or for bioartificial organ development. Although alginate solution is known to have low antiviral activity, the same property regarding alginate gel has not yet been studied. The aim of this work is to investigate the potential protective effect of alginate encapsulation against hepatitis C virus (HCV infection for a hepatic cell line (HuH-7 normally permissive to the virus. Our results showed that alginate hydrogel protects HuH-7 cells against HCV when the supernatant was loaded with HCV. In addition, alginate hydrogel blocked HCV particle release out of the beads when the HuH-7 cells were previously infected and encapsulated. There was evidence of interaction between the molecules of alginate hydrogel and HCV, which was dose- and incubation time-dependent. The protective efficiency of alginate hydrogel towards HCV infection was confirmed against a variety of viruses, whether or not they were enveloped. This promising interaction between an alginate matrix and viruses, whose chemical mechanisms are discussed, is of great interest for further medical therapeutic applications based on tissue engineering.

  11. Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1.

    Science.gov (United States)

    Tong, Xin; Mirzoeva, Salida; Veliceasa, Dorina; Bridgeman, Bryan B; Fitchev, Philip; Cornwell, Mona L; Crawford, Susan E; Pelling, Jill C; Volpert, Olga V

    2014-11-30

    Plant flavonoid apigenin prevents and inhibits UVB-induced carcinogenesis in the skin and has strong anti-proliferative and anti-angiogenic properties. Here we identify mechanisms, by which apigenin controls these oncogenic events. We show that apigenin acts, at least in part, via endogenous angiogenesis inhibitor, thrombospondin-1 (TSP1). TSP1 expression by the epidermal keratinocytes is potently inhibited by UVB. It inhibits cutaneous angiogenesis and UVB-induced carcinogenesis. We show that apigenin restores TSP1 in epidermal keratinocytes subjected to UVB and normalizes proliferation and angiogenesis in UVB-exposed skin. Importantly, reconstituting TSP1 anti-angiogenic function in UVB-irradiated skin with a short bioactive peptide mimetic representing exclusively its anti-angiogenic domain reproduced the anti-proliferative and anti-angiogenic effects of apigenin. Cox-2 and HIF-1α are important mediators of angiogenesis. Both apigenin and TSP1 peptide mimetic attenuated their induction by UVB. Finally we identified the molecular mechanism, whereby apigenin did not affect TSP1 mRNA, but increased de novo protein synthesis. Knockdown studies implicated the RNA-binding protein HuR, which controls mRNA stability and translation. Apigenin increased HuR cytoplasmic localization and physical association with TSP1 mRNA causing de novo TSP1 synthesis. HuR cytoplasmic localization was, in turn, dependent on CHK2 kinase. Together, our data provide a new mechanism, by which apigenin controls UVB-induced carcinogenesis.

  12. Cannabinoid HU210 Protects Isolated Rat Stomach against Impairment Caused by Serum of Rats with Experimental Acute Pancreatitis

    Science.gov (United States)

    Cao, Ming-hua; Li, Yong-yu; Xu, Jing; Feng, Ya-jing; Lin, Xu-hong; Li, Kun; Han, Tong; Chen, Chang-Jie

    2012-01-01

    Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS), proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis. PMID:23285225

  13. Effect of route of infection on outcome of Toxoplasma gondii infection in hu-PBL SCID mice.

    Science.gov (United States)

    Meyer, Desiree J; Allan, Jane E; Beaman, Miles H

    2013-03-01

    Toxoplasma gondii (T. gondii) causes serious infection, especially in immunocompromised hosts. The relevance of animal models of toxoplasmosis to human disease is unclear, but have indicated that the route of Toxoplasma infection may affect the outcome. A humanized model of toxoplasmosis of immunocompromised mice (i.e. hu-PBL SCID), using the intraperitoneal (IP) route demonstrated long-term engraftment of human cells and worsening of inflammation compared to controls. In this study, we examined the effect of route of infection on this hu-PBL SCID model using a Toxoplasma strain (i.e. DAG) isolated from an immunocompromised human. Oral infection led to an asymptomatic infection, whereas animals infected by the IP route succumbed more quickly to infection. Human cells, detected through species-specific β-actin mRNA, were not as prominent in IP-infected animals as compared to orally infected and uninfected animals. There was evidence of control of toxoplasmosis in some orally infected animals, and this was associated with the presence of human cells in multiple tissues. Thus, the route of infection dramatically affects the outcome of infection, either by affecting parasite replication or expansion of human immune cells. Further studies of oral Toxoplasma infection using hu-PBL SCID mice may help in developing chemotherapies and immunotherapeutic strategies for toxoplasmosis.

  14. A Conjugated Aptamer-Gold Nanoparticle Fluorescent Probe for Highly Sensitive Detection of rHuEPO-α

    Directory of Open Access Journals (Sweden)

    Zhaoyang Zhang

    2011-11-01

    Full Text Available We present here a novel conjugated aptamer-gold nanoparticle (Apt-AuNPs fluorescent probe and its application for specific detection of recombinant human erythropoietin-α (rHuEPO-α. In this nanobiosensor, 12 nm AuNPs function as both a nano-scaffold and a nano-quencher (fluorescent energy acceptor, on the surface of which the complementary sequences are linked (as cODN-AuNPs and pre-hybridized with carboxymethylfluorescein (FAM-labeled anti-rHuEPO-α aptamers. Upon target protein binding, the aptamers can be released from the AuNP surface and the fluorescence signal is restored. Key variables such as the length of linker, the hybridization site and length have been designed and optimized. Full performance evaluation including sensitivity, linear range and interference substances are also described. This nanobiosensor provides a promising approach for a simple and direct quantification of rHuEPO-α concentrations as low as 0.92 nM within a few hours.

  15. Comment on "Tropospheric temperature response to stratospheric ozone recovery in the 21st century" by Hu et al. (2011

    Directory of Open Access Journals (Sweden)

    M. Previdi

    2012-01-01

    Full Text Available Stratospheric ozone recovery is expected to figure prominently in twenty-first century climate change. In a recent paper, Hu et al. (2011 argue that one impact of ozone recovery will be to enhance the warming of the surface-troposphere system produced by increases in well-mixed greenhouse gases; furthermore, this enhanced warming would be strongest in the Northern Hemisphere, which is surprising since previous studies have consistently shown the effects of stratospheric ozone changes to be most pronounced in the Southern Hemisphere. Hu et al. (2011 base their claims largely on differences in the simulated temperature change between two groups of IPCC climate models, one group which included stratospheric ozone recovery in its twenty-first century simulations and a second group which did not. Both groups of models were forced with the same increases in well-mixed greenhouse gases according to the A1B emissions scenario. In the current work, we compare the surface temperature responses of the same two groups of models in a different experiment in which atmospheric CO2 was increased by 1% per year until doubling. We find remarkably similar differences in the simulated surface temperature change between the two sets of models as Hu et al. (2011 found for the A1B experiment, suggesting that the enhanced warming which they attribute to stratospheric ozone recovery is actually a reflection of different responses of the two model groups to greenhouse gas forcing.

  16. Morphological and kinematic signatures of a binary central star in the planetary nebula Hu 2-1

    CERN Document Server

    Miranda, L F; Guerrero, M; Vázquez, R A; Gómez, Y; Miranda, Luis F.; Torrelles, Jose M.; Guerrero, Martin A.; Vazquez, Roberto; Gomez, Yolanda

    2000-01-01

    We present narrow-band optical images, VLA-A 3.6 cm continuum and H92alpha emission line data and high resolution long-slit [N II] spectra of Hu 2-1. The formation of Hu 2-1 appears dominated by anisotropic mass ejection during the late AGB stage of its progenitor and by variable, ``precessing'' collimated bipolar outflows during the proto-PN and/or early PN phases. The data strongly support the existence of a binary central star at center of Hu 2-1: (1) the brightness distribution of the bipolar lobes and inner shell is point-symmetric, and the bipolar lobes show departures from axial symmetry; (2) the position of the central star is off-center; (3) mass ejection towards the equatorial plane is detected; (4) ``precessing'' collimated outflows are present. Besides all this circumstantial evidences, the analysis of the kinematics shows that the systemic velocity of the bipolar outflows does not coincide with the systemic velocity of the nebula. We propose that this velocity difference is a direct evidence of o...

  17. Modeling and predicting hemorrhagic fever with renal syndrome trends based on meteorological factors in Hu County, China.

    Directory of Open Access Journals (Sweden)

    Dan Xiao

    Full Text Available Hu County is a serious hemorrhagic fever with renal syndrome (HFRS epidemic area, with notable fluctuation of the HFRS epidemic in recent years. This study aimed to explore the optimal model for HFRS epidemic prediction in Hu.Three models were constructed and compared, including a generalized linear model (GLM, a generalized additive model (GAM, and a principal components regression model (PCRM. The fitting and predictive adjusted R2 of each model were calculated. Ljung-Box Q tests for fitted and predicted residuals of each model were conducted. The study period was stratified into before (1971-1993 and after (1994-2012 vaccine implementation epochs to avoid the confounding factor of vaccination.The autocorrelation of fitted and predicted residuals of the GAM in the two epochs were not significant (Ljung-Box Q test, P>.05. The adjusted R2 for the predictive abilities of the GLM, GAM, and PCRM were 0.752, 0.799, and 0.665 in the early epoch, and 0.669, 0.756, and 0.574 in the recent epoch. The adjusted R2 values of the three models were lower in the early epoch than in the recent epoch.GAM is superior to GLM and PCRM for monthly HFRS case number prediction in Hu County. A shift in model reliability coincident with vaccination implementation demonstrates the importance of vaccination in HFRS control and prevention.

  18. Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis.

    Science.gov (United States)

    Nakamoto, Hidetomo; Mimura, Taku; Honda, Nobuko

    2008-10-01

    Maintenance of the red blood cell volume is a fundamental aspect of ensuring oxygen supply to the tissue. Recombinant human erythropoietin (rHuEPO) was approved for marketing in Japan in 1990 for the treatment of anemia in patients on dialysis. Recombinant human erythropoietin caused a significant increase in hemoglobin (Hb) levels in patients on dialysis. However, not all have a good response to rHuEPO therapy; the causes of rHuEPO failure include iron deficiency, infection, uremia, and interaction of some drugs. Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia, or fatigue. To clarify the effect of TJ-48 on erythropoietin-resistant anemia, we studied the effect of TJ-48 in patients on hemodialysis with erythropoietin-resistant anemia. We divided 42 end-stage renal disease patients on hemodialysis with erythropoietin-resistant anemia (Hbrenal disease patients. This effect was, at least in part, due to the anti-inflammatory effect of TJ-48 in patients on hemodialysis.

  19. Bone and muscle assessment in patients undergoing total hip arthroplasty using HU based analysis

    Directory of Open Access Journals (Sweden)

    Þröstur Pétursson

    2012-09-01

    Full Text Available Total hip arthroplasty (THA is performed with or without the use of bone cement. The lack of reliable clinical guidelines for deciding which one to implement has encouraged this approach of joint clinical and engineering with the following objectives: 1. Validate quadriceps muscles and femur bone atrophy by extracting the mineral density from Computer Tomographic (CT images. 2. Validate computational processes based on 3-D modeling and Finite Element Methods (FEM. A clinical trial was started, where 36 volunteer patients underwent THA surgery for the first time: 18 receiving cemented implant and 18 receiving uncemented implant. The patients were CT scanned prior-, immediately after and 12 months post-surgery. The CT data are further processed to segment muscles and bones and to create 3D-models for the simulation and for calculating bone mineral density (BMD. Furthermore quadriceps muscle density Hounsfield (HU based value is calculated from the segmented file on healthy and operated leg. These preliminary results indicate computational tools and methods that are able to quantitatively analyse patient’s condition pre and post-surgery. The BMD and muscle density measurement in correlation with the fracture risk analysis display a potential method for eligibility to receive non-cemented implant; the preliminary results show that also elderly that according with current clinical evaluation receives a cemented implant are suitable for the non-cemented type. The risk for structural failure during THA surgery is estimated by calculating femoral bone fracture risk index (FRI as a ratio between compressive stress during surgery and estimated failure stress on bone. The correlations with the BMD observations during the clinical trial will assess and validate this potential predictor tool.

  20. Publicidad y consumo de alimentos en estudiantes de Huánuco (Perú

    Directory of Open Access Journals (Sweden)

    María Luisa Sevillano García

    2012-10-01

    Full Text Available Las importantes carencias nutritivas apreciadas en estudiantes del distrito de Huánuco (Perú, junto con la publicidad televisiva de productos de dudosa calidad nutricional observada, nos llevó a plantear y desarrollar una investigación con el objeto de analizar la relación entre ambos fenómenos titulada: Influencia de los anuncios televisivos en el consumo de alimentos publicitados durante el 2010, cuyo resumen se presenta en este artículo. En la investigación planteamos un estudio correlacional con una muestra de 120 escolares de diversas instituciones educativas, a quienes se aplicaron satisfactoriamente encuestas, entrevistas y guía de evaluación física; también se analizó la publicidad emitida por los canales de televisión sobre alimentos y su contenido nutricional. El análisis inferencial aplicado fue Ji cuadrado (?2. Con esta investigación se ha demostrado que el estado de salud de los escolares está afectado, siendo muy agudo respecto a la caries dental, problema que se atribuye al consumo de ciertos alimentos. Se constata que existe relación positiva, con alta significancia estadística, entre la adherencia a los anuncios televisivos y el consumo de alimentos publicitados de alto contenido en sodio, calcio, azúcar y de calorías por los escolares estudiados; así mismo, se prueba la interdependencia entre la exposición a los anuncios televisivos y el consumo de alimentos con productos de alto contenido en grasa que merecen ser vigilados y controlados por los responsables.

  1. Benchmark critical experiments on low-enriched uranium oxide systems with H/U = 0. 77

    Energy Technology Data Exchange (ETDEWEB)

    Tuck, G; Oh, I

    1979-08-01

    Ten benchmark experiments were performed at the Critical Mass Laboratory at Rockwell International's Rocky Flats Plant, Golden, Colorado, for the US Nuclear Regulatory Commission. They provide accurate criticality data for low-enriched damp uranium oxide (U/sub 3/O/sub 8/) systems. The core studied consisted of 152 mm cubical aluminum cans containing an average of 15,129 g of low-enriched (4.46% /sup 235/U) uranium oxide compacted to a density of 4.68 g/cm/sup 3/ and with an H/U atomic ratio of 0.77. One hundred twenty five (125) of these cans were arranged in an approx. 770 mm cubical array. Since the oxide alone cannot be made critical in an array of this size, an enriched (approx. 93% /sup 235/U) metal or solution driver was used to achieve criticality. Measurements are reported for systems having the least practical reflection and for systems reflected by approx. 254-mm-thick concrete or plastic. Under the three reflection conditions, the mass of the uranium metal driver ranged from 29.87 kg to 33.54 kg for an oxide core of 1864.6 kg. For an oxide core of 1824.9 kg, the weight of the high concentration (351.2 kg U/m/sup 3/) solution driver varied from 14.07 kg to 16.14 kg, and the weight of the low concentration (86.4 kg U/m/sup 3/) solution driver from 12.4 kg to 14.0 kg.

  2. HuMiTar: A sequence-based method for prediction of human microRNA targets

    Directory of Open Access Journals (Sweden)

    Chen Ke

    2008-12-01

    Full Text Available Abstract Background MicroRNAs (miRs are small noncoding RNAs that bind to complementary/partially complementary sites in the 3' untranslated regions of target genes to regulate protein production of the target transcript and to induce mRNA degradation or mRNA cleavage. The ability to perform accurate, high-throughput identification of physiologically active miR targets would enable functional characterization of individual miRs. Current target prediction methods include traditional approaches that are based on specific base-pairing rules in the miR's seed region and implementation of cross-species conservation of the target site, and machine learning (ML methods that explore patterns that contrast true and false miR-mRNA duplexes. However, in the case of the traditional methods research shows that some seed region matches that are conserved are false positives and that some of the experimentally validated target sites are not conserved. Results We present HuMiTar, a computational method for identifying common targets of miRs, which is based on a scoring function that considers base-pairing for both seed and non-seed positions for human miR-mRNA duplexes. Our design shows that certain non-seed miR nucleotides, such as 14, 18, 13, 11, and 17, are characterized by a strong bias towards formation of Watson-Crick pairing. We contrasted HuMiTar with several representative competing methods on two sets of human miR targets and a set of ten glioblastoma oncogenes. Comparison with the two best performing traditional methods, PicTar and TargetScanS, and a representative ML method that considers the non-seed positions, NBmiRTar, shows that HuMiTar predictions include majority of the predictions of the other three methods. At the same time, the proposed method is also capable of finding more true positive targets as a trade-off for an increased number of predictions. Genome-wide predictions show that the proposed method is characterized by 1.99 signal

  3. miR-29b, miR-205 and miR-221 enhance chemosensitivity to gemcitabine in HuH28 human cholangiocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kinya Okamoto

    Full Text Available BACKGROUND AND AIMS: Cholangiocarcinoma (CCA is highly resistant to chemotherapy, including gemcitabine (Gem treatment. MicroRNAs (miRNAs are endogenous, non-coding, short RNAs that can regulate multiple genes expression. Some miRNAs play important roles in the chemosensitivity of tumors. Here, we examined the relationship between miRNA expression and the sensitivity of CCA cells to Gem. METHODS: Microarray analysis was used to determine the miRNA expression profiles of two CCA cell lines, HuH28 and HuCCT1. To determine the effect of candidate miRNAs on Gem sensitivity, expression of each candidate miRNA was modified via either transfection of a miRNA mimic or transfection of an anti-oligonucleotide. Ontology-based programs were used to identify potential target genes of candidate miRNAs that were confirmed to affect the Gem sensitivity of CCA cells. RESULTS: HuCCT1 cells were more sensitive to Gem than were HuH28 cells, and 18 miRNAs were differentially expressed whose ratios over ± 2log2 between HuH28 and HuCCT1. Among these 18 miRNAs, ectopic overexpression of each of three downregulated miRNAs in HuH28 (miR-29b, miR-205, miR-221 restored Gem sensitivity to HuH28. Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to Gem treatment. Selective siRNA-mediated downregulation of either of two software-predicted targets, PIK3R1 (target of miR-29b and miR-221 or MMP-2 (target of miR-29b, also conferred Gem sensitivity to HuH28. CONCLUSIONS: miRNA expression profiling was used to identify key miRNAs that regulate Gem sensitivity in CCA cells, and software that predicts miRNA targets was used to identify promising target genes for anti-tumor therapies.

  4. MiR-291b-3p Induces Apoptosis in Liver Cell Line NCTC1469 by Reducing the Level of RNA-binding Protein HuR

    Directory of Open Access Journals (Sweden)

    Jun Guo

    2014-03-01

    Full Text Available Background: There is increasing evidence that miRNAs are involved in cellular apoptosis. However, the specific role of miR-291b-3p in apoptosis has not been elucidated. In the present study, we investigated the effect of miR-291b-3p on NCTC1469 cell growth and apoptosis. Methods: Cell viability and apoptosis were examined in NCTC1469 cells transfected with miR-291b-3p mimics, inhibitor miRNA or negative control. Using computational miRNA target prediction databases, HuR was predicted as a target of miR-291b-3p. Luciferase assay, immunofluorescence and western blot were used to further explore the effects of miR-291b-3p on HuR expression. In addition, the effect of HuR on cell apoptosis was evaluated using a HuR-specific siRNA. Results: TNF-α-induced hepatocyte apoptosis was accompanied by enhanced expression of miR-291b-3p, suggesting that miR-291b-3p might contribute to the apoptotic process. Follow-up experiments showed that upregulation of miR-291b-3p decreased cell viability and induced NCTC1469 cell apoptosis. Additionally, similar to the activity of miR-519, which is another member of the same miRNA family, miR-291b-3p suppressed HuR translation through binding to the HuR coding region (CR. We further showed that the downregulation of HuR expression by miR-291b-3p was accompanied by reduced Bcl-2 expression. Moreover, knockdown of HuR also impaired Bcl-2 expression and increased the ratio of Bax/Bcl-2. More significantly, downregulation of miR-291b-3p failed to increase Bcl2 expression in NCTC1469 cells that were co-transfected with siRNA-HuR. Finally, inhibition of miR-291b-3p led to reduced apoptosis, while knockdown of HuR by siRNA promoted apoptosis, even in NCTC1469 cells that were co-transfected with the miR-291b-3p inhibitor. Conclusion: The current data suggested that miR-291b-3p contributed to NCTC1469 cell apoptosis by regulating the expression of HuR, which in turn increased Bcl-2 stability.

  5. President Hu is in India but Who Am I in China?%胡主席在印度,我却在中国

    Institute of Scientific and Technical Information of China (English)

    Rajesh Kanoi (Jack)

    2007-01-01

    @@ Today, Sunday morning, I sit thinking and typing at my computer. My thoughts are in my homeland, India and my body is in China. The body is here and mind there for a good reason. Mr. Hu is president and I am resident and both are in each other's countries (what a difference the absence of one small letter makes!). Mr. Hu will return in a few days and I will stay on longer.

  6. HuGE Watch: tracking trends and patterns of published studies of genetic association and human genome epidemiology in near-real time.

    Science.gov (United States)

    Yu, Wei; Wulf, Anja; Yesupriya, Ajay; Clyne, Melinda; Khoury, Muin Joseph; Gwinn, Marta

    2008-09-01

    HuGE Watch is a web-based application for tracking the evolution of published studies on genetic association and human genome epidemiology in near-real time. The application allows users to display temporal trends and spatial distributions as line charts and google maps, providing a quick overview of progress in the field. http://www.hugenavigator.net/HuGENavigator/startPageWatch.do

  7. Mechanisms leading to sustained reversion of beta-thalassemia in mice by doxycycline-controlled Epo delivery from muscles.

    Science.gov (United States)

    Samakoglu, Selda; Bohl, Delphine; Heard, Jean Michel

    2002-12-01

    Erythropoiesis has been considered as a potential treatment for beta-thalassemia. Although Epo secretion from genetically engineered muscles allowed long-term correction of the disease in the mouse, repeated injections of rHuEpo were disappointing in human patients. Whether different mechanisms operate in humans and mice or whether Epo exhibits different biological activity depending on the administration route is currently unknown. We provide evidence that mechanisms recruited over a 36-week follow-up in beta-thalassemic mice were similar to those acting during stress-induced erythropoiesis in humans. beta-Thalassemic mice were rendered steadily normocythemic by the intramuscular injection of a tetracycline-inducible AAV vector encoding mouse Epo. Doxycycline dosage was adapted to hematocrit. Circulating red blood cells essentially synthesized beta-minor globin, the mouse equivalent to human gamma-globin. Quantification of erythroid progenitors indicated a steady-state expansion of erythroid burst-forming units programmed for beta-minor globin synthesis and a hastening of their maturation to hemoglobin-synthesizing cells. We discuss hypotheses that could account for the failure to recruit this mechanism over the long term in beta-thalassemic patients and raise the possibility of Epo gene therapy trials to treat beta-thalassemia.

  8. IgG autoantibodies against interleukin 1 alpha in sera of normal individuals

    DEFF Research Database (Denmark)

    Svenson, M; Poulsen, L K; Fomsgaard, A;

    1989-01-01

    molecular weight 125I fraction was achieved with an excess of unlabelled rIL-1 alpha but not with rIL-1 beta. The serum factors binding to [125I]rIL-1 alpha were located in the molecular weight range 100,000-200,000, judged by fractionation on a Sephacryl S-400 column, and the factors were bound...

  9. Boosted beta regression.

    Directory of Open Access Journals (Sweden)

    Matthias Schmid

    Full Text Available Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1. Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures.

  10. RNA-binding protein HuR sequesters microRNA-21 to prevent translation repression of proinflammatory tumor suppressor gene programmed cell death 4.

    Science.gov (United States)

    Poria, D K; Guha, A; Nandi, I; Ray, P S

    2016-03-31

    Translation control of proinflammatory genes has a crucial role in regulating the inflammatory response and preventing chronic inflammation, including a transition to cancer. The proinflammatory tumor suppressor protein programmed cell death 4 (PDCD4) is important for maintaining the balance between inflammation and tumorigenesis. PDCD4 messenger RNA translation is inhibited by the oncogenic microRNA, miR-21. AU-rich element-binding protein HuR was found to interact with the PDCD4 3'-untranslated region (UTR) and prevent miR-21-mediated repression of PDCD4 translation. Cells stably expressing miR-21 showed higher proliferation and reduced apoptosis, which was reversed by HuR expression. Inflammatory stimulus caused nuclear-cytoplasmic relocalization of HuR, reversing the translation repression of PDCD4. Unprecedentedly, HuR was also found to bind to miR-21 directly, preventing its interaction with the PDCD4 3'-UTR, thereby preventing the translation repression of PDCD4. This suggests that HuR might act as a 'miRNA sponge' to regulate miRNA-mediated translation regulation under conditions of stress-induced nuclear-cytoplasmic translocation of HuR, which would allow fine-tuned gene expression in complex regulatory environments.

  11. Changes in Cellular mRNA Stability, Splicing, and Polyadenylation through HuR Protein Sequestration by a Cytoplasmic RNA Virus

    Directory of Open Access Journals (Sweden)

    Michael D. Barnhart

    2013-11-01

    Full Text Available The impact of RNA viruses on the posttranscriptional regulation of cellular gene expression is unclear. Sindbis virus causes a dramatic relocalization of the cellular HuR protein from the nucleus to the cytoplasm in infected cells. This is to the result of the expression of large amounts of viral RNAs that contain high-affinity HuR binding sites in their 3′ UTRs effectively serving as a sponge for the HuR protein. Sequestration of HuR by Sindbis virus is associated with destabilization of cellular mRNAs that normally bind HuR and rely on it to regulate their expression. Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs as a result of sequestration of HuR protein by the 3′ UTR of transcripts of this cytoplasmic RNA virus. These studies suggest a molecular mechanism of virus-host interaction that probably has a significant impact on virus replication, cytopathology, and pathogenesis.

  12. UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes.

    Science.gov (United States)

    Fazekas, B; Polyánka, H; Bebes, A; Tax, G; Szabó, K; Farkas, K; Kinyó, A; Nagy, F; Kemény, L; Széll, M; Ádám, É

    2014-11-01

    Ultraviolet (UV) B is the most prominent physical carcinogen in the environment leading to the development of various skin cancers. We have previously demonstrated that the human ortholog of the Arabidopsis thaliana constitutive photomorphogenesis 1 (COP1) protein, huCOP1, is expressed in keratinocytes in a UVB-regulated manner and is a negative regulator of p53 as a posttranslational modifier. However, it was not known whether huCOP1 plays a role in mediating the UVB-induced early transcriptional responses of human keratinocytes. In this study, we report that stable siRNA-mediated silencing of huCOP1 affects the UVB response of several genes within 2 h of irradiation, indicating that altered huCOP1 expression sensitizes the cells toward UVB. Pathway analysis identified a molecular network in which 13 of the 30 examined UVB-regulated genes were organized around three central proteins. Since the expression of the investigated genes was upregulated by UVB in the siCOP1 cell line, we hypothesize that huCOP1 is a repressor of the identified pathway. Several members of the network have been implicated previously in the pathogenesis of non-melanoma skin cancers; therefore, clarifying the role of huCOP1 in these skin diseases may have clinical relevance in the future.

  13. Effect of HU308 on microglia induced by LPS in secretion of NO and IL-6%HU308对脂多糖诱导小胶质细胞分泌NO及IL-6的影响

    Institute of Scientific and Technical Information of China (English)

    赵建云; 邓展进; 刘瑞珍

    2014-01-01

    Objective To study the effect in secretion of NO and IL-6 of cannabinoid CB2 receptor agonist (HU308) on microglia induced by lipopolysaccharide (LPS). Methods vitro culture BV-2 microglia were divided into control group, LPS stimulation group and intervention group (LPS + HU308). The morphological changes in microglia were observed by microscope, the proliferation in microglia was detected by CCK-8, the NO contents were detected by Griess reaction, the IL-6 contents were detected by ELISA. Results A large number of microglia in LPS stimulation group showed auxetic body, stubby or disappeared pseudopodium and necrotic cells, cell proliferation was poor, the expression level of NO and IL-6 increased significantly. After the intervention of CB2 receptor agonist (HU308), most of microglia showed slightly large body, obvious pseudopodia and light damage, cell proliferation was better, the expression of inflammatory factor decreased significantly. Conclusion Activating CB2 receptors expressing in microglia can alleviate the excessive activation of microglia caused by LPS, inhibit the secretion of N0 and IL-6, so as to achieve the protective effect of central nervous system inflammatory injury.%目的:研究大麻素CB2受体激动剂HU308对脂多糖(LPS)诱导小胶质细胞激活后NO及IL-6分泌的影响。方法体外培养小鼠小胶质细胞株(BV-2细胞),分为对照组、LPS刺激组及干预组(LPS+HU308)。通过显微镜观察各组小胶质细胞的形态学变化,CCK-8法检测各组小胶质细胞的增殖情况,Griess法检测各组NO含量,ELISA法检测各组IL-6水平。结果LPS刺激组的小胶质细胞中出现大量胞体增大,伪足粗短或消失的细胞和一些坏死细胞,细胞增殖较差,NO及IL-6表达水平显著增高。经大麻素CB2受体激动剂HU308干预后,大部分细胞胞体稍大,伪足尚明显,细胞破坏程度轻,增殖较好,炎性因子表达均明显下降。结论激动小

  14. Double Beta Decay

    CERN Document Server

    Elliott, Steven R

    2011-01-01

    At least one neutrino has a mass of about 50 meV or larger. However, the absolute mass scale for the neutrino remains unknown. Furthermore, the critical question: Is the neutrino its own antiparticle? is unanswered. Studies of double beta decay offer hope for determining the absolute mass scale. In particular, zero-neutrino double beta decay (\\BBz) can address the issues of lepton number conservation, the particle-antiparticle nature of the neutrino, and its mass. A summary of the recent results in \\BBz, and the related technologies will be discussed in the context of the future \\BBz\\ program.

  15. Beta and Gamma Gradients

    DEFF Research Database (Denmark)

    Løvborg, Leif; Gaffney, C. F.; Clark, P. A.;

    1985-01-01

    Experimental and/or theoretical estimates are presented concerning, (i) attenuation within the sample of beta and gamma radiation from the soil, (ii) the gamma dose within the sample due to its own radioactivity, and (iii) the soil gamma dose in the proximity of boundaries between regions...... of differing radioactivity. It is confirmed that removal of the outer 2 mm of sample is adequate to remove influence from soil beta dose and estimates are made of the error introduced by non-removal. Other evaluations include variation of the soil gamma dose near the ground surface and it appears...

  16. Purification and characterization of a novel chlorpyrifos hydrolase from Cladosporium cladosporioides Hu-01.

    Science.gov (United States)

    Gao, Yan; Chen, Shaohua; Hu, Meiying; Hu, Qiongbo; Luo, Jianjun; Li, Yanan

    2012-01-01

    Chlorpyrifos is of great environmental concern due to its widespread use in the past several decades and its potential toxic effects on human health. Thus, the degradation study of chlorpyrifos has become increasing important in recent years. A fungus capable of using chlorpyrifos as the sole carbon source was isolated from organophosphate-contaminated soil and characterized as Cladosporium cladosporioides Hu-01 (collection number: CCTCC M 20711). A novel chlorpyrifos hydrolase from cell extract was purified 35.6-fold to apparent homogeneity with 38.5% overall recovery by ammoniumsulfate precipitation, gel filtration chromatography and anion-exchange chromatography. It is a monomeric structure with a molecular mass of 38.3 kDa. The pI value was estimated to be 5.2. The optimal pH and temperature of the purified enzyme were 6.5 and 40°C, respectively. No cofactors were required for the chlorpyrifos-hydrolysis activity. The enzyme was strongly inhibited by Hg²⁺, Fe³⁺, DTT, β-mercaptoethanol and SDS, whereas slight inhibitory effects (5-10% inhibition) were observed in the presence of Mn²⁺, Zn²⁺, Cu²⁺, Mg²⁺, and EDTA. The purified enzyme hydrolyzed various organophosphorus insecticides with P-O and P-S bond. Chlorpyrifos was the preferred substrate. The Km and Vmax values of the enzyme for chlorpyrifos were 6.7974 μM and 2.6473 μmol·min⁻¹, respectively. Both NH2-terminal sequencing and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometer (MALDI-TOF-MS) identified an amino acid sequence MEPDGELSALTQGANS, which shared no similarity with any reported organophosphate-hydrolyzing enzymes. These results suggested that the purified enzyme was a novel hydrolase and might conceivably be developed to fulfill the practical requirements to enable its use in situ for detoxification of chlorpyrifos. Finally, this is the first described chlorpyrifos hydrolase from fungus.

  17. Trichoderma .beta.-glucosidase

    Science.gov (United States)

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

    2006-01-03

    The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl3, and the corresponding BGL3 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL3, recombinant BGL3 proteins and methods for producing the same.

  18. Roughing up Beta

    DEFF Research Database (Denmark)

    Bollerslev, Tim; Li, Sophia Zhengzi; Todorov, Viktor

    Motivated by the implications from a stylized equilibrium pricing framework, we investigate empirically how individual equity prices respond to continuous, or \\smooth," and jumpy, or \\rough," market price moves, and how these different market price risks, or betas, are priced in the cross-section...

  19. Applied Beta Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Rich, B.L.

    1986-01-01

    Measurements of beta and/or nonpenetrating exposure results is complicated and past techniques and capabilities have resulted in significant inaccuracies in recorded results. Current developments have resulted in increased capabilities which make the results more accurate and should result in less total exposure to the work force. Continued development of works in progress should provide equivalent future improvements.

  20. Beta thalassemia - a review

    Directory of Open Access Journals (Sweden)

    R Jha

    2014-09-01

    Full Text Available Thalassemia is a globin gene disorder that results in a diminished rate of synthesis of one or more of the globin chains. About 1.5% of the global population (80 to 90 million people are carriers of beta Thalassemia. More than 200 mutations are described in beta thalassemia. However not all mutations are common in different ethnic groups. The only effective way to reduce burden of thalassemia is to prevent birth of homozygotes. Diagnosis of beta thalassemia can be done by fetal DNA analysis for molecular defects of beta thalassemia or by fetal blood analysis. Hematopoietic stem cell transplantation is the only available curative approach for Thalassemia. Many patients with thalassemia in underdeveloped nations die in childhood or adolescence. Programs that provide acceptable care, including transfusion of safe blood and supportive therapy including chelation must be established.DOI: http://dx.doi.org/10.3126/jpn.v4i8.11609 Journal of Pathology of Nepal; Vol.4,No. 8 (2014 663-671

  1. A Bite of Hu Flavour in Diets of Tang Dynasty%唐代舌尖上的胡味

    Institute of Scientific and Technical Information of China (English)

    刘锡涛

    2015-01-01

    Tang Dynasty was an innovative, open and tolerant society with booming economy and constant re-newals, which was characterized by strong Hu flavor in diet. There were plenty kinds of Hu diets on staples, vegetables, fruits, wines and flavourings. While pastries were the staple diet, there were such vegetables as spinach, cucumber, eggplant, preserved pickle, lettuce and such fruits as golden peach, grape, date and fla-vourings as sugar, parsley, pepper and such wine as grape wine, long-gao wine. The popularity of Hu diet in Tang Dynasty accelerates the multi-ethnic mélange of dietetic cultures.%唐代是个改革、开放与包容的社会,经济发展,吐旧纳新,人们在饮食上多体现出胡味现象,胡食品种繁多,集中体现在主食、蔬菜、水果、酒及调味品上。主食多吃面饼,蔬菜主要有菠菜、黄瓜、茄子、榨菜、莴苣等,水果有金桃、葡萄、波斯枣等,调味品主要有蔗糖、香菜、胡椒等,酒有葡萄酒、龙膏酒等水果酒。唐代胡食的盛行,加快了我国多民族饮食文化的融合发展。

  2. Beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    2016-01-01

    Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin...... and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades...... in the expansion of the beta cell mass in human pregnancy, and the relative roles of endocrine factors and nutrients....

  3. Les structures génotypiques multilocus des populations d'huîtres plates en France

    Directory of Open Access Journals (Sweden)

    Françoise BLANC

    1987-09-01

    Full Text Available La structure génétique des populations de l'huître plate Ostrea edulis est décrite sur la base des génotypes multilocus. Associée au traitement des données de type multivarié, cette nouvelle procédure permet d'identifier les sous-ensembles génétiques intrapopulationnels qui peuvent être repérés dans un échantillon composite résultant de transferts comme dans la lagune de Thau.

  4. pp32 (ANP32A expression inhibits pancreatic cancer cell growth and induces gemcitabine resistance by disrupting HuR binding to mRNAs.

    Directory of Open Access Journals (Sweden)

    Timothy K Williams

    Full Text Available The expression of protein phosphatase 32 (PP32, ANP32A is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1, a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C, but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK, causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR, while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy.

  5. Saturated fatty acids induce post-transcriptional regulation of HAMP mRNA via AU-rich element-binding protein, human antigen R (HuR).

    Science.gov (United States)

    Lu, Sizhao; Mott, Justin L; Harrison-Findik, Duygu Dee

    2015-10-02

    Iron is implicated in fatty liver disease pathogenesis. The human hepcidin gene, HAMP, is the master switch of iron metabolism. The aim of this study is to investigate the regulation of HAMP expression by fatty acids in HepG2 cells. For these studies, both saturated fatty acids (palmitic acid (PA) and stearic acid (SA)) and unsaturated fatty acid (oleic acid (OA)) were used. PA and, to a lesser extent, SA, but not OA, up-regulated HAMP mRNA levels, as determined by real-time PCR. To understand whether PA regulates HAMP mRNA at the transcriptional or post-transcriptional level, the transcription inhibitor actinomycin D was employed. PA-mediated induction of HAMP mRNA expression was not blocked by actinomycin D. Furthermore, PA activated HAMP 3'-UTR, but not promoter, activity, as shown by reporter assays. HAMP 3'-UTR harbors a single AU-rich element (ARE). Mutation of this ARE abolished the effect of PA, suggesting the involvement of ARE-binding proteins. The ARE-binding protein human antigen R (HuR) stabilizes mRNA through direct interaction with AREs on 3'-UTR. HuR is regulated by phosphorylation-mediated nucleo-cytoplasmic shuttling. PA activated this process. The binding of HuR to HAMP mRNA was also induced by PA in HepG2 cells. Silencing of HuR by siRNA abolished PA-mediated up-regulation of HAMP mRNA levels. PKC is known to phosphorylate HuR. Staurosporine, a broad-spectrum PKC inhibitor, inhibited both PA-mediated translocation of HuR and induction of HAMP expression. Similarly, rottlerin, a novel class PKC inhibitor, abrogated PA-mediated up-regulation of HAMP expression. In conclusion, lipids mediate post-transcriptional regulation of HAMP throughPKC- and HuR-dependent mechanisms.

  6. HuR and podoplanin expression is associated with a high risk of malignant transformation in patients with oral preneoplastic lesions

    Science.gov (United States)

    Habiba, Umma; Kitamura, Tetsuya; Yanagawa-Matsuda, Aya; Higashino, Fumihiro; Hida, Kyoko; Totsuka, Yasunori; Shindoh, Masanobu

    2016-01-01

    The risk of malignant transformation in oral preneoplastic lesions (OPLs) is challenging to assess. The objective of the present study was to determine the expression of ELAV like RNA binding protein 1 (HuR) and podoplanin in OPLs, and to evaluate the use of each protein as biomarkers for the risk assessment of malignant transformations. Immunohistochemistry for HuR and podoplanin was performed on the tissues of 51 patients with OPL, including cases of low grade dysplasia (LGD) and high grade dysplasia (HGD). The association between the protein expression patterns and clinicopathological parameters, including oral cancer free survival (OCFS) time, was analyzed during the follow-up period. HuR and podoplanin expression was observed in 28 (55%) and 36 (71%) of 51 patients, respectively. Kaplan-Meier analysis showed that the expression of HuR and podoplanin was associated with the risk of progression to oral cancer (P<0.05). Multivariate analysis revealed that HuR and podoplanin expression was associated with a 2.93-fold (95% confidence interval (CI), 0.98–10.34; P=0.055) and 2.06-fold (95% CI, 0.55–8.01; P=0.283) increase in risk of malignant transformation, respectively. The risk of OPL malignant transformation was considerably increased with the coexpression of HuR and podoplanin compared with the histological grading (95% CI, 1.64–23.59; P=0.005). The results of the present study demonstrated that the expression of HuR and podoplanin associates with malignant transformation and suggests that the proteins may be used as biomarkers to identify OPL patients with an increased risk of cancer development. PMID:27899983

  7. GC–MS-Based Metabonomic Profiling Displayed Differing Effects of Borna Disease Virus Natural Strain Hu-H1 and Laboratory Strain V Infection in Rat Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Siwen Liu

    2015-08-01

    Full Text Available Borna disease virus (BDV persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC–MS metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12, Strain V-infected cells (n = 12, and CON cells (n = 11. Partial least squares discriminant analysis (PLS-DA was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON, 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON, and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V. Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.

  8. Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory

    Science.gov (United States)

    Pascale, Alessia; Gusev, Pavel A.; Amadio, Marialaura; Dottorini, Tania; Govoni, Stefano; Alkon, Daniel L.; Quattrone, Alessandro

    2004-01-01

    Neuronal ELAV-like proteins (HuB, HuC, and HuD) are highly conserved RNA-binding proteins able to selectively associate with the 3′ UTR of a subset of target mRNAs and increase their cytoplasmic stability and rate of translation. We previously demonstrated the involvement of these proteins in learning, reporting that they undergo a sustained up-regulation in the hippocampus of mice trained in a spatial discrimination task. Here, we extend this finding, showing that a similar up-regulation occurs in the hippocampus of rats trained in another spatial learning paradigm, the Morris water maze. HuD, a strictly neuron-specific ELAV-like protein, is shown to increase after learning, with a preferential binding to the cytoskeletal fraction. HuD up-regulation is associated with an enhancement of GAP-43 mRNA and protein levels, with an apparently increased HuD colocalization with the GAP-43 mRNA and an increased association of neuronal ELAV-like proteins with the GAP-43 mRNA. These learning-dependent biochemical events appear to be spatiotemporally controlled, because they do not occur in another brain region involved in learning, the retrosplenial cortex, and at the level of protein expression they show extinction 1 month after training despite memory retention. By contrast, HuD mRNA levels still remain increased after 1 month in the CA1 region. This persistence may have implications for long-term memory recall. PMID:14745023

  9. HuR and podoplanin expression is associated with a high risk of malignant transformation in patients with oral preneoplastic lesions.

    Science.gov (United States)

    Habiba, Umma; Kitamura, Tetsuya; Yanagawa-Matsuda, Aya; Higashino, Fumihiro; Hida, Kyoko; Totsuka, Yasunori; Shindoh, Masanobu

    2016-11-01

    The risk of malignant transformation in oral preneoplastic lesions (OPLs) is challenging to assess. The objective of the present study was to determine the expression of ELAV like RNA binding protein 1 (HuR) and podoplanin in OPLs, and to evaluate the use of each protein as biomarkers for the risk assessment of malignant transformations. Immunohistochemistry for HuR and podoplanin was performed on the tissues of 51 patients with OPL, including cases of low grade dysplasia (LGD) and high grade dysplasia (HGD). The association between the protein expression patterns and clinicopathological parameters, including oral cancer free survival (OCFS) time, was analyzed during the follow-up period. HuR and podoplanin expression was observed in 28 (55%) and 36 (71%) of 51 patients, respectively. Kaplan-Meier analysis showed that the expression of HuR and podoplanin was associated with the risk of progression to oral cancer (P<0.05). Multivariate analysis revealed that HuR and podoplanin expression was associated with a 2.93-fold (95% confidence interval (CI), 0.98-10.34; P=0.055) and 2.06-fold (95% CI, 0.55-8.01; P=0.283) increase in risk of malignant transformation, respectively. The risk of OPL malignant transformation was considerably increased with the coexpression of HuR and podoplanin compared with the histological grading (95% CI, 1.64-23.59; P=0.005). The results of the present study demonstrated that the expression of HuR and podoplanin associates with malignant transformation and suggests that the proteins may be used as biomarkers to identify OPL patients with an increased risk of cancer development.

  10. Construction of Eukaryotic Expression Vector Containing HuCTLA4Ig and its Expression in Mammalian Cells%HuCTLA4Ig真核表达载体的构建及其表达

    Institute of Scientific and Technical Information of China (English)

    祁小平; 钱军华; 谢晋; 马宝骊

    2000-01-01

    用RT-PCR方法从人外周血单个核细胞总RNA中分别扩增出CTLA4的胞膜外区基因和Igγ1恒定区基因,将它们拼接后插入质粒pcDNA3.将重组的HuCTLA4Ig/pcDNA质粒转染细胞,经筛选得到了高效、稳定表达HuCTLA4Ig的克隆.培养上清经ProteinA亲和层析柱纯化后,所得蛋白在非还原条件下SDS-PAGE呈分子量为11kD的一条带;FACS检测显示该纯化蛋白与B7分子有良好的结合能力;在体外能抑制MLR的增殖反应.

  11. TGF-beta and osteoarthritis.

    NARCIS (Netherlands)

    Blaney Davidson, E.N.; Kraan, P.M. van der; Berg, W.B. van den

    2007-01-01

    OBJECTIVE: Cartilage damage is a major problem in osteoarthritis (OA). Growth factors like transforming growth factor-beta (TGF-beta) have great potential in cartilage repair. In this review, we will focus on the potential therapeutic intervention in OA with TGF-beta, application of the growth facto

  12. Conditions for $\\beta$-perfectness

    NARCIS (Netherlands)

    Keijsper, J.C.M.; Tewes, M.

    2000-01-01

    A $\\beta$-perfect graph is a simple graph $G$ such that $\\chi(G')=\\beta(G')$ for every induced subgraph $G'$ of $G$, where $\\chi(G')$ is the chromatic number of $G'$, and $\\beta(G')$ is defined as the maximum over all induced subgraphs $H$ of $G'$ of the minimum vertex degree in $H$. The vertices of

  13. Misleading Betas: An Educational Example

    Science.gov (United States)

    Chong, James; Halcoussis, Dennis; Phillips, G. Michael

    2012-01-01

    The dual-beta model is a generalization of the CAPM model. In the dual-beta model, separate beta estimates are provided for up-market and down-market days. This paper uses the historical "Anscombe quartet" results which illustrated how very different datasets can produce the same regression coefficients to motivate a discussion of the…

  14. The role of chromatin-associated protein Hbsu in beta-mediated DNA recombination is to facilitate the joining of distant recombination sites.

    Science.gov (United States)

    Alonso, J C; Gutierrez, C; Rojo, F

    1995-11-01

    The beta recombinase is unable to mediate in vitro DNA recombination between two directly oriented recombination sites unless a bacterial chromatin-associated protein (Bacillus subtilis Hbsu or Escherichia [correction of Eschrichia] coli HU] is provided. By electron microscopy, we show that the role of Hbsu is to help in joining the recombination sites to form a stable synaptic complex. Some evidence supports the fact that Hbsu works by recognizing and stabilizing a DNA structure at the recombination site, rather than by serving as a bridge between beta recombinase dimers through a protein-protein interaction. We show that the mammalian HMG1 protein, which shares neither sequence nor structural homology with Hbsu, can also stimulate beta-mediated recombination. These chromatin-associated proteins share the property of binding to DNA in a relatively non-specific fashion, bending it, and having a marked preference for altered DNA structures. Hbsu, HU or HMG1 proteins probably bind specifically at the crossing-over region, since at limiting protein-DNA molar ratios they could not be outcompeted by an excess of a DNA lacking the crossing over site. Distamycin, a minor groove binder that induces local distortions in DNA, did not affect the binding of beta protein to DNA, but inhibited the formation of the synaptic complex.

  15. HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Liang Peir-In

    2012-12-01

    Full Text Available Abstract Background HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs. Methods In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS, metastasis-free survival (MeFS, urinary bladder recurrence-free survival (UBRFS, and various clinicopathological factors. Results HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005. Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p p p = 0.0370 in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS. Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035 and MeFS (p = 0.0015 in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015. Conclusions HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive

  16. Differential regulation of chemoattractant-stimulated beta 2, beta 3, and beta 7 integrin activity.

    Science.gov (United States)

    Sadhu, C; Masinovsky, B; Staunton, D E

    1998-06-01

    Leukocyte adhesion to endothelium and extravasation are dynamic processes that require activation of integrins. Chemoattractants such as IL-8 and FMLP are potent activators of leukocyte integrins. To compare the chemoattractant-stimulated activation of three integrins, alpha 4 beta 7, alpha L beta 2, and alpha V beta 3, in the same cellular context, we expressed an IL-8 receptor (IL-8RA) and FMLP receptor (FPR) in the lymphoid cell line JY. Chemoattractants induced a rapid increase in alpha L beta 2- and alpha V beta 3-dependent JY adhesion within 5 min, and it was sustained for 30 min. In contrast, stimulation of alpha 4 beta 7-dependent adhesion was transient, returning to basal levels by 30 min. The activation profiles of the integrins were similar regardless of whether IL-8 or FMLP was used for induction. We also demonstrate that alpha 4 beta 7-dependent adhesion was uniquely responsive to the F actin-disrupting agent cytochalasin D and the protein kinase C (PKC) inhibitor chelerythrin. While alpha V beta 3- and alpha L beta 2-mediated cell adhesion was significantly reduced by cytochalasin D, alpha 4 beta 7-mediated adhesion was enhanced. Chelerythrin inhibited both the IL-8 and PMA activation of alpha L beta 2 and alpha V beta 3. In contrast, inducible alpha 4 beta 7 activity was unaffected, and basal activity was increased. These findings demonstrate that the mechanism of alpha 4 beta 7 regulation by chemoattractants is different from that of alpha L beta 2 and alpha V beta 3 and that it appears to involve distinct cytoskeletal and PKC dependencies. In addition, PKC activity may be a positive or negative regulator of integrin-dependent adhesion.

  17. A new human cholangiocellular carcinoma cell line (HuCC-T1) producing carbohydrate antigen 19/9 in serum-free medium.

    Science.gov (United States)

    Miyagiwa, M; Ichida, T; Tokiwa, T; Sato, J; Sasaki, H

    1989-06-01

    A human cholangiocellular carcinoma cell line, HuCC-T1, was established in vitro from the malignant cells of ascites of a 56-yr-old patient. Histologic findings of the primary liver tumor revealed a moderately differentiated adenocarcinoma. Tumor cells from the ascites have been cultured with RPMI 1640 medium containing 0.2% lactalbumin hydrolysate and the cultured cells grew as monolayers with a population doubling time of 74 h during exponential growth at Passage 25. They had an epithelial-like morphology and were positive for mucine staining. Ultrastructural studies revealed the presence of microvilli on the cell surface and poorly developed organelles in the cytoplasm. The HuCC-T1 cell was tumorigenic in nude mice. The number of chromosomes in HuCC-T1 ranged from 61 to 80. These human cholangiocellular carcinoma cells in serum-free medium secreted several tumor markers, including carbohydrate antigen 19/9, carbohydrate antigen 125, carcinoembryonic antigen, and tissue polypeptide antigen. The carbohydrate antigen 19/9 secretion level of HuCC-T1 cells cultured in RPMI 1640 medium with 1% fetal bovine serum was sixfold higher than that with 0.2% lactalbumin hydrolysate. These findings suggest that HuCC-T1 will provide useful information to clarify the mechanism of tumor marker secretion and tumor cell growth in the human cholangiocellular carcinoma.

  18. Comparison between two treatment protocols with recombinant Human Erythropoietin (rHuEpo in the treatment of late anemia in neonates with Rh-Isoimmunization

    Directory of Open Access Journals (Sweden)

    A.A. Zuppa

    2012-08-01

    Full Text Available Objectve. The Rh-hemolytic disease can lead to a late anemia by hemolytic and hyporigenerative mechanism. We compared the effectiveness of rHuEPO in two care protocols that differ for doses of rHuEPO administrated and for timing of administration. Methods. A cohort of 14 neonates was investigated. The neonates were treated with two different protocols. Protocol A: a dose of 200 U/kg/day of rHuEpo administered subcutaneously starting from the end of the second week of life; Protocol B: a dose of 400 U/kg/day of rHuEpo administered subcutaneously starting from the end of the first week of life. Results. The hematocrit values in the protocol A group decreased during treatment (32,5% vs 25,2%, whereas the hematocrit value in protocol B group remained almost stable (38,7% vs 42,8%. The mean numbers of platelets remained stable in both groups while neutrophils increased in protocol A group and decreased in protocol B (p<0,05. Reticulocyte count increased during treatment in both groups, although only in protocol B group it was statistically significative (p<0,05. Conclusions. Our results suggest a similar efficacy between the two treatment protocols. Increasing doses of rHuEPO do not seem enhancing their effectiveness and the incidence of side effects.

  19. Pharmacological Progress of HuZhang%中药虎杖药理作用研究进展

    Institute of Scientific and Technical Information of China (English)

    黄海量

    2012-01-01

    总结近年来关于中药虎杖中有效成分治疗心血管系统、消化系统、呼吸系统、内分泌系统、生殖系统、免疫系统等疾病的文献报道,发现虎杖含有的丰富活性成分具有多项药理作用,临床应用日益广泛,但其毒理研究和有效成分提取方法的报道鲜见.%Literature and reports on effective constituents of HuZhang (Polygonum cuspidatum) in treating the diseases of cardiovascular system, digestive system, respiratory system, endocrine system, reproductive system, immune system and so on were concluded in recent years and the result of study showed that rich active constituents in HuZhang had pharmacological functions and were widely used day by day, but toxicological studies and extraction of effective constituent were rarely reported.

  20. Optimization and risk analyses for rule curves of reservoir operation: application to Tien-Hua-Hu Reservoir in Taiwan.

    Science.gov (United States)

    Kuo, J T; Hsu, N S; Chiu, S K

    2006-01-01

    Tien-Hua-Hu Reservoir is currently under planning by the Water Resources Agency, Taiwan to meet the increasing water demands of central Taiwan arising from rapid growth of domestic water supply, and high-tech industrial parks. This study develops a simulation model for the ten-day period reservoir operation to calculate the ten-day water shortage index under varying rule curves. A genetic algorithm is coupled to the simulation model to find the optimal rule curves using the minimum ten-day water shortage index as an objective function. This study generates many sets of synthetic streamflows for risk, reliability, resiliency, and vulnerability analyses of reservoir operation. ARMA and disaggregation models are developed and applied to the synthetic streamflow generation. The optimal rule curves obtained from this study perform better in the ten-day shortage index when compared to the originally designed rule curves from a previous study. The optimal rule curves are also superior to the originally designed rule curves in terms of vulnerability. However, in terms of reliability and resiliency, the optimal rule curves are inferior to the those originally designed. Results from this study have provided in general a set of improved rule curves for operation of the Tien-Hua-Hu Reservoir. Furthermore, results from reliability, resiliency and vulnerability analyses offer much useful information for decision making in reservoir operation.

  1. r-huEPO在胃肠道恶性肿瘤患者围手术期应用

    Institute of Scientific and Technical Information of China (English)

    缪传文; 李继坤; 温玉刚; 周立生; 李旭

    2006-01-01

    胃肠道恶性肿瘤往往伴有程度不等的贫血,以往临床上除了输血疗效确切外,只有使用各种生血制剂,主要是铁剂,往往起效缓慢,难以令人满意。而输血由于血源紧张,还有各种输血的并发症,及传播各种严重传染病性疾病的危险,使用受到限制。重组人促红细胞生成素(recombinant erythropoietin)的围手术期红细胞动员也越来越受到临床重视,有研究表现大剂量应用r-huEPO有明显的红细胞动员作用。2003年-2005年,我们应用r-huEPO治疗胃肠道恶性肿瘤伴贫血的手术患者276例,取得了较好的疗效。

  2. Nuclear Import Analysis of Two Different Fluorescent Marker Proteins into Hepatocyte Cell Lines (HuH-7 Cell

    Directory of Open Access Journals (Sweden)

    Aris Haryanto

    2015-10-01

    Full Text Available The application of fluorescent proteins as expression markers and protein fusion partners has provedimmensely valuable for resolving the organization of biological events in living cells. EGFP and DsRed2 arecommonly fluorescent marker protein which is used for biotechnology and cell biology research. The presentstudy was designed to identify the expression vector that suitable to ligate with DNA encoding HBV coreprotein for intracellular localization study in hepatocyte cell, which were expressed as fusion proteins. We alsocompared and quantified the expressed fluorescent protein which predominantly localized in the cellcompartment. The results indicated that DsRed2 shown as less than ideal for intracellular localization study ofthan EGFP, because of its tetrameric structure of the fluorescent protein and when fused to a protein of interest,the fusion protein often forms aggregates in the living cells. In contrast, EGFP fluorescent protein shown a muchhigher proportion of cytoplasmic localization, thus being more suitable for analysis of intracellular localizationthan DsRed2 fluorescent protein. EGFP fluorescent protein is also capable to produce a strong green fluorescencewhen excited by blue light, without any exogenously added substrate or cofactor, events inside living cell canthus be visualized in a non-invasive way. Based on our present quantitative data and some reasons above shownthat EGFP is more suitable than DsRed2 as a fluorescent marker protein for intracellular localization study intoHuH-7 cell.Keywords: EGFP, DsRed2 fluorescent protein , HuH-7 cell, HBV, intracellular localization

  3. Beta-thalassemia

    Directory of Open Access Journals (Sweden)

    Origa Raffaella

    2010-05-01

    Full Text Available Abstract Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands, dilated myocardiopathy, liver fibrosis and cirrhosis. Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes, gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely

  4. Beta-thalassemia.

    Science.gov (United States)

    Galanello, Renzo; Origa, Raffaella

    2010-05-21

    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  5. Beta-thalassemia

    Science.gov (United States)

    2010-01-01

    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  6. Realized Beta GARCH

    DEFF Research Database (Denmark)

    Hansen, Peter Reinhard; Lunde, Asger; Voev, Valeri Radkov

    2014-01-01

    We introduce a multivariate generalized autoregressive conditional heteroskedasticity (GARCH) model that incorporates realized measures of variances and covariances. Realized measures extract information about the current levels of volatilities and correlations from high-frequency data, which...... is particularly useful for modeling financial returns during periods of rapid changes in the underlying covariance structure. When applied to market returns in conjunction with returns on an individual asset, the model yields a dynamic model specification of the conditional regression coefficient that is known...... as the beta. We apply the model to a large set of assets and find the conditional betas to be far more variable than usually found with rolling-window regressions based exclusively on daily returns. In the empirical part of the paper, we examine the cross-sectional as well as the time variation...

  7. Beta and muon decays

    Energy Technology Data Exchange (ETDEWEB)

    Galindo, A.; Pascual, P.

    1967-07-01

    These notes represent a series of lectures delivered by the authors in the Junta de Energia Nuclear, during the Spring term of 1965. They were devoted to graduate students interested in the Theory of Elementary Particles. Special emphasis was focussed into the computational problems. Chapter I is a review of basic principles (Dirac equation, transition probabilities, final state interactions.) which will be needed later. In Chapter II the four-fermion punctual Interaction is discussed, Chapter III is devoted to the study of beta-decay; the main emphasis is given to the deduction of the formulae corresponding to electron-antineutrino correlation, electron energy spectrum, lifetimes, asymmetry of electrons emitted from polarized nuclei, electron and neutrino polarization and time reversal invariance in beta decay. In Chapter IV we deal with the decay of polarized muons with radiative corrections. Chapter V is devoted to an introduction to C.V.C. theory. (Author)

  8. Magic Baseline Beta Beam

    CERN Document Server

    Agarwalla, Sanjib Kumar; Raychaudhuri, Amitava

    2007-01-01

    We study the physics reach of an experiment where neutrinos produced in a beta-beam facility at CERN are observed in a large magnetized iron calorimeter (ICAL) at the India-based Neutrino Observatory (INO). The CERN-INO distance is close to the so-called "magic" baseline which helps evade some of the parameter degeneracies and allows for a better measurement of the neutrino mass hierarchy and $\\theta_{13}$.

  9. Coroutine Sequencing in BETA

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger;

    In object-oriented programming, a program execution is viewed as a physical model of some real or imaginary part of the world. A language supporting object-oriented programming must therefore contain comprehensive facilities for modeling phenomena and concepts form the application domain. Many ap...... applications in the real world consist of objects carrying out sequential processes. Coroutines may be used for modeling objects that alternate between a number of sequential processes. The authors describe coroutines in BETA...

  10. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis

    2008-01-01

    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  11. Mouse monocyte/macrophage cell line J774A.1 migration induced by the activation of CB1 depends on HuR%激活大麻素受体1诱导的单核巨噬细胞J774A.1的迁移依赖RNA结合蛋白HuR

    Institute of Scientific and Technical Information of China (English)

    赵中新; 常娜; 盖菁菁; 田蕾; 李丽英

    2016-01-01

    目的 研究大麻素受体1(cannabinoid receptor 1,CB1)在单核巨噬细胞迁移中的重要作用以及RNA结合蛋白人抗原R (human antigen R,HuR)参与其中的可能机制.方法 选用单核巨噬细胞系J774A.1,应用琼脂糖凝胶电泳和免疫荧光染色技术鉴定J774A.1中CB1以及HuR的表达;ACEA和AM281分别为CB1的药理学激动剂和拮抗剂,应用Boyden chamber法检测ACEA和AM281对J774A.1迁移活性的影响.HuR的基因干扰用于确定激活CB1诱导的J774A.1迁移功能是否依赖HuR;胞质蛋白的分离用于探究激活CB1是否能引起J774A.1胞质中HuR的富集;RT-qPCR和Western blotting法检测CB1和HuR mRNA和蛋白质的变化情况.结果 该研究证明J774A.1在基因和蛋白质水平上均表达CB1和HuR;激活CB1能够促进J774A.1的迁移(P<0.01)并且能够被其药理学拮抗剂AM281所抑制;激活CB1诱导的J774A.1的迁移依赖HuR;激活CB1促进了J774A.1胞质中HuR的富集进一步影响了CB1的表达,由此HuR参与了激活CB1诱导的J774A.1的迁移.结论 激活CB1能够诱导单核巨噬细胞系J774A.1的迁移,且此过程依赖RNA结合蛋白HuR.

  12. LHCb: $2\\beta_s$ measurement at LHCb

    CERN Multimedia

    Conti, G

    2009-01-01

    A measurement of $2\\beta_s$, the phase of the $B_s-\\bar{B_s}$ oscillation amplitude with respect to that of the ${\\rm b} \\rightarrow {\\rm c^{+}}{\\rm W^{-}}$ tree decay amplitude, is one of the key goals of the LHCb experiment with first data. In the Standard Model (SM), $2\\beta_s$ is predicted to be $0.0360^{+0.0020}_{-0.0016} \\rm rad$. The current constraints from the Tevatron are: $2\\beta_{s}\\in[0.32 ; 2.82]$ at 68$\\%$CL from the CDF experiment and $2\\beta_{s}=0.57^{+0.24}_{-0.30}$ from the D$\\oslash$ experiment. Although the statistical uncertainties are large, these results hint at the possible contribution of New Physics in the $B_s-\\bar{B_s}$ box diagram. After one year of data taking at LHCb at an average luminosity of $\\mathcal{L}\\sim2\\cdot10^{32}\\rm cm^{-2} \\rm s^{-1}$ (integrated luminosity $\\mathcal{L}_{\\rm int}\\sim 2 \\rm fb^{-1}$), the expected statistical uncertainty on the measurement is $\\sigma(2\\beta_s)\\simeq 0.03$. This uncertainty is similar to the $2\\beta_s$ value predicted by the SM.

  13. Human-derived IgG level as an indicator for EBV-associated lymphoma model in Hu-PBL/SCID chimeras.

    Science.gov (United States)

    Tang, Yunlian; He, Rongfang; Zhang, Yang; Liu, Fang; Cheng, Ailan; Wu, Yimou; Gan, Runliang

    2011-05-09

    Epstein-Barr virus (EBV) has a close association with various types of human lymphomas. Animal models are essential to elucidate the pathogenesis of human EBV-associated lymphomas. The aim of the present study is to evaluate the association between human IgG concentration and EBV-associated lymphoma development in huPBL/SCID mice. Human peripheral blood lymphocytes (hu-PBL) from EBV-seropositive donors were inoculated intraperitoneally into SCID mouse. Immunohistochemical staining was used to examine differentiated antigens of tumor cells. EBV infection of the induced tumors was detected by in situ hybridization. IgG concentrations in the serums of 12 SCID mice were measured by unidirectional immunodiffusion assay. 21 out of 29 mice developed tumors in their body. Immunohistochemical staining showed that all induced tumors were LCA (leukocyte common antigen) positive, B-cell markers (CD20, CD79a) positive, and T-cell markers (both CD3 and CD45RO) negative. The tumors can be diagnosed as human B-cell lymphomas by these morphological and immunohistochemical features. In situ hybridization exhibited resultant tumor cells had EBV encoded small RNA-1 (EBER-1). Human-derived IgG could be found in the serum from SCID mice on the 15th day following hu-PBL transplantation, and IgG levels increased with the tumor development in 6 hu-PBL/SCID chimeras. Intraperitoneal transfer of hu-PBLs from EBV+ donors to SCID mice leads to high human IgG levels in mouse serum and B cell lymphomas. Our findings suggest that increasing levels of human-derived IgG in peripheral blood from hu-PBL/SCID mice could be used to monitor EBV-related human B-cell lymphoma development in experimental animals.

  14. Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells.

    Science.gov (United States)

    Li, Ruilin; Hu, Siyi; Chang, Yan; Zhang, Zhihui; Zha, Zhao; Huang, Hui; Shen, Guodong; Liu, Jing; Song, Lihua; Wei, Wei

    2016-04-15

    Human epidermal growth factor receptor 2 (HER2) is one of the most studied tumor-associated antigens for cancer immunotherapy. An engineered anti-HER-2 chimeric A21 antibody (chA21) is a chimeric antibody targeted to subdomain I of the HER2 extracellular domain. Here, we report the anti-tumor activity of the novel engineered monoclonal antibody humanized chA21 (HuA21) that targets HER2 on the basis of chA21, and we describe the underlying mechanisms. Our results reveal that HuA21 markedly inhibits the proliferation and migration of HER2-overexpressing breast cancer cells and causes enhanced antibody-dependent cell-mediated cytotoxicity potency against HER2-overexpressing tumor cells. In particular, HuA21, but not trastuzumab (Tra), markedly suppresses growth and enhances the internalization of the antibody in Tra-resistant BT-474 breast cancer cells. These characteristics are highly associated with the intrinsic ability of HuA21 to down-regulate HER2 activation and inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) signaling pathways. Furthermore, the combination of HuA21 with Tra synergistically enhances the anti-tumor effects in vitro and in vivo and inhibits HER2 activation and the ERK1/2 and Akt signaling pathways. Altogether, our results suggest that HuA21 may represent a unique anti-HER2 antibody with potential as a therapeutic candidate alone or in combination with other anti-HER2 reagents in cancer therapy.

  15. Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruilin Li

    2016-04-01

    Full Text Available Human epidermal growth factor receptor 2 (HER2 is one of the most studied tumor-associated antigens for cancer immunotherapy. An engineered anti-HER-2 chimeric A21 antibody (chA21 is a chimeric antibody targeted to subdomain I of the HER2 extracellular domain. Here, we report the anti-tumor activity of the novel engineered monoclonal antibody humanized chA21 (HuA21 that targets HER2 on the basis of chA21, and we describe the underlying mechanisms. Our results reveal that HuA21 markedly inhibits the proliferation and migration of HER2-overexpressing breast cancer cells and causes enhanced antibody-dependent cell-mediated cytotoxicity potency against HER2-overexpressing tumor cells. In particular, HuA21, but not trastuzumab (Tra, markedly suppresses growth and enhances the internalization of the antibody in Tra-resistant BT-474 breast cancer cells. These characteristics are highly associated with the intrinsic ability of HuA21 to down-regulate HER2 activation and inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2 and protein kinase B (Akt signaling pathways. Furthermore, the combination of HuA21 with Tra synergistically enhances the anti-tumor effects in vitro and in vivo and inhibits HER2 activation and the ERK1/2 and Akt signaling pathways. Altogether, our results suggest that HuA21 may represent a unique anti-HER2 antibody with potential as a therapeutic candidate alone or in combination with other anti-HER2 reagents in cancer therapy.

  16. HIV-1 Pathogenesis and Therapeutic Intervention in the SCID-hu Thy/Liv Mouse: A Model for Primary HIV-1 Infection in the Human Thymus

    OpenAIRE

    Su, Lishan

    1997-01-01

    The SCID-hu Thy/Liv mouse is a model for the analysis of human thymopoiesis. It has been constructed by engrafting fragments of human fetal liver and thymus into the immunodeficient C.B-17 scid/scid (SCID) mouse. The resulting ‘Thy/Liv’ organ promotes long-term differentiation of human T cells. Given the apparently normal physiology of the SCID-hu Thy/Liv organ, it has been used to explore the pathophysiologic mechanisms of HIV-1 infection in vivo, and to test therapeutic modalities such as a...

  17. HIV-1 infection and CD4 T cell depletion in the humanized Rag2-/-γc-/- (RAG-hu mouse model

    Directory of Open Access Journals (Sweden)

    Connick Elizabeth

    2006-11-01

    Full Text Available Abstract Background The currently well-established humanized mouse models, namely the hu-PBL-SCID and SCID-hu systems played an important role in HIV pathogenesis studies. However, despite many notable successes, several limitations still exist. They lack multi-lineage human hematopoiesis and a functional human immune system. These models primarily reflect an acute HIV infection with rapid CD4 T cell loss thus limiting pathogenesis studies to a short-term period. The new humanized Rag2-/-γc-/- mouse model (RAG-hu created by intrahepatic injection of CD34 hematopoietic stem cells sustains long-term multi-lineage human hematopoiesis and is capable of mounting immune responses. Thus, this model shows considerable promise to study long-term in vivo HIV infection and pathogenesis. Results Here we demonstrate that RAG-hu mice produce human cell types permissive to HIV-1 infection and that they can be productively infected by HIV-1 ex vivo. To assess the capacity of these mice to sustain long-term infection in vivo, they were infected by either X4-tropic or R5-tropic HIV-1. Viral infection was assessed by PCR, co-culture, and in situ hybridization. Our results show that both X4 and R5 viruses are capable of infecting RAG-hu mice and that viremia lasts for at least 30 weeks. Moreover, HIV-1 infection leads to CD4 T cell depletion in peripheral blood and thymus, thus mimicking key aspects of HIV-1 pathogenesis. Additionally, a chimeric HIV-1 NL4-3 virus expressing a GFP reporter, although capable of causing viremia, failed to show CD4 T cell depletion possibly due to attenuation. Conclusion The humanized RAG-hu mouse model, characterized by its capacity for sustained multi-lineage human hematopoiesis and immune response, can support productive HIV-1 infection. Both T cell and macrophage tropic HIV-1 strains can cause persistent infection of RAG-hu mice resulting in CD4 T cell loss. Prolonged viremia in the context of CD4 T cell depletion seen in this

  18. Inhibition of cytosolic Phospholipase A2 prevents prion peptide-induced neuronal damage and co-localisation with Beta III Tubulin

    Directory of Open Access Journals (Sweden)

    Last Victoria

    2012-08-01

    Full Text Available Abstract Background Activation of phospholipase A2 (PLA2 and the subsequent metabolism of arachidonic acid (AA to prostaglandins have been shown to play an important role in neuronal death in neurodegenerative disease. Here we report the effects of the prion peptide fragment HuPrP106-126 on the PLA2 cascade in primary cortical neurons and translocation of cPLA2 to neurites. Results Exposure of primary cortical neurons to HuPrP106-126 increased the levels of phosphorylated cPLA2 and caused phosphorylated cPLA2 to relocate from the cell body to the cellular neurite in a PrP-dependent manner, a previously unreported observation. HuPrP106-126 also induced significant AA release, an indicator of cPLA2 activation; this preceded synapse damage and subsequent cellular death. The novel translocation of p-cPLA2 postulated the potential for exposure to HuPrP106-126 to result in a re-arrangement of the cellular cytoskeleton. However p-cPLA2 did not colocalise significantly with F-actin, intermediate filaments, or microtubule-associated proteins. Conversely, p-cPLA2 did significantly colocalise with the cytoskeletal protein beta III tubulin. Pre-treatment with the PLA2 inhibitor, palmitoyl trifluoromethyl ketone (PACOCF3 reduced cPLA2 activation, AA release and damage to the neuronal synapse. Furthermore, PACOCF3 reduced expression of p-cPLA2 in neurites and inhibited colocalisation with beta III tubulin, resulting in protection against PrP-induced cell death. Conclusions Collectively, these findings suggest that cPLA2 plays a vital role in the action of HuPrP106-126 and that the colocalisation of p-cPLA2 with beta III tubulin could be central to the progress of neurodegeneration caused by prion peptides. Further work is needed to define exactly how PLA2 inhibitors protect neurons from peptide-induced toxicity and how this relates to intracellular structural changes occurring in neurodegeneration.

  19. Commentary of Hu Yihong' s Animation Theory%胡依红动画理论述评

    Institute of Scientific and Technical Information of China (English)

    屈立丰

    2012-01-01

    本文对上海美影厂女动画家胡依红的动画理论思想与动画创作实践做了简单梳理,细致分析了其“动画创新论”和“动画本体论”的理论来源和框架构成,对其动画理论思想和动画实践之间的互动关系进行了初步讨论。%This paper gave a brief introduction of the animation theory and creations by Hu Yihong, a female animator from Shanghai Animation Film Studio, made a detailed analysis of the sources and framework of her "ani- mation innovation theory" and "animation ontology", and finally presented a tentative discussion about the interac- tion between her ideology of animation theory and animation creation.

  20. A New Arthropod, Guangweicaris Luo, Fu et Hu gen. nov.from the Early Cambrian Guanshan Fauna, Kunming, China

    Institute of Scientific and Technical Information of China (English)

    LUO Huilin; FU Xiaoping; HU Shixue; LI Yong; HOU Shuguang; YOU Ting; PANG Jiyuan; LIU Qi

    2007-01-01

    The Guanshan Fauna is a soft-bodied fauna dominated by arthropods (including trilobites,trilobitoides, Tuzoia, Isoxys, and bradorids) in association with priapulids, brachiopods,anomalocaridids, vetulicoliids, sponges, chancellorids, and echinoderms. This paper reports and describes a new arthropod from the yellowish green mudstone at the lower part of the Wulongqing Formation, Canglangpuan Stage, Lower Cambrian in Kunming, Yunnan, China. The stratigraphic and geographic distribution, classification, fossil preservation, life style of this new arthropod and comparisons with other fossil arthropods are also discussed in details. The discovery and research of the non-mineralized arthropod, Guangweicaris Luo, Fu et Hu gen. nov. from the Guanshan Fauna adds new members to the taxonomic list and provides new information to the evolution of early arthropods.Furthermore, this study would shed new light into the "Cambrian Explosion" and the evolution of early life.

  1. Chinese President Hu Jintao and Austrian President Heinz Fischer Send Messages of Congratulations on 2006 China Year in Austria

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    <正>Editor’s note: In January 2004, Benita Ferrero-Waldner, Austrian foreign minister at the time, announced that China Year would be held in Austria in 2006 to mark the 35th anniversary of the establishment of diplomatic relations between Austria and China and to promote understanding of China and bilateral cooperation. The two sides decided after consultation that the activities for the China Year would be jointly organized by the Austria-China Friendship Association and the Chinese People’s Association for Friendship with Foreign Countries. The governments of the two countries attach great importance to the holding of the China Year. Chinese President Hu Jintao, Austrian President Heinz Fischer and Federal Chancellor Wolfgang Schussel and other state leaders

  2. Effects of vesicular-arbuscular mycorrhizae on the drought resistance of wild jujube (Zizyphs spinosus Hu) seedlings

    Institute of Scientific and Technical Information of China (English)

    LU Jinying; LIU Min; MAO Yongmin; SHEN Lianying

    2007-01-01

    The current study explored the effects of vesicular-arbuscular mycorrhizae (VAM) inoculation on the growth and water requirement of pot-grown wild jujube (Zizyphs spinosus Hu).Three water regimes (20%,40% and 60% of soil water content) were conducted.The VAM inoculation could significantly increase plant growth (including plant height,leaf area,and fresh and dry mass),enhance relative leaf water content,photosynthetic rates,transpiration rates and stomatal conductance,and improve plant drought tolerance.The water consumption of the mycorrhizal plants producing 1 g of dry matter was 18.7%-26.6% lower than the consumption of non-mycorrhizal plants grown under the same soil water content conditions.

  3. Simultaneous beta and gamma spectroscopy

    Science.gov (United States)

    Farsoni, Abdollah T.; Hamby, David M.

    2010-03-23

    A phoswich radiation detector for simultaneous spectroscopy of beta rays and gamma rays includes three scintillators with different decay time characteristics. Two of the three scintillators are used for beta detection and the third scintillator is used for gamma detection. A pulse induced by an interaction of radiation with the detector is digitally analyzed to classify the type of event as beta, gamma, or unknown. A pulse is classified as a beta event if the pulse originated from just the first scintillator alone or from just the first and the second scintillator. A pulse from just the third scintillator is recorded as gamma event. Other pulses are rejected as unknown events.

  4. A computational screen for site selective A-to-I editing detects novel sites in neuron specific Hu proteins

    Directory of Open Access Journals (Sweden)

    Furey Terrence S

    2010-01-01

    Full Text Available Abstract Background Several bioinformatic approaches have previously been used to find novel sites of ADAR mediated A-to-I RNA editing in human. These studies have discovered thousands of genes that are hyper-edited in their non-coding intronic regions, especially in alu retrotransposable elements, but very few substrates that are site-selectively edited in coding regions. Known RNA edited substrates suggest, however, that site selective A-to-I editing is particularly important for normal brain development in mammals. Results We have compiled a screen that enables the identification of new sites of site-selective editing, primarily in coding sequences. To avoid hyper-edited repeat regions, we applied our screen to the alu-free mouse genome. Focusing on the mouse also facilitated better experimental verification. To identify candidate sites of RNA editing, we first performed an explorative screen based on RNA structure and genomic sequence conservation. We further evaluated the results of the explorative screen by determining which transcripts were enriched for A-G mismatches between the genomic template and the expressed sequence since the editing product, inosine (I, is read as guanosine (G by the translational machinery. For expressed sequences, we only considered coding regions to focus entirely on re-coding events. Lastly, we refined the results from the explorative screen using a novel scoring scheme based on characteristics for known A-to-I edited sites. The extent of editing in the final candidate genes was verified using total RNA from mouse brain and 454 sequencing. Conclusions Using this method, we identified and confirmed efficient editing at one site in the Gabra3 gene. Editing was also verified at several other novel sites within candidates predicted to be edited. Five of these sites are situated in genes coding for the neuron-specific RNA binding proteins HuB and HuD.

  5. Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

    Directory of Open Access Journals (Sweden)

    Cheryl A Stoddart

    Full Text Available BACKGROUND: The SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals. METHODOLOGY/PRINCIPAL FINDINGS: Endpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3 as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions. CONCLUSION: Given the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans.

  6. Dieta de roedores sigmodontinos (Cricetidae en los bosques montanos tropicales de Huánuco, Perú

    Directory of Open Access Journals (Sweden)

    Maggie C. Noblecilla

    2013-06-01

    Full Text Available Se analizó el contenido estomacal de cinco especies de roedores sigmodontinos: Akodon orophilus, Microry-zomys altissimus, M. minutus, Thomasomys notatus yT. kalinowskii, procedentes de los bosques montanos de Huánuco, Perú (2564 - 3850 m de altitud. Concluimos que A. orophiluses insectívora por haber presentado un alto volumen de artrópodos (adultos y larvas en el contenido estomacal (90,1%; mientras que T. notatusy T. kalinowskiison principalmente herbívoras por el alto volumen de materia vegetal, 89% y 67,75% respectiva-mente; y que M. altissimusy M. minutusson omnívoras por presentar volúmenes similares tanto para vegetales como para artrópodos. Thomasomys kalinowskiies considerada generalista por la mayor amplitud de nicho (4,61, mientras A. orophiluses considerada especialista por el menor valor (1,70. Akodon orophilusmostró una preferencia por el consumo de artrópodos adultos al tener un bajo coeficiente de variación (CV= 20% y también un significativo aumento en el consumo de larvas de artrópodos en la época húmeda, siendo la única especie con variación estacional en la dieta. Por otro lado, la sobreposición de nicho fue menor a 0,75 en el 80% de los pares de especies comparados, indicando una baja similitud en la dieta. La mayor similitud en la dieta se observó entre M. altissimus- T. notatus(0,822 y M. minutus - T. kalinowskii(0,816. Se concluye que estos roedores sigmodontinos, simpátricos en los bosques montanos de Huánuco, exhiben dietas disímiles, probablemente como una estrategia para evitar o aminorar la competencia interespecífica.

  7. Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

    Science.gov (United States)

    Stoddart, Cheryl A; Bales, Cheryl A; Bare, Jennifer C; Chkhenkeli, George; Galkina, Sofiya A; Kinkade, April N; Moreno, Mary E; Rivera, José M; Ronquillo, Rollie E; Sloan, Barbara; Black, Paul L

    2007-08-01

    The SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals. Endpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions. Given the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans.

  8. Beta section Beta: biogeographical patterns of variation and taxonomy.

    NARCIS (Netherlands)

    Letschert, J.P.W.

    1993-01-01

    In Chapter 1 an account is given of the historical subdivision of the genus Beta and its sections, and the relations of the sections are discussed. Emphasis is given to the taxonomic treatment of wild section Beta by various authors. The Linnaean names B. vulgaris L. and B. maritima L. are lectotypi

  9. Infección por Gnathostoma (Spirurida: Gnathostomatidae en Hoplias microlepis: prevalencia, correlación con la talla del pez, huéspedes e implicaciones para salud pública en Ecuador

    Directory of Open Access Journals (Sweden)

    Juan José Alava

    2009-12-01

    Conclusiones. La gnathostomiasis sigue siendo prevalente en la zona costera de Ecuador y el agente patógeno es aún encontrado en el huésped intermediario. Diversos mamíferos neotropicales estarían actuando como huésped reservorio definitivo en el ciclo biológico de Gnathostoma en Ecuador.

  10. Cyclic modular beta-sheets.

    Science.gov (United States)

    Woods, R Jeremy; Brower, Justin O; Castellanos, Elena; Hashemzadeh, Mehrnoosh; Khakshoor, Omid; Russu, Wade A; Nowick, James S

    2007-03-07

    The development of peptide beta-hairpins is problematic, because folding depends on the amino acid sequence and changes to the sequence can significantly decrease folding. Robust beta-hairpins that can tolerate such changes are attractive tools for studying interactions involving protein beta-sheets and developing inhibitors of these interactions. This paper introduces a new class of peptide models of protein beta-sheets that addresses the problem of separating folding from the sequence. These model beta-sheets are macrocyclic peptides that fold in water to present a pentapeptide beta-strand along one edge; the other edge contains the tripeptide beta-strand mimic Hao [JACS 2000, 122, 7654] and two additional amino acids. The pentapeptide and Hao-containing peptide strands are connected by two delta-linked ornithine (deltaOrn) turns [JACS 2003, 125, 876]. Each deltaOrn turn contains a free alpha-amino group that permits the linking of individual modules to form divalent beta-sheets. These "cyclic modular beta-sheets" are synthesized by standard solid-phase peptide synthesis of a linear precursor followed by solution-phase cyclization. Eight cyclic modular beta-sheets 1a-1h containing sequences based on beta-amyloid and macrophage inflammatory protein 2 were synthesized and characterized by 1H NMR. Linked cyclic modular beta-sheet 2, which contains two modules of 1b, was also synthesized and characterized. 1H NMR studies show downfield alpha-proton chemical shifts, deltaOrn delta-proton magnetic anisotropy, and NOE cross-peaks that establish all compounds but 1c and 1g to be moderately or well folded into a conformation that resembles a beta-sheet. Pulsed-field gradient NMR diffusion experiments show little or no self-association at low (

  11. HuCNS-SC Human NSCs Fail to Differentiate, Form Ectopic Clusters, and Provide No Cognitive Benefits in a Transgenic Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Samuel E. Marsh

    2017-02-01

    Full Text Available Transplantation of neural stem cells (NSCs can improve cognition in animal models of Alzheimer's disease (AD. However, AD is a protracted disorder, and prior studies have examined only short-term effects. We therefore used an immune-deficient model of AD (Rag-5xfAD mice to examine long-term transplantation of human NSCs (StemCells Inc.; HuCNS-SCs. Five months after transplantation, HuCNS-SCs had engrafted and migrated throughout the hippocampus and exhibited no differences in survival or migration in response to β-amyloid pathology. Despite robust engraftment, HuCNS-SCs failed to terminally differentiate and over a quarter of the animals exhibited ectopic human cell clusters within the lateral ventricle. Unlike prior short-term experiments with research-grade HuCNS-SCs, we also found no evidence of improved cognition, no changes in brain-derived neurotrophic factor, and no increase in synaptic density. These data, while disappointing, reinforce the notion that individual human NSC lines need to be carefully assessed for efficacy and safety in appropriate long-term models.

  12. Short communication. Employment of molecular markers to develop tetraploid “supermale” asparagus from andromonoecious plants of the landrace ‘Morado de Huétor’

    Directory of Open Access Journals (Sweden)

    Jose J. Regalado

    2014-10-01

    Full Text Available The aim of this work was the development of new “supermale” genotypes retaining the highest genetic diversity possible of the tetraploid asparagus landrace ‘Morado de Huétor’. The elite andromonoecious male HT664 of the ‘Morado de Huétor’ asparagus landrace and the andromonoecious hybrid male HC027, obtained by crossing between this landrace and a commercial cultivar of Asparagus officinalis, were selected for self-pollination to produce possible “supermales” with genes of ‘Morado de Huétor’ (SMHT. To confirm the hybrid nature of HC027, we characterized this genotype with EST-SSR (Expressed Sequence Tag-derived Simple Sequence Repeats markers. We also adopted the sex-linked marker Asp1-T7 for sex determination in ‘Morado de Huétor’ and the resulting hybrids between this landrace and other commercial cultivars. Asp1-T7 marker was used for the selection and genotyping of SMHT. “All-male” cultivars with a different genetic background can be generated by crossing females with these new “supermale” genotypes, and the agronomical traits of these new cultivars would be very different from the “all-male” cultivars currently available in the market, making them extremely interesting for asparagus breeding programs.

  13. On the Theoretical Character of Hu Jintao's Youth Viewpoint%胡锦涛同志青年观的理论品格思想研究

    Institute of Scientific and Technical Information of China (English)

    邹洪伟

    2009-01-01

    Mr. Hu Jintao has delivered lots pithy opinions on the youth work and the healthy growth of Chi-nese youths, with which Mr. Hu has developed the Marxist youth theory to its new level. This paper makes a brief illustration of the guidelines, the kernel, the goal and the historical mission of the youth work and the healthy growth of Chinese youths mentioned by Mr. Hu, trying to discuss the theoretical character of Mr. Hu Jintao's youth viewpoint.%胡锦涛同志对中国青年成长成才和青年工作提出了诸多精辟的观点,开拓了马克思主义青年观的新境界.本文就其中青年成长成才和青年工作的指导思想、核心、努力目标和历史使命等问题进行了简要阐述,充分展现胡锦涛同志青年观的理论品格.

  14. Purchase of Microwave Reactors for Implementation of Small-scale Microwave-accelerated Organic Chemistry Laboratory Program in Undergraduate Curriculum and Synthetic Chemistry Research at HU

    Science.gov (United States)

    2015-05-16

    Microwave-accelerated Organic Chemistry Laboratory Program in Undergraduate Curriculum and Synthetic Chemistry Research at HU The views, opinions and/or...Research Triangle Park, NC 27709-2211 Microwave laboratory facility, Undergraduate organic chemistry laboratory, Implementation/Development of...Purchase of Microwave Reactors for Implementation of Small-scale Microwave-accelerated Organic Chemistry Laboratory Program in Undergraduate

  15. HuD promotes BDNF expression in brain neurons via selective stabilization of the BDNF long 3'UTR mRNA.

    Directory of Open Access Journals (Sweden)

    Megan Allen

    Full Text Available Complex regulation of brain-derived neurotrophic factor (BDNF governs its intricate functions in brain development and neuronal plasticity. Besides tight transcriptional control from multiple distinct promoters, alternative 3'end processing of the BDNF transcripts generates either a long or a short 3'untranslated region (3'UTR. Previous reports indicate that distinct RNA sequence in the BDNF 3'UTRs differentially regulates BDNF production in the brain to accommodate neuronal activity changes, conceivably through differential interactions with undefined trans-acting factors that regulate stability and translation of these BDNF mRNA isoforms. In this study, we report that the neuronal RNA-binding protein (RBP HuD interacts with a highly conserved AU-rich element (ARE specifically located in the BDNF long 3'UTR. Such interaction is necessary and sufficient for selective stabilization of mRNAs that contain the BDNF long 3'UTR in vitro and in vivo. Moreover, in a HuD transgenic mouse model, the BDNF long 3'UTR mRNA is increased in the hippocampal dentate granule cells (DGCs, leading to elevated expression of BDNF protein that is transported and stored in the mossy fiber (MF terminals. Our results identify HuD as the first trans-acting factor that enhances BDNF expression specifically through the long 3'UTR and a novel mechanism that regulates BDNF protein production in selected neuronal populations by HuD abundance.

  16. The problem of the ethical root of truth (A tribute to Antonio Rodríguez Huéscar on his birth centenary

    Directory of Open Access Journals (Sweden)

    Juan Padilla

    2013-12-01

    Full Text Available This paper deals with the meaning of truth as «coincidence of man with himself» accordingto Ortega y Gasset and his disciple rodríguez huéscar. What the concept does not mean and which implications it has are also explained.

  17. PARP1 promotes gene expression at the post-transcriptional level by modulating the RNA-binding protein HuR

    Science.gov (United States)

    Ke, Yueshuang; Han, Yanlong; Guo, Xiaolan; Wen, Jitao; Wang, Ke; Jiang, Xue; Tian, Xue; Ba, Xueqing; Boldogh, Istvan; Zeng, Xianlu

    2017-01-01

    Poly(ADP-ribosyl)ation (PARylation) is mainly catalysed by poly-ADP-ribose polymerase 1 (PARP1), whose role in gene transcription modulation has been well established. Here we show that, in response to LPS exposure, PARP1 interacts with the adenylateuridylate-rich element-binding protein embryonic lethal abnormal vision-like 1 (Elavl1)/human antigen R (HuR), resulting in its PARylation, primarily at site D226. PARP inhibition and the D226 mutation impair HuR's PARylation, nucleocytoplasmic shuttling and mRNA binding. Increases in mRNA level or stability of pro-inflammatory cytokines/chemokines are abolished by PARP1 ablation or inhibition, or blocked in D226A HuR-expressing cells. The present study demonstrates a mechanism to regulate gene expression at the post-transcriptional level, and suggests that blocking the interaction of PARP1 with HuR could be a strategy to treat inflammation-related diseases that involve increased mRNA stability. PMID:28272405

  18. Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment

    DEFF Research Database (Denmark)

    Johnsen, Hanne; Geisler, C; Juvonen, E

    2011-01-01

    SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant me...

  19. Investigation of the HU-density conversion method and comparison of dose distribution for dose calculation on MV cone beam CT images

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Joo; Lee, Seu Ran; Suh, Tae Suk [Dept. of Biomedical Engineering, The Catholic University of Korea, Bucheon (Korea, Republic of)

    2011-11-15

    Modern radiation therapy techniques, such as Image-guided radiation therapy (IGRT), Adaptive radiation therapy (ART) has become a routine clinical practice on linear accelerators for the increase the tumor dose conformity and improvement of normal tissue sparing at the same time. For these highly developed techniques, megavoltage cone beam computed tomography (MVCBCT) system produce volumetric images at just one rotation of the x-ray beam source and detector on the bottom of conventional linear accelerator for real-time application of patient condition into treatment planning. MV CBCT image scan be directly registered to a reference CT data set which is usually kilo-voltage fan-beam computed tomography (kVFBCT) on treatment planning system and the registered image scan be used to adjust patient set-up error. However, to use MV CBCT images in radiotherapy, reliable electron density (ED) distribution are required. Patients scattering, beam hardening and softening effect caused by different energy application between kVCT, MV CBCT can cause cupping artifacts in MV CBCT images and distortion of Houns field Unit (HU) to ED conversion. The goal of this study, for reliable application of MV CBCT images into dose calculation, MV CBCT images was modified to correct distortion of HU to ED using the relationship of HU and ED from kV FBCT and MV CBCT images. The HU-density conversion was performed on MV CBCT image set using Dose difference map was showing in Figure 1. Finally, percentage differences above 3% were reduced depending on applying density calibration method. As a result, total error co uld be reduced to under 3%. The present study demonstrates that dose calculation accuracy using MV CBCT image set can be improved my applying HU-density conversion method. The dose calculation and comparison of dose distribution from MV CBCT image set with/without HU-density conversion method was performed. An advantage of this study compared to other approaches is that HU

  20. The best-beta CAPM

    NARCIS (Netherlands)

    Zou, L.

    2006-01-01

    The issue of 'best-beta' arises as soon as potential errors in the Sharpe-Lintner-Black capital asset pricing model (CAPM) are acknowledged. By incorporating a target variable into the investor preferences, this study derives a best-beta CAPM (BCAPM) that maintains the CAPM's theoretical appeal and

  1. Beta decay of Cu-56

    NARCIS (Netherlands)

    Borcea, R; Aysto, J; Caurier, E; Dendooven, P; Doring, J; Gierlik, M; Gorska, M; Grawe, H; Hellstrom, M; Janas, Z; Jokinen, A; Karny, M; Kirchner, R; La Commara, M; Langanke, K; Martinez-Pinedo, G; Mayet, P; Nieminen, A; Nowacki, F; Penttila, H; Plochocki, A; Rejmund, M; Roeckl, E; Schlegel, C; Schmidt, K; Schwengner, R; Sawicka, M

    2001-01-01

    The proton-rich isotope Cu-56 was produced at the GSI On-Line Mass Separator by means of the Si-28(S-32, p3n) fusion-evaporation reaction. Its beta -decay properties were studied by detecting beta -delayed gamma rays and protons. A half-Life of 93 +/- 3 ms was determined for Cu-56. Compared to the p

  2. Integration of BETA with Eclipse

    DEFF Research Database (Denmark)

    Andersen, Peter; Madsen, Ole Lehrmann; Enevoldsen, Mads Brøgger

    2004-01-01

    This paper presents language interoperability issues appearing in order to implement support for the BETA language in the Java-based Eclipse integrated development environment. One of the challenges is to implement plug-ins in BETA and be able to load them in Eclipse. In order to do this, some form...

  3. Beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    2016-01-01

    Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin and...

  4. Measurements of sin 2 $\\beta$

    CERN Document Server

    Tricomi, A

    2000-01-01

    A review of the most recent measurements of the CP violating parameter sin 2 beta from LEP and CDF is reported. These yield an average value of sin 2 beta =0.91+or-0.35, giving a confidence level that CP violation in the B system has been observed of almost 99%. (10 refs).

  5. Beta-hemolytic streptococcal bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Hans Ulrik; Kolmos, Hans Jørn; Frimodt-Møller, Niels

    2002-01-01

    Bacteremia with beta-hemolytic Streptococci groups A, B, C and G has a mortality rate of approximately 20%. In this study we analyzed the association of various patient risk factors with mortality. Records from 241 patients with beta-hemolytic streptococcal bacteremia were reviewed with particular...

  6. Beta Function and Anomalous Dimensions

    DEFF Research Database (Denmark)

    Pica, Claudio; Sannino, Francesco

    2011-01-01

    We demonstrate that it is possible to determine the coefficients of an all-order beta function linear in the anomalous dimensions using as data the two-loop coefficients together with the first one of the anomalous dimensions which are universal. The beta function allows to determine the anomalou...

  7. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-02-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  8. Beta systems error analysis

    Science.gov (United States)

    1984-01-01

    The atmospheric backscatter coefficient, beta, measured with an airborne CO Laser Doppler Velocimeter (LDV) system operating in a continuous wave, focussed model is discussed. The Single Particle Mode (SPM) algorithm, was developed from concept through analysis of an extensive amount of data obtained with the system on board a NASA aircraft. The SPM algorithm is intended to be employed in situations where one particle at a time appears in the sensitive volume of the LDV. In addition to giving the backscatter coefficient, the SPM algorithm also produces as intermediate results the aerosol density and the aerosol backscatter cross section distribution. A second method, which measures only the atmospheric backscatter coefficient, is called the Volume Mode (VM) and was simultaneously employed. The results of these two methods differed by slightly less than an order of magnitude. The measurement uncertainties or other errors in the results of the two methods are examined.

  9. Detrimental ELAVL-1/HuR-dependent GSK3β mRNA stabilization impairs resolution in acute respiratory distress syndrome

    Science.gov (United States)

    Hoffman, Olivia; Burns, Nana; Vadász, István; Eltzschig, Holger K.; Edwards, Michael G.

    2017-01-01

    A hallmark of acute respiratory distress syndrome (ARDS) is accumulation of protein-rich edema in the distal airspaces and its removal is critical for patient survival. Previous studies have shown a detrimental role of Glycogen Synthase Kinase (GSK) 3β during ARDS via inhibition of alveolar epithelial protein transport. We hypothesized that post-transcriptional regulation of GSK3β could play a functional role in ARDS resolution. To address this hypothesis, we performed an in silico analysis to identify regulatory genes whose expression correlation to GSK3β messenger RNA utilizing two lung cancer cell line array datasets. Among potential regulatory partners of GSK3β, these studies identified the RNA-binding protein ELAVL-1/HuR (Embryonic Lethal, Abnormal Vision, Drosophila-Like) as a central component in a likely GSK3β signaling network. ELAVL-1/HuR is a RNA-binding protein that selectively binds to AU-rich elements of mRNA and enhances its stability thereby increasing target gene expression. Subsequent studies with siRNA suppression of ELAVL-1/HuR demonstrated deceased GSK3β mRNA and protein expression and improved clearance of FITC-albumin in A549 cells. Conversely, stabilization of ELAVL-1/HuR with the proteasome inhibitor MG-132 resulted in induction of GSK3β at mRNA and protein level and attenuated FITC-albumin clearance. Utilizing ventilator-induced lung injury or intra-tracheal installation of hydrochloric acid to induce ARDS in mice, we observed increased mRNA and protein expression of ELAVL-1/HuR and GSK3β. Together, our findings indicate a previously unknown interaction between GSK3β and ELAV-1 during ARDS, and suggest the inhibition of the ELAV-1- GSK3β pathways as a novel ARDS treatment approach. PMID:28196122

  10. The Anti-Inflammatory Effect and Intestinal Barrier Protection of HU210 Differentially Depend on TLR4 Signaling in Dextran Sulfate Sodium-Induced Murine Colitis.

    Science.gov (United States)

    Lin, Sisi; Li, Yongyu; Shen, Li; Zhang, Ruiqin; Yang, Lizhi; Li, Min; Li, Kun; Fichna, Jakub

    2017-02-01

    Ulcerative colitis (UC) is strongly associated with inflammation and intestinal barrier disorder. The nonselective cannabinoid receptor agonist HU210 has been shown to ameliorate inflamed colon in colitis, but its effects on intestinal barrier function and extraintestinal inflammation are unclear. To investigate the effects and the underlying mechanism of HU210 action on the UC in relation to a role of TLR4 and MAP kinase signaling. Wild-type (WT) and TLR4 knockout (Tlr4 (-/-)) mice were exposed to 4% dextran sulfate sodium (DSS) for 7 days. The effects of HU210 on inflammation and intestinal barrier were explored. Upon DSS challenge, mice suffered from bloody stool, colon shortening, intestinal mucosa edema, pro-inflammatory cytokine increase and intestinal barrier destruction with goblet cell depletion, increased intestinal microflora accompanied with elevated plasma lipopolysaccharide, reduced mRNA expression of the intestinal tight junction proteins, and abnormal ratio of CD4(+)/CD8(+) T cells in the intestinal Peyer's patches. Pro-inflammatory cytokines in the plasma and the lung, as well as pulmonary myeloperoxidase activity, indicators of extraintestinal inflammation were increased. Protein expression of p38α and pp38 was up-regulated in the colon of WT mice. Tlr4 (-/-) mice showed milder colitis. HU210 reversed the intestinal barrier changes in both strains of mice, but alleviated inflammation only in WT mice. Our study indicates that in experimental colitis, HU210 displays a protective effect on the intestinal barrier function independently of the TLR4 signaling pathway; however, in the extraintestinal tissues, the anti-inflammatory action seems through affecting TLR4-mediated p38 mitogen-activated protein kinase pathway.

  11. Cytoplasmic expression of HuR may be a valuable diagnostic tool for determining the potential for malignant transformation of oral verrucous borderline lesions

    Science.gov (United States)

    HABIBA, UMMA; KITAMURA, TETSUYA; YANAGAWA-MATSUDA, AYA; HIDA, KYOKO; HIGASHINO, FUMIHIRO; OHIRO, YOICHI; TOTSUKA, YASUNORI; SHINDOH, MASANOBU

    2014-01-01

    Oral verrucous carcinoma (OVC) is a low grade variant of oral squamous cell carcinoma, and oral verrucous hyperplasia (OVH) is a benign lesion without malignant features. However, pathologists are sometimes presented with borderline lesions and are indecisive as to diagnose them as benign or malignant. Thus, these lesions are tentatively termed oral verrucous lesions (OVLs). HuR is an ARE mRNA-binding protein, normally localized in the nucleus but cytoplasmic exportation is frequently observed in cancer cells. The present study aimed to elucidate whether expression of the HuR protein facilitates the diagnosis of true malignant lesions. Clinicopathological features were evaluated, and immunohistochemical analysis for p53, Ki67 and HuR proteins was performed in 48 cases of OVH, OVC and OVL, and the outcomes were correlated using appropriate statistical analysis. The association of these three proteins in relation to malignant transformation was analyzed after a 3-year follow-up of 25 OVL cases. The basal characteristics (age, gender and location) of all cases had no significant association with the types of lesions. Gingiva (39.4%) was the common site for all lesions. Distribution of the examined proteins had a significant association with the lesions. As compared with the OVLs, the number of immunostained-positive cells was significantly higher in the OVCs and lower in the OVH cases. During follow-up, 24% of the OVLs underwent malignant transformation for which high HuR expression and a diffuse staining pattern in the epithelium were observed. Taken together, the high degree of HuR expression with diffuse staining pattern in the epithelium may be an effective diagnostic tool that determines the potential of OVLs for malignant transformation. PMID:24534848

  12. Cytoplasmic expression of HuR may be a valuable diagnostic tool for determining the potential for malignant transformation of oral verrucous borderline lesions.

    Science.gov (United States)

    Habiba, Umma; Kitamura, Tetsuya; Yanagawa-Matsuda, Aya; Hida, Kyoko; Higashino, Fumihiro; Ohiro, Yoichi; Totsuka, Yasunori; Shindoh, Masanobu

    2014-04-01

    Oral verrucous carcinoma (OVC) is a low grade variant of oral squamous cell carcinoma, and oral verrucous hyperplasia (OVH) is a benign lesion without malignant features. However, pathologists are sometimes presented with borderline lesions and are indecisive as to diagnose them as benign or malignant. Thus, these lesions are tentatively termed oral verrucous lesions (OVLs). HuR is an ARE mRNA-binding protein, normally localized in the nucleus but cytoplasmic exportation is frequently observed in cancer cells. The present study aimed to elucidate whether expression of the HuR protein facilitates the diagnosis of true malignant lesions. Clinicopathological features were evaluated, and immunohistochemical analysis for p53, Ki67 and HuR proteins was performed in 48 cases of OVH, OVC and OVL, and the outcomes were correlated using appropriate statistical analysis. The association of these three proteins in relation to malignant transformation was analyzed after a 3-year follow-up of 25 OVL cases. The basal characteristics (age, gender and location) of all cases had no significant association with the types of lesions. Gingiva (39.4%) was the common site for all lesions. Distribution of the examined proteins had a significant association with the lesions. As compared with the OVLs, the number of immunostained-positive cells was significantly higher in the OVCs and lower in the OVH cases. During follow-up, 24% of the OVLs underwent malignant transformation for which high HuR expression and a diffuse staining pattern in the epithelium were observed. Taken together, the high degree of HuR expression with diffuse staining pattern in the epithelium may be an effective diagnostic tool that determines the potential of OVLs for malignant transformation.

  13. Interleukin 1β Regulation of the System xc- Substrate-specific Subunit, xCT, in Primary Mouse Astrocytes Involves the RNA-binding Protein HuR.

    Science.gov (United States)

    Shi, Jingxue; He, Yan; Hewett, Sandra J; Hewett, James A

    2016-01-22

    System xc(-) is a heteromeric amino acid cystine/glutamate antiporter that is constitutively expressed by cells of the CNS, where it functions in the maintenance of intracellular glutathione and extracellular glutamate levels. We recently determined that the cytokine, IL-1β, increases the activity of system xc(-) in CNS astrocytes secondary to an up-regulation of its substrate-specific light chain, xCT, and that this occurs, in part, at the level of transcription. However, an in silico analysis of the murine xCT 3'-UTR identified numerous copies of adenine- and uridine-rich elements, raising the possibility that undefined trans-acting factors governing mRNA stability and translation may also contribute to xCT expression. Here we show that IL-1β increases the level of mRNA encoding xCT in primary cultures of astrocytes isolated from mouse cortex in association with an increase in xCT mRNA half-life. Additionally, IL-1β induces HuR translocation from the nucleus to the cytoplasm. RNA immunoprecipitation analysis reveals that HuR binds directly to the 3'-UTR of xCT in an IL-1β-dependent manner. Knockdown of endogenous HuR protein abrogates the IL-1β-mediated increase in xCT mRNA half-life, whereas overexpression of HuR in unstimulated primary mouse astrocytes doubles the half-life of constitutive xCT mRNA. This latter effect is accompanied by an increase in xCT protein levels, as well as a functional increase in system xc(-) activity. Altogether, these data support a critical role for HuR in mediating the IL-1β-induced stabilization of astrocyte xCT mRNA.

  14. Type-Ⅰcannabinoid receptor mediates down-regulation of CXCR4 in astrocytes by cannabinoid HU210%Ⅰ型大麻素受体介导大麻素HU210对星型胶质细胞CXCR4水平下调

    Institute of Scientific and Technical Information of China (English)

    朱舟; 韩静; 张遐; 徐逸

    2016-01-01

    目的 探寻大麻素抑制中枢神经系统免疫反应的机制,为大麻素临床药物的合理应用提供实验依据.方法 用不同浓度的HU210刺激培养的星形胶质细胞,利用Western blot检测并比较刺激组和未刺激组细胞CXCR4蛋白水平的差异,进而用Ⅰ型大麻素受体(type-1 cannabinoid receptor,CB1R)拮抗剂AM281刺激细胞后,观察HU210对CXCR4表达的影响.结果 Western blot检测结果显示,高浓度HU210能下调星形胶质细胞CXCR4表达,AM28能阻断HU210所致的CXCR4下调.结论 HU210经由CB1R下调CXCR4,这可能是大麻发挥免疫抑制作用的机理之一.

  15. Intestinal lactase as an autologous beta-galactosidase reporter gene for in vivo gene expression studies.

    Science.gov (United States)

    Salehi, Siamak; Eckley, Lorna; Sawyer, Greta J; Zhang, Xiaohong; Dong, Xuebin; Freund, Jean-Noel; Fabre, John W

    2009-01-01

    Intestinal lactase has potential as an autologous beta-galactosidase reporter gene for long-term gene expression studies in vivo, using chromogenic, luminescent, and fluorogenic substrates developed for Escherichia coli beta-galactosidase. In normal rat tissues, reactivity with a chromogenic fucopyranoside (X-Fuc, the preferred substrate of lactase) was present only at the lumenal surface of small intestine epithelial cells. Full-length lactase (domains I-IV), mature lactase (domains III and IV), and a cytosolic form of mature lactase (domains III and IV, without the signal sequence or transmembrane region) were evaluated. Transfection of HuH-7 cells in vitro, and hydrodynamic gene delivery to the liver in vivo, resulted in excellent gene expression. The full-length and mature (homodimeric, membrane-bound) forms reacted strongly with X-Fuc but not with the corresponding galactopyranoside (X-Gal). However, the presumptively monomeric cytosolic lactase unexpectedly reacted equally well with both substrates. The fluorogenic substrate fluorescein-di-beta-D-galactopyranoside was cleaved by cytosolic lactase, but not by full-length or mature lactase. Full-length lactase, when expressed ectopically in hepatocytes in vivo, localized exclusively to the bile canalicular membrane. Intestinal lactase is highly homologous in mice, rats, and humans and has considerable potential for evaluating long-term gene expression in experimental animals and the clinic.

  16. [Serum beta 2 microglobulin (beta 2M) following renal transplantation].

    Science.gov (United States)

    Pacheco-Silva, A; Nishida, S K; Silva, M S; Ramos, O L; Azjen, H; Pereira, A B

    1994-01-01

    Although there was an important improvement in graft and patient survival the last 10 years, graft rejection continues to be a major barrier to the success of renal transplantation. Identification of a laboratory test that could help to diagnose graft rejection would facilitate the management of renal transplanted patients. PURPOSE--To evaluate the utility of monitoring serum beta 2M in recently transplanted patients. METHODS--We daily determined serum beta 2M levels in 20 receptors of renal grafts (10 from living related and 10 from cadaveric donors) and compared them to their clinical and laboratory evolution. RESULTS--Eight patients who presented immediate good renal function following grafting and did not have rejection had a mean serum beta 2M of 3.7 mg/L on the 4th day post transplant. The sensitivity of the test for the diagnosis of acute rejection was 87.5%, but the specificity was only 46%. Patients who presented acute tubular necrosis (ATN) without rejection had a progressive decrease in their serum levels of beta 2M, while their serum creatinine changed as they were dialyzed. In contrast, patients with ATN and concomitance of acute rejection or CSA nephrotoxicity presented elevated beta 2M and creatinine serum levels. CONCLUSION--Daily monitoring of serum beta 2M does not improve the ability to diagnose acute rejection in patients with good renal function. However, serum beta 2M levels seemed to be useful in diagnosing acute rejection or CSA nephrotoxicity in patients with ATN.

  17. A novel murine model of Cooley anemia and its rescue by lentiviral-mediated human beta-globin gene transfer.

    Science.gov (United States)

    Rivella, Stefano; May, Chad; Chadburn, Amy; Rivière, Isabelle; Sadelain, Michel

    2003-04-15

    Patients affected by beta-thalassemia major require lifelong transfusions because of insufficient or absent production of the beta chain of hemoglobin (Hb). A minority of patients are cured by allogeneic bone marrow transplantation. In the most severe of the hitherto available mouse models of beta-thalassemia, a model for human beta-thalassemia intermedia, we previously demonstrated that globin gene transfer in bone marrow cells is curative, stably raising Hb levels from 8.0-8.5 to 11.0-12.0 g/dL in long-term chimeras. To fully assess the therapeutic potential of gene therapy in the context of a lethal anemia, we now have created an adult model of beta(0)-thalassemia major. In this novel model, mice engrafted with beta-globin-null (Hbb(th3/th3)) fetal liver cells succumb to ineffective erythropoiesis within 60 days. These mice rapidly develop severe anemia (2-4 g/dL), massive splenomegaly, extramedullary hematopoiesis (EMH), and hepatic iron overload. Remarkably, most mice (11 of 13) treated by lentivirus-mediated globin gene transfer were rescued. Long-term chimeras with an average 1.0-2.4 copies of the TNS9 vector in their hematopoietic and blood cells stably produced up to 12 g/dL chimeric Hb consisting of mu alpha(2):hu beta(2) tetramers. Pathologic analyses indicated that erythroid maturation was restored, while EMH and iron overload dramatically decreased. Thus, we have established an adult animal model for the most severe of the hemoglobinopathies, Cooley anemia, which should prove useful to investigate both genetic and pharmacologic treatments. Our findings demonstrate the remarkable efficacy of lentivirus-mediated globin gene transfer in treating a fulminant blood disorder and strongly support the efficacy of gene therapy in the severe hemoglobinopathies.

  18. Modelo de gestión cultural: Una experiencia con el Qhapaq Ñan en Huánuco

    Directory of Open Access Journals (Sweden)

    Denesy Palacios Jiménez

    2014-06-01

    Full Text Available Objetivos: Plantear el aprovechamiento del patrimonio cultural arqueológico del Qhapaq Ñan en Huánuco en condición de parque cultural, mediante un modelo eficiente de gestión cultural basada en la investigación, protección, conservación y uso social, para convertir a este lugar en un destino turístico y así contribuir con un proyecto no solo para salvaguardarlo sino también para incrementar los ingresos económicos y reducir los niveles de pobreza en la zona. Métodos: Se trata de un estudio que describe y recoge experiencias de gestión cultural respecto a cómo se aprovecha en otros sitios el legado o patrimonio cultural arqueológico, tanto en el ámbito mundial como nacional. La investigación fue cuantitativa y cualitativa, con un alcance correlacional. Se usó el diseño descriptivo, comparativo, analítico, histórico, deductivo. Resultados: El estudio plantea la necesidad de optimizar los recursos para el aprovechamiento del Qhapaq Ñan como parque cultural a través de una adecuada gestión cultural, y que dicho parque comprenderá 68,34 km, desde el tambo de Tambococha o Tunsucancha hasta el tambo de Taparako, por ser uno de los tramos mejor conservados e involucra importantes zonas de patrimonio cultural material e inmaterial. Conclusiones: El Camino Inca en Huánuco es uno de los patrimonios más importantes del país, y es posible ser impulsado como un parque cultural mediante un modelo de gestión cultural, si tenemos en cuenta las diversas experiencias de gestión en el país y en mundo, cuyos aportes deben servir de apoyo para un modelo de gestión en este campo.

  19. Experiments on double beta decay

    Energy Technology Data Exchange (ETDEWEB)

    Busto, J. [Neuchatel Univ. (Switzerland). Inst. de Physique

    1996-11-01

    The Double Beta Decay, and especially ({beta}{beta}){sub 0{nu}} mode, is an excellent test of Standard Model as well as of neutrino physics. From experimental point of view, a very large number of different techniques are or have been used increasing the sensitivity of this experiments quite a lot (the factor of 10{sup 4} in the last 20 years). In future, in spite of several difficulties, the sensitivity would be increased further, keeping the interest of this very important process. (author) 4 figs., 5 tabs., 21 refs.

  20. Dosimetry of {beta} extensive sources; Dosimetria de fuentes {beta} extensas

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E.L.; Lallena R, A.M. [Departamento de Fisica Moderna, Universidad de Granada, E-18071 Granada (Spain)

    2002-07-01

    In this work, we have been studied, making use of the Penelope Monte Carlo simulation code, the dosimetry of {beta} extensive sources in situations of spherical geometry including interfaces. These configurations are of interest in the treatment of the called cranealfaringyomes of some synovia leisure of knee and other problems of interest in medical physics. Therefore, its application can be extended toward problems of another areas with similar geometric situation and beta sources. (Author)

  1. Evolution of outer membrane beta-barrels from an ancestral beta beta hairpin.

    Science.gov (United States)

    Remmert, M; Biegert, A; Linke, D; Lupas, A N; Söding, J

    2010-06-01

    Outer membrane beta-barrels (OMBBs) are the major class of outer membrane proteins from Gram-negative bacteria, mitochondria, and plastids. Their transmembrane domains consist of 8-24 beta-strands forming a closed, barrel-shaped beta-sheet around a central pore. Despite their obvious structural regularity, evidence for an origin by duplication or for a common ancestry has not been found. We use three complementary approaches to show that all OMBBs from Gram-negative bacteria evolved from a single, ancestral beta beta hairpin. First, we link almost all families of known single-chain bacterial OMBBs with each other through transitive profile searches. Second, we identify a clear repeat signature in the sequences of many OMBBs in which the repeating sequence unit coincides with the structural beta beta hairpin repeat. Third, we show that the observed sequence similarity between OMBB hairpins cannot be explained by structural or membrane constraints on their sequences. The third approach addresses a longstanding problem in protein evolution: how to distinguish between a very remotely homologous relationship and the opposing scenario of "sequence convergence." The origin of a diverse group of proteins from a single hairpin module supports the hypothesis that, around the time of transition from the RNA to the protein world, proteins arose by amplification and recombination of short peptide modules that had previously evolved as cofactors of RNAs.

  2. Hepatitis B Virus X Upregulates HuR Protein Level to Stabilize HER2 Expression in Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chao-Ming Hung

    2014-01-01

    Full Text Available Hepatitis B virus- (HBV- associated hepatocellular carcinoma (HCC is the most common type of liver cancer. However, the underlying mechanism of HCC tumorigenesis is very complicated and HBV-encoded X protein (HBx has been reported to play the most important role in this process. Activation of downstream signal pathways of epidermal growth factor receptor (EGFR family is known to mediate HBx-dependent HCC tumor progression. Interestingly, HER2 (also known as ErbB2/Neu/EGFR2 is frequently overexpressed in HBx-expressing HCC patients and is associated with their poor prognosis. However, it remains unclear whether and how HBx regulates HER2 expression. In this study, our data showed that HBx expression increased HER2 protein level via enhancing its mRNA stability. The induction of RNA-binding protein HuR expression by HBx mediated the HER2 mRNA stabilization. Finally, the upregulated HER2 expression promoted the migration ability of HBx-expressing HCC cells. These findings deciphered the molecular mechanism of HBx-mediated HER2 upregulation in HBV-associated HCC.

  3. New Light-Travel Time Models and Orbital Stability Study of the Proposed Planetary System HU Aquarii

    CERN Document Server

    Hinse, Tobias C; Gozdziewski, Krzysztof; Haghighipour, Nader; Lee, Chung-Uk; Scullion, Eamon M

    2011-01-01

    In this work we propose a new orbital architecture for the two proposed circumbinary planets around the polar eclipsing binary HU Aquarii. We base the new two-planet, light-travel time model on the result of a Monte Carlo simulation driving a least-squares Levenberg-Marquardt minimisation algorithm on the observed eclipse egress times. Our best-fitting model with $\\chi_{r}^2=1.43$ resulted in high final eccentricities for the two companions leading to an unstable orbital configuration. From a large ensemble of initial guesses we examined the distribution of final eccentricities and semi-major axes for different $\\chi_{r}^2$ parameter intervals and encountered qualitatively a second population of best-fitting parameters. The main characteristic of this population is described by low-eccentric orbits favouring long-term orbital stability of the system. We present our best-fitting model candidate for the proposed two-planet system and demonstrate orbital stability over one million years using numerical integrati...

  4. Characterization and hepatoprotective effect of polysaccharides from Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou sarcocarp.

    Science.gov (United States)

    Yue, Yuan; Wu, Shuangchan; Zhang, Huifang; Zhang, Xuyan; Niu, Yunhui; Cao, Xiaoqin; Huang, Fuwei; Ding, Hong

    2014-12-01

    The polysaccharides from Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou sarcocarp (PWJS) is evaluated for the chemical composition, antioxidant activity and hepatoprotective effect. The characteristics of PWJS were determined by FT-IR spectral and HPLC analysis. The antioxidant activity was investigated using in vitro systems. An in vivo study of PWJS against CCl4 induced liver injury was also conducted. HPLC analysis showed that PWJS is an acidic heteropolysaccharide, rich in glucose (38.59%), arabinose (23.16%), galacturonic acid (17.64%) and galactose (10.44%). PWJS displayed strong antioxidant activity in vitro. In the in vivo study, PWJS treatment lowered the serum levels of ALT and AST in CCl4-intoxicated mice. Additionally, levels of antioxidant enzymes (SOD and CAT) and GSH were elevated in liver damage mice by PWJS intervention, while content of MDA was lessened. Meanwhile, PWJS reverses the suppression of Nrf2 nuclear translocation, and increases the protein expression of HO-1, GSTα and NQO1 in liver damage mice. Hematoxylin-eosin staining showed that the condition of liver damage was mitigated. This study demonstrates that PWJS reverses hepatotoxicity in CCl4-intoxicated mice through the mechanisms of antioxidant activity, as well as an augmentation of the Nrf2 pathway in liver tissue.

  5. A Network Pharmacology Approach to Uncover the Pharmacological Mechanism of XuanHuSuo Powder on Osteoarthritis

    Science.gov (United States)

    Zhang, Xinyue; Luo, Shilin; Zhang, Baixia; Duan, Xiaojie; Zhang, Zhiqian; Wang, Wenqi; Wang, Yun; Sun, Yikun

    2016-01-01

    As the most familiar type of arthritis and a chronic illness of the joints, Osteoarthritis (OA) affects a great number of people on the global scale. XuanHuSuo powder (XHSP), a conventional herbal formula from China, has been extensively applied in OA treatment. Nonetheless, its pharmacological mechanism has not been completely expounded. In this research, a network pharmacology approach has been chosen to study the pharmacological mechanism of XHSP on OA, and the pharmacology networks were established based on the relationship between four herbs found in XHSP, compound targets, and OA targets. The pathway enrichment analysis revealed that the significant bioprocess networks of XHSP on OA were regulation of inflammation, interleukin-1β (IL-1β) production and nitric oxide (NO) biosynthetic process, response to cytokine or estrogen stimuli, and antiapoptosis. These effects have not been reported previously. The comprehensive network pharmacology approach developed by our research has revealed, for the first time, a connection between four herbs found in XHSP, corresponding compound targets, and OA pathway systems that are conducive to expanding the clinical application of XHSP. The proposed network pharmacology approach could be a promising complementary method by which researchers might better evaluate multitarget or multicomponent drugs on a systematic level. PMID:27110264

  6. Renal Protective Effect of Xiao-Chai-Hu-Tang on Diabetic Nephropathy of Type 1-Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Chun-Ching Lin

    2012-01-01

    Full Text Available Xiao-Chai-Hu-Tang (XCHT, a traditional Chinese medicine formula consisting of seven medicinal plants, is used in the treatment of various diseases. We show here that XCHT could protect type-1 diabetic mice against diabetic nephropathy, using streptozotocin (STZ-induced diabetic mice and high-glucose (HG-exposed rat mesangial cell (RMC as models. Following 4 weeks of oral administration with XCHT, renal functions and renal hypertrophy significantly improved in the STZ-diabetic mice, while serum glucose was only moderately reduced compared to vehicle treatment. Treatment with XCHT in the STZ-diabetic mice and HG-exposed RMC resulted in a decrease in expression levels of TGF-β1, fibronectin, and collagen IV, with concomitant increase in BMP-7 expression. Data from DPPH assay, DHE stain, and CM-H2DCFDA analysis indicated that XCHT could scavenge free radicals and inhibit high-glucose-induced ROS in RMCs. Taken together, these results suggest that treatment with XCHT can improve renal functions in STZ-diabetic mice, an effect that is potentially mediated through decreasing oxidative stress and production of TGF-β1, fibronectin, and collagen IV in the kidney during development of diabetic nephropathy. XCHT, therefore merits further investigation for application to improve renal functions in diabetic disorders.

  7. Synergistic Anticancer Effects of Vorinostat and Epigallocatechin-3-Gallate against HuCC-T1 Human Cholangiocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Tae Won Kwak

    2013-01-01

    Full Text Available The aim of this study was to investigate the effect of the combination of vorinostat and epigallocatechin-3-gallate against HuCC-T1 human cholangiocarcinoma cells. A novel chemotherapy strategy is required as cholangiocarcinomas rarely respond to conventional chemotherapeutic agents. Both vorinostat and EGCG induce apoptosis and suppress invasion, migration, and angiogenesis of tumor cells. The combination of vorinostat and EGCG showed synergistic growth inhibitory effects and induced apoptosis in tumor cells. The Bax/Bcl-2 expression ratio and caspase-3 and -7 activity increased, but poly (ADP-ribose polymerase expression decreased when compared to treatment with each agent alone. Furthermore, invasion, matrix metalloproteinase (MMP expression, and migration of tumor cells decreased following treatment with the vorinostat and EGCG combination compared to those of vorinostat or EGCG alone. Tube length and junction number of human umbilical vein endothelial cells (HUVECs decreased as well as vascular endothelial growth factor expression following vorinostat and EGCG combined treatment. These results indicate that the combination of vorinostat and EGCG had a synergistic effect on inhibiting tumor cell angiogenesis potential. We suggest that the combination of vorinostat and EGCG is a novel option for cholangiocarcinoma chemotherapy.

  8. Trigeminal Neuralgia as the First Clinical Manifestation of Anti-Hu Paraneoplastic Syndrome Induced by a Borderline Ovarian Mucinous Tumor

    Directory of Open Access Journals (Sweden)

    Hossein Kalanie

    2014-01-01

    Full Text Available Paraneoplastic neurologic syndrome (PNS is an uncommon manifestation of cancer that is not caused by the tumor or metastasis. Trigeminal neuralgia (TN is an initial symptom of this disease, but it has rarely been reported in the literature. Here, we report the case of a 76-year-old woman who presented with classic TN, followed by limbic encephalitis due to an underlying ovarian intestinal-type mucinous borderline tumor, with the presence of anti-Hu antibodies. She recovered quickly after removal of the tumor and was essentially free of symptoms 2 weeks after surgery. Because PNS precedes the tumor in approximately 60% of cases, its rapid detection and treatment are crucial. Therefore, we propose that PNS be considered during the management of TN when brain imaging is normal, as it is followed by other central and/or peripheral neurological manifestations as well as the presence of systemic symptoms such as anemia, fatigability, loss of appetite, or weight loss.

  9. Bioactive comparison of main components from unripe fruits of Rubus chingii Hu and identification of the effective component.

    Science.gov (United States)

    Zhang, Tian-Tian; Yang, Li; Jiang, Jian-Guo

    2015-07-01

    Dried and unripe fruit of Rubus chingii Hu, known as "Fu-pen-zi" in Chinese, has been used as a food and tonic in China for a long time. In order to analyze its effective ingredients, polysaccharides, flavonoids, saponins and alkaloids were extracted from the unripe fruits and their contents were determined. The in vitro antioxidant, anticomplementary and anticancer activities against human lung adenocarcinoma A549 cells of the four major constituents were investigated. Results showed that total flavonoids exhibited an obvious antioxidant activity, which was very close to ascorbic acid. The anticomplementary and anticancer activities of flavonoids were also the best among the four chemical compositions. Therefore, extraction process optimization of flavonoids was conducted using response surface methodology. The optimal conditions were as follows: extraction temperature 72.8 °C, ethanol concentration 30.67%, extraction time 2.66 h, and a liquid/solid ratio of 19.54 : 1. In addition, total flavonoids were subsequently separated by column chromatography and the major flavonoid was identified as tiliroside. Further experimental data revealed that tiliroside treatment could suppress the proliferation and induced the apoptosis of A549 cells.

  10. 胡绳史料学思想初探%Preliminary Study on Hu Sheng' s Thoughts of Historical Materials

    Institute of Scientific and Technical Information of China (English)

    胡现岭

    2012-01-01

    Hu Sheng was critical to the historians who were good at historical materials,arguing that their work was only the initial stage of historical research.This attitude didn' t mean that he ignored the important role of historical materials.He pointed out that we should guide historical materials by Marxism and historical data should service views;In addition,when carrying out the work of historical materials,we should estimate its value at the same time.%胡绳对以史料见长的史家一贯持批评态度,认为他们的工作只是停留在史学研究的初始阶段,但这并不表明他不重视史料在史学研究中的作用,而是提出以马克思主义来指导史料工作,在对史料进行考证的同时对其价值的高低做出评判,强调史料要为观点服务。

  11. Karyotypes of Akodon orophilus Osgood 1913 and Thomasomys sp. (Rodentia: Sigmodontinae from Huánuco, Peru

    Directory of Open Access Journals (Sweden)

    Víctor Pacheco

    2012-10-01

    Full Text Available Conventional chromosomal preparations were made of three native mice from Huánuco, Peru: a male and a female of Thomasomys sp., and a male of Akodon orophilus. Thomasomys sp. had a karyotype of 2n = 42, XY (n = 21, meanwhile A. orophilus presented 2n = 22, XY (n = 11. Comparisons between chromosomal pairs from the existent literature indicate that both are new karyotypes. Thomasomys sp. has a distinct sexual Y chromosome, the only metacentric (m reported for the genus. The chromosomes X and Y of A. orophilus are acrocentrics (a; and the length of chromosome Y (2/3 of the length of X distinguishes A. orophilus from other congeneric. Because the structural differences between the sexual chromosomes usually generates mechanism of reproductive isolation at intraspecific level and are bigger still in interspecific crosses, we concluded that the karyotypes reported here support the validity of the species A. orophilus and suggest that Thomasomys sp. represents a new species to science.

  12. Optimization of in vitro HBV replication and HBsAg production in HuH7 cell line.

    Science.gov (United States)

    Cavallone, Daniela; Moriconi, Francesco; Colombatto, Piero; Oliveri, Filippo; Bonino, Ferruccio; Brunetto, Maurizia Rossana

    2013-04-01

    The Gunther's vector-free method (GM), using PCR-amplified full length HBV-DNA (fl-HBV-DNA), is currently the best in vitro HBV replication system despite the low intracellular HBV-DNA production. The replication efficiency and HBsAg secretion of 12 isolates from HBsAg/HBeAg positive sera by GM, Monomer-Linear-Sticky-Ends-DNA (MLSE) and Monomer-Circular-Closed (MCC) were compared in HuH7 cells. Eight of twelve genomes (67%) were replication competent by GM; however direct sequencing (DS) showed that more than 80% of input DNA was undigested in spite of SapI treatment. Replication Intermediates (RI) were detected earlier (24 vs. 48h) and in higher amounts (2.51±0.32 and 6.43±0.43 fold) by MCC than GM or MLSE. By MCC 10 of 12 genomes (83%) were replication competent and 7 produced high RI levels. RI and HBsAg kinetics correlated positively in MCC (R=0.696, p=0.017 overall; R=0.928, p=0.008), but not in GM (R=-0.437, p=0.179 overall; R=-0.395, p=0.439) in genotype D isolates. In conclusion, HBV-DNA circularization prior transfection improves in vitro viral replication and replication competent HBsAg production, mimicking better the in vivo conditions.

  13. Beta-2 Microglobulin Tumor Marker

    Science.gov (United States)

    ... services. Advertising & Sponsorship: Policy | Opportunities Beta-2 Microglobulin Tumor Marker Share this page: Was this page helpful? Also ... Microglobulin, Serum, Urine, or CSF Related tests: Albumin , Tumor Markers , CSF Analysis All content on Lab Tests Online ...

  14. Questions Students Ask: Beta Decay.

    Science.gov (United States)

    Koss, Jordan; Hartt, Kenneth

    1988-01-01

    Answers a student's question about the emission of a positron from a nucleus. Discusses the problem from the aspects of the uncertainty principle, beta decay, the Fermi Theory, and modern physics. (YP)

  15. Beta Function and Anomalous Dimensions

    CERN Document Server

    Pica, Claudio

    2010-01-01

    We demonstrate that it is possible to determine the coefficients of an all-order beta function linear in the anomalous dimensions using as data the two-loop coefficients together with the first one of the anomalous dimensions which are universal. The beta function allows to determine the anomalous dimension of the fermion masses at the infrared fixed point, and the resulting values compare well with the lattice determinations.

  16. Expression of transforming growth factor-beta (TGF-beta) receptors, TGF-beta 1 and TGF-beta 2 production and autocrine growth control in osteosarcoma cells.

    Science.gov (United States)

    Kloen, P; Jennings, C L; Gebhardt, M C; Springfield, D S; Mankin, H J

    1994-08-01

    Transforming growth factor-beta (TGF-beta) is a polypeptide with multiple physiological functions. Isoforms of this growth factor have important roles in control of the cell cycle, in regulation of cell-cell interactions and in growth and development. Malignant transformation has been shown to be associated with increased expression of TGF-beta. Since bone is the largest storage site and producer of TGF-beta, we speculated on the existence of an autocrine mechanism in osteosarcoma, a malignant bone tumor. Expression of TGF-beta cell surface receptors, effects on growth of TGF-beta and TGF-beta antibodies and production of 2 TGF-beta isoforms were studied in a panel of 7 osteosarcoma cell lines. In contrast to most previous reports on the effects of TGF-beta on osteosarcoma cell growth, we found a mitogenic effect of TGF-beta 1 in 4 of 7 osteosarcoma cell lines. Receptor profiles for TGF-beta were aberrant in 5 of the 7 cell lines tested, and production of TGF-beta 1 and TGF-beta 2 varied among cell lines. Addition of anti-TGF-beta antagonized the effects of endogenous TGF-beta. Our results suggest a potential role of TGF-beta in autocrine growth control of osteosarcoma cells.

  17. Polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Morant, Marc

    2017-02-07

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  18. Avaliação dos óbitos ocorridos no Hospital Universitário da Universidade Federal de Santa Catarina (HU/UFSC Evaluation of deaths occurred at the University Hospital (HU/UFSC

    Directory of Open Access Journals (Sweden)

    Rachel Duarte Moritz

    2008-10-01

    Full Text Available OBJETIVO: Avaliar os óbitos ocorridos no HU/UFSC. Comparar o perfil dos pacientes que morreram nas enfermarias com o daqueles que morreram na UTI. Verificar se os óbitos foram considerados esperados (E e não evitáveis (NE. Constatar se houve recusa/suspensão de terapêutica (RST precedendo a morte. MÉTODOS: Obtivemos dados por meio de ficha elaborada pela Comissão de Óbito Hospitalar (COH, na qual constavam os aspectos demográficos, clínicos e terapêuticos dos pacientes e a avaliação da COH sobre a expectativa/evitabilidade dos óbitos. RESULTADOS: Analisamos os dados dos 326 pacientes com mais de 14 anos, que morreram entre julho/2004 e dezembro/2005. Desses, 128 morreram na UTI (G1 e 198 nas enfermarias (G2. A RST precedeu 38,2% dos óbitos no G1 e 2% no G2 (pOBJECTIVE: To evaluate the deaths which occurred at the HU/UFSC. To compare the profile of patients who died in the wards with that of patients who died in the ICU. To classify deaths which were expected or not, and avoidable or not. To verify how often withholding or withdrawing (WW therapy preceded death. METHODS: Archives of the Hospital Death Commission (HDC were analyzed. The clinical and demographic records were retrieved from the HDC data bank. Deaths were classified by the HDC as expected or not and avoidable or not. RESULTS: Data from 326 dead persons over 14 years of age were analyzed. One hundred and twenty eight deaths occurred in the ICU (G1 and 198 in the wards (G2. WW therapy preceded 38.2% of deaths in G1 and 2% in G2 (p<0.001. The main WW therapies were vasoactive drugs and antibiotics. Almost 20% of deaths were unexpected/avoidable in G1. In G2 6.5% were considered unexpected and 5% avoidable (p<0.005. Patients in G1 were younger and mostly male (p<0.005. Do-not-resuscitate orders were registered in 48.4% of patients' medical charts in G2 and 6.3% in G1 (p<0.001. Cardiopulmonary resuscitation was performed in 23.4% of patients in G1 and in 5.5% in G2 (p<0

  19. 22(R)-hydroxycholesterol induces HuR-dependent MAP kinase phosphatase-1 expression via mGluR5-mediated Ca(2+)/PKCα signaling.

    Science.gov (United States)

    Kim, Hyunmi; Woo, Joo Hong; Lee, Jee Hoon; Joe, Eun-Hye; Jou, Ilo

    2016-08-01

    MAP kinase phosphatase (MKP)-1 plays a pivotal role in controlling MAP kinase (MAPK)-dependent (patho) physiological processes. Although MKP-1 gene expression is tightly regulated at multiple levels, the underlying mechanistic details remain largely unknown. In this study, we demonstrate that MKP-1 expression is regulated at the post-transcriptional level by 22(R)-hydroxycholesterol [22(R)-HC] through a novel mechanism. 22(R)-HC induces Hu antigen R (HuR) phosphorylation, cytoplasmic translocation and binding to MKP-1 mRNA, resulting in stabilization of MKP-1 mRNA. The resulting increase in MKP-1 leads to suppression of JNK-mediated inflammatory responses in brain astrocytes. We further demonstrate that 22(R)-HC-induced phosphorylation of nuclear HuR is mediated by PKCα, which is activated in the cytosol by increases in intracellular Ca(2+) levels mediated by the phospholipase C/inositol 1,4,5-triphosphate receptor (PLC/IP3R) pathway and translocates from cytoplasm to nucleus. In addition, pharmacological interventions reveal that metabotropic glutamate receptor5 (mGluR5) is responsible for the increases in intracellular Ca(2+) that underlie these actions of 22(R)-HC. Collectively, our findings identify a novel anti-inflammatory mechanism of 22(R)-HC, which acts through PKCα-mediated cytoplasmic shuttling of HuR to post-transcriptionally regulate MKP-1 expression. These findings provide an experimental basis for the development of a RNA-targeted therapeutic agent to control MAPK-dependent inflammatory responses.

  20. Intratumoral hu14.18-IL-2 (IC) induces local and systemic antitumor effects that involve both activated T and NK cells as well as enhanced IC retention.

    Science.gov (United States)

    Yang, Richard K; Kalogriopoulos, Nicholas A; Rakhmilevich, Alexander L; Ranheim, Erik A; Seo, Songwon; Kim, Kyungmann; Alderson, Kory L; Gan, Jacek; Reisfeld, Ralph A; Gillies, Stephen D; Hank, Jacquelyn A; Sondel, Paul M

    2012-09-01

    hu14.18-IL-2 (IC) is an immunocytokine consisting of human IL-2 linked to hu14.18 mAb, which recognizes the GD2 disialoganglioside. Phase 2 clinical trials of i.v. hu14.18-IL-2 (i.v.-IC) in neuroblastoma and melanoma are underway and have already demonstrated activity in neuroblastoma. We showed previously that intratumoral hu14.18-IL-2 (IT-IC) results in enhanced antitumor activity in mouse models compared with i.v.-IC. The studies presented in this article were designed to determine the mechanisms involved in this enhanced activity and to support the future clinical testing of intratumoral administration of immunocytokines. Improved survival and inhibition of growth of both local and distant tumors were observed in A/J mice bearing s.c. NXS2 neuroblastomas treated with IT-IC compared with those treated with i.v.-IC or control mice. The local and systemic antitumor effects of IT-IC were inhibited by depletion of NK cells or T cells. IT-IC resulted in increased NKG2D receptors on intratumoral NKG2A/C/E⁺ NKp46⁺ NK cells and NKG2A/C/E⁺ CD8⁺ T cells compared with control mice or mice treated with i.v.-IC. NKG2D levels were augmented more in tumor-infiltrating lymphocytes compared with splenocytes, supporting the localized nature of the intratumoral changes induced by IT-IC treatment. Prolonged retention of IC at the tumor site was seen with IT-IC compared with i.v.-IC. Overall, IT-IC resulted in increased numbers of activated T and NK cells within tumors, better IC retention in the tumor, enhanced inhibition of tumor growth, and improved survival compared with i.v.-IC.

  1. A new species of frog of the genus Pristimantis from Tingo María National Park, Huánuco Department, central Peru (Anura, Craugastoridae)

    Science.gov (United States)

    Chávez, Germán; Catenazzi, Alessandro

    2016-01-01

    Abstract A new species of Craugastoridae frog encountered from 1000–1700 m in elevation in the premontane forests of the Peruvian central Andes is described. The new species is similar in appearance to many other species of Pristimantis, but is easily distinguishable from these species by having bright red coloration on the groin, posterior surface of thighs, and shanks. The new species is only known for two localities 27 km apart in the Huánuco Region. PMID:27587978

  2. Contents of the heavy metals nickel and lead in leaves of Paulownia elongata S.Y. Hu and Paulownia fortunei Hems. in Serbia

    OpenAIRE

    2009-01-01

    A comparative study was carried out on the capabilities of the two species Paulownia elongata S. Y. Hu and Paulownia fortunei Hems. as biomonitors of atmospheric (and soil) heavy-metal pollution. Research on content of the heavy metals nickel (Ni) and lead (Pb) in leaves of the species Paulownia elongata growing under urban and suburban conditions with the comparison to the concentration of these elements in leaves of the species Paulownia elongata and Paulownia fortunei on an experimental pl...

  3. La presencia de Ixodes luciae en el noroeste argentino y nuevos huéspedes para Ixodes pararicinus y algunas especies de Amblyomma (Acari: Ixodidae

    Directory of Open Access Journals (Sweden)

    Analía G. AUTINO

    2006-01-01

    Full Text Available El análisis de una colección de garrapatas de mamíferos del noroeste argentino, depositados en la Colección de Anexos de la Colección Mamíferos Lillo (CML de la Universidad Nacional de Tucumán, permitió ampliar el área de distribución de Ixodes luciae Sénevet, a las provincias de Salta y Tucumán e incrementar su rango de huéspedes al roedor sigmodontino Calomys callosus (Rengger y a los marsupiales de la familia Didelphidae Micoureus constantiae (Thomas, Thylamys cinderella Thomas y Thylamys venustus (Thomas. Se registró a C. callosus y Oligoryzomys destructor (Tschudi como nuevos huéspedes de Ixodes pararicinus Keirans & Clifford, y a los Carnivora Lycalopex gymnocercus (Fischer y Oncifelis geoffroyi (d ́Orbigny & Gervais como nuevos huéspedes de Amblyomma neumanni Ribaga y Amblyomma parvum Aragão, respectivamente. Adicionalmente, se observó la infestación de Lutreolina crassicaudata (Desmarest (Didelphidae por I. luciae y la presencia de Amblyomma tigrinum Koch, sobre L. gymnocercus. Ninfas de Amblyomma sp. se obtuvieron de Akodon Meyen (Sigmodontinae.

  4. Effects of r—HuEPO on the biophysical characteristics of erythrocyte membrane in patients with anemia of chronic renal failure

    Institute of Scientific and Technical Information of China (English)

    SHIHONGLIAN; FAJUNYANG; 等

    1994-01-01

    Using electron spin resonance (ESR) spin labeling technique,we have studied the conformation of sulfhydryl groups(-SH) binding sites in membrane proteins and mem brane fluidity of red blood cells(RBCs) from two groups of patients with anemia of chronic renal failure(ACRF).One of the groups is composed of patients who were untreated with recombinant human erythropoietin(r-HuEPO),and the other is composed of patients who were treated with r-HuEPO.The results indicated:1)the conformation of SH group binding site in RBC membrane proteins from former group was different from those of healty people.2)the fluidity in the region near the surface of RBC membrane from former group was lower than those of healthy people.3)However,the above biophysical properties of RBC membrane from later group were normal.We concluded that RBC membrane in patients with ACRF was abnormal,and the treatment of r-HuEPO may promote the production of normal RBCs,thus ameliorate the biophysical properties of RBCs from the patients with ACRF.

  5. HuR and Ago2 Bind the Internal Ribosome Entry Site of Enterovirus 71 and Promote Virus Translation and Replication.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lin

    Full Text Available EV71 (enterovirus 71 RNA contains an internal ribosomal entry site (IRES that directs cap-independent initiation of translation. IRES-dependent translation requires the host's translation initiation factors and IRES-associated trans-acting factors (ITAFs. We reported recently that mRNA decay factor AUF1 is a negative-acting ITAF that binds IRES stem-loop II. We also reported that the small RNA-processing enzyme Dicer produces at least four small RNAs (vsRNAs from the EV71 IRES. One of these, vsRNA1, derived from IRES stem-loop II, reduces IRES activity and virus replication. Since its mechanism of action is unknown, we hypothesized that it might control association of ITAFs with the IRES. Here, we identified the mRNA stability factor HuR and the RISC subunit Argonaute 2 (Ago2 as two ITAFs that bind stem-loop II. In contrast to AUF1, HuR and Ago2 promote EV71 IRES activity and virus replication. In vitro RNA-binding assays revealed that vsRNA1 can alter association of Ago2, HuR, and AUF1 with stem-loop II. This presents a possible mechanism by which vsRNA1 could control viral translation and replication.

  6. 论胡锦涛党建思想的基本价值%On the fundamental value of the Party building thought Hu Jintao

    Institute of Scientific and Technical Information of China (English)

    李强

    2011-01-01

    Since Sixteenth National Congress of the Communist Party of China,Hu Jintao as general secretary of the party leadership to actively promote the construction of the new great project,and achieved fruitful theoretical results,the formation of a building thought Hu.Hu building thought to enrich and develop Marxism in the ideological theory of party building treasury,for the party is always ahead of the times,firmly implement the Party's governing mission to provide a scientific theory and a powerful ideological weapon.%党的十六大以来,以胡锦涛为总书记的领导集体积极推进党的建设的伟大工程,取得了丰硕的理论成果,并形成了胡锦涛党建思想。胡锦涛党建思想丰富和发展了马克思主义党建理论的思想宝库,为使党始终走在时代前列,坚定不移实现党的执政使命,提供了科学理论和强大的思想武器。

  7. A comparative study of oral health attitudes and behavior using the Hiroshima University-Dental Behavioral Inventory (HU-DBI) between dental and civil engineering students in Colombia.

    Science.gov (United States)

    Jaramillo, Jorge A; Jaramillo, Fredy; Kador, Itzjak; Masuoka, David; Tong, Liyue; Ahn, Chul; Komabayashi, Takashi

    2013-03-01

    The aim of this study was to use the Hiroshima University - Dental Behavioral Inventory (HU-DBI) to compare oral health attitudes and behavior of dental and civil engineering students in Colombia. The HU-DBI's survey consisting of twenty dichotomous responses (agree-disagree) regarding tooth brushing, was completed at University Antonio Narino for the dental students and the University of Cauca for the civil engineering students. The Spanish version of the HU-DBI questionnaire was taken by 182 of 247 dental students and 411 of 762 engineering students. The data was-statistically analyzed by the chi-square test and backward logistic regression. Compared to the engineering students, the dental students were more likely to agree with questions such as "I am bothered by the color of my gums"(OR = 2.2, 95% CI: 1.3-3.7),"I think I can clean my teeth well without using toothpaste" (OR = 3.0, 95% CI: 1.5-5.9), "I have used a dye to see how clean my teeth are" (OR = 2.9, 95% CI: 1.9-4.3), and "I have had my dentist tell me that I brush very well" (OR = 2.0, 95% CI: 1.3-3.1). The dental education curriculum in a dental school compared to a civil engineering school in Colombia indicated that a three-phase curriculum in didactics and clinics increased oral health attitudes and behavior from entry to graduation.

  8. The GERDA experiment on 0{nu}{beta}{beta} decay

    Energy Technology Data Exchange (ETDEWEB)

    Freund, Kai [Eberhard Karls Universitaet Tuebingen (Germany); Collaboration: GERDA-Collaboration

    2012-07-01

    The Gerda (Germanium Detector Array) collaboration searches for the neutrinoless double beta decay (0{nu}{beta}{beta}) of {sup 76}Ge. The existence of this decay would give rise to the assumption that the neutrino is a Majorana particle, i.e. its own antiparticle. A measured half-life could be used to determine the effective neutrino mass and hence resolve the neutrino mass hierarchy problem. Germanium diodes, isotopically enriched in {sup 76}Ge, are used as both source and detector. Due to the low rate of this decay (T{sub 1/2}>10{sup 25} y), the experimental background must be reduced to a level of 10{sup -2}counts/(kg y keV) or better in the region around Q{sub {beta}{beta}}. To minimize background from cosmogenically produced secondary particles, a low Z shielding is employed. Thus, the naked diodes are operated in a liquid argon cryostat, which is surrounded by a water tank acting as both passive shield and active muon Cherenkov veto. Gerda started the commissioning runs in 2010 and in November 2011, the first phase of data taking with enriched detectors has begun. In this talk, the first year of the experiment is summarized.

  9. In-trap decay spectroscopy for {beta}{beta} decays

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Thomas

    2011-01-18

    The presented work describes the implementation of a new technique to measure electron-capture (EC) branching ratios (BRs) of intermediate nuclei in {beta}{beta} decays. This technique has been developed at TRIUMF in Vancouver, Canada. It facilitates one of TRIUMF's Ion Traps for Atomic and Nuclear science (TITAN), the Electron Beam Ion Trap (EBIT) that is used as a spectroscopy Penning trap. Radioactive ions, produced at the radioactive isotope facility ISAC, are injected and stored in the spectroscopy Penning trap while their decays are observed. A key feature of this technique is the use of a strong magnetic field, required for trapping. It radially confines electrons from {beta} decays along the trap axis while X-rays, following an EC, are emitted isotropically. This provides spatial separation of X-ray and {beta} detection with almost no {beta}-induced background at the X-ray detector, allowing weak EC branches to be measured. Furthermore, the combination of several traps allows one to isobarically clean the sample prior to the in-trap decay spectroscopy measurement. This technique has been developed to measure ECBRs of transition nuclei in {beta}{beta} decays. Detailed knowledge of these electron capture branches is crucial for a better understanding of the underlying nuclear physics in {beta}{beta} decays. These branches are typically of the order of 10{sup -5} and therefore difficult to measure. Conventional measurements suffer from isobaric contamination and a dominating {beta} background at theX-ray detector. Additionally, X-rays are attenuated by the material where the radioactive sample is implanted. To overcome these limitations, the technique of in-trap decay spectroscopy has been developed. In this work, the EBIT was connected to the TITAN beam line and has been commissioned. Using the developed beam diagnostics, ions were injected into the Penning trap and systematic studies on injection and storage optimization were performed. Furthermore, Ge

  10. Analysis of betaS and betaA genes in a Mexican population with African roots.

    Science.gov (United States)

    Magaña, María Teresa; Ongay, Zoyla; Tagle, Juan; Bentura, Gilberto; Cobián, José G; Perea, F Javier; Casas-Castañeda, Maricela; Sánchez-López, Yoaly J; Ibarra, Bertha

    2002-01-01

    To investigate the origin of the beta(A) and beta(S) genes in a Mexican population with African roots and a high frequency of hemoglobin S, we analyzed 467 individuals (288 unrelated) from different towns in the states of Guerrero and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was 12.8%, which may represent a public health problem. The frequencies of the beta-haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37 beta(S)). We observed 15 different beta(A) haplotypes, the most common of which were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise distributions and Nei's genetic distance analysis using 32 worldwide populations showed that the beta(A) genes are more closely related to those of Mexican Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%, respectively. Comparison of these haplotypes with 17 other populations revealed a high similitude with the population of the Central African Republic. These data suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals from the Costa Chica region.

  11. ESR1 Gene Polymorphisms and Prostate Cancer Risk: A HuGE Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Mei Wang

    Full Text Available Many published data on the association between single nucleotide polymorphisms (SNPs in the ESR1 gene and prostate cancer susceptibility are inconclusive. The aim of this Human Genome Epidemiology (HuGE review and meta-analysis is to derive a more precise estimation of this relationship.A literature search of PubMed, Embase, Web of Science and Chinese Biomedical (CBM databases was conducted from their inception through July 1st, 2012. Crude odds ratios (ORs with 95% confidence intervals (CIs were calculated to assess the strength of association.Twelve case-control studies were included with a total 2,165 prostate cancer cases and 3,361 healthy controls. When all the eligible studies were pooled into the meta-analysis, ESR1 PvuII (C>T and XbaI (A>G polymorphisms showed no association with the risk of prostate cancer. However, in the stratified analyses based on ethnicity and country, the results indicated that ESR1 PvuII (C>T polymorphism was significantly associated with increased risk of prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G polymorphism may significantly increase the risk of prostate cancer among American population. Furthermore, we also performed a pooled analysis for all eligible case-control studies to explore the role of codon 10 (T>C, codon 325 (C>G, codon 594 (G>A and +261G>C polymorphisms in prostate cancer risk. Nevertheless, no significant associations between these polymorphisms and the risk of prostate cancer were observed.Results from the current meta-analysis indicate that ESR1 PvuII (C>T polymorphism may be a risk factor for prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G polymorphism may increase the risk of prostate cancer among American population.

  12. CYP3A4*1B polymorphism and cancer risk: a HuGE review and meta-analysis.

    Science.gov (United States)

    Zhou, Li-Ping; Yao, Fan; Luan, Hong; Wang, Yin-Ling; Dong, Xi-Hua; Zhou, Wen-Wen; Wang, Qi-Hui

    2013-04-01

    CYP450 3A4 (CYP3A4), encoded by the CYP3A4 gene, is a major enzyme catalyzing the metabolism of both endogenous and exogenous agents that may play a role in the etiology of carcinogenesis. Several potentially functional polymorphisms of the CYP3A4 gene have been implicated in cancer risk, but individually published studies have shown inconclusive results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate the association between CYP3A4*1B (rs2740574 A > G) polymorphism and cancer risk. Eleven studies were included with a total of 3,810 cancer patients and 3,173 healthy controls. We found that the G allele and GG genotype of CYP3A4*1B polymorphism were associated with increased risk of cancers using the fixed effects model (allele model: odds ratio (OR) = 1.24, 95 %CI: 1.09-1.42, P = 0.001; recessive model: OR = 1.77, 95 %CI: 1.30-2.41, P cancer type showed that the G allele and G carrier (AG + GG) of CYP3A4*1B polymorphism had significant associations with increased risk of prostate cancer, but not with breast cancer, leukemia, or other cancers. With further subgroup analysis based on different ethnicities, the results indicated that the GG genotype of CYP3A4*1B polymorphism might increase the risk of cancer among African populations. However, similar associations were not observed among Caucasian and Asian populations. Results from the current meta-analysis indicate that the G allele and GG genotype of CYP3A4*1B polymorphism might be associated with increased cancer risk, especially for prostate cancer among African populations.

  13. Bai-hu-tang, ancient chinese medicine formula, may provide a new complementary treatment option for sepsis.

    Science.gov (United States)

    Lin, Chien-Jung; Su, Yi-Chang; Lee, Cheng-Hung; Li, Tsai-Chung; Chen, Yun-An; Lin, Sunny Jui-Shan

    2013-01-01

    Bai-Hu-Tang (BHT) has been broadly applied to treating the early stage of acute infection with systemic inflammation for two thousand years in Chinese medicine. We explore whether BHT is beneficial in treating sepsis and its effects on proinflammatory cytokine, interleukin-6, and anti-inflammatory cytokine interleukin-10, in which both play key roles in the progress of sepsis. Thirty-six male Sprague-Dawley rats were randomized into six groups, with cecal ligation and puncture (CLP) performed in all but the sham-control group. Rats in CLP + BHT-L6 and CLP + BHT-H6 groups, respectively, received a low (0.45 g/kg) and high doses (0.9 g/kg) of BHT, 6 hrs postoperatively. CLP + BHT-L12 and CLP + BHT-H12 groups, respectively, received low and high doses of BHT, 12 hrs postoperatively. Sham-control and sepsis-control groups received distilled water (1 mL) as vehicle, 6 hrs postoperatively. Serial blood samples were drawn before operation, as baseline, and at 4, 8, and 12 hrs postoperatively for IL-6 and IL-10 assay. All rats were monitored for 3 days for survival study. Rats in the CLP + BHT-H6 group had significantly higher survival rate (80%) and significantly lower levels of both IL-6 and IL-10 at 12 hrs postoperatively than those in the sepsis-control group. Results suggested that BHT may be a new complementary treatment option for sepsis.

  14. Redescription and molecular analysis of Myxobolus shantungensis Hu, 1965 (Myxozoa: Myxosporea) infecting common carp Cyprinus carpio haematopterus.

    Science.gov (United States)

    Liu, Yang; Gu, Zemao; Zhang, Yunchao; Zeng, Lingbing

    2011-12-01

    Myxobolus shantungensis Hu, 1965 infects gill arches of common carp Cyprinus carpio haematopterus (Temminck and Schlegel), causing serious pathological effects on host fish. An inadequate original description and absence of molecular data make accurate early diagnosis challenging. To augment the original description, M. shantungensis is redescribed here using morphological and molecular biological methods. Mature spores of M. shantungensis were ellipsoidal or apple shaped in frontal view and lemon shaped in lateral view, averaging 8.2  ±  0.3 μm (8.0-9.0 μm) ×  10.1 ±  0.5 μm (9.2-11.1 μm)  ×  6.9  ±  0.3 μm (6.0-7.4 μm). Some spores had three to four "V"-shaped valve edge markings on the posterior of the spore. The two equal polar capsules were oval, measuring 4.3  ±  0.3 μm (3.8-5.0 μm)  ×  3.2  ±  0.2 μm (2.8-3.5 μm), situated at the anterior extremity of the spore. Polar filaments coiled with six to seven turns. Scanning electron microscopy revealed that the surface of mature spores of M. shantungensis was generally pitted with a number of irregular ridges in shape. M. shantungensis is also characterized on the molecular level using the sequence of the small subunit ribosomal RNA gene. A BLAST search revealed that this sequence did not match any available sequences in GenBank.

  15. Genetic polymorphisms of CASR and cancer risk: evidence from meta-analysis and HuGE review

    Directory of Open Access Journals (Sweden)

    Jeong S

    2016-02-01

    Full Text Available Sohyun Jeong, Jae Hyun Kim, Myeong Gyu Kim, Nayoung Han, In-Wha Kim, Therasa Kim, Jung Mi Oh College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea Background: CASR gene appears to be involved in cancer biology and physiology. However, a number of studies investigating CASR polymorphisms and cancer risks have presented inconclusive results. Thus, a systematic review and a meta-analysis of the effect of CASR polymorphisms on several cancer risks were performed to suggest a statistical evidence for the association of CASR polymorphisms with cancer risks.Methods: MEDLINE, EMBASE, Web of Science, Scopus, and the HuGE databases were searched. Nineteen articles of case–control and cohort studies were included for the final analysis.Results: The colorectal cancer risk was reduced in proximal (odds ratio [OR] =0.679, P=0.001 and distal (OR =0.753, P=0.026 colon sites with GG genotype of CASR rs1042636 and increased in distal colon site (OR =1.418, P=0.039 with GG genotype of rs1801726 by additive genetic model. The rs17251221 demonstrated noticeable associations that carrying a homozygote variant increases breast and prostate cancer risk considerably.Conclusion: The significant association of CASR polymorphisms with several cancer risks was observed in this review. In particular, the act of CASR polymorphisms as a tumor suppressor or an oncogene differs by cancer site and can be the research target for tumorigenesis. Keywords: rs1042636, rs1801725, rs1801726, systematic review, colorectal cancer

  16. Beta-blockers for hypertension

    Science.gov (United States)

    Wiysonge, Charles S; Bradley, Hazel A; Volmink, Jimmy; Mayosi, Bongani M; Opie, Lionel H

    2017-01-01

    Background Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012. Objectives To assess the effects of beta-blockers on morbidity and mortality endpoints in adults with hypertension. Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015. Selection criteria Randomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults. Data collection and analysis We selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or random-effects meta-analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies

  17. beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis.

    Science.gov (United States)

    Del Senno, L; Pirastu, M; Barbieri, R; Bernardi, F; Buzzoni, D; Marchetti, G; Perrotta, C; Vullo, C; Kan, Y W; Conconi, F

    1985-01-01

    Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in a beta(+), homozygote and in a beta (+), beta(0) 39 (nonsense mutation at codon 39) double heterozygote is approximately 20% and 10% respectively of total non-alpha globin synthesis. Despite some overlapping of the results, similar beta globin synthesis levels have been obtained in 43 beta(+)-thalassaemia patients. This suggests that in the Po river delta region the most common thalassaemic genes are beta(0) 39 and beta(+) IVS I. Images PMID:2580095

  18. The Utility of Human Plasma-Derived Butyrylcholinesterase (huBuChE) as a Therapeutic Measure in the Absence of Pre-Treatment or Conventional Post-Poisoning Therapies Against Nerve Agent

    Science.gov (United States)

    2011-10-01

    Human butyrylcholinesterase (huBuChE) has investigational new drug (IND) status in the U.S. as a pretreatment against organophosphate poisoning in humans...huBuChE) as a therapeutic measure in the absence of pre-treatment or conventional post- poisoning therapies against nerve agent. PRINCIPAL...absence of pre- treatment or conventional post- poisoning therapies against nerve agent. 5a. CONTRACT NUMBER W81WXH-10- -0044 5b. GRANT NUMBER 5c

  19. Smart Beta or Smart Alpha

    DEFF Research Database (Denmark)

    Winther, Kenneth Lillelund; Steenstrup, Søren Resen

    2016-01-01

    Smart beta has become the flavor of the decade in the investment world with its low fees, easy access to rewarded risk premiums, and appearance of providing good investment results relative to both traditional passive benchmarks and actively managed funds. Although we consider it well documented...... that smart beta investing probably will do better than passive market capitalization investing over time, we believe many are coming to a conclusion too quickly regarding active managers. Institutional investors are able to guide managers through benchmarks and risk frameworks toward the same well......-documented smart beta risk premiums and still motivate active managers to avoid value traps, too highly priced small caps, defensives, etc. By constructing the equity portfolios of active managers that resemble the most widely used risk premiums, we show that the returns and risk-adjusted returns measures...

  20. Beta emitters and radiation protection

    DEFF Research Database (Denmark)

    Jødal, Lars

    2009-01-01

    , and 90Y, using data from a freely available database. Bremsstrahlung yields were calculated for 90Y shielded by lead, aluminium, or perspex. Bremsstrahlung spectrum from 90Y shielded by perspex was measured, and attenuation of spectrum by lead was calculated. Whole-body and finger doses to persons...... preparing 90Y-Zevalin were measured. CONCLUSIONS. Good laboratory practice is important to keep radiation doses low. To reduce bremsstrahlung, 90Y should not be shielded by lead but instead perspex (10 mm) or aluminium (5 mm). Bremsstrahlung radiation can be further reduced by adding a millimetre of lead......BACKGROUND. Beta emitters, such as 90Y, are increasingly being used for cancer treatment. However, beta emitters demand other precautions than gamma emitters during preparation and administration, especially concerning shielding. AIM. To discuss practical precautions for handling beta emitters...

  1. A.~()HU

    African Journals Online (AJOL)

    officer training college to improve the professional ... exercises'. ... in 1924 of the first Labour Government, headed by ... infantry tactics and stressed riding skills. At heart, ... sergeant and cadet Prince Henry, third son of .... 'Vorld, are led by men trained at Sandhurst (for stu- .... lurst does not need a 'system' to maintain its high.

  2. Neutrinoless double beta decay experiments

    CERN Document Server

    Zuber, K

    2006-01-01

    The study of neutrinoless double beta decay is of outmost importance for neutrino physics. It is considered to be the gold plated channel to probe the fundamental character of neutrinos and to determine the neutrino mass. From the experimental point about nine different isotopes are explored for the search. After a general introduction follows a short discussion on nuclear matrix element calculations and supportive measurements. The current experimental status of double beta searches is presented followed by a short discussion of the ideas and proposals for large scale experiments.

  3. The microbial oxidation of (-)-beta-pinene by Botrytis cinerea.

    Science.gov (United States)

    Farooq, Afgan; Choudhary, M Iqbal; Tahara, Satoshi; Rahman, Atta-ur; Başer, K Hüsnü Can; Demirci, Fatih

    2002-01-01

    (-)-beta-pinene, a flavor and fragrance monoterpene is an important constituent of essential oils of many aromatic plants. It was oxidized by a plant-pathogenic fungus, Botrytis cinerea to afford four metabolites characterized as (-)-6a-hydroxy-beta-pinene, (-)-4beta,5beta-dihydroxy-beta-pinene, (-)-2beta,3beta-dihydroxypinane, and (-)-4beta-hydroxy-beta-pinene-6-one by detailed spectroscopic studies along with other known metabolites.

  4. A {beta} - {gamma} coincidence; Metodo de coincidencias {beta} - {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Agullo, F.

    1960-07-01

    A {beta} - {gamma} coincidence method for absolute counting is given. The fundamental principles are revised and the experimental part is detailed. The results from {sup 1}98 Au irradiated in the JEN 1 Swimming pool reactor are given. The maximal accuracy is 1 per cent. (Author) 11 refs.

  5. Beta thalassaemia mutations in Turkish Cypriots.

    Science.gov (United States)

    Sozuoz, A; Berkalp, A; Figus, A; Loi, A; Pirastu, M; Cao, A

    1988-01-01

    Using oligonucleotide hybridisation or restriction endonuclease analysis, we have characterised the molecular defect in 94 patients with thalassaemia major and four with thalassaemia intermedia of Turkish Cypriot descent. We found that four mutations, namely beta+ IVS-1 nt 110, beta zero IVS-1 nt, beta+ IVS-1 nt 6, and beta+ IVS-2 nt 745 were prevalent, accounting for 69.9%, 11.7%, 8.7%, and 5.6% respectively of the beta thalassaemia chromosomes. This information may help in the organisation of a large scale prevention programme based on fetal diagnosis of beta thalassaemia by DNA analysis in the Turkish population. PMID:3236356

  6. Cardiovascular effects of ethanol extract of Rubus chingii Hu (Rosaceae) in rats: an in vivo and in vitro approach.

    Science.gov (United States)

    Su, X H; Duan, R; Sun, Y Y; Wen, J F; Kang, D G; Lee, H S; Cho, K W; Jin, S N

    2014-06-01

    Rubus chingii Hu (Rosaceae) is an important traditional Chinese medicine that has been used to improve function of the kidney and treat excessive polyuria. However, the effects of Rubus chingii on the cardiovascular system and its pharmacological mechanisms of action have not been studied. The aim of the present study was to evaluate the cardiovascular effects of ethanol extract of Rubus chingii (ERC) in rats. The changes in systolic blood pressure and heart rate of rats and vascular tone of aortic rings in in vitro were measured using pressure transducer and force transducer, respectively, connected to a multichannel recording system. ERC decreased systolic blood pressure and heart rate in a concentration-dependent manner. ERC induced vasorelaxation in a concentration-dependent manner. The ERC-induced vasorelaxation was not observed in the absence of the endothelium. The vasorelaxant effect of ERC was significantly attenuated by inhibition of endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), or Ca(2+) entry from extracellular sources with L-NAME, ODQ, diltiazem, or extracellular Ca(2+) depletion, respectively. Similarly, an inhibition of Akt with wortmannin attenuated the ERC-induced vasorelaxation. Modulators of the store-operated Ca(2+) entry, thapsigargin, Gd(3+), and 2-aminoethyl diphenylborinate markedly attenuated the ERC-induced vasorelaxation. Furthermore, 4-aminopyridine an inhibitor of voltage-dependent K(+) (KV) channel, significantly attenuated the ERC-induced vasorelaxation. However, tetraethylammonium and glibenclamide, had no significant effect on the ERC-induced vasorelaxation. Indomethacin, atropine, and propranolol had no effects on the ERC-induced vasorelaxation. The present study demonstrates that ERC induces vasorelaxation via endothelium-dependent two-step signaling: an activation of the Ca(2+)-eNOS-NO signaling in the endothelial cells and then subsequent stimulation of the NO-sGC-cGMP-KV channel signaling in the vascular

  7. Beta-carotene as antioxidant

    NARCIS (Netherlands)

    Bast, A.; Plas, R.M. van der; Berg, H. van den; Haenen, G.R.M.M.

    1996-01-01

    Objective: Beta-carotene has been shown to exhibit a good radical-trapping antioxidant activity in vitro. We were interested to see if dietary β-carotene in combination with various intake levels for vitamin A would also inhibit lipid peroxidation. Design: Sixty male Wistar rats received vitamin A (

  8. Beta Cell Workshop 2013 Kyoto

    DEFF Research Database (Denmark)

    Heller, R Scott; Madsen, Ole D; Nielsen, Jens Høiriis

    2013-01-01

    The very modern Kyoto International Conference Center provided the site for the 8th workshop on Beta cells on April 23-26, 2013. The preceding workshops were held in Boston, USA (1991); Kyoto, Japan (1994); Helsingør, Denmark (1997); Helsinki, Finland (2003); El Perello, Spain (2006); Peebles...

  9. Estimating $\\beta$-mixing coefficients

    CERN Document Server

    McDonald, Daniel J; Schervish, Mark

    2011-01-01

    The literature on statistical learning for time series assumes the asymptotic independence or ``mixing' of the data-generating process. These mixing assumptions are never tested, nor are there methods for estimating mixing rates from data. We give an estimator for the $\\beta$-mixing rate based on a single stationary sample path and show it is $L_1$-risk consistent.

  10. A biblioterapia na humanização da assistência hospitalar do Hospital Universitário da Universidade Federal de Santa Catarina – HU/UFSC/Bibliotherapy for the hospital care humanization in the university hospital of Santa Catarina Federal University – HU/UFSC

    Directory of Open Access Journals (Sweden)

    Eva Seitz

    2008-01-01

    Full Text Available Este artigo tem por finalidade apresentar resultados do estudo realizado com pacientes, acompanhantes e funcionários das Unidades de Internação Cirúrgica do Hospital Universitário da Universidade Federal de Santa Catarina (UIC/HU/UFSC. O foco central foi o de verificar até que ponto a prática biblioterapêutica e as atividades de lazer contribuem no processo de Humanização da Assistência Hospitalar dos pacientes internados nas (UIC/HU/UFSC, na percepção dos pacientes, acompanhantes, funcionários da enfermagem e assistentes sociais da referida unidade de internação. Foram entrevistados 16 pacientes, 11 acompanhantes e 13 funcionários da enfermagem e assistentes sociais. As atividades de lazer analisadas neste estudo foram a prática biblioterapêutica, as atividades do grupo Reaja e a dança. Trata-se de uma pesquisa quantitativa e qualitativa. Quanto ao procedimento técnico, a presente pesquisa é classificada como estudo de caso, no qual, utilizou-se, para a coleta dos dados a entrevista estruturada e, cujos resultados demonstram que as atividades contribuem muito na Humanização da Assistência Hospitalar dos pacientes internados na UIC/HU/UFSC. This article has for purpose to present resulted of the study carried through with patients, companions and employees of the Units of Surgical Internment of the University Hospital of the Federal University of Santa Catarina (UIC/HU/UFSC. The central focus was to verify until point the practical library-therapy and the activities of leisure contribute in the process of Humanization of the Hospital Assistance of the patients interned in (UIC/HU/UFSC, in the perception of the patients, companions, employees of the nursing and social assistants of the related unit of internment. 16 patients, 11 companions and 13 social employees of the nursing and assistants had been interviewed. The analyzed activities of leisure in this study had been the practical library-therapy, the activities of

  11. Anti-Hu,Yo antibodies in patients with positive serum AQP4 antibody%水通道蛋白-4抗体阳性患者血清抗Hu、Yo抗体的检测

    Institute of Scientific and Technical Information of China (English)

    龙友明; 单福兰; 解龙昌; 陈梦宇; 郑杨波; 高聪; 杨宁

    2014-01-01

    Objective To evaluate the positive rates of serum anti‐Hu , and anti‐Yo antibodies in patients with positive serum aquaporin‐4 (AQP4) antibodies .Methods A consecutive cohort of 80 subjects were analyzed retrospectively . First , sera of patients were tested for AQP4 antibodies in an indirect immunofluorescence assay employing HEK‐293 cells transected with recombinant human AQP4 .Second ,anti‐Hu ,and anti‐Yo antibodies were tested with monkey cerebellum substrate by an indirect immunofluorescence assay .Results Eighty patients with positive AQP4 antibodies were confirmed in the present study .Only one of the examined sera was positive for anti‐Yo antibody (1.25% , 1/80 ) and none was positive for anti‐Hu antibodies .This patient suffered from optic neuritis and transverse myelitis , ranging over three vertebral segments on spinal MRI .Conclusions Anti‐Hu and anti‐Yo antibodies were rare in our patients with positive serum AQP4 antibodies .%目的:观察抗 Hu 抗体和抗 Yo 抗体在水通道蛋白‐4(AQP4)抗体阳性患者中的出现情况。方法检测收集80例 AQP4抗体阳性患者,以间接免疫荧光方法检血清抗 Hu 抗体、Yo 抗体,并回顾性分析抗 Hu 抗体、抗 Yo 抗体阳性患者的临床资料及诊断。 AQP4抗体检测:先以转染 AQP4基因的人胚肾293细胞结合血清中的 AQP4抗体,之后采用免疫荧光方法检测;抗 Hu 抗体、抗 Yo 抗体检测:先以猴小脑冰冻切片结合血清中的抗体,之后采用免疫荧光法检测。结果80例患者中,均未检测到抗 Hu 抗体,仅1例 NMO 患者血清抗 Yo 抗体阳性。结论抗 Hu 抗体和抗 Yo 抗体在无肿瘤的 AQP4抗体阳性患者中少见。

  12. Beta-2-mikroglobulin ved medicinske sygdomme

    DEFF Research Database (Denmark)

    Hansen, P B; Olsen, Niels Vidiendal

    1989-01-01

    -beta 2M. beta 2M is a sensitive but non-specific parameter in inflammation and infection. Determination of beta 2M in saliva has been found to be of value in Sjögren's syndrome. In HIV-positive patients, a high serum-beta 2M level is a poor prognostic sign. Determinations of CSF-beta 2M in AIDS patients......-interstitial nephropathy, increased quantities of beta 2M are excreted in the urine. If the rate of glomerular filtration is reduced, serum-beta 2M is increased and this is also the case in persons with increased cell division despite normal renal function. Serum-beta 2M is, therefore, raised in numerous malignant...... must be presumed to be of value not only in the diagnosis of cerebral AIDS and other (latent) CNS infections but also to demonstrate complicating cerebral malignant lymphomata at an early stage....

  13. How Do Beta Blocker Drugs Affect Exercise?

    Science.gov (United States)

    ... Aneurysm More How do beta blocker drugs affect exercise? Updated:Aug 22,2017 Beta blockers are a ... about them: Do they affect your ability to exercise? The answer can vary a great deal, depending ...

  14. Interferon Beta-1a Intramuscular Injection

    Science.gov (United States)

    Interferon beta-1a intramuscular injection is used to reduce the number of episodes of symptoms and slow ... and problems with vision, speech, and bladder control). Interferon beta-1a is in a class of medications ...

  15. Interferon Beta-1a Subcutaneous Injection

    Science.gov (United States)

    Interferon beta-1a subcutaneous injection is used to reduce episodes of symptoms and slow the development of ... and problems with vision, speech, and bladder control). Interferon beta-1a is in a class of medications ...

  16. Neutron Beta Decay Studies with Nab

    CERN Document Server

    Baeßler, S; Alonzi, L P; Balascuta, S; Barrón-Palos, L; Bowman, J D; Bychkov, M A; Byrne, J; Calarco, J R; Chupp, T; Vianciolo, T V; Crawford, C; Frlež, E; Gericke, M T; Glück, F; Greene, G L; Grzywacz, R K; Gudkov, V; Harrison, D; Hersman, F W; Ito, T; Makela, M; Martin, J; McGaughey, P L; McGovern, S; Page, S; Penttilä, S I; Počanić, D; Rykaczewski, K P; Salas-Bacci, A; Tompkins, Z; Wagner, D; Wilburn, W S; Young, A R

    2012-01-01

    Precision measurements in neutron beta decay serve to determine the coupling constants of beta decay and allow for several stringent tests of the standard model. This paper discusses the design and the expected performance of the Nab spectrometer.

  17. Traumatic Brain Injury, Microglia, and Beta Amyloid

    OpenAIRE

    Mannix, Rebekah C.; Whalen, Michael J

    2012-01-01

    Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer's Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (A\\(\\beta\\)). Data from both AD and TBI studies suggest that microglia play a central role in A\\(\\beta\\) accumulation after TBI. This paper focuses on the current research on the role of microglia response to A\\(\\beta\\) after TBI.

  18. The beta-decay of Al-22

    NARCIS (Netherlands)

    Achouri, NL; Santos, FDO; Lewitowicz, M; Blank, B; Aysto, J; Canchel, G; Czajkowski, S; Dendooven, P; Emsallem, A; Giovinazzo, J; Guillet, N; Jokinen, A; Larid, AM; Longour, C; Perajarvi, K; Smirnova, N; Stanoiu, M

    2006-01-01

    In an experiment performed at the LISE3 facility of GANIL, we studied the decay of Al-22 produced by the fragmentation of a Ar-36 primary beam. A beta-decay half-life of T-1/2 = 91.1 +/- 0.5ms was measured. The beta-delayed one- and two-proton emission as well as beta-alpha and beta-delayed gamma-de

  19. Neoclassical transport in high [beta] tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Cowley, S.C.

    1992-12-01

    Neoclassical, transport in high [beta] large aspect ratio tokamaks is calculated. The variational method introduced by Rosenbluth, et al., is used to calculate the full Onsager matrix in the banana regime. These results are part of a continuing study of the high [beta] large aspect ratio equilibria introduced in Cowley, et al. All the neoclassical coefficients are reduced from their nominal low [beta] values by a factor ([var epsilon]/q[sup 2][beta])[sup [1/2

  20. Generation of a infectious cDNA clone of highly pathogenic porcine reproductive and respiratory syndrome virus HuN4%高致病性猪繁殖与呼吸综合征病毒HuN4株感染性分子克隆的建立及拯救病毒的鉴定

    Institute of Scientific and Technical Information of China (English)

    张善瑞; 周艳君; 朱建平; 童武; 姜一峰; 童光志

    2011-01-01

    In this study, a infectious cDNA clone of highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) strain HuN4 was generated by cloning of the 6 overlapped RT-PCR fragments into pBlueScript II SK(+), designated pHuN4. In addition, sp6 promoter at 5'-terminus and a Not I site in Poly(A) tail at 3'-terminus were introduced into the cDNA of PRRSV for viral RNA transcription in vitro and the pHuN4 linearization, respectively. Furthmore, the A at 14,680 nt was replaced by G (silent mutation) to generate restriction enzyme Mlu I site as molecular marker for identification of rescued virus. The pHuN4 was linearized and transcribed in vitro, the transcripts were transfected primarily into BHK cells and then Marc 145 cells, the virus was successfully rescued from Marc 145 cells identified by indirect immofluorescent assay and Mlu I digestion. The rescued virus showed similar growth curve to its parental virus HuN4 strain. All the piglets infected with the fifth passage of the rescued virus developed clinical signs at 3 day-past-infection and died within 20 days. The results showed that the rescued virus remained similar biological characterizations as its parental virus. The pHuN4 developed in the study by reverse genetic system might provide a platform for further study on pathogenesis mechanism of highly pathogenic PRRSV.%为构建高致病性猪繁殖与呼吸综合征病毒(PRRSV)感染性克隆,本实验根据PRRSV HuN4株基因组序列设计并合成PRRSV特异性引物,应用RT-PCR技术分6段扩增了PRRSV HuN4株全基因组cDNA.将扩增的各个cDNA部分重叠片段分别克隆于pBlueScript Ⅱ SK(+)载体中构建了感染性重组质粒pHuN4.并在病毒cDNA 5′末端引入sp6启动子序列便于后期的体外转录获得病毒的转录本,在3'末段Poly (A)尾引入Not Ⅰ酶切位点用于线性化pHuN4;此外,将HuN4基因组第14680位的A沉默突变为G产生一个Mlu Ⅰ酶切位点作为鉴定拯救病毒的分子标记.pHu

  1. Biodegradation of chlorpyrifos and its hydrolysis product 3,5,6-trichloro-2-pyridinol by a new fungal strain Cladosporium cladosporioides Hu-01.

    Science.gov (United States)

    Chen, Shaohua; Liu, Chenglan; Peng, Chuyan; Liu, Hongmei; Hu, Meiying; Zhong, Guohua

    2012-01-01

    Intensive use of chlorpyrifos has resulted in its ubiquitous presence as a contaminant in surface streams and soils. It is thus critically essential to develop bioremediation methods to degrade and eliminate this pollutant from environments. We present here that a new fungal strain Hu-01 with high chlorpyrifos-degradation activity was isolated and identified as Cladosporium cladosporioides based on the morphology and 5.8S rDNA gene analysis. Strain Hu-01 utilized 50 mg·L(-1) of chlorpyrifos as the sole carbon of source, and tolerated high concentration of chlorpyrifos up to 500 mg·L(-1). The optimum degradation conditions were determined to be 26.8°C and pH 6.5 based on the response surface methodology (RSM). Under these conditions, strain Hu-01 completely metabolized the supplemented chlorpyrifos (50 mg·L(-1)) within 5 d. During the biodegradation process, transient accumulation of 3,5,6-trichloro-2-pyridinol (TCP) was observed. However, this intermediate product did not accumulate in the medium and disappeared quickly. No persistent accumulative metabolite was detected by gas chromatopraphy-mass spectrometry (GC-MS) analysis at the end of experiment. Furthermore, degradation kinetics of chlorpyrifos and TCP followed the first-order model. Compared to the non-inoculated controls, the half-lives (t(1/2)) of chlorpyrifos and TCP significantly reduced by 688.0 and 986.9 h with the inoculum, respectively. The isolate harbors the metabolic pathway for the complete detoxification of chlorpyrifos and its hydrolysis product TCP, thus suggesting the fungus may be a promising candidate for bioremediation of chlorpyrifos-contaminated water, soil or crop.

  2. El farmacéutico en el contexto de las enfermedades raras y los medicamentos huérfanos The pharmacist, rare diseases and orphan medicines

    Directory of Open Access Journals (Sweden)

    C. Nagore

    2008-01-01

    Full Text Available El tratamiento de las enfermedades raras muchas veces resulta complicado debido a las dificultades que plantean la investigación y desarrollo de medicamentos huérfanos por parte de la industria farmacéutica. Una de las mayores preocupaciones de este grupo de pacientes tan escaso y diverso al mismo tiempo, es el acceso a los fármacos disponibles. La Agencia Europea del Medicamento establece la denominación de medicamentos huérfanos y los incentivos y bases necesarias para su comercialización. La mayoría de los medicamentos huérfanos por sus especiales características, exigen una adecuada vigilancia y control. Los servicios de farmacia hospitalarios están activamente implicados en su gestión y dispensación, así como en un correcto seguimiento farmacoterapéutico de los pacientes.Treatment of rare diseases is often complicated due to the difficulties posed by the research and development of medicines by the pharmacological industry. One of the greatest concerns of this group of patients, which is both scarce and diverse, is access to available medicines. The European Medicine Agency establishes the term orphan medicines and the incentives and bases for their commercialisation. Due to their special characteristics, the majority of orphan medicines require suitable vigilance and control. The hospital pharmacy services are actively involved in their management and supply, as well as in a correct pharmacotherapeutic monitoring of the patients.

  3. Exploiting a novel miR-519c-HuR-ABCG2 regulatory pathway to overcome chemoresistance in colorectal cancer.

    Science.gov (United States)

    To, Kenneth K W; Leung, W W; Ng, Simon S M

    2015-11-01

    Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. While surgery remains the mainstay of treatment for early stage CRC, adjuvant chemotherapy is usually given to reduce the risk of recurrence after colectomy. Overexpression of a multidrug resistance (MDR) transporter ABCG2 in vitro has been shown to cause resistance to 5-fluorouracil (5-FU) and irinotecan, components of the most commonly adopted regimens for treating CRC. Both anticancer drugs are known ABCG2 substrates. An effective way to predict drug response may provide guidance for better cancer treatment. We investigated the effect of ABCG2 dysregulation on cancer cell sensitivity to chemotherapy using pairs of snap-frozen paraffin-embedded archival blocks of human colorectal cancer tissues and their matched non-cancerous colon tissues from CRC patients. In CRC patients responding to chemotherapy, the tumors were found to have remarkable lower ABCG2 expression than the adjacent normal colon tissues. On the contrary, the tumors from patients not responding to 5-FU-based chemotherapy have higher ABCG2 level than the adjacent normal tissues. The high ABCG2 expression in the tumor is associated with the concomitant overexpression of the mRNA binding protein HuR but a low expression of miR-519c because miR-519c is known to target both ABCG2 and HuR. Further investigation in CRC cell lines revealed that the ABCG2 overexpression was caused by an interplay between miR-519c, HuR and the length of the 3' untranslated region (UTR) of ABCG2. These parameters may be further developed as useful biomarkers to predict patient response to adjuvant chemotherapy. Besides being predictive biomarkers, the microRNAs and mRNA binding protein identified may also be potential drug targets for modulating ABCG2 to combat resistance in CRC chemotherapy.

  4. ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model

    Directory of Open Access Journals (Sweden)

    Matsubara Tsukasa

    2010-09-01

    Full Text Available Abstract Background The anti-human Fas/APO-1/CD95 (Fas mouse/human chimeric monoclonal IgM antibody ARG098 (ARG098 targets the human Fas molecule. The cytotoxic effects of ARG098 on cells isolated from RA patients, on normal cells in vitro, and on RA synovial tissue and cartilage in vivo using implanted rheumatoid tissues in an SCID mouse model (SCID-HuRAg were investigated to examine the potential of ARG098 as a therapy for RA. Methods ARG098 binding to each cell was analyzed by cytometry. The effects of ARG098 on several cells were assessed by a cell viability assay in vitro. Effects on the RA synovium, lymphocytes, and cartilage were assessed in vivo using the SCID-HuRAg mouse model. Results ARG098 bound to cell surface Fas molecules, and induced apoptosis in Fas-expressing RA synoviocytes and infiltrating lymphocytes in the RA synovium in a dose-dependent manner. However, ARG098 did not affect the cell viability of peripheral blood mononuclear cells of RA patients or normal chondrocytes. ARG098 also induced apoptosis in RA synoviocytes and infiltrating lymphocytes in the RA synovium in vivo. The destruction of cartilage due to synovial invasion was inhibited by ARG098 injection in the modified SCID-HuRAg mouse model. Conclusions ARG098 treatment suppressed RA synovial hyperplasia through the induction of apoptosis and prevented cartilage destruction in vivo. These results suggest that ARG098 might become a new therapy for RA.

  5. Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huët anomaly.

    Science.gov (United States)

    Maksimova, Nadezda; Hara, Kenju; Nikolaeva, Irina; Chun-Feng, Tan; Usui, Tomoaki; Takagi, Mineo; Nishihira, Yasushi; Miyashita, Akinori; Fujiwara, Hiroshi; Oyama, Tokuhide; Nogovicina, Anna; Sukhomyasova, Aitalina; Potapova, Svetlana; Kuwano, Ryozo; Takahashi, Hitoshi; Nishizawa, Masatoyo; Onodera, Osamu

    2010-08-01

    Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome. To identify a causative gene for SOPH syndrome. Genomewide homozygosity mapping was conducted in 33 patients in 30 families. The disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome. These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huët anomaly.

  6. Biodegradation of chlorpyrifos and its hydrolysis product 3,5,6-trichloro-2-pyridinol by a new fungal strain Cladosporium cladosporioides Hu-01.

    Directory of Open Access Journals (Sweden)

    Shaohua Chen

    Full Text Available Intensive use of chlorpyrifos has resulted in its ubiquitous presence as a contaminant in surface streams and soils. It is thus critically essential to develop bioremediation methods to degrade and eliminate this pollutant from environments. We present here that a new fungal strain Hu-01 with high chlorpyrifos-degradation activity was isolated and identified as Cladosporium cladosporioides based on the morphology and 5.8S rDNA gene analysis. Strain Hu-01 utilized 50 mg·L(-1 of chlorpyrifos as the sole carbon of source, and tolerated high concentration of chlorpyrifos up to 500 mg·L(-1. The optimum degradation conditions were determined to be 26.8°C and pH 6.5 based on the response surface methodology (RSM. Under these conditions, strain Hu-01 completely metabolized the supplemented chlorpyrifos (50 mg·L(-1 within 5 d. During the biodegradation process, transient accumulation of 3,5,6-trichloro-2-pyridinol (TCP was observed. However, this intermediate product did not accumulate in the medium and disappeared quickly. No persistent accumulative metabolite was detected by gas chromatopraphy-mass spectrometry (GC-MS analysis at the end of experiment. Furthermore, degradation kinetics of chlorpyrifos and TCP followed the first-order model. Compared to the non-inoculated controls, the half-lives (t(1/2 of chlorpyrifos and TCP significantly reduced by 688.0 and 986.9 h with the inoculum, respectively. The isolate harbors the metabolic pathway for the complete detoxification of chlorpyrifos and its hydrolysis product TCP, thus suggesting the fungus may be a promising candidate for bioremediation of chlorpyrifos-contaminated water, soil or crop.

  7. THE ALPHA/BETA-HYDROLASE FOLD

    NARCIS (Netherlands)

    OLLIS, DL; CHEAH, E; CYGLER, M; FROLOW, F; FRANKEN, SM; HAREL, M; REMINGTON, SJ; SILMAN, [No Value; SCHRAG, J; SUSSMAN, JL; VERSCHUEREN, KHG; GOLDMAN, A

    1992-01-01

    We have identified a new protein fold-the alpha/beta-hydrolase fold-that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta-sheet, not barrel, of eight beta-sheets connected by alpha-helices. These

  8. Beta-lactamases in Enterobacteriaceae in broilers

    NARCIS (Netherlands)

    Dierikx, C.M.

    2013-01-01

    Resistance to cephalosprins due to the production of extended spectrum beta-lactamases (ESBLs) or plasmid mediated AmpC beta-lactamases is increasingly found in infections in humans outside the hospital. The genes encoding for these beta-lactamases are located on mobile DNA (plasmids), which can be

  9. THE ALPHA/BETA-HYDROLASE FOLD

    NARCIS (Netherlands)

    OLLIS, DL; CHEAH, E; CYGLER, M; FROLOW, F; FRANKEN, SM; HAREL, M; REMINGTON, SJ; SILMAN, [No Value; SCHRAG, J; SUSSMAN, JL; VERSCHUEREN, KHG; GOLDMAN, A

    1992-01-01

    We have identified a new protein fold-the alpha/beta-hydrolase fold-that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta-sheet, not barrel, of eight beta-sheets connected by alpha-helices. These

  10. Beta-lactamases in Enterobacteriaceae in broilers

    NARCIS (Netherlands)

    Dierikx, C.M.

    2013-01-01

    Resistance to cephalosprins due to the production of extended spectrum beta-lactamases (ESBLs) or plasmid mediated AmpC beta-lactamases is increasingly found in infections in humans outside the hospital. The genes encoding for these beta-lactamases are located on mobile DNA (plasmids), which can be

  11. Higher-Order Beta Matching with Solutions in Long Beta-Eta Normal Form

    DEFF Research Database (Denmark)

    Støvring, Kristian

    2006-01-01

    up to beta-eta equivalence is a long-standing open problem.We show that higher-order matching up to beta-eta equivalence is decidable if and only if a restricted form of higher-order matching up to beta equivalence is decidable: the restriction is that solutions must be in long beta-eta normal form....

  12. A novel cantharidin analog N-Benzylcantharidinamide reduces the expression of MMP-9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji-Yeon; Chung, Tae-Wook; Choi, Hee-Jung [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Lee, Chang Hyun [Department of Anatomy, College of Korean Medicine, Woosuk University, Wanju-gun, Jeonbuk (Korea, Republic of); Eun, Jae Soon; Han, Young Taek [College of Pharmacy, Woosuk University, Wanju-gun, Jeonbuk (Korea, Republic of); Choi, Jun-Yong [Department of Internal Medicine, Korean Medicine Hospital, School of Korean Medicine, Pusan National University, Yangsan 626-870 (Korea, Republic of); Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Kim, So-Yeon; Han, Chang-Woo [Department of Internal Medicine, Korean Medicine Hospital, School of Korean Medicine, Pusan National University, Yangsan 626-870 (Korea, Republic of); Jeong, Han-Sol, E-mail: jhsol33@pusan.ac.kr [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Ha, Ki-Tae, E-mail: hagis@pusan.ac.kr [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of)

    2014-05-02

    Highlights: • We examined the inhibition of N-Benzylcantharidinamide on MMP-9-mediated invasion. • Unlike cantharidin, N-Benzylcantharidinamide has very low toxicity on Hep3B cells. • The reduced MMP-9 expression was due to HuR-mediated decrease of mRNA stability. • We suggest N-Benzylcantharidinamide as a novel inhibitor of MMP-9-related invasion. - Abstract: Invasion and metastasis are major causes of malignant tumor-associated mortality. The present study aimed to investigate the molecular events underlying inhibitory effect of N-Benzylcantharidinamide, a novel synthetic analog of cantharidin, on matrix metalloproteinase-9 (MMP-9)-mediated invasion in highly metastatic hepatocellular carcinoma Hep3B cells. In this investigation, among six analogs of cantharidin, only N-Benzylcantharidinamide has the inhibitory action on MMP-9 expression at non-toxic dose. The MMP-9 expression and invasion of Hep3B cells were significantly suppressed by treatment of N-Benzylcantharidinamide in a dose-dependent manner. On the other hand, the transcriptional activity of MMP-9 promoter and nuclear levels of NF-κB and AP-1 as the main transcriptional factors inducing MMP-9 expression were not affected by it although the level of MMP-9 mRNA was reduced by treatment of N-Benzylcantharidinamide. Interestingly, the stability of MMP-9 mRNA was significantly reduced by N-Benzylcantharidinamide-treatment. In addition, the cytosolic translocation of human antigen R (HuR), which results in the increase of MMP-9 mRNA stability through interaction of HuR with 3′-untranslated region of MMP-9 mRNA, was suppressed by treatment of N-Benzylcantharidinamide, in a dose-dependent manner. Taken together, it was demonstrated, for the first time, that N-Benzylcantharidinamide suppresses MMP-9 expression by reducing HuR-mediated MMP-9 mRNA stability for the inhibition of invasive potential in highly metastatic Hep3B cells.

  13. Reflexiones bioéticas en torno a las enfermedades raras y huérfanas con impacto en el sistema bucodentario

    Directory of Open Access Journals (Sweden)

    Gilberto Cely Galindo

    2011-01-01

    Full Text Available Este artículo está dirigido a odontopediatras que forman parte de grupos interdisciplinarios de investigación y terapia clínica, a los pacientes y sus familias con problemas genéticos de las llamadas "enfermedades raras y huérfanas". Estas enfermedades sistémicas tienen repercusiones severas bucodentales. El énfasis lo ponemos en las reflexiones bioéticas que orientan la acción investigativa y terapéutica.

  14. Did Hu Shi Really Believe in Traditional Chinese Medicine%胡适对中医究竟持什么态度

    Institute of Scientific and Technical Information of China (English)

    祖述宪

    2001-01-01

    胡适是20世纪初中国新文化运动的领袖和思想家,但是,80年代后期以来,我国出版的有关他的生平的著作中,根据胡适所作的“题陆仲安秋室研经图”,认为中医陆仲安早年治愈过他的“糖尿病、慢性肾炎和心脏病”,因而断言胡适相信中医药。仔细检阅胡适的日记、书信和文章,可以得出完全不同的结论。尽管1920—1921年胡适生的那场病,开始时有医生怀疑可能是心脏病或肾炎,但很快就否定了。胡适虽然死于心肌梗塞,但他第一次冠心病发作是1938年底。实际上,中医陆仲安为他治疗的只不过是胡适所说的“小病”,是自限性的,而且胡适一再申明他根本不曾生过糖尿病和慢性肾炎。上述陆仲安治愈胡适糖尿病等疾病的说法纯属以讹传讹,或有意夸张造谣,这件事在中医界至今仍有影响。胡适自称是“信仰西医的人”,并且支持他的友人批评中医,这些批评在今天仍然具有重要的现实意义。%Dr.Hu Shi(or Hu Shih,1891—1962),pioneer of China's New CulturalMovement in the early 20th century,is not only a great thinker but also the leader of the Vernacular Movement and the subsequent literary revolution in China.His progressive and scientific attitude to academic research is epitomized by his advocacy of “dare to propose new hypotheses and then subject them to rigorous and methodical examination”.Several books published since the late 1980's claim that Hu Shi was a believer in traditional Chinese medicine(TCM).The basis for this assertion is his inscription of a painting titled “Lu Zhong-an Studying Medical Classics in Autumn” in 1921,which was done in gratitude after Hu Shi was cured by the practitioner of Chinese medicine Lu Zhong-an of diabetes,chronic nephritis and heart disease.However,a thorough review of Hu Shi's diary,letters and articles reveals that though he suffered his first heart attack in

  15. Nuevas citas y huéspedes de Phenacoccus para la Argentina (Hemiptera: Pseudococcidae New records and host plants of Phenacoccus from Argentina (Hemiptera: Pseudococcidae

    Directory of Open Access Journals (Sweden)

    María C. Granara de Willink

    2003-12-01

    Full Text Available Se cita por primera vez para la Argentina a: Phenacoccus madeirensis Green, Phenacoccus manihoti Matile-Ferrero y Phenacoccus solenopsis Tinsley y se dan a conocer nuevos huéspedes de Phenacoccus crassus Granara de Willink, Phenacoccus parvus Morrison y Phenacoccus similis Granara de Willink.Phenacoccus madeirensis Green, Phenacoccus manihoti Matile-Ferrero and Phenacoccus solenopsis Tinsley, first records from Argentina and new hosts plants of Phenacoccus crassus Granara de Willink, Phenacoccus parvus Morrison y Phenacoccus similis Granara de Willink.

  16. Efecto de una intervención educativa sobre los conocimientos de teniasis/cisticercosis en una comunidad rural de Huánuco, Perú 2005

    OpenAIRE

    Elsa Palacios-Flores; Eler Borneo-Cantalicio

    2008-01-01

    Objetivo. Evaluar el efecto de una intervención educativa sobre los conocimientos de teniasis/cisticercosis en los pobladores de la localidad de Queropalca, Huánuco. Materiales y métodos. Se realizó un ensayo comunitario, en el cual se aplicó una estrategia educativo comunicacional sobre los factores de riesgo de teniasis/cisticercosis, consistente en metodologías participativas de visitas casa en casa y campañas de promoción en toda la jurisdicción durante seis meses (junio a diciembre del 2...

  17. Un mecenas de la educación: Francisco de Solís, fundador del Colegio Menor de Huérfanos

    Directory of Open Access Journals (Sweden)

    Miguel Á. MARTÍN SÁNCHEZ

    2009-11-01

    Full Text Available RESUMEN: Durante el siglo XVI se fundaron en la Universidad de Salamanca multitud de colegios universitarios. Uno de esos colegios, fue el menor de la Concepción de Huérfanos, primer colegio universitario que se funda para amparar niños pobres y huérfanos. El fundador de este colegio fue Francisco de Solís Quiñones y Montenegro, obispo de Bagnorea, secretario y médico particular de Paulo III, entre otras cosas. Este mecenas de la educación, decidió invertir su fortuna en la construcción y dotación de un colegio donde niños pobres y huérfanos, preferiblemente de la ciudad de Salamanca, pudiesen estudiar en la Universidad hasta graduarse en la ciencia que eligiesen. La figura de tan ilustre salmantino ha pasado prácticamente desapercibida, a pesar de su relevancia. Con este trabajo se pretende dar a conocer una de las personalidades más relevantes del panorama renacentista salmantino, por la importancia y trascendencia social y educativa que tuvo su obra.ABSTRACT: During the 16* century, a lot of colleges were founded at the University of Salamanca. One of those colleges, was the Concepción de Huérfanos Minor College, the first college that is founded for protecting poor children and orphans. This college founder was Francisco de Solís Quiñones y Montenegro, bishop of Bagnorea, secretary and personal physician of Paulo III, among other things. This patron of education, decided to spend his fortune on building and endowment of a school where poor children and orphans, in the town of Salamanca preferably, were able to go to university until they graduated in the science they chose. This Salamancan s outstanding figure has gone unnoticed in spite of his importance. In this work, it's tried to introduce one of the most important personalities in Salamancan Renaissance panorama, because of the importance and social and educative implications his work had.

  18. Liver iron is a major regulator of hepcidin gene expression via BMP/SMAD pathway in a rat model of chronic renal failure under treatment with high rHuEPO doses.

    Science.gov (United States)

    Ribeiro, Sandra; Garrido, Patrícia; Fernandes, João; Rocha-Pereira, Petronila; Costa, Elísio; Belo, Luís; Reis, Flávio; Santos-Silva, Alice

    2016-05-01

    Hepcidin is the major central regulator of iron metabolism, controlling iron absorption and mobilization. Considering its interaction with several factors that are altered in chronic kidney disease (CKD), particularly in hyporesponsive CKD patients under therapy with high recombinant human erythropoietin (rHuEPO) doses, it was aimed to study the impact of increasing rHuEPO doses on the regulation of iron-hepcidin metabolism. The blood, cellular, and tissue studies, using the remnant kidney rat model of CKD induced by 5/6 nephrectomy, under rHuEPO (100, 200, 400, and 600 IU/Kg body weight [BW]/week) treatment during 3 weeks were performed. It was found that the rHuEPO stimulus triggered a first wave to achieve correction of anemia, by inhibiting hepcidin synthesis, favoring erythropoiesis and iron absorption; this continuous stimulus enhanced iron absorption leading to iron overload, as showed by the hepatic iron deposits found in rats treated with higher rHuEPO dose that seems to trigger the upregulation of hepcidin synthesis through the activation of the BMP6/SMAD pathway. The data suggested that liver iron overload was an important stimuli for hepcidin synthesis, stronger than the inhibitory effect of high rHuEPO doses; moreover, the findings raised the hypothesis that when high inflammation (triggering hepcidin expression) was associated with increased iron stores in hemodialysis patients, hepcidin expression was also upregulated via BMP6, enhancing hepcidin synthesis, leading, therefore, to worsening of anemia and, eventually, to a hyporesponse/resistance to rHuEPO therapy. © 2016 BioFactors, 42(3):296-306, 2016.

  19. Synthesis of new 10 beta-propargylic and 11 beta-allenic steroidal spirolactones.

    Science.gov (United States)

    Faraj, H; Aumelas, A; Claire, M; Rondot, A; Auzou, G

    1991-11-01

    As part of continuing studies on the synthesis of new, biologically interesting 11 beta-substituted steroidal spirolactones, we describe here the competition between 10 beta-propargylation and 11 beta-allenylation. Grignard addition of allenyl magnesium bromide to an appropriate 5,10-epoxy-9(11)-olefin provides 10 beta-propargylation or 11 beta-allenylation. The role of the catalytic effect of copper chloride and of the solvent is evaluated. Confirmation of the structural assignments of these new 3,3-ethylenethioxy-10 beta-propargyl (or 11 beta-allenyl)-19-nor-17 alpha-pregna-4,9-diene-21,17-carbolactones is reported.

  20. beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis.

    OpenAIRE

    del Senno, L; Pirastu, M; Barbieri, R.; De Bernardi, F.; Buzzoni, D; Marchetti, G.; Perrotta, C; Vullo, C; Kan, Y W; Conconi, F

    1985-01-01

    Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in...

  1. Beta genus papillomaviruses and skin cancer.

    Science.gov (United States)

    Howley, Peter M; Pfister, Herbert J

    2015-05-01

    A role for the beta genus HPVs in keratinocyte carcinoma (KC) remains to be established. In this article we examine the potential role of the beta HPVs in cancer revealed by the epidemiology associating these viruses with KC and supported by oncogenic properties of the beta HPV proteins. Unlike the cancer associated alpha genus HPVs, in which transcriptionally active viral genomes are invariably found associated with the cancers, that is not the case for the beta genus HPVs and keratinocyte carcinomas. Thus a role for the beta HPVs in KC would necessarily be in the carcinogenesis initiation and not in the maintenance of the tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Specific Triazine Herbicides Induce Amyloid-beta(42) Production

    NARCIS (Netherlands)

    Portelius, Erik; Durieu, Emilie; Bodin, Marion; Cam, Morgane; Pannee, Josef; Leuxe, Charlotte; Mabondzo, Aloise; Oumata, Nassima; Galons, Herve; Lee, Jung Yeol; Chang, Young-Tae; Stuber, Kathrin; Koch, Philipp; Fontaine, Gaelle; Potier, Marie-Claude; Manousopoulou, Antigoni; Garbis, Spiros D.; Covaci, Adrian; Van Dam, Debby; De Deyn, Peter; Karg, Frank; Flajolet, Marc; Omori, Chiori; Hata, Saori; Suzuki, Toshiharu; Blennow, Kaj; Zetterberg, Henrik; Meijer, Laurent

    2016-01-01

    Proteolytic cleavage of the amyloid-beta protein precursor (A beta PP) ecretases leads to extracellular release of amyloid-beta (A beta) peptides. Increased production of A beta(42) over A beta(40) and aggregation into oligomers and plaques constitute an Alzheimer's disease (AD) hallmark. Identifyin

  3. Specific Triazine Herbicides Induce Amyloid-beta(42) Production

    NARCIS (Netherlands)

    Portelius, Erik; Durieu, Emilie; Bodin, Marion; Cam, Morgane; Pannee, Josef; Leuxe, Charlotte; Mabondzo, Aloise; Oumata, Nassima; Galons, Herve; Lee, Jung Yeol; Chang, Young-Tae; Stuber, Kathrin; Koch, Philipp; Fontaine, Gaelle; Potier, Marie-Claude; Manousopoulou, Antigoni; Garbis, Spiros D.; Covaci, Adrian; Van Dam, Debby; De Deyn, Peter; Karg, Frank; Flajolet, Marc; Omori, Chiori; Hata, Saori; Suzuki, Toshiharu; Blennow, Kaj; Zetterberg, Henrik; Meijer, Laurent

    2016-01-01

    Proteolytic cleavage of the amyloid-beta protein precursor (A beta PP) ecretases leads to extracellular release of amyloid-beta (A beta) peptides. Increased production of A beta(42) over A beta(40) and aggregation into oligomers and plaques constitute an Alzheimer's disease (AD) hallmark.

  4. Tafonomia del yacimiento de vertebrados pleistoceno de Huéscar-1 (Granada, españa

    Directory of Open Access Journals (Sweden)

    Alberdi, M. T.

    2003-08-01

    Full Text Available This work analyses the sedimentary and taphonomic processes that induced the selective preservation and spatial distribution of Húescar-1 bone assemblage (early Galerian. The bone fossil remains are associated with an alluvial fan system that flowed into a lacustrine area with calcareous sedimentation. The fossils show numerous scratch and abrasion marks produced during their transportation as channel lag. The remains appear in three sedimentological settings: in paleochannel filling-up sequences, in pockets built at the outlet of the channels in the lacustrine area, and scattered within calcareous silts. Nevertheless, most of them are found in the second instante. The cumulative process was attritional as pointed out by the mortality profiles of Equus altidens and could be explained by selective predation and/or seasonal bone accumulation. The notably small number of artiodactyl species, particularly in the typical foms of bush or forest habitats and the presence of amphibious forms (Hippopotamus are indicative of an open grassland habitat. The aquatic birds represent the autochthonous component of the association. For each bone recovered severa1 variables were measured, the data obtained underwent graphic and statistical treatment that provided useful information for the site taphonomic interpretation.Se estudia el conjunto de procesos sedimentarios y rasgos tafonómicos que condicionaron la preservación selectiva y disposición espacial de los restos de vertebrados que forman el yacimiento de edad Galeriense inferior de Huéscar-l. Los restos óseos están asociados a un sistema de abanicos aluviales que desembocaba en una zona lacustre carbonatada amplia. Es un conjunto transportado donde los restos muestran numerosas señales de abrasión y arrastre. Los restos óseos aparecen en tres situaciones sedimentológicas: carga de fondo en el relleno de los paleocanales, bolsadas formadas en el punto de la desembocadura y dispersos espor

  5. Future double beta decay experiments

    Energy Technology Data Exchange (ETDEWEB)

    Piquemal, F. [Laboratoire Souterrain de Modane, Modane (France); Centre d' Etudes Nucleaire, Bordeaux-Gradignan (France)

    2013-02-15

    The search of neutrinoless double beta decay is very challenging because of the expected half-life of the process and the backgrounds from the natural radioactivity. Many projects exist to try to reach a sensitivity of ∼50 meV on the effective neutrino mass corresponding to a mass of isotopes of ∼100 kg. In this article some of the futur projects are presented.

  6. Abstraction Mechanisms in the BETA Programming Language

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger

    1983-01-01

    . It is then necessary that the abstraction mechanisms are powerful in order to define more specialized constructs. BETA is an object oriented language like SIMULA 67 ([SIMULA]) and SMALLTALK ([SMALLTALK]). By this is meant that a construct like the SIMULA class/subclass mechanism is fundamental in BETA. In contrast...... to SMALLTALK, BETA is a language in the ALGOL 60 ([ALGOL]) family. SIMULA 67 is a system description and a programming language. The DELTA language ([DELTA]) is a system description language only, allowing description of full concurrency, continuous change and component interaction, developed from a SIMULA......The BETA programming language is developed as part of the BETA project. The purpose of this project is to develop concepts, constructs and tools in the field of programming and programming languages. BETA has been developed from 1975 on and the various stages of the language are documented in [BETA...

  7. Myokardinfarkt und Beta-Blocker

    Directory of Open Access Journals (Sweden)

    Stühlinger H-G

    2003-01-01

    Full Text Available Im Rahmen eines akuten koronaren Syndroms (akuter Herzinfarkt, Angina pectoris kommt es, aufgrund eines Ungleichgewichtes zwischen Angebot und Bedarf, zu einem akuten Mangel an Sauerstoff im Herzmuskel. Ursache ist eine reduzierte Sauerstoffzufuhr durch verengte bzw. verschlossene Gefäße. Bis zur Behebung der Ursache vergehen oft mehrere Stunden. In dieser Phase muß - durch Verminderung des Sauerstoffbedarfs im Herzmuskel - eine Verlangsamung der Nekroseentwicklung erreicht werden. Das Ausmaß der Nekrose wird reduziert, somit die für die Langzeitprognose wichtige Linksventrikelfunktion verbessert. Eine Verminderung des Sauerstoffbedarfs erreicht man durch kontrollierte Frequenzsenkung mittels intravenöser Beta-Blockade. In optimaler Weise wird diese Methode durch die Anwendung eines kardioselektiven Beta-Blockers mit kurzer Halbwertszeit durchgeführt. Beta-Blocker haben nicht nur auf die Nekroseentwicklung, sondern auch auf die Inzidenz von Rhythmusstörungen - besonders in der Akutphase - Auswirkungen. Vor allem die mit dieser therapeutischen Maßnahme verbundene Reduktion von Kammerflimmern ist von großer Bedeutung.

  8. A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family.

    Science.gov (United States)

    Morell, R; Friedman, T B; Moeljopawiro, S; Hartono; Soewito; Asher, J H

    1992-07-01

    Waardenburg syndrome type 1 (WS1) is an autosomal dominant disorder characterized by deafness, dystopia canthorum, heterochromia iridis, white forelock, and premature greying. A similar phenotype is caused in the mouse by mutations in the Pax-3 gene. This observation, together with comparisons of conserved syntenies in the murine and human genetic maps, suggested that at least some WS1 mutations should occur in HuP2, the probable human homolog of Pax-3. Two mutations in the HuP2 sequence of individuals with WS1 have been reported recently. Both of them occur in the highly conserved paired box region of the gene, which encodes a DNA binding domain. The functional consequences of these mutations are at present speculative. We report here a 14 bp deletion in the paired domain encoded by exon 2 of HuP2 in an Indonesian family segregating for WS1. This frameshift mutation results in a premature termination codon in exon 3. The HuP2 product is a truncated protein lacking most of the paired domain and all of the predicted homeo domain. We propose that the WS1 phenotype in this family is due to loss of function of HuP2 and discuss two mechanisms for the dominant effect of this mutation.

  9. Tissue-specific promoter usage and diverse splicing variants of found in neurons, an ancestral Hu/ELAV-like RNA-binding protein gene of insects, in the direct-developing insect Gryllus bimaculatus.

    Science.gov (United States)

    Watanabe, T; Aonuma, H

    2014-02-01

    Hu/ELAV-like RNA-binding proteins (RBPs) are involved in the post-transcriptional regulation of RNA metabolism including splicing, transport, translational control and turnover. The Hu/ELAV-like RBP genes are predominantly expressed in neurons, and are therefore used as common neuronal markers in many animals. Although the expression patterns and functions of the Hu/ELAV-like RBP genes have been extensively studied in the model insect Drosophila melanogaster, little is known in basal direct-developing insects. In the present study, we performed an identification and expression analysis of the found in neurons (fne) gene, an ancestral insect Hu/ELAV-like RBP gene, in the cricket Gryllus bimaculatus. Contrary to expectation that the Gryllus fne transcript would be predominantly expressed in the nervous system, expression analysis revealed that the Gryllus fne gene is expressed broadly. In addition, we discovered that alternative promoter usage directs tissue-specific and embryonic stage-dependent regulation of fne expression, and that alternative splicing contributes to the generation of diverse sets of fne transcripts. Our data provide novel insights into the evolutionary diversification of the Hu/ELAV-like RBP gene family in insects. © 2013 The Royal Entomological Society.

  10. HU Sirong distinguishes key points of treating cor pulmonale heart failure%胡思荣辨治肺心病心衰

    Institute of Scientific and Technical Information of China (English)

    左明晏

    2016-01-01

    胡思荣教授从事中、西医临床及科研工作40余年,积累了丰富的医疗经验。胡师精于仲景学说,兼通温病各家诸说,擅长运用相关理论辨治肺心病心衰。提倡从痰饮论治肺心病心衰,认为肺心病阳虚为本,痰饮为基本病因,以温化痰饮为主--务,灵活运用温药除其湿,采用中病既止之法则。%Professor HU Sirong engaged in clinical and scientific research between Chinese and western medicine more than 40 years,has accumulated rich experience in health care. Hu teacher skilled in zhang zhongjing theory,and warm disease all said,are good at using relevant theory of treating cor pulmonale heart failure. Advocates from phlegm retention differentiation of cor pulmonale heart failure,thought that Yang deficiency and phlegm retention as the basic etiology,phlegm drink warm as the main priority,and flexible use of medicine in addition to the wet warm,adopt the rules of disease in both check.

  11. El zorro Andino, P seudalopes P seudalopes P culpaeus , un nuevo huésped para Corynosoma obtuscens (Acanthocephala en el Perú*

    Directory of Open Access Journals (Sweden)

    Manuel Tantaleán

    2013-04-01

    Full Text Available Se describe la presencia de Corynosoma obtuscens Lincicome, 1943 (Acanthocephala, Polymor- Corynosoma obtuscens L i n c i c o m e , 1 9 4 3 ( A c a n t h o c e p h a l a , P o l y m o r - Corynosoma obtuscens phidae en el intestino delgado del zorro andino Pseudalopex culpaeus (Molina, 1782 procedente Pseudalopex culpaeus ( M o l i n a , 1 7 8 2 p r o c e d e n t e Pseudalopex culpaeus de San Juan de Marcona, Departamento de Ica, Perú. Esta es la segunda vez que se registra la infección natural de un mamífero terrestre por C. obtuscens en el Perú, por lo que se considera C. obtuscens en el Perú, por lo que se considera C. obtuscens a P. culpaeus como huésped defi nitivo accidental P. culpaeus como huésped defi nitivo accidental P. culpaeus ; además se comenta la posibilidad de que éste acantocefalo infecte al hombre.

  12. Spatio-Temporal Patterns of Urban-Rural Development and Transformation in East of the “Hu Huanyong Line”, China

    Directory of Open Access Journals (Sweden)

    Zhichao Hu

    2016-02-01

    Full Text Available Urban-rural development and transformation is profoundly changing the socioeconomic system as well as the natural environment. The study uses the AHP (Analytic Hierarchy Process method to construct a top-down index of human activity based around five dimensions (population, land, industry, society, and environment to evaluate the spatial characteristics in the region east of the Hu Huanyong line, China, in 1994 and 2010. Then, we investigate the spatial-temporal pattern using the methods of hotspot analysis, local Moran’s I index and Pearson correlation coefficient. The calculation showed that: (1 northeast China was experiencing an economic recession during study period, and the implementation of revitalization plan have not controlled the recession trend yet; (2 Pearson correlation analysis showed that the improvement of population quality promote the development of industry and society systems significantly during study period; and (3 negative correlation between Population Development Index (PDI change and Population Transformation Index (PTI change (along with the Society Transformation Index (STI change and Industry Transformation Index (ITI change reflected that east of the Hu Huanyong line, China was in a “demographic dividend” period. Then, with the help of SOFM neural network algorithm, we divided the study area into six types of region, and found that municipalities, provincial capitals, Yangtze River Delta region and cities on the North China Plain owned the greatest development, while cities in southwest and northeast China showed relatively poor development during study period.

  13. Hepatitis B Virus X Protein Stimulates Proliferation, Wound Closure and Inhibits Apoptosis of HuH-7 Cells via CDC42

    Science.gov (United States)

    Xu, Yongru; Qi, Yingzi; Luo, Jing; Yang, Jing; Xie, Qi; Deng, Chen; Su, Na; Wei, Wei; Shi, Deshun; Xu, Feng; Li, Xiangping; Xu, Ping

    2017-01-01

    Chronic hepatitis B virus (HBV) infection has been considered as the major cause of hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) has been reported to be oncogenic. The underlying mechanisms of HBV-related HCC are not fully understood, and the role played by the HBx protein in HBV induced carcinogenesis remains controversial. CDC42, a member of the Rho GTPase family, has been reported to be overexpressed in several different cancers, including HBV-related HCC. However, the specific role of CDC42 in HCC development remains unclear. Here, we investigated the cellular mechanisms by which CDC42 was responsible for the higher proliferation of HuH-7 cells mediated by HBx. We found that the expression level of CDC42 and its activity were significantly increased in HuH-7-HBx cells. The deficiency of CDC42 using the CRISPR/Cas9 system and inhibition by specific inhibitor CASIN led to the reduction of HBx-mediated proliferation. Furthermore, we observed that IQ Motif Containing GTPase Activating Protein 1 (IQGAP1), the downstream mediator of the CDC42 pathway, might be involved in the carcinogenesis induced by HBx. Therefore, the HBx/CDC42/IQGAP1 signaling pathway may potentially play an important role in HBx-mediated carcinogenesis. PMID:28282856

  14. Analysis of the spatiotemporal expression of major genes in the TGF-β/Smad signaling pathway and correlation analysis using Hu sheep muscle tissue.

    Science.gov (United States)

    Wang, Q Z; Su, R; Lv, X Y; Gao, W; Chen, L; Bao, J J; Yu, J R; Wang, L H; Sun, W

    2016-05-23

    The mRNA expression levels of key genes (Smads, MSTN, and MyoG) in the TGF-β/Smad signaling pathway in Hu sheep at different growth stages (2 days, 2 months, and 6 months of age) and in different skeletal muscles (longissimus dorsi muscle and soleus muscle) and different genders were detected; and correlation of the Smad family (Smad2, Smad3, Smad4, and Smad7), MSTN, MyoG expressions was analyzed in Hu sheep. The results showed that the expression of Smads was higher in the soleus muscle than in the longissimus dorsi muscle; the expressions of Smad2, Smad3, and Smad4 were significantly higher in 2-day-old sheep than in sheep belonging to the other age groups (P muscle tissues, expression of Smad2 was significantly positively correlated (P < 0.01) with that of Smad3. The expression of Smad3 was significantly positively correlated (P < 0.01) with that of Smad4, which showed that the Smad family genes could have an inhibitory effect on the TGF-β/Smad signaling pathway.

  15. HuR and TIA1/TIAL1 Are Involved in Regulation of Alternative Splicing of SIRT1 Pre-mRNA

    Directory of Open Access Journals (Sweden)

    Wenhui Zhao

    2014-02-01

    Full Text Available SIRT1 is a pleiotropic protein that plays critical and multifunctional roles in metabolism, senescence, longevity, stress-responses, and cancer, and has become an important therapeutic target across a range of diseases. Recent research demonstrated that SIRT1 pre-mRNA undergoes alternative splicing to produce different isoforms, such as SIRT1 full-length and SIRT1-∆Exon8 variants. Previous studies revealed these SIRT1 mRNA splice variants convey different characteristics and functions to the protein, which may in turn explain the multifunctional roles of SIRT1. However, the mechanisms underlying the regulation of SIRT1 alternative splicing remain to be elucidated. Our objective is to search for new pathways that regulate of SIRT1 alternative splicing. Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances: HuR increased SIRT1-∆Exon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-∆Exon8 mRNA levels. This study provides novel insight into how the alternative splicing of SIRT1 pre-mRNA is regulated, which has fundamental implications for understanding the critical and multifunctional roles of SIRT1.

  16. From the Ethnic History of Asia – the Dōnghú, Wūhuán and Xiānbēi Proto-Mongolian Tribes

    Directory of Open Access Journals (Sweden)

    Nenad Vidaković

    2012-04-01

    Full Text Available The aim of this paper is to present the history of the Dōnghú, Wūhuán and Xiānbēi Proto-Mongolian tribes in the period from the 4th century B.C. to the end of the 3rd century A.D. The history of the ancient nomadic peoples who lived north of China is written in Chinese dynasty chronicles. Proto-Mongolian tribes from the 1st century B.C. are called Dōnghú in Chinese sources. The earliest news on them originates from the Warring States Period (4th – 3rd century B.C., and tells of a conflict with the northern Chinese states. Other types of sources on the history of the Proto-Mongolian tribes are archaeological findings, which associate Mongolian ethnogenesis with slab grave cultures and the Lower Xiàjiādiàn. Linguists find the materials for the research on Mongolian ethnogenesis in the Altaic linguistic family, which the Mongolian language belongs to as well. Based on the mentioned sources, the change in the political situation in the steppes at the end of the 3rd century B.C., when the people of Xiōngnú created a powerful state and conquered the Dōnghúes, is described in the paper. The remains of the shattered Dōnghúes, who had mostly migrated to the north, have been recorded in Chinese chronicles under new topoethnonyms: Xiānbēi and Wūhuán. The weakening and fall of the Xiōngnúes’ state enabled the Proto-Mongolian tribes to re-enter the historical scene. At the end of the 1st century B.C. the Chinese Hàn Empire firstly established relations with the Wūhuán tribes and in the middle of the 1st century A.D. with the Xiānbēi tribes, too. In the beginning both tribal alliances acknowledged the supreme authority of China and carried out frontier service. Under the guidance of tribal chiefs the tribes started to run an independent policy and attack China’s border areas during the 2nd century A.D. In the conclusion, the author describes the period when the Wūhuán and Xiānbēi tribes were at the peak of their power

  17. $\\beta$-particle energy-summing correction for $\\beta$-delayed proton emission measurements

    CERN Document Server

    Meisel, Z; Crawford, H L; Cyburt, R H; Grinyer, G F; Langer, C; Montes, F; Schatz, H; Smith, K

    2016-01-01

    A common approach to studying $\\beta$-delayed proton emission is to measure the energy of the emitted proton and corresponding nuclear recoil in a double-sided silicon-strip detector (DSSD) after implanting the $\\beta$-delayed proton emitting ($\\beta$p) nucleus. However, in order to extract the proton-decay energy, the measured energy must be corrected for the additional energy implanted in the DSSD by the $\\beta$-particle emitted from the $\\beta$p nucleus, an effect referred to here as $\\beta$-summing. We present an approach to determine an accurate correction for $\\beta$-summing. Our method relies on the determination of the mean implantation depth of the $\\beta$p nucleus within the DSSD by analyzing the shape of the total (proton + recoil + $\\beta$) decay energy distribution shape. We validate this approach with other mean implantation depth measurement techniques that take advantage of energy deposition within DSSDs upstream and downstream of the implantation DSSD.

  18. Metalo-beta-lactamases Metallo-beta-lactamases

    Directory of Open Access Journals (Sweden)

    Rodrigo Elisandro Mendes

    2006-04-01

    Full Text Available Nos últimos anos tem sido observada maior incidência de bacilos Gram-negativos resistentes a cefalosporinas de espectro ampliado no ambiente hospitalar, ocasionando, assim, maior uso de betalactâmicos mais potentes, como os carbapenens. A utilização de carbapenens exerce maior pressão seletiva sobre a microbiota hospitalar, o que pode ocasionar aumento da resistência a esses agentes. Entre os mecanismos de resistência a carbapenens mais comumente identificados estão a produção de betalactamases, como, por exemplo, as pertencentes à classe D de Ambler e as que pertencem à classe B de Ambler, ou metalo-beta-lactamases (MbetaL. Essas últimas hidrolisam todos betalactâmicos comercialmente disponíveis, sendo a única exceção o monobactam aztreonam. Desde o início da década de 1990, novos genes que codificam MbetaLs têm sido descritos em microrganismos clinicamente importantes, como Pseudomonas spp., Acinetobacter spp. e membros da família Enterobacteriaceae. O encontro desses microrganismos não-sensíveis a carbapenens pode ser submetido a metodologias fenotípicas para detecção da produção de MbetaL com o intuito de auxiliar a Comissão de Controle de Infecção Hospitalar (CCIH e prevenir a disseminação desses determinantes de resistência, uma vez que genes que codificam MbetaLs estão contidos em estruturas genéticas que propiciam sua mobilidade de forma muito efetiva, sendo então facilmente disseminados.Increase isolation of Gram-negative bacilli resistant to broad-spectrum cephalosporin has been observed during the last few years, thus determining the use of more potent beta-lactams, such as carbapenems. The use of these antimicrobial agents may lead to the emergence of carbapenem resistant Gram-negative bacilli in the nosocomial environment. Carbapenem resistance may be due to the production of Ambler class D beta-lactamase or Ambler class B beta-lactamase, also called metallo-beta-lactamase (MbetaL. Apart from

  19. Les risques conchylicoles en Baie de Quiberon. Première partie : le risque de mortalité virale du naissain d’huître creuse Crassostra gigas. Rapport final du projet Risco 2010-2013

    OpenAIRE

    Mazurie, Joseph; Stanisiere, Jean-yves; Langlade, Aime; Bouget, Jean-francois; Dumas, Franck; Treguier, Cathy; Leclerc,Emilie; Ravaud, Emilie; Quinsat, Kevin; Gabellec, Raoul; Retho, Michael; Cochet, Helene; Dreano, Alain

    2013-01-01

    L’étude « Risco », labellisée Pôle Mer et financée par la Région Bretagne, mobilise à la fois des socio-économistes, des biologistes et des professionnels. Elle vise à comprendre et gérer les facteurs de mortalités massives d’huîtres creuses (Crassostrea gigas) enregistrées par les concessionnaires de baie de Quiberon (France, 56), à partir de 2006 sur les huîtres adultes et 2008 sur le naissain. Le protocole engagé en 2010, avec un volet expérimental basé sur le suivi mensuel de lots d’huîtr...

  20. 利用微卫星标记分析湖羊GDF8区域的遗传多样性%Genetic Polymorphism in GDF8 Region of HU Sheep Based on Microsatellite DNA

    Institute of Scientific and Technical Information of China (English)

    吴文忠; 钱建共; 陈玲; 孙伟

    2009-01-01

    [Objective] This study was to analyze the genetic polymorphism in GDF8 Region of HU sheep. [Method] Four microsatellite loci including BMS1591, TEXAN-2, FCB128 and BM81124 mapped on GDF8 region of chromosome No. 2 of sheep that may be correlated with growth performance were chosen to detect the molecular genetics foundation of growth performance of Hu sheep. [Result] Four microsatellite loci detected were high in heterozygosity, more in effective alleles number and rich in polymorphic information, all the three indices passed through the high polymorphic level (PIC>0.5). [Conclusion] The four microsatellite loci detected could be used to estimate the genetic polymorphism of growth performance of Hu sheep.

  1. The RNA-binding protein HuD is required for GAP-43 mRNA stability, GAP-43 gene expression, and PKC-dependent neurite outgrowth in PC12 cells.

    Science.gov (United States)

    Mobarak, C D; Anderson, K D; Morin, M; Beckel-Mitchener, A; Rogers, S L; Furneaux, H; King, P; Perrone-Bizzozero, N I

    2000-09-01

    The RNA-binding protein HuD binds to a regulatory element in the 3' untranslated region (3' UTR) of the GAP-43 mRNA. To investigate the functional significance of this interaction, we generated PC12 cell lines in which HuD levels were controlled by transfection with either antisense (pDuH) or sense (pcHuD) constructs. pDuH-transfected cells contained reduced amounts of GAP-43 protein and mRNA, and these levels remained low even after nerve growth factor (NGF) stimulation, a treatment that is normally associated with protein kinase C (PKC)-dependent stabilization of the GAP-43 mRNA and neuronal differentiation. Analysis of GAP-43 mRNA stability demonstrated that the mRNA had a shorter half-life in these cells. In agreement with their deficient GAP-43 expression, pDuH cells failed to grow neurites in the presence of NGF or phorbol esters. These cells, however, exhibited normal neurite outgrowth when exposed to dibutyryl-cAMP, an agent that induces outgrowth independently from GAP-43. We observed opposite effects in pcHuD-transfected cells. The GAP-43 mRNA was stabilized in these cells, leading to an increase in the levels of the GAP-43 mRNA and protein. pcHuD cells were also found to grow short spontaneous neurites, a process that required the presence of GAP-43. In conclusion, our results suggest that HuD plays a critical role in PKC-mediated neurite outgrowth in PC12 cells and that this protein does so primarily by promoting the stabilization of the GAP-43 mRNA.

  2. Resistance training & beta-hydroxy-beta-methylbutyrate supplementation on hormones

    Directory of Open Access Journals (Sweden)

    Hamid Arazi

    2015-10-01

    Full Text Available RESUMOIntroduction:In recent years, there was an increased interest on the effects of beta-hydroxy-beta-methylbutyrate (HMB supplementation on skeletal muscle due to its anti-catabolic effects.Objectives:To investigate the effect of HMB supplementation on body composition, muscular strength and anabolic-catabolic hormones after resistance training.Methods:Twenty amateur male athletes were randomly assigned to supplement and control groups in a double-blind crossover design and participated in four weeks resistance training. Before and after the test period fasting blood samples were obtained to determine anabolic (the growth hormone and testosterone and catabolic (cortisol hormones, and fat mass, lean body mass (LBM and muscular strength were measured. Dependent and independent t-tests were used to analyze data.Results:After the training period, there were no significant differen-ces between the groups with respect to fat mass, LBM and anabolic-catabolic hormones. HMB supplementation resulted in a significantly greater strength gain (p≤0.05.Conclusion:Greater increase in strength for HMB group was not accompanied by body composition and basal circulating anabolic-catabolic hormonal changes. It seems that HMB supplementation may have beneficial effects on neurological adaptations of strength gain.

  3. New synthesis of. beta. -lactams

    Energy Technology Data Exchange (ETDEWEB)

    Wong, P.K.; Madhavarao, M.; Marten, D.F.; Rosenblum, M.M.

    1977-04-13

    The authors recently reported the regiospecific addition of heteroatomic nucleophiles to a number of Fp(olefin) cations (Fp = eta/sup 5/-C/sub 5/H/sub 5/Fe(CO)/sub 2/). Furthermore, it has been shown that oxidatively induced ligand transfer in FpR complexes (R-Fe-CO ..-->.. FeCOR) leads to carboxylation of R with retention of configuration at the migrating carbon center. It is now shown that an appropriate combination of these processes provides a facile and stereospecific synthesis of mono- and bicyclic ..beta..-lactams from olefins.

  4. [Heterocygous beta thalassaemia (author's transl)].

    Science.gov (United States)

    Méndez Aparicio, F

    1978-01-01

    Two girls with an heterocigotic beta-thalassemy are presented in this study. Case 1 has an hypochromic and microtic anaemia with an enormous splenomegaly, increased osmotic resistence of red blood cells in salted solution and increase of A2 hemoglobin. This situation is associated with an increase of the glucolitic intraerythrocitic enzimes. Case 2 showed increase of A2 hemoglobine, but this anomaly was associated with decrease of intraerythrocitic enzimatic rate. First clinical signs of erythrocitic disturbances was an acute hemolytic crisis developed by the supply of the sulphometoxipiridacine. The erythroquinetic study showed a decrease of the average life of the red blood cells in both patients.

  5. 胡锦涛的公民政治参与思想%Hu Jingtao's Ideology of Citizens' Politic Participation

    Institute of Scientific and Technical Information of China (English)

    杨平

    2012-01-01

    Hu Jingtao's ideology of citizens' politic participation is the same with that of Marxist revolutionary teachers and the different leading generations of the CPC.Hu Jingtao thinks that people's democracy is soul of socialism.We should broadly persuade people to join in the management of public affairs.He thinks citizens' participation should be in line with the reform of politic system.We should strengthen participating degree for the citizens in joining in public policy-making,and make full use of democratic parties and social associations in citizens' politic participation.We should enlarge the orderly politic participation by putting forward basic democracy and guarantee ordinary Party members' politic participation by putting forward democracy inside the Party.Hu Jingtao's ideology of citizens' politic participation is the focusing reflection of the new achievement from Marxist theory of political participation.%胡锦涛的公民政治参与思想是和马克思主义革命导师以及中国共产党历代领导人的政治参与理论一脉相承的。胡锦涛认为,人民民主是社会主义的生命,要广泛动员人民参加公共事务的管理,公民政治参与要和政治体制改革相适应,要提高公民对公共决策的参与度,发挥民主党派和社会组织在公民政治参与中的作用,要通过发展基层民主扩大公民有序政治参与,通过发展党内民主保障普通党员的政治参与权。胡锦涛的公民政治参与思想是马克思主义政治参与理论中国化最新成果的集中体现。

  6. DOSoReMI.hu: collection of countrywide DSM products partly according to GSM.net specifications, partly driven by specific user demands

    Science.gov (United States)

    Pásztor, László; Laborczi, Annamária; Takács, Katalin; Szatmári, Gábor; Illés, Gábor; Bakacsi, Zsófia; Szabó, József

    2017-04-01

    Due to former soil surveys and mapping activities significant amount of soil information has accumulated in Hungary. In traditional soil mapping the creation of a new map was troublesome and laborious. As a consequence, robust maps were elaborated and rather the demands were fitted to the available map products. Until recently spatial soil information demands have been serviced with the available datasets either in their actual form or after certain specific and often enforced, thematic and spatial inference. Considerable imperfection may occur in the accuracy and reliability of the map products, since there might be significant discrepancies between the available data and the expected information. The DOSoReMI.hu (Digital, Optimized, Soil Related Maps and Information in Hungary) project was started intentionally for the renewal of the national soil spatial infrastructure in Hungary. During our activities we have significantly extended the potential, how soil information requirements could be satisfied. Soil property, soil type as well as functional soil maps were targeted. The set of the applied digital soil mapping techniques has been gradually broadened incorporating and eventually integrating geostatistical, data mining and GIS tools. Soil property maps have been compiled partly according to GSM.net specifications, partly by slightly or more strictly changing some of their predefined parameters (depth intervals, pixel size, property etc.) according to the specific demands on the final products. The elaborated primary maps were further processed, since even DOSoReMI.hu intended to take steps for the regionalization of higher level soil information (processes, functions, and services) involving crop models in the spatial modelling. The framework of DOSoReMI.hu also provides opportunity for the elaboration of goal specific soil maps, with the prescription of the parameters (thematic, resolution, accuracy, reliability etc.) characterizing the map product. As a

  7. Metabolic signalling in pancreatic beta cells

    OpenAIRE

    Piipari, K.

    2011-01-01

    The main function of pancreatic beta cells is to maintain correct glucose homeostasis within the body by secretion of insulin in response to increased blood glucose concentration. Beta cell dysfunction contributes to the pathogenesis of diabetes. Using transgenic mouse models, the work described in this thesis has investigated the role of AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3K) in beta cell function and their role in the regulation of ...

  8. Sawtooth crashes at high beta on JET

    Energy Technology Data Exchange (ETDEWEB)

    Alper, B.; Huysmans, G.T.A.; Sips, A.C.C. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Nave, M.F.F. [Universidade Tecnica, Lisbon (Portugal). Inst. Superior Tecnico

    1994-07-01

    The sawtooth crashes on JET display features which depend on beta. The main observation is a transient bulging of flux surfaces (duration inferior to 30 microsec.), which is predominantly on the low field side and extends to larger radii as beta increases. This phenomenon reaches the plasma boundary when beta{sub N} exceeds 0.5 and in these cases is followed by an ELM within 50 microsec. These sawtooth/ELM events limit plasma performance. Modelling of mode coupling shows qualitative agreement between observations of the structure of the sawtooth precursor and the calculated internal kink mode at high beta. (authors). 6 refs., 5 figs.

  9. Milk Intolerance, Beta-Casein and Lactose

    Directory of Open Access Journals (Sweden)

    Sebely Pal

    2015-08-01

    Full Text Available True lactose intolerance (symptoms stemming from lactose malabsorption is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  10. Milk Intolerance, Beta-Casein and Lactose.

    Science.gov (United States)

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-08-31

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  11. International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)

    National Research Council Canada - National Science Library

    Wilson, Jacob M; Fitschen, Peter J; Campbell, Bill; Wilson, Gabriel J; Zanchi, Nelo; Taylor, Lem; Wilborn, Colin; Kalman, Douglas S; Stout, Jeffrey R; Hoffman, Jay R; Ziegenfuss, Tim N; Lopez, Hector L; Kreider, Richard B; Smith-Ryan, Abbie E; Antonio, Jose

    2013-01-01

    Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB...

  12. Nuclear emulsion with molybdenum filling for observation of $\\beta\\beta$ decay

    CERN Document Server

    Ashitkov, V D; Barabash, A S; Bradnova, V Ya; Chernyavsky, M M; Konovalov, S I; Okat'eva, N M; Orlova, G I; Polukhina, N G; Pozharova, E A; Smirnitsky, V A; Starkov, N I; Vladimirov, M S; Umatov, V I

    2010-01-01

    The usage of nuclear emulsion with molybdenum filling for observation of $\\beta\\beta$ decay are shown to be possible. Estimates for 1 kg of $^{100}$Mo with zero background give the sensitivity for the $0\

  13. Challenges in Double Beta Decay

    Directory of Open Access Journals (Sweden)

    Oliviero Cremonesi

    2014-01-01

    Full Text Available In the past ten years, neutrino oscillation experiments have provided the incontrovertible evidence that neutrinos mix and have finite masses. These results represent the strongest demonstration that the electroweak Standard Model is incomplete and that new Physics beyond it must exist. In this scenario, a unique role is played by the Neutrinoless Double Beta Decay searches which can probe lepton number conservation and investigate the Dirac/Majorana nature of the neutrinos and their absolute mass scale (hierarchy problem with unprecedented sensitivity. Today Neutrinoless Double Beta Decay faces a new era where large-scale experiments with a sensitivity approaching the so-called degenerate-hierarchy region are nearly ready to start and where the challenge for the next future is the construction of detectors characterized by a tonne-scale size and an incredibly low background. A number of new proposed projects took up this challenge. These are based either on large expansions of the present experiments or on new ideas to improve the technical performance and/or reduce the background contributions. In this paper, a review of the most relevant ongoing experiments is given. The most relevant parameters contributing to the experimental sensitivity are discussed and a critical comparison of the future projects is proposed.

  14. New Definition of Micro-Lecture:Walking from Technology Development to Effective Design-An Interview to Pro.Hu Xiaoyong from South China Normal University and Mr.Hu Tiesheng from Foshan Education Bureau%微课新界定:从技术开发迈向有效设计--访华南师范大学胡小勇教授和佛山教育局胡铁生老师

    Institute of Scientific and Technical Information of China (English)

    冯智慧; 郑晓丹

    2015-01-01

    Leaderette:In recent years,micro-lecture has become a big event in the field of education and "nationwide micro-lecture" phenomenon almost emerged.How to understand and define the characteristics of micro-lecture?How to recognize the function of micro-lecture rationally?How to go beyond from micro-lecture technology development to effective design?In order to answer these questions,we interview Professor Hu Xiaoyong and Mr.Hu Tiesheng to introduce the new thinking in the micro-lecture tide to us.

  15. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype.

    Directory of Open Access Journals (Sweden)

    Geert A Martens

    Full Text Available BACKGROUND AND METHODOLOGY: The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators. PRINCIPAL FINDINGS: A panel of 332 conserved beta cell biomarker genes was found to discriminate both isolated and laser capture microdissected beta cells from all other examined cell types. Of all conserved beta cell-markers, 15% were strongly beta cell-selective and functionally associated to hormone processing, 15% were shared with neuronal cells and associated to regulated synaptic vesicle transport and 30% with immune plus gut mucosal tissues reflecting active protein synthesis. Fasting specifically down-regulated the latter cluster, but preserved the neuronal and strongly beta cell-selective traits, indicating preserved differentiated state. Analysis of consensus binding site enrichment indicated major roles of CREB/ATF and various nutrient- or redox-regulated transcription factors in maintenance of differentiated beta cell phenotype. CONCLUSIONS: Conserved beta cell marker genes contain major gene clusters defined by their beta cell selectivity or by their additional abundance in either neural cells or in immune plus gut mucosal cells. This panel can be used as a template to identify changes in the differentiated state of beta cells.

  16. Ultra high performance liquid chromatography with tandem mass spectrometry for rapid separation and identification of main constituents in Chinese herbal formula Xuan Hu Suo San.

    Science.gov (United States)

    Tang, Huaqi; Zhang, Xinyue; Luo, Shilin; Shang, Fei; Chen, Jianping; Wang, Jinghong; Duan, Xiaojie; Gao, Xiaoyan; Sun, Yikun

    2017-02-15

    Xuan Hu Suo San (XHSS) is a traditional Chinese medicine that has been extensively applied in the treatment of osteoarthritis for many years, however, its chemical composition has not yet been elucidated. Thus, a rapid, efficient, and precise method based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied in both positive- and negative-ion modes to rapidly separate and identify the main chemical ingredients in XHSS for the first time. Finally, with the optimised separation and detection method, a total of 57 compounds were simultaneously separated within 13 min, among which 14 compounds were confirmed by comparing retention time and MS data with reference standards and others were tentatively identified by comparing with reference literatures. This rapid and sensitive approach is highly useful for the identification and characterisation of chemical constituents, and provides fundamental and extensive information supporting further metabolic and pharmacokinetic studies of XHSS.

  17. Acentuación de la enfermedad experimental de injerto contra huésped con el agregado de esplenocitos murinos

    OpenAIRE

    2010-01-01

    En un trabajo anterior se presentó en un modelo de Enfermedad de Rechazo de Injerto vs Huésped (EICH) en ratones ablacionados con ciclofosfamida y trasplantados con células de médula ósea con hemi-disparidad genética una alteración del ciclo celular, con detención en la fase G2-M de las células del epitelio intestinal y de la piel de ratones, asociada a un aumento de la apoptosis. Con el fin de intentar profundizar en los mecanismos de producción de daño epitelial en la EICH se modificó el mo...

  18. Essais de prégrossissement de l'huître plate (Ostrea edulis) à partir de naissain capté en Méditerranée

    OpenAIRE

    Dupuy, Blandine

    1988-01-01

    La maîtrise du prégrossissement d'huîtres plates s'avère indispensable pour valoriser sur le littoral Languedocien le naissain capté en mer ouverte. Cet essai effectue la comparaison de trois sites : - en mer ouverte à - 20 mètres à Gruissan sur une concession mytilicole. - en étang à proximité d'une zone d'élevage de palourdes à Port-la-Nouvelle. - en bassin aménagé pour l'élevage de crevettes dans les marais de Campignol. A partir de naissain de 0,5 cm en mai-juin, on a obtenu d...

  19. A dual model HU conversion from MRI intensity values within and outside of bone segment for MRI-based radiotherapy treatment planning of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Korhonen, Juha, E-mail: juha.p.korhonen@hus.fi [Clinical Research Institute Helsinki University Central Hospital Ltd., POB-700, 00029 HUS (Finland); Department of Oncology, Helsinki University Central Hospital, POB-180, 00029 HUS (Finland); Kapanen, Mika [Clinical Research Institute Helsinki University Central Hospital Ltd., POB-700, 00029 HUS (Finland); Department of Oncology, Helsinki University Central Hospital, POB-180, 00029 HUS (Finland); Department of Medical Physics, Tampere University Hospital, POB-2000, 33521 Tampere (Finland); Keyriläinen, Jani; Seppälä, Tiina; Tenhunen, Mikko [Department of Oncology, Helsinki University Central Hospital, POB-180, 00029 HUS (Finland)

    2014-01-15

    Purpose: The lack of electron density information in magnetic resonance images (MRI) poses a major challenge for MRI-based radiotherapy treatment planning (RTP). In this study the authors convert MRI intensity values into Hounsfield units (HUs) in the male pelvis and thus enable accurate MRI-based RTP for prostate cancer patients with varying tissue anatomy and body fat contents. Methods: T{sub 1}/T{sub 2}*-weighted MRI intensity values and standard computed tomography (CT) image HUs in the male pelvis were analyzed using image data of 10 prostate cancer patients. The collected data were utilized to generate a dual model HU conversion technique from MRI intensity values of the single image set separately within and outside of contoured pelvic bones. Within the bone segment local MRI intensity values were converted to HUs by applying a second-order polynomial model. This model was tuned for each patient by two patient-specific adjustments: MR signal normalization to correct shifts in absolute intensity level and application of a cutoff value to accurately represent low density bony tissue HUs. For soft tissues, such as fat and muscle, located outside of the bone contours, a threshold-based segmentation method without requirements for any patient-specific adjustments was introduced to convert MRI intensity values into HUs. The dual model HU conversion technique was implemented by constructing pseudo-CT images for 10 other prostate cancer patients. The feasibility of these images for RTP was evaluated by comparing HUs in the generated pseudo-CT images with those in standard CT images, and by determining deviations in MRI-based dose distributions compared to those in CT images with 7-field intensity modulated radiation therapy (IMRT) with the anisotropic analytical algorithm and 360° volumetric-modulated arc therapy (VMAT) with the Voxel Monte Carlo algorithm. Results: The average HU differences between the constructed pseudo-CT images and standard CT images of each

  20. 麻核桃资源保护与开发利用研究%Conservation, Exploration and Utilization of Juglan hebeinesis Hu Resources

    Institute of Scientific and Technical Information of China (English)

    裴东; 李容海; 刘兆发; 王富强

    2006-01-01

    麻核桃(juglans hopeiensis Hu)不仅是核桃属植物中分布范围最窄,数量最少的一个种,而且是我国特有的种,但是多年来没有引起足够重视,研究报道很少,本文对麻核桃资源和生产情况进行了初步调查,并根据坚果外观变化鉴定出11个类型,目的是为资源保护和良种选育奠定基础.

  1. 沙伯基础创新塑料高强度Ultem HU1004树脂具备多重灭菌处理能力

    Institute of Scientific and Technical Information of China (English)

    Grace Tu

    2011-01-01

    最近,沙伯基础创新塑料公布第三方测试结果,证实超强UltemHU1004聚醚酰亚胺(PEI)树脂具备多重灭菌处理能力。该高性能树脂之前一直应用于其他技术,如今测试证实可在STERRADNX誖过氧化氢等离子低温灭菌过程中使用,让医疗保健供应商可以灵活选择托盘、电子医疗设备和其他设备的主要灭菌方式。

  2. 具有多重灭菌处理能力的高强度Ultem HU1004树脂

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    多重灭菌处理能力经沙伯基础创新塑料公布的第三方测试结果证实,超强Ultem HU1004聚醚酰亚胺(PEI)树脂具备多重灭菌处理能力。也就是说,该高性能树脂可在STERRAD NX 过氧化氢等离子低温灭菌过程中使用,使医疗保健供应商可以灵活选择托盘、医疗电子设备和其他医用设备的主要灭菌方式。

  3. Mössbauer Study of Ceramic Finds from the Galería de las Ofrendas, Chavín de Huántar

    Science.gov (United States)

    Lumbreras, L. G.; Gebhard, R.; Häusler, W.; Kauffmann-Doig, F.; Riederer, J.; Sieben, G.; Wagner, U.

    2003-09-01

    Ceramic finds from the Galería de las Ofrendas at Chavín de Huántar and surface finds from the settlement of Chavín were characterised by combining the results of archaeological typology with archaeometric studies using neutron activation analysis, Mössbauer spectroscopy, X-ray diffraction and thin-section microscopy. Sherds from the pyramid Tello are included in the study as representative of local material. The analyses show that the vessels were made from different raw materials and that different firing procedures were used in their production. Sherds of certain styles largely exhibit similar types of Mössbauer patterns and in many instances also have similar element compositions. This supports the archaeological notion that the vessels were brought to Chavín from the provinces, perhaps on the occasion of a festivity.

  4. Evaluación del riesgo sísmico del centro histórico de la Ciudad de Huánuco

    OpenAIRE

    Marín Guillen, Félix

    2012-01-01

    Las ciudades ubicadas en áreas de peligrosidad sísmica moderada o baja tienden a menospreciar el peligro sísmico y a descuidar precauciones básicas de protección frente a los terremotos, conllevando a un aumento de su vulnerabilidad y en consecuencia elevar el riesgo sísmico, que a su vez aumenta con el tiempo. En el presente estudio se obtuvieron escenarios de daño para el centro histórico de la ciudad de Huánuco, mediante una aproximación que posibilita y efectúa un análisis edificio a e...

  5. Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment

    DEFF Research Database (Denmark)

    Johnsen, Hanne; Geisler, C; Juvonen, E;

    2011-01-01

    methionyl human G-CSF (filgrastim, r-metHuG-CSF) (experimental arm A) or routine chemotherapy plus filgrastim (conventional arm B). The primary objective was to evaluate the side effects and toxicity during priming and mobilization. The secondary objectives were efficacy by the level of blood......-circulating PBPCs, the number of harvest days and the time to three-lineage engraftment after autografting. First, during priming 5 patients had 8 serious events, 4 in each arm. A summary of all adverse events revealed 30 (94%) patients suffering from 132 events of all grading. Second, neutropenia...... and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34(+) cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial...

  6. Ultrasound-assisted extraction methodology as a tool to improve the antioxidant properties of herbal drug Xiao-chia-hu-tang.

    Science.gov (United States)

    Liu, Chu-Ting; Wu, Ching-Yi; Weng, Yih-Ming; Tseng, Chin-Yin

    2005-06-03

    Xiao-chai-hu-tang (XCHT) is an important Chinese herbal prescription for curing many types of liver diseases. The contents of bioactive constituents (saikosaponins a, c and d, baicalin, baicalein, and glycyrrhizic acid), and antioxidant properties of XCHT extracts prepared with ultrasound-assisted (US) extraction in combination with ethanol (up to 95%) as extraction modifier were studied. The results showed that the US extraction significantly increased the bioactive constituents concentrations and antioxidant properties of XCHT extracts when compared with the XCHT prepared with traditional boiling-water extraction. Among the XCHT extracts made with US extraction, the sample prepared with 95% ethanol showed the highest bioactive constituent concentrations and the best antioxidant functionalities. The results suggest that US extraction of XCHT is feasible to replace the traditional time-consuming and low efficiency preparation procedure in the future modernized and commercialized manufacture of this highly valuable Chinese herbal medicine.

  7. Imperfect World of beta beta-decay Nuclear Data Sets

    Energy Technology Data Exchange (ETDEWEB)

    Pritychenko, B. [Brookhaven National Lab. (BNL), Upton, NY (United States). NNDC

    2015-01-03

    The precision of double-beta ββ-decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for ββ-decay T2v1/2 is consistent with large nuclear reaction and structure data sets and provides validation of experimental half-lives. A complementary analysis of the decay uncertainties indicates deficiencies due to small size of statistical samples, and incomplete collection of experimental information. Further experimental and theoretical efforts would lead toward more precise values of-decay half-lives and nuclear matrix elements.

  8. Isotope Effects in the Bonds of beta-CrOOH and beta-CrOOD

    DEFF Research Database (Denmark)

    Nørlund Christensen, A.; Hansen, P.; Lehmann, M. S.

    1976-01-01

    Samples of orthorhombic chromium oxide hydroxide, beta -CrOOH, and the deuterated compound, beta -CrOOD, were prepared hydrothermally. The crystal structures were determined by powder profile refinement technique using neutron diffraction data. Unit cells are: beta -CrOOH: a equals 4. 862(2) A, b...

  9. The pharmacokinetics of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in the rat

    NARCIS (Netherlands)

    Frijlink, H W; Visser, J; Hefting, N R; Oosting, R; Meijer, D K; Lerk, C F

    1990-01-01

    Hydroxypropyl-beta-cyclodextrin was analyzed by HPLC using postcolumn complexation with phenolphthalein and negative colorimetric detection, with a detection limit of 20 micrograms/ml. The pharmacokinetics of beta-cyclodextrin and of hydroxypropyl-beta-cyclodextrin were studied after intravenous adm

  10. The pharmacokinetics of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in the rat

    NARCIS (Netherlands)

    Frijlink, H W; Visser, J; Hefting, N R; Oosting, R; Meijer, D K; Lerk, C F

    1990-01-01

    Hydroxypropyl-beta-cyclodextrin was analyzed by HPLC using postcolumn complexation with phenolphthalein and negative colorimetric detection, with a detection limit of 20 micrograms/ml. The pharmacokinetics of beta-cyclodextrin and of hydroxypropyl-beta-cyclodextrin were studied after intravenous adm

  11. An imidazoline compound completely counteracts interleukin-1[beta] toxic effects to rat pancreatic islet [beta] cells

    DEFF Research Database (Denmark)

    Papaccio, Gianpaolo; Nicoletti, Ferdinando; Pisanti, Francesco A

    2002-01-01

    In vitro studies have demonstrated that interleukin (IL)-1beta decreases insulin and DNA contents in pancreatic islet beta cells, causing structural damage, that it is toxic to cultured human islet beta cells and that it is able to induce apoptosis in these cells....

  12. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H

    2011-01-01

    The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...

  13. The impact of beta-elemene on beta-tubulin of human hepatoma hepg2 cells

    Institute of Scientific and Technical Information of China (English)

    Yuqiu Mao; Liying Ban; Jielin Zhang; Li Hou; Xiaonan Cui

    2014-01-01

    Objective:The aim of this study was to investigate the impact of beta-elemene injection on the growth and beta-tubulin of human hepatocarcinoma HepG2 cells. Methods:cellproliferation was assessed by MTT assay. cellcycle distribution was detected by flow cytometry (FCM). The mRNA expression of beta-tubulin was measured by RT-PCR. West-ern blot analysis was used to determine protein expression of beta-tubulin and the polymerization of beta-tubulin. Results:Beta-elemene injection inhibited HepG2 cells proliferation in a dose-and time-dependent manner;FCM analysis indicated beta-elemene injection induced cellcycle arrested at S phase. RT-PCR and western-blot analysis showed that beta-elemene injection down-regulated beta-tubulin expression at both mRNA and protein levels, presenting a dose-dependent manner. Moreover, beta-elemene injection reduced the polymerization of microtubules in a dose-dependent manner. Conclusion:Beta-elemene injection can inhibit the proliferation of hepatoma HepG2 cells, the mechanism might be partly related to the down-regulation of beta-tubulin and inhibition of microtubular polymerization.

  14. Expressions of GSK-3beta, Beta-Catenin and PPAR-Gamma in Medulloblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiong Zhang; Lu Si; Yu Li; Can Mi

    2009-01-01

    Objective: To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application.Methods: Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues.Results: The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal (P<0.05). Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation.Conclusion: Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.

  15. Radiation-induced polymerization of {beta}(+)-pinene and synthesis of optically active {beta}(+)/{beta}(-)pinene polymers and copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Cataldo, Franco, E-mail: franco.cataldo@fastwebnet.i [Lupi Chemical Research, Via Casilina 1626/A, 00133 Rome (Italy); Lilla, Edo; Ursini, Ornella [Institute of Chemical Methodologies, CNR, Via Salaria Km. 29300, Monterotondo Stazione 00016, Rome (Italy)

    2011-06-15

    Poly-{beta}(+)-pinene (pB(+)p) was synthesized with {gamma} irradiation of the monomer {beta}(+)-pinene in bulk under vacuum at 1181 kGy. Also scalemic mixtures of {beta}(+)-pinene and {beta}(-)-pinene were irradiated at 1181 kGy to obtain synthetic copolymers of pB(+)/B(-)p. For comparison also {beta}(-)-pinene was converted into poly-{beta}(-)-pinene (pB(-)p) under the identical conditions adopted for its enantiomer. Furthermore pB(+)p and pB(-)p were also synthesized by thermal processing under the action of a chemical free radical initiator. The optical rotatory dispersion (ORD) of all pBp resins synthesized were accurately studied in the spectral range comprised between 375 and 625 nm and a curious asymmetry in the ORD of pB(+)p versus the ORD of pB(-)p is reported. Furthermore, it is shown that (+)-p-menth-1-ene and (-)-p-menth-1-ene are useful as a model compounds for the pBp resins and for the explanation of the amplification of the optical activity of the {beta}(+)-pinene and {beta}(-)-pinene after their ring-opening polymerization to pB(+)p and pB(-)p. The pBp resins were studied also by FT-IR spectroscopy and by thermal analysis (TGA and DTG).

  16. 试论胡风文学主体性内涵%On the Connotations of Hu Feng’s Literature Subjectivity

    Institute of Scientific and Technical Information of China (English)

    吴亚南

    2012-01-01

      胡风是中国第一个真正实质意义上建立了完整的以马克思主义思想为基础的主体性现实主义理论体系的文艺思想家。他结合时代历史语境和自身艺术实践,提出了“主观战斗精神”等一系列强调文艺主体性作用的文学主张,丰富了中国马克思主义文学批评的理论内涵,有效拓宽了马克思主义文学批评的知识视野和理论空间。论文分别从主体性思考的知识逻辑起点、实践主体性视野、历史条件下的复合主体性内涵三个方面探讨胡风对中国马克思主义文学批评理论建设的贡献。%  Hu Feng is the first Chinese critic who truly establishes subjective realism literature theory based on Marxist literary criticism. Combining historical context of times and his own artistic practice, he advo⁃cates subjective fighting spirit and series of literary claims which emphasize literary subjective importance. His literary claims enrich the connotations of Chinese Marxist literary criticism. and also effectively broaden the vi⁃sion and theoretical space. This paper mainly expounds about Hu Feng’s contribution from three aspects to the construction of Chinese Marxist literary criticism:the knowledge and logic starting point of subjective thinking, practical vision of subjectivity, the compound subjectivities of historical conditions.

  17. Communication Memoir between Hu Yaobang and Mao Zedong%胡耀邦与毛泽东交往实录(下)

    Institute of Scientific and Technical Information of China (English)

    李佑新; 吴璇

    2016-01-01

    胡耀邦是久经考验的忠诚的共产主义战士,伟大的无产阶级革命家、政治家,我军杰出的政治工作者,长期担任党的重要领导职务的卓越领导人。从20世纪30年代在陕北初识毛泽东,历经难忘的抗大时光和革命岁月,到新中国成立后主政川北、投身青年团工作、整顿中国科学院,胡耀邦得到了毛泽东的关怀、教育和培养,并始终追随毛泽东的事业。%Hu Yaobang was a long-tested loyal communist fighter,a great proletarian revolutionist,a statesman and an outstanding political worker of the people’s army,a brilliant leader who held the important post of the Party for a long time.From the 1930’s in the Northern Shaanxi he met Mao Zedong,and passed an unforgettable time in the Anti-Japanese military and political college and revolution years,to head the admin-istration in the Northern Sichuan Province,devote himself to the Communist Youth League and rectify the Chi-nese Academy of Sciences after the founding of new China,Hu Yaobang had been taken care of,educated and cultivated by Mao Zedong.He followed Mao Zedong’s career all his time.

  18. 胡适对五四运动的认识与思考%Hu Shi’ s Understanding and Thinking on the May 4th Movement

    Institute of Scientific and Technical Information of China (English)

    周良发

    2015-01-01

    胡适对五四运动的态度,前后有明显变化,由起初赞扬继而深表同情,及至晚年的批评。胡适认为五四运动的爆发除了中国政府的外交失败,还与北京高校学生庆祝一战胜利的游行活动有关,而五四运动的价值在于独立人格的形成,并成为社会发展的主要推力。胡适没有系统研究五四运动,但其言说仍对后世学人的形上致思颇多启发意义。%Hu Shi’ s attitude had a significant change about the May 4th Movement.He praised and showed sympathy in his early life, but later he harshly criticized.He thought that the May 4th outbreak was due to Chinese government diplomatic failure, and it’ s related to Peking university students to celebrate the end of the First World War.The May 4th value lied in the formation of the independent personality, and became the main thrust of social development.Hu Shi didn’ t study May 4th Movement systemical-ly, but what he said had a lot of inspiration significance for the later scholars.

  19. Analysis of the kinetic of expression of tristetraprolin and HuR by rheumatoid arthritis patients pheripheral blood mononuclear cells stimulated with lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    G. Ferraccioli

    2011-09-01

    Full Text Available Objective. Given the role of TNF-α in Rheumatoid Arthritis (RA we decided to define the characteristics of the TNF- α synthesis by peripheral blood mononuclear cells (PBMNCs obtained from active-aggressive RA patients giving a particular attention to the modulation of the expression of two fundamental proteins in TNF-α mRNA stability regulation, Tristetraprolin (TTP and HuR. Methods. 11 RA patients with active disease were enrolled in the study before their entry in 2 double blind protocols: Infliximab versus MTX and Etanercept versus MTX. 9 healthy blood donors were taken as controls. PBMNCs obtained by Ficoll centrifugation and plastic adherence were stimulated with lipopolysaccharide (LPS and TNF-α was measured in the supernatant during 8 hours by ELISA. At each time point the cells were harvested and analysed for TNF- α, TTP and HuR mRNA expression by semi-quantitative PCR. Results. MNCs TNF-α secretion after LPS stimulation did not differ significantly between RA and control subjects, even if a tendency towards a more prompt response was observed in the patients. More importantly only the DMARDs responsive patients (DAS <3.7 at the 6th month, with a minimal reduction of 1.2 points disclosed precociously (at the first month a significant change in the profile of TNF-α secretion and maintained it until the 6th month. The “normalization” of the synthetic behaviour was accompanied by the resetting in the regulation of the expression of the TTP, that appeared significantly different in the patients before and after therapy. Conclusions. Independently from the type of therapy, responsive patients demonstrate a rapid change in the cellular biology at the systemic level that might drive the resolution of the phlogistic process at the synovial level.

  20. 基于中值滤波和Hu矩向量的手语识别%Sign language recognition based on Hu invariant moments and euclidean distance

    Institute of Scientific and Technical Information of China (English)

    华斌; 夏利娜

    2011-01-01

    To increase accuracy rate of sign language recognition, a recognition method based on Hu invariant moments and euclidean distance of sign language image is introduced. Firstly, its 7Hu moments are calculated, the recognition of 30 letter gestures is performed by computing distance between matching and template image to recognize image. The algorithm remains constant when the image rotates,transfers and scales. The method overcomes the impact of illumination in capturing image and marginal information loss caused by image segmentation. The experiments show the validity of this method especitaly a successful result of images with a high rate of pepper-andsalt noise.%为提高手语图像的正识率,提出一种基于中值滤波和Hu不变矩特征量相结合的手语识别方法,对待匹配图像进行预处理,计算图像的7Hu矩特征量,通过欧氏距离计算与标准手语特征向量的相似程度,识别手语,对旋转、缩放和平移等图像的非本质性改变具有很好的鲁棒性,克服了手语图像采集中光照不均的影响和传统手语识别中基于图像分割造成的边缘信息损失.实验结果表明了该方法对手语识别的有效性,特别是对含有椒盐噪声信噪比较高的图像具有很好的效果.

  1. Beta-glucosidase I variants with improved properties

    Energy Technology Data Exchange (ETDEWEB)

    Bott, Richard R.; Kaper, Thijs; Kelemen, Bradley; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus; Kralj, Slavko; Kruithof, Paulien; Nikolaev, Igor; Van Der Kley, Wilhelmus Antonious Hendricus; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander

    2016-09-20

    The present disclosure is generally directed to enzymes and in particular beta-glucosidase variants. Also described are nucleic acids encoding beta-glucosidase variants, compositions comprising beta-glucosidase variants, methods of using beta-glucosidase variants, and methods of identifying additional useful beta-glucosidase variants.

  2. Beta-glucosidase variants and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Wogulis, Mark; Harris, Paul; Osborn, David

    2017-06-27

    The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.

  3. Cloning and characterization of human liver cytosolic beta-glycosidase

    NARCIS (Netherlands)

    De Graaf, M; Van Veen, IC; Van Der Meulen-Muileman, IH; Gerritsen, WR; Pinedo, HM; Haisma, HJ

    2001-01-01

    Cytosolic beta -glucosidase (EC 3.2.1.21) from mammalian liver is a member of the family 1 glycoside hydrolases and is known for its ability to hydrolyse a range of beta -D-glycosides. including beta -D-glucoside acid beta -D-galactoside. We therefore refer to this enzyme as cytosolic beta

  4. Dosimetry of low-energy beta radiation

    Energy Technology Data Exchange (ETDEWEB)

    Borg, J.

    1996-08-01

    Useful techniques and procedures for determination of absorbed doses from exposure in a low-energy {beta} radiation field were studied and evaluated in this project. The four different techniques included were {beta} spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical low-energy {beta} radiation field a moderated spectrum from a {sup 14}C source (E{sub {beta}},{sub max} =156 keV) was chosen for the study. The measured response of a Si(Li) detector to photons (bremsstrahlung) showed fine agreement with the MC calculated photon response, whereas the difference between measured and MC calculated responses to electrons indicates an additional dead layer thickness of about 12 {mu}m in the Si(Li) detector. The depth-dose profiles measured with extrapolation chambers at two laboratories agreed very well, and it was confirmed that the fitting procedure previously reported for {sup 147}Pm depth-dose profiles is also suitable for {beta} radiation from {sup 14}C. An increasing difference between measured and MC calculated dose rates for increasing absorber thickness was found, which is explained by limitations of the EGS4 code for transport of very low-energy electrons (below 10-20 keV). Finally a study of the thermally stimulated exoelectron emission (TSEE) response of BeO thin film dosemeters to {beta} radiation for radiation fields with maximum {beta} energies ranging from 67 keV to 2.27 MeV is reported. For maximum {beta} energies below approximately 500 keV, a decrease in the response amounting to about 20% was observed. It is thus concluded that a {beta} dose higher than about 10 {mu}Gy can be measured with these dosemeters to within 0 to -20% independently of the {beta}energy for E{sub {beta}},{sub max} values down to 67 keV. (au) 12 tabs., 38 ills., 71 refs.

  5. Adverse effects of hydroxyurea in beta-thalassemia intermedia patients: 10 years' experience.

    Science.gov (United States)

    Karimi, Mehran; Cohan, Nader; Mousavizadeh, Kazem; Moosavizadeh, Kazem; Falahi, Mohammad Javad; Haghpanah, Sezaneh

    2010-04-01

    The aim of this study was to evaluate the tolerance and adverse effects of hydroxyurea (HU) in thalassemia intermedia (TI) patients who had been treated by HU for a period of 10 years. One hundred forty-three TI patients, including 78 male and 65 female, median age 21 years old (range: 5-37 years old), who were treated by HU were investigated as a case study, and 106 TI, including 63 male and 43 female, median age 22 years old (range: 5-39 years old), who were not treated by any HU as a control group. Mean dose of HU treatment was 10.74 mg/kg/day (range: 8-12 mg/kg/day) and adverse effects of HU were recorded in 44 (30.7%) patients. Dermatologic side effects were most commonly seen, followed by neurological and gastrointestinal adverse effects. There were not any reports of hematologic toxicity or any signs of bone marrow suppression during HU treatment. Statistical analysis showed a positive correlation between advancing age and the presence of adverse effects during HU treatment (P treatment and the presence of adverse effects (P > .05). It was also observed that splenectomized patients more frequently experienced adverse effects of HU (P minor and can be tolerated without needs of discontinuation of treatment.

  6. Difference Existed Is Difficult to Obtain Agreement: Hu Feng's View on May 4th Different from the Mainstream and Its Influence on Hu Feng's Doom%“存异”难以“求同”——胡风“五四”观异于主流的歧见及其对胡风命运的影响

    Institute of Scientific and Technical Information of China (English)

    谢刚

    2012-01-01

    如何看待“五四”,是审视胡风思想内质及其与左翼主流分歧的一个关键角度。两者在“五四”总主题的认识上并无差异,而在“五四”领导者的认定及历史意义的阐发上却有不同。胡风认为:经过真切实践的鲁迅在“五四”时期已经成为共产主义知识分子.理当居于“五四”领导者之列,这与权威的“鲁迅转变论”产生龃龉;“五四”的历史意义主要在于文学/文化层面,而非政治范畴。“五四”的反封建传统较之其反帝传统更为根本和重要。这些独异之见动摇了主流意识形态合法性论证的逻辑,是导致胡风悲剧命运的重要祸根。%How to look on May 4th is key point that surveys Hu Feng's thought and its divergence with Left Wing's main thought. Both had no difference on cognition of main thesis of May 4th but difference on leader and historical significance of May 4th, Hu Feng argued that Lu Xun had become communist through personal experience in May 4th period and should become a leader of May 4th. The view had discord with authoritative conclusion about Lu Xun change. Hu Feng thought that historical significance of May 4th focused on literature or culture not on political category and anti-feudalism was more fundamental and important than anti-imperialism tradition. These unique views shook demonstrative logic of legitimacy of the mainstream ideology, which led to Hu Feng's tragic doom.

  7. Nebivolol : third-generation beta-blockade

    NARCIS (Netherlands)

    de Boer, Rudolf A.; Voors, Adriaan A.; van Veldhuisen, Dirk J.

    2007-01-01

    Nebivolol is a third generation beta-blocker. It is highly selective for the beta 1-adrenoceptor, and has additional nitric oxide-mediated vasodilating and antioxidant properties, along with a favourable metabolic profile. Nebivolol is well tolerated by patients with hypertension and heart failure.

  8. Shielding for beta-gamma radiation.

    Science.gov (United States)

    Fletcher, J J

    1993-06-01

    The build-up factor, B, for lead was expressed as a polynominal cubic function of the relaxation length, mu x, and incorporated in a "general beta-gamma shielding equation." A computer program was written to determine shielding thickness for polyenergetic beta-gamma sources without resorting to the conventional "add-one-HVL" method.

  9. Antibodies against chromosomal beta-lactamase

    DEFF Research Database (Denmark)

    Giwercman, B; Rasmussen, J W; Ciofu, Oana

    1994-01-01

    bronchopulmonary P. aeruginosa infection (CF + P) but in none of the CF patients with no or intermittent P. aeruginosa infection. Anti-beta-lactamase antibodies were present in serum from CF + P patients after six antipseudomonal courses (median) and correlated with infection with a beta-lactam-resistant strain...

  10. Venus: Geology of Beta Regio rift system

    Science.gov (United States)

    Nikishin, A. M.; Borozdin, V. K.; Bobina, N. N.

    1992-01-01

    Beta Regio is characterized by the existence of rift structures. We compiled new geologic maps of Beta Regio according to Magellan data. There are many large uplifted tesserae on beta upland. These tesserae are partly buried by younger volcanic cover. We can conclude, using these observations, that Beta upland formed mainly due to lithospheric tectonic uplifting and was only partly constructed by volcanism. Theia Mons is the center of the Beta rift system. Many rift belts are distributed radially to Theia Mons. Typical widths of rifts are 40-160 km. Rift valleys are structurally represented by crustal grabens or half-grabens. There are symmetrical and asymmetrical rifts. Many rifts have shoulder uplifts up to 0.5-1 km high and 40-60 km wide. Preliminary analysis for rift valley structural cross sections lead to the conclusion that rifts originated due to 5-10 percent crustal extension. Many rifts traverse Beta upland and spread to the surrounding lowlands. We can assume because of these data that Beta rift system has an active-passive origin. It formed due to regional tectonic lithospheric extension. Rifting was accelerated by upper-mantle hot spot origination under the center of passive extension (under the Beta Regio).

  11. The beta subunit of casein kinase II

    DEFF Research Database (Denmark)

    Boldyreff, B; Piontek, K; Schmidt-Spaniol, I;

    1991-01-01

    cDNAs encoding the beta subunit of pig and mouse CKII were isolated. The porcine cDNA was expressed as a fusion protein in Escherichia coli and used for the production of anti-CKII-beta subunit specific antibodies....

  12. Localization of thymosin beta-4 in tumors

    DEFF Research Database (Denmark)

    Larsson, L. -I.; Holck, Susanne

    2007-01-01

    Overexpression of thymosin beta-4 has been linked to malignant progression but the localization of this polypeptide within tumors is incompletely known. We therefore examined breast cancers for thymosin beta-4 using immunofluorescence. Reactive cells were identified with monoclonal cell marker...... in the tumor microenvironment may modulate tumor behavior....

  13. Connexins and beta-cell functions

    NARCIS (Netherlands)

    Cigliola, V.; Chellakudam, V.; Arabi Eter, W.; Meda, P.

    2013-01-01

    Proper functioning of pancreatic islets requires that numerous beta-cells are properly coordinated. With evolution, many mechanisms have converged, which now allow individual beta-cells to sense the state of activity of their neighbors as well as the changes taking place in the extracellular medium,

  14. BETA-ADRENOBLOCKERS AND PLATELET AGGREGATION. CARVEDILOL

    Directory of Open Access Journals (Sweden)

    A. N. Zakirova

    2008-01-01

    Full Text Available Approaches evolution to studying of beta-blockers influence on platelet aggregation is reviewed. The current view on of beta-blocker antiplatelet effects is presented on the basis of physical and chemical drug properties (water repellency, dipole moment, molecular mass. Trail results on carvedilol influence on platelet aggregation are focused.

  15. Beta-agonists and animal welfare

    Science.gov (United States)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  16. Signaling from beta1- and beta2-adrenergic receptors is defined by differential interactions with PDE4

    DEFF Research Database (Denmark)

    Richter, Wito; Day, Peter; Agrawal, Rani

    2008-01-01

    Beta1- and beta2-adrenergic receptors (betaARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by beta1AR but not beta2AR signaling, and chronic stimulation of the two receptors has opposing...

  17. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H

    2011-01-01

    of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture......The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...

  18. alpha,beta-difunctionalization of alpha,beta-unsaturated carbonyl compounds through borylation reaction

    OpenAIRE

    Palau Lluch, Gerard

    2015-01-01

    Esta tesis presenta los resultados pertenecientes a nuevas metodologias aplicadas hacia la obtención de productos alfa-funcionalizados y beta-borilados que no tienen precedente en la bibliografia, a partir de cetonas alfa,beta-insaturadas. Las funcionalizaciones estudiadas han sido utilizando fluor, para obtener alfa-fluoro beta-boryl cetonas; halogenos, para obtener alfa-halo beta-boril cetonas (siendo los halogenos cloro y bromo); y finalmente la difuncionalización de cetonas alfa,beta-insa...

  19. Nuclear emulsion with molybdenum filling for observation of {beta}{beta} decay

    Energy Technology Data Exchange (ETDEWEB)

    Ashitkov, V.D. [Institute of Theoretical and Experimental Physics, B. Cheremushkinskaya 25, 117218 Moscow (Russian Federation); Bagulya, A.V. [Lebedev Physical Institute, Leninsky Prospect 53, 119991 Moscow (Russian Federation); Barabash, A.S., E-mail: barabash@itep.r [Institute of Theoretical and Experimental Physics, B. Cheremushkinskaya 25, 117218 Moscow (Russian Federation); Bradnova, V.Ya. [Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); Chernyavsky, M.M. [Lebedev Physical Institute, Leninsky Prospect 53, 119991 Moscow (Russian Federation); Konovalov, S.I. [Institute of Theoretical and Experimental Physics, B. Cheremushkinskaya 25, 117218 Moscow (Russian Federation); Okat' eva, N.M.; Orlova, G.I.; Polukhina, N.G. [Lebedev Physical Institute, Leninsky Prospect 53, 119991 Moscow (Russian Federation); Pozharova, E.A.; Smirnitsky, V.A. [Institute of Theoretical and Experimental Physics, B. Cheremushkinskaya 25, 117218 Moscow (Russian Federation); Starkov, N.I.; Vladimirov, M.S. [Lebedev Physical Institute, Leninsky Prospect 53, 119991 Moscow (Russian Federation); Umatov, V.I. [Institute of Theoretical and Experimental Physics, B. Cheremushkinskaya 25, 117218 Moscow (Russian Federation)

    2010-09-21

    The usage of nuclear emulsion with molybdenum powder filling ({approx}5% by weight of dry emulsion) for observation of {beta}{beta} decay is shown to be possible. Estimates for 1 kg of {sup 100}Mo with zero background give the sensitivity for the 0{nu}{beta}{beta} decay of {sup 100}Mo at the level of {approx}1.5x10{sup 24}yr for 1 yr of measurement. Promising elements for the double beta decay search, besides molybdenum ({sup 100}Mo), are also {sup 82}Se, {sup 150}Nd, {sup 96}Zr, {sup 130}Te, {sup 116}Cd, and {sup 48}Ca.

  20. A neonate with the Pelger-Huët anomaly, cleft lip and palate, and agenesis of the corpus callosum, with a chromosomal microdeletion involving 1q41 to 1q42.12.

    Science.gov (United States)

    Christensen, R D; Yaish, H M

    2012-03-01

    We observed a neonate with cleft lip and palate, 13 sets of ribs, agenesis of the corpus callosum, slightly small penis, hypoglycemia, and what initially appeared to be a marked leukocyte 'left shift' on complete blood count, but which was actually a Pelger-Huët anomaly. A chromosomal microdeletion was identified at1q41-42.12.

  1. Phase I/II clinical and pharmacokinetic study evaluating a fully human monoclonal antibody against EGFr (HuMax-EGFr) in patients with advanced squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Bastholt, Lars; Specht, Lena; Jensen, Kenneth;

    2007-01-01

    reactions varied from few days to 2 months. No DLTs were observed and MTD was not reached. In the two highest dose groups, 7 of 11 patients obtained a PR or SD and 9 patients obtained metabolic PR or SD. CONCLUSIONS: HuMax-EGFr can be safely administered in doses up to 8 mg/kg, and preliminary data...

  2. Experimental beta-alaninuria induced by (aminooxyacetate.

    Directory of Open Access Journals (Sweden)

    Kurozumi Y

    1999-02-01

    Full Text Available Experimental beta-alaninuria was induced in rats by injection of (aminooxyacetate (AOA, a potent inhibitor of aminotransferases, in order to elucidate the pathogenesis of hyper-beta-alaninemia. A 27-fold increase of beta-alanine (BALA excretion was induced by subcutaneous injection of 1 5 mg of AOA per kg of body weight. A 13-fold and a 9-fold increase of beta-aminoisobutyric acid (BAIBA and gamma-aminobutyric acid (GABA, respectively, were also induced simultaneously by the AOA injection. Identification of BALA and BAIBA isolated from the rat urine was performed by chromatographic and mass spectrometric analyses. The effects of AOA injection on the tissue levels of these amino acids were also studied. Contents of BALA in the liver and kidney and GABA in the brain increased significantly in response to AOA injection. The present study indicates that BALA transaminase is involved in hyper-beta-alaninemia.

  3. Precision measurements in 20F beta decay

    Science.gov (United States)

    Hughes, Maximilian; Naviliat-Cuncic, Oscar; Voytas, Paul; George, Elizabeth; Paulauskas, Stan; Huyan, Xueying

    2017-01-01

    Precision measurements of the shape of the beta particle energy spectrum provide a sensitive window to search for new interactions beyond the standard model. The decay of 20F offers an attractive system due to the simple decay scheme for a coincidence measurement. A beam of 20F ions, produced at the National Superconducting Cyclotron Laboratory, was implanted into a beta-detector. A gamma-ray detection system surrounded the beta detector to detect the beta-delayed gammas in coincidence to reduce the background. Preliminary analysis of these data focus on the half-life of 20F due to the statistical inconsistency of previous work. Monte Carlo simulations are ongoing to analyze the shape of the beta energy spectrum. Results of the analysis of the half-life will be presented. Supported by National Science Foundation Grant PHY-1102511.

  4. Ranking Beta Sheet Topologies of Proteins

    DEFF Research Database (Denmark)

    Fonseca, Rasmus; Helles, Glennie; Winter, Pawel

    2010-01-01

    One of the challenges of protein structure prediction is to identify long-range interactions between amino acids.  To reliably predict such interactions, we enumerate, score and rank all beta-topologies (partitions of beta-strands into sheets, orderings of strands within sheets and orientations...... of paired strands) of a given protein.  We show that the beta-topology corresponding to the native structure is, with high probability, among the top-ranked. Since full enumeration is very time-consuming, we also suggest a method to deal with proteins with many beta-strands. The results reported...... in this paper are highly relevant for ab initio protein structure prediction methods based on decoy generation. The top-ranked beta-topologies can be used to find initial conformations from which conformational searches can be started. They can also be used to filter decoys by removing those with poorly...

  5. Beta-glucuronidase in physiology and disease.

    Science.gov (United States)

    Basińska, Agnieszka; Floriańczyk, Bolesław

    2003-01-01

    beta-glucoronidase (EC 3.2.1.31) is a lysosomal enzyme catylysing the decomposition of beta-D-glucoronides--compounds arising as a result of the combination of beta-D-glucoronic acid and a number of compounds both exo- and endogenous, containing hydroxylic, carboxylic, amine, imine or thiol groups. The most common test evaluating the activity of the enzyme is that using phenolphtalein glucoronide as a biosynthetic substrate. The freed aglycons are colorimetrically assayed. The activity of beta-glucoronidase increases in many pathological conditions: liver infammations, cirrhosis of the liver, inflammations of other organs, cholestatic jaundice, tuberculosis, sarcoidosis and also in neoplasms. Many authors point to beta-glucoronidase as a sensitive indicator signalling cell damage.

  6. The search for neutrinoless double beta decay

    CERN Document Server

    Gomez-Cadenas, J J; Mezzetto, M; Monrabal, F; Sorel, M

    2011-01-01

    In the last few years the search for neutrinoless double beta decay has evolved from being almost a marginal activity in neutrino physics to one of the highest priorities for understanding neutrinos and the origin of mass. There are two main reasons for this paradigm shift: the discovery of neutrino oscillations, which clearly established the existence of massive neutrinos; and the existence of an unconfirmed, but not refuted, claim of evidence for neutrinoless double decay in 76Ge. As a consequence, a new generation of experiments, employing different detection techniques and {\\beta}{\\beta} isotopes, is being actively promoted by experimental groups across the world. In addition, nuclear theorists are making remarkable progress in the calculation of the neutrinoless double beta decay nuclear matrix elements, thus eliminating a substantial part of the theoretical uncertainties affecting the particle physics interpretation of this process. In this report, we review the main aspects of the double beta decay pro...

  7. Recommendations for the clinical practice: Standards, options and recommendations 2003 for the use of recombinant erythropoietin (alpha and beta epoetine, alpha darbepoetine, EPO) in the taking charge of anemia in oncology for the patients treated by radiotherapy, update; Recommandations pour la pratique clinique: Standards, Options et Recommandations 2003 pour l'utilisation de l'erythropoietine recombinante (epoetine alfa et beta, darbepoetine alfa, EPO) dans la prise en charge de l'anemie en cancerologie pour les patients traites par radiotherapie, mise a jour

    Energy Technology Data Exchange (ETDEWEB)

    Marchal, Ch. [Centre Alexis-Vautrin, oncologue-radiotherapeute, 54 - Nancy (France); Spaeth, C. [Centre Alexis-Vautrin, oncologue medical, 54 - Nancy (France); Casadevall, N. [Hopital Hotel-Dieu, hematologue, 75 - Paris (France); Daouphars, M. [Hopital Notre-Dame-de-Bon-Secours, pharmacien, 57 - Metz (France); Marec-Berard, P. [Centre Leon-Berard, oncologue-pediatre, 69 - Lyon (France); Fabre, N. [FNCLCC, methodologiste, 75 - Paris (France); Haugh, M. [FNCLCC, methodologiste, 75 - Paris (France)

    2004-06-01

    Standards, Options and Recommendations for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy - UPDATE 2003. Context. - 'The Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the twenty French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives. - To update the Standards, Options and Recommendations clinical practice guidelines for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy. Methods. - The working group identified the questions requiring up-dating from the previous guideline. Medline and Embase were searched using specific search strategies from January 1999 to October 2002. Literature monitoring was performed to identify randomized clinical trials published between October 2002 to November 2003. In addition several Internet sites were searched in October 2002. Results. - There is no standard attitude for use of rHuEPO in patients undergoing radiotherapy. There is no evidence to support use of rHuEPO in patients with ENT cancer receiving radiotherapy alone. In patients undergoing curative radiotherapy, it is recommended to correct anaemia under 10 g/dL using transfusion rather than rHuEPO. When the haemoglobin concentration is between 12 g/dL and 14 g/dL initial use of rHuEPO can be an option under certain conditions for radio-chemotherapy if the risk of

  8. Research Upregulation of CD23 (FcεRII Expression in Human Airway Smooth Muscle Cells (huASMC in Response to IL-4, GM-CSF, and IL-4/GM-CSF

    Directory of Open Access Journals (Sweden)

    Lew D Betty

    2005-05-01

    Full Text Available Abstract Background Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE. Methods Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence. Results The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4, 15.6 ± 2.7% (GM-CSF and 32.9 ± 13.9% (IL-4/GMCSF combination(n = 3. The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc. Conclusion CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue

  9. Painlev\\'e representation of Tracy-Widom$_\\beta$ distribution for $\\beta = 6$

    CERN Document Server

    Rumanov, Igor

    2014-01-01

    In \\cite{betaFP1}, we found explicit Lax pairs for the soft edge of beta ensembles with even integer values of $\\beta$. Using this general result, the case $\\beta=6$ is further considered here. This is the smallest even $\\beta$, when the corresponding Lax pair and its relation to Painlev\\'e II (PII) have not been known before, unlike cases $\\beta=2$ and $4$. It turns out that again everything can be expressed in terms of the Hastings-McLeod solution of PII. In particular, a second order nonlinear ODE for the logarithmic derivative of Tracy-Widom distribution for $\\beta=6$ involving the PII function in the coefficients, is found, which allows one to compute asymptotics for the distribution function. The ODE is a consequence of a linear system of three ODEs for which the local Painlev\\'e analysis yields series solutions with exponents in the set $4/3$, $1/3$ and $-2/3$.

  10. The lipolytic effect of beta 1- and beta 2-adrenoceptor activation in healthy human volunteers.

    Science.gov (United States)

    Haffner, C A; Kendall, M J; Maxwell, S; Hughes, B

    1993-01-01

    1. We investigated the effect of activation beta 1- and beta 2-adrenoceptors on the process of lipolysis in human volunteers. Ten male subjects underwent a single-blind randomized cross-over trial using infusions of terbutaline (a specific beta 2-adrenoceptor agonist), xamoterol (a partial beta 1-agonist with beta 2-adrenoceptor blocking activity) and saline (placebo control). The effect of these infusions on plasma potassium, glucose, free fatty acids (FFA) (total and individual) and insulin levels was studied. 2. Terbutaline infusion induced a significant rise in plasma glucose and a fall in plasma potassium in keeping with its beta 2-adrenoceptor stimulant properties. Xamoterol infusion had no significant effect on these values. Terbutaline infusion caused a greater rise in total and individual FFA than xamoterol, but both effects were significantly different from placebo. 3. The possible reasons for these results and their implications on the beta-adrenergic control of lipolysis are discussed. PMID:8383517

  11. Genetics Home Reference: mucolipidosis III alpha/beta

    Science.gov (United States)

    ... Health Conditions mucolipidosis III alpha/beta mucolipidosis III alpha/beta Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Mucolipidosis III alpha/beta is a disorder that affects many parts ...

  12. Genetics Home Reference: mucolipidosis II alpha/beta

    Science.gov (United States)

    ... Health Conditions mucolipidosis II alpha/beta mucolipidosis II alpha/beta Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Mucolipidosis II alpha/beta (also known as I-cell disease) is ...

  13. Expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated and nuclear transfer derived bovine pregnancies.

    Science.gov (United States)

    Ravelich, S R; Shelling, A N; Wells, D N; Peterson, A J; Lee, R S F; Ramachandran, A; Keelan, J A

    2006-01-01

    Bovine nuclear transfer pregnancies are characterized by a high incidence of placental abnormalities, notably, increased placentome size and deficiencies in trophoblast cell function and establishment of placental vasculature. Alterations in gene expression during placental growth and development may contribute to the appearance of large placentomes in pregnancies derived from nuclear transfer. The placenta synthesizes a number of cytokines and growth factors, including the transforming growth factor-betas (TGF-betas) that are involved in the establishment, maintenance and/or regulation of pregnancy. All forms of TGF-beta and their receptors are present at the fetal-maternal interface of the bovine placentome, where they are thought to play an important role in regulating growth, differentiation, and function of the placenta. Using real-time RT-PCR, we have examined the expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated (AI) and nuclear transfer (NT)-derived bovine pregnancies at days 50, 100 and 150 of gestation. TGF-beta1, TGF-beta2 and TGF-beta3 mRNA expression increased by 2.0-2.8-fold, while TGF-betaRI and TGF-betaRII mRNA expression decreased by 1.7-2.0-fold in NT placentomes compared to AI controls at all gestational ages examined. These findings indicate that NT placentomes may be resistant to the growth suppressive effects of TGF-betas and could contribute to the placental proliferative abnormalities observed in NT-derived placentas. Alternatively, deficiencies in placentation may provide a mechanism whereby TGF-betas are dysregulated in NT pregnancies.

  14. Expression and Purification of Functional HuGALNT3 without the Transmembrane Domain (huGALNT3-sol) in Pichia pastoris%重组人GALNT3-sol蛋白在毕赤酵母中的高效表达和活性鉴定

    Institute of Scientific and Technical Information of China (English)

    孔蕴; 郜海涛; 李树芳; 王鹏; 顾国锋; 顾黎

    2012-01-01

    目的:为了获得有催化活性的人乙酰半乳糖胺转移酶3(GALNT3),构建了GALNT3可溶性区域(GALNT3-sol)的真核分泌表达载体,在巴斯德毕赤酵母中表达并纯化GALNT3-sol蛋白,体外检测其转糖基活性.方法:以构建好的pET15b/GALNT3-sol为模板进行PCR,扩增编码人GALNT3-sol的cDNA片段(1755 bp),将其克隆至真核表达载体pPIC9K,载体线性化后采用电击法转化毕赤酵母GS115.通过MD平板和G418平板筛选出阳性高拷贝重组菌株.阳性菌株经过甲醇诱导表达人GALNT3-sol重组蛋白,表达上清进行Ni-NAT分离纯化.分别采用SDS-PAGE和Western blot鉴定纯化的重组蛋白,并使用HPLC和MALDI-TOF/MS分析其转糖基化反应的活性.结果:成功构建了能够分泌表达GALNT3-sol的毕赤酵母菌株.阳性表达菌株在BMMY培养基(pH 6.0)中20℃培养,经0.5%甲醇诱导表达96 h,摇瓶表达量可达5mg/L.SDS-PAGE和Western blot结果显示表达重组蛋白为糖基化形式.活性检测显示表达的重组蛋白具有转糖基活性.结论:成功获得可以高效分泌表达具有活性的人GALNT3-sol蛋白的毕赤酵母菌株,为进一步研究人GALNT3的性质及其应用提供了基础.%Objective: In order to research the bioactivity of GALNT3, the truncated part of GALNT3 (huGALNT3-sol) which was deleted of the hydrophobic trans-membrane domain were obtained using Pichia pastoris expression system, and assayed the transferring GalNAc activity of recombinant huGALNT3-sol. Methods; The gene of human GALNT3-sol (1 755 bp)was amplified from pET15b/ GALNTi-sol and cloned into expression vector pPIC9k, and the recombinant plasmid was transformed into Pichia pastoris GS115 strain through electroporation. The high copy recombinant strains with high-level huGALNT3-sol production were screened out by MD plate and G418. High level of huGALNT3-sol was obtained in BMMY medium the induction of methanol, and purified from the supernatant with Ni-NAT. The identity of

  15. HuD蛋白对肛门直肠畸形子鼠直肠末端肠神经系统的影响%The impact of the HuD protein on the intestinal nervous system in the rectal end of animal models of congenital anorectal malformation

    Institute of Scientific and Technical Information of China (English)

    孔萌; 刘远梅; 金祝; 高明娟; 曲颜; 郑泽兵

    2016-01-01

    Objective To investigate the expression of the HuD protein in the rectal end of anorectal malformation (ARM) embryonic rats and to explore the effect of HuD expression on the development of the intestinal nervous system.Methods 20 adult pregnant Sprague Dawley rats were randomized into a control (n =10) and ARM (induced by ethylenethiourea) group (n =10).On the 20th day after pregnancy,the cesarean section fetus were obtained for morphological observations and abnormal statistics.Using hematoxylin-eosin (HE) staining to detect the perineum of sagittal gross specimen.Using immunohistochemistry (IHC) and Western blotting to detect the protein expression levels of HuD of distal rectum in fetal rats.Results The normal control group was given birth to 108 fetal rats whose survival rate was 100.0% and no rectal abnormal openings,the ARM group was given birth to 94 fetal rats whose survival rate was 93.6% and ARM rate was 96.8%.In HE staining,there was no opening at the end of the distal rectum of the ARM fetuses,the end of the rectum had thickened muscular layer and covered by hyperplastic squamous epithelial without intestinal gland distribution.The number of submucosal and myenteric plexus alse reduced significantly in ARM fetuses compared with controls (143.60 ± 14.93 vs.335.90 ± 10.46,P <0.01).The immunohistochemistry and Western blotting analysis showed that the concentration of the HuD protein in the ARM group was significantly lower than that in the control group (312.90 ± 53.40 vs.456.40 ± 57.13;0.24 ± 0.05 vs.0.45 ± 0.06,P < 0.01).Conclusion The HuD protein was abnormally expressed in the rectal end of the ARM embryonic rats and may participate in the development and maturation of the enteric nervous system (ENS).This study may provide a useful theoretical reference for the treatment of postoperative defecation dysfunction in ARM patients.%目的 检测HuD蛋白在肛门直肠畸形(ARM)子鼠直肠末端组织中的表达,探讨其可能对肠

  16. Functions of A[beta], sAPP[alpha] and sAPP[beta] : similarities and differences

    National Research Council Canada - National Science Library

    Chasseigneaux, Stephanie; Allinquant, Bernadette

    2012-01-01

    ...), which also generates the soluble peptide APP[beta] (sAPP[beta]). An antagonist and major APP metabolic pathway involves cleavage by alpha secretase, which releases sAPP[alpha]. Although soluble A[beta...

  17. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  18. Evidence for Novel [beta]-Sheet Structures in Iowa Mutant [beta]-Amyloid Fibrils

    Energy Technology Data Exchange (ETDEWEB)

    Tycko, Robert; Sciarretta, Kimberly L.; Orgel, Joseph P.R.O.; Meredith, Stephen C.; (IIT); (NIH); (UC)

    2009-07-24

    Asp23-to-Asn mutation within the coding sequence of {beta}-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-A{beta}40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-A{beta}40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10{sup -3} min{sup -1} and 1.07 x 10{sup -4} min{sup -1} for D23N-A{beta}40 and the wild-type peptide WT-A{beta}40, respectively) and without a lag phase. Electron microscopy shows that D23N-A{beta}40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-{beta} pattern, with a sharp reflection at 4.7 {angstrom} and a broad reflection at 9.4 {angstrom}, which is notably smaller than the value for WT-A{beta}40 fibrils (10.4 {angstrom}). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-A{beta}40 fibrils containing the in-register, parallel {beta}-sheet structure commonly found in WT-A{beta}40 fibrils and most other amyloid fibrils. Antiparallel {beta}-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through 13C-13C and 15N-13C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-A{beta}40 fibrils and the unusual vasculotropic clinical picture in these patients.

  19. Glycosylphosphatidylinositol-Anchored Anti-HIV scFv Efficiently Protects CD4 T Cells from HIV-1 Infection and Deletion in hu-PBL Mice.

    Science.gov (United States)

    Ye, Chaobaihui; Wang, Weiming; Cheng, Liang; Li, Guangming; Wen, Michael; Wang, Qi; Zhang, Qing; Li, Dan; Zhou, Paul; Su, Lishan

    2017-02-01

    Despite success in viral inhibition and CD4 T cell recovery by highly active antiretroviral treatment (HAART), HIV-1 is still not curable due to the persistence of the HIV-1 reservoir during treatment. One patient with acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation from a homozygous CCR5 Δ32 donor has had no detectable viremia for 9 years after HAART cessation. This case has inspired a field of HIV-1 cure research focusing on engineering HIV-1 resistance in permissive cells. Here, we employed a glycosylphosphatidylinositol (GPI)-scFv X5 approach to confer resistance of human primary CD4 T cells to HIV-1. We showed that primary CD4 T cells expressing GPI-scFv X5 were resistant to CCR5 (R5)-, CXCR4 (X4)-, and dual-tropic HIV-1 and had a survival advantage compared to control cells ex vivo In a hu-PBL mouse study, GPI-scFv X5-transduced CD4 T cells were selected in peripheral blood and lymphoid tissues upon HIV-1 infection. Finally, GPI-scFv X5-transduced CD4 T cells, after being cotransfused with HIV-infected cells, showed significantly reduced viral loads and viral RNA copy numbers relative to CD4 cells in hu-PBL mice compared to mice with GPI-scFv AB65-transduced CD4 T cells. We conclude that GPI-scFv X5-modified CD4 T cells could potentially be used as a genetic intervention against both R5- and X4-tropic HIV-1 infections. Blocking of HIV-1 entry is one of most promising approaches for therapy. Genetic disruption of the HIV-1 coreceptor CCR5 by nucleases in T cells is under 2 clinical trials and leads to reduced viremia in patients. However, the emergence of viruses using the CXCR4 coreceptor is a concern for therapies applying single-coreceptor disruption. Here, we report that HIV-1-permissive CD4 T cells engineered with GPI-scFv X5 are resistant to R5-, X4-, or dual-tropic virus infection ex vivo In a preclinical study using hu-PBL mice, we show that CD4 T cells were protected and that GPI-scFv X5-transduced cells were

  20. Los orígenes del Colegio Menor de la Concepción de Huérfanos de Salamanca

    Directory of Open Access Journals (Sweden)

    Miguel A. MARTÍN SÁNCHEZ

    2009-12-01

    Full Text Available RESUMEN: El Colegio Menor de la Concepción de Huérfanos de la Universidad de Salamanca es uno más de la gran cantidad de colegios que se fundaron al amparo del estudio salmantino en el siglo XVI. Fundado por Francisco de Solís, obispo de Bagnorea y secretario de Paulo III, durante tres siglos facilitó y proporcionó amparo y educación a multitud de estudiantes pobres que no tenían recursos para ello. Fundado en la primera mitad del siglo XVI, durante esta centuria se asentó y comenzó su andadura, que terminaría en el siglo XIX. Este trabajo realiza un análisis sobre los primeros años de vida del Colegio, analizando cuestiones tan importantes como su fundación, las bulas fundacionales, el fundador, las primeras constituciones o la matrícula durante el siglo XVI, entre otras. Fue el siglo XVI el siglo de su nacimiento y consolidación, realizando durante esta centuria un gran esfuerzo institucional, como demuestra el hecho de la elaboración de las primeras constituciones, la construcción del edificio, o la incorporación a la Universidad de Salamanca, por ejemplo. A lo largo de estas páginas realizaremos un recorrido por los orígenes del primer colegio universitario que se crea para el amparo de niños pobres y huérfanos, permitiéndoles estudiar desde la gramática hasta graduarse en la ciencia que mejor les pareciere. La obra social y educativa del Colegio permitió la progresión y ascenso social de multitud de estudiantes pobres y huérfanos con talento, que de otra forma nunca hubieran podido realizar estudios en la Universidad, puesto que carecían de recursos para ello.ABSTRACT: The Conception of Orphans Minor College of the University of Salamanca is one more of the great quantity of colleges that were founded under protection of Salamancan Study in the 16th century. It was founded by Francisco de Solís, bishop of Bagnorea and secretary of Paulo III, provided protection and education to many poor students without

  1. Internação domiciliar: o perfil dos pacientes assistidos pelo Programa HU em Casa Home care: profile of patients attended by a home care program

    Directory of Open Access Journals (Sweden)

    Daniella Reis Barbosa Martelli

    2011-01-01

    Full Text Available Internação domiciliar é uma modalidade de atendimento à saúde que está se transformando em uma alternativa importante para minimizar alguns dos principais problemas inerentes aos sistemas de saúde vigentes, especialmente os da rede pública. O objetivo do estudo foi descrever o perfil sociodemográfico e clínico da população assistida pelo Programa de Internação Domiciliar (PID HU em Casa do Hospital Universitário Clemente de Faria da Universidade Estadual de Montes Claros. O estudo foi descritivo e retrospectivo por meio da análise de prontuários, realizada de maio de 2005 a maio de 2008. Foram analisados 137 pacientes, sendo 75 do gênero feminino (54,7% e 62 do masculino (45,3%. O grupo de 61 a 80 anos foi mais prevalente (37,2% e 73% dos pacientes residiam em bairros periféricos do município de Montes Claros-MG. Dos agravos mais comuns na primeira internação, a pneumonia foi prevalente, 22 casos (16,1%. A maioria dos pacientes foi encaminhada ao PID pela clinica médica (84,7%, com intervalo de maior prevalência de duas a três internações (42,4%. Do total de pacientes, 120 (87,6% permaneceram internados por 16 a 30 dias e 51,8% não necessitaram passar novamente pelo PID para uma segunda internação. Com relação à resolutividade clínica, 130 (94,9% tiveram alta clínica, no PID, na primeira internação. O PID mostrou-se ser um programa de alta resolutividade, atendendo mais ao público idoso feminino, de baixa renda e com períodos de internação relativamente curtos.The home care is a modality of health care which is becoming an important alternative to minimize some of mainly relevant problems of world health, especially the public health network. This paper aimed to describe the socio-demographic and clinical population assisted by the Home Care Program HU em Casa, of the University Hospital Clemente de Faria, Universidade Estadual de Montes Claros. It is a descriptive and retrospective study analyzing

  2. La masacre de Ambo: Histoire d'une revolte paysanne, département de Huánuco, Pérou, 1962-1963

    Directory of Open Access Journals (Sweden)

    2004-01-01

    Full Text Available À travers l’histoire de la révolte de la communauté de Huaylla y Aclacancha (vallée d’Ambo, département de Huánuco il est possible de comprendre comment s’organisent les paysans comuneros pour défendre leurs terres communautaires. L’analyse des requêtes paysannes envoyées aux autorités gouvernementales dévoile l’importance pour la communauté de faire valoir la légitimité de ses droits de propriété, en s’appuyant à la fois sur des actions légales et sur des occupations de terre. Cependant l’utilisation simultanée de ces moyens de revendication n’explique pas en soi le dérapage vers la violence, connu dans la presse comme la masacre de Ambo (la tuerie d’Ambo. Seule une étude des contextes dans lesquels interagissent tous les acteurs concernés (comuneros, syndicalistes, autorités politiques, policiers et hacendados peut permettre de saisir pourquoi les réclamations de cette communauté ont débouché sur la mort de comuneros. A través la historia de la lucha de la comunidad de Huaylla y Aclacancha (provincia de Ambo, departamento de Huánuco se puede comprender cómo se organizan los comuneros para defender sus tierras comunales. El análisis de las solicitudes enviadas por los comuneros a las autoridades gubernamentales nos muestra la importancia, para la comunidad, de hacer valer tanto la legitimidad de sus derechos de propiedad como, al mismo tiempo, apoyarse sobre acciones legales y ocupaciones de tierras. La utilización simultánea de esos medios de reivindicación no explica en sí el deslizamiento violento, conocido en la prensa como la masacre de Ambo. Pero sí, el análisis de los contextos en los cuales interactuan todos los actores de ese drama (comuneros, sindicalistas, autoridades políticas, gardias civiles y hacendados nos permite comprender por qué las reclamaciones de esta comunidad desembocan en la muerte de comuneros. Through a history of the community’s rebellion (Huaylla y Aclacancha, in

  3. Dosimetry of Low-Energy Beta Radiation

    DEFF Research Database (Denmark)

    Borg, Jette

    Useful techniques and procedures for derermination of absorbed doses from exposure in a low-energy beta radiation were studied and evaluated. The four techniques included were beta spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical...... low-energy beta radiation field a moderated spectrum from a carbon-14 source was used. The measured responce of a Si(Li) detector to photons (bremsstrahlung) showed fine agreemant with the MC calculated photon response, whereas the difference between measured and MC calculated response to electrons...

  4. Silent ischemia and beta-blockade

    DEFF Research Database (Denmark)

    Egstrup, K

    1991-01-01

    and should also be directed at the other coronary artery risk factors of the patients. The effects of beta-blockers, which reduce the duration and frequency of silent ischemic episodes, is well described. The effect is most pronounced in the morning, when the frequency of ischemia is highest......, and the mechanism of action seems mainly mediated through a reduction in myocardial oxygen demand. beta-Blockers have shown effectiveness in both effort-induced angina and mixed angina, and increased anti-ischemic potency may be achieved by combination therapy with a calcium antagonist. Abrupt withdrawal of beta-blockers...

  5. Scintillating bolometers for Double Beta Decay search

    CERN Document Server

    Gironi, Luca

    2009-01-01

    In the field of Double Beta Decay (DBD) searches, the use of high resolution detectors in which background can be actively discriminated is very appealing. Scintillating bolometers containing a Double Beta Decay emitter can largely fulfill this very interesting possibility. In this paper we present the latest results obtained with CdWO4 and CaMoO4 crystals. Moreover we report, for the first time, a very interesting feature of CaMoO4 bolometers: the possibility to discriminate beta-gamma events from those induced by alpha particles thanks to different thermal pulse shape.

  6. The theory of beta-decay

    CERN Document Server

    Strachan, Charles

    1969-01-01

    The Theory of Beta-Decay covers the formulas, theories, probabilities, and spectra of beta-decay. This book is divided into 2 parts compassing 12 chapters, and starts with the introduction to the neutrino and the quantum theoretical background, explaining the basic phenomenon of beta-decay and the emission of electrons. The subsequent chapters deal with the interaction and the transition probability, as well as formulas of solutions. These topics are followed by discussions on the developments in the non-conservation of parity and helicity, the two-component theory of the neutrino, possible i

  7. Dosimetry of Low-Energy Beta Radiation

    DEFF Research Database (Denmark)

    Borg, Jette

    Useful techniques and procedures for derermination of absorbed doses from exposure in a low-energy beta radiation were studied and evaluated. The four techniques included were beta spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical...... low-energy beta radiation field a moderated spectrum from a carbon-14 source was used. The measured responce of a Si(Li) detector to photons (bremsstrahlung) showed fine agreemant with the MC calculated photon response, whereas the difference between measured and MC calculated response to electrons...

  8. Syntheses of stable isotope-labeled 6 beta-hydroxycortisol, 6 beta-hydroxycortisone, and 6 beta-hydroxytestosterone.

    Science.gov (United States)

    Furuta, Takashi; Suzuki, Atsushi; Matsuzawa, Mitsuhiro; Shibasaki, Hiromi; Kasuya, Yasuji

    2003-09-01

    A method is described for the preparation of two types of multi-labeled 6 beta-hydroxycortisol containing either five deuterium atoms at C-19 methyl and C-1 methylene or four 13C atoms at C-1, C-2, C-4, and C-19 in addition to the five deuterium atoms for use as analytical internal standards for gas chromatography-mass spectrometry (GC-MS). BMD derivatives of [1,1,19,19,19-2H(5)]cortisone and [1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone (cortisone-2H(5)-BMD and cortisone-13C(4),2H(5)-BMD) were first synthesized via indan synthon method starting from optical active 11-oxoindanylpropionic acid and labeled isopropenyl anion ([1,1,3,3,3-2H(5)]- or [1,3-13C(2),1,1,3,3,3-2H(5)]isopropenyl anion). The labeled isopropenyl anion was prepared from commercially available [1,1,1,3,3,3-2H(6)]- or [1,3-13C(2),1,1,1,3,3,3-2H(6)]acetone. Ultraviolet (UV) irradiated autoxidation at C-6 position of 3-ethyl-3,5-dienol ether derivatives of the labeled cortisone-BMDs gave 6 beta-hydroxy-[1,1,19,19,19-2H(5)]cortisone-BMD and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone-BMD, respectively, as a mixture of 6 beta- and 6 alpha-epimers in a ratio of 4:1. Separation of 6 beta- and 6 alpha-epimers by thin-layer chromatography (TLC) and subsequent hydrolysis of the BMD group at C-17 gave pure labeled 6 beta-hydroxycortisone. After protecting the keto group at C-3 of the labeled 6 beta-hydroxycortisone-BMD as semicarbazone, reduction of 11-keto group with NaBH(4) and subsequent removal of the C-3 and C-17 protecting groups gave 6beta-hydroxy-[1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-2H(5)) and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-13C(4),2H(5)), respectively, as a mixture of 6 beta- and 6 alpha-epimers (6 beta:6 alpha=4.4:1). The isotopic compositions of 6 beta-hydroxycortisol-2H(5) and 6 beta-hydroxycortisol-13C(4),2H(5) were 90.9 and 92.1 at.%, respectively. Furthermore, 6 beta-hydroxy-[1 alpha,16,16,17 alpha-2H(4

  9. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel

    2006-03-01

    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  10. La estrategia diplomática-militar de España reflejada en la correspondencia extraoficial del Duque de Huéscar entre 1747 y 1748

    Directory of Open Access Journals (Sweden)

    Naiara Pavía Dopazo

    2014-02-01

    Full Text Available En este artículo se pretende contribuir al conocimiento de los sucesos bélicos acaecidos en Génovadurante la primavera de 1747, a través del intercambio de correspondencia inédita entre algunos delos principales aliados españoles de esta república, capitaneados por Carvajal y Ensenada que encontraronen don Fernando de Silva, duque de Huéscar (luego de Alba, el mejor enlace para la conformaciónde una red social que permitiera un conocimiento extraoficial que mejorara la capacidad deactuación a favor de los intereses de España en dicha república. Un análisis interpersonal de un hechohistórico que pone de manifiesto la «tensa relación» diplomática entre Francia y España, unidas porel Pacto de Familia de 1743 y que determinó las estrategias diplomáticas llevadas por ambos durantelas negociaciones de la paz de Aquisgrán, que puso fin a la Guerra de Sucesión Austriaca.With this article we’re trying to contribute to the knowledge of the warlike events occurred in Genoaduring the spring of 1747, through the exchange of unknown correspondence among some of theprincipal Spanish allies of this republic, led by Carvajal and Ensenada who found in don Fernando ofSilva, Duke of Huéscar (later Duke of Alba, the best link for the conformation of a social network thatallowed an unofficial knowledge in order to improve the capacity of action in favour of the interestsof Spain in the above mentioned republic. An interpersonal analysis of a historical fact that revealsthe diplomatic «tense relationship” between France and Spain, joined by the Family agreement of 1743and that was decisive for the diplomatic strategies accomplished by both of them during thenegotiations of the Peace of Aachen (Aix-la-Chapelle, which came to an end with the War of theAustrian Succession.

  11. On Contributions of Hu Shi’s Reading Lvshi Chunqiu%胡适《读吕氏春秋》的贡献

    Institute of Scientific and Technical Information of China (English)

    王启才

    2015-01-01

    Reading Lvshi Chunqiu,collected in Collections ofHu Shi Essays III (vol.3 ),is a research paper on Lvshi Chunqiu written by Hu Shi in 1930.Shifting from the traditional emphasis on textual interpretation,the paper adopted a cont-rastive perspective,focusing on human desire and nature,and proposed quite a few valuable points of view.Based on histori-cal evidence,the paper took a broad scope of vision in writing,its writing style and manner were easy to accept,and its meth-od and conclusion were fresh and new.The paper preliminarily changed the roadmap of later research on Lvshi Chunqiu and became the pioneering work in the modern history of Lvshi Chunqiu research.%写于1930年,后收入《胡适文存三集》卷三的《读吕氏春秋》,是胡适的一篇研究《吕氏春秋》的论文。该文打破了有汉以来研究《吕氏春秋》只重视文本解释的局限,采用了中西比较的思路与方法,从人欲、人性的思想高度审视把握《吕氏春秋》,提出了不少现在看来仍不失为有价值的观点与问题。文章视野开阔,论从史出,文风明白晓畅,易于接受,方法与结论都令人耳目一新,初步改变了以后《吕氏春秋》研究的路向,在近代《吕氏春秋》研究史上具有开拓之功。

  12. Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

    Energy Technology Data Exchange (ETDEWEB)

    Caselli, E.; Powers, R.A.; Blaszczak, L.C.; Wu, C.Y.E.; Prati, F.; Shoichet, B.K. (NWU)

    2010-03-05

    Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well as four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta}-lactamases. Surprisingly

  13. 直接分子克隆法构建重组腺病毒AdHu5-mfsp27的研究%Direct molecular cloning to construct recombinant AdHu5-mfsp27 and its amplification and purification

    Institute of Scientific and Technical Information of China (English)

    王群; 贾蓓; 魏晓宇; 黄文祥; 周向阳

    2012-01-01

    Objective The aim of this study was to construct recombinant AdHu5-040-mfsp27 (cds) using direct molecular cloning and obtain viruses with a high titer and level of purity for laboratory and clinical trials. Methods The target gene mfsp27 was cloned into pShuttle and located between two rare restriction enzymes (REs) (I-ceuI and PI-sceI). After digestion, gel ligation, and transformation, recombinants were selected and confirmed by specific RE cutting and sequencing. The candidate recombinant plasmid was then linearized and transfected into HEK293 cells. After infection and expansion, the crude virus stock was collected and purified by modified cesium chloride gradient centrifugation. The virus multiplicity of infection (MOD was measured by series dilution of the stock. Results Recombinant AdHu5-040-fsp27 (cds) was successfully constructed. The titer (O. D. measurement) was as high as to 1 × 1013 VP/ ml and MOI was 1. 44 × 1011. The ratio of the two values was 69. 44. The recombinant virus had potent ability to infect HEK293 cells. Conclusion Direct molecular cloning to construct recombinant Ad Hu5-040-fsp27 (cds) is better than homologous recombination because it takes less time and it provides highly positive clones with fewer mutations of target genes. Modified cesium chloride gradient centrifugation combined with a liquid chromatography column and biogels is a simple and efficient way to obtain purified viruses in high tilers and with a high level of activity. This provides an experimental basis for the study of gene function and the industrial production of recombinant adenovirus.%目的 采用直接分子克隆体外连接的方法构建重组腺病毒AdHu5-040-mfsp27(cds),高效高质量扩增和纯化重组腺病毒以满足实验及临床研究的需求. 方法 将mfsp27克隆至穿梭质粒pSh CMV intron eGFP两个稀有限制性内切酶之间(I-ceuI和PI-sceI)(与腺病毒骨架质粒相同),回收酶切片段后连接,用合适的感受态细胞转

  14. Synthesis of mesoporous Beta and Sn-Beta zeolites and their catalytic performances.

    Science.gov (United States)

    Jin, Junjiang; Ye, Xinxin; Li, Yongsheng; Wang, Yanqin; Li, Liang; Gu, Jinlou; Zhao, Wenru; Shi, Jianlin

    2014-06-14

    Mesoporous Beta zeolite has been successfully prepared through hydrothermal synthesis in the presence of cationic ammonium-modified chitosan as the meso-template. Through a subsequent solid-gas reaction between highly dealuminated mesoporous Beta zeolite and SnCl4 steam at an elevated temperature, mesoporous Sn-Beta has been facilely obtained. It was revealed that the addition of cationic chitosan induced the nanocrystal aggregation to particle sizes of ∼300 nm, giving rise to the intercrystalline/interparticle mesoporosity. In the Sn-implanting procedure, Sn species were demonstrated to be doped into the framework of the resulting mesoporous Beta zeolite in a tetrahedral environment without structural collapse. Due to the micro/mesoporous structures, both mesoporous Beta and Sn-Beta exhibited superior performances in α-pinene isomerization, Baeyer-Villiger oxidation of 2-adamantanone by hydrogen peroxide and the isomerization of glucose in water, respectively.

  15. Systematic Risk on Istanbul Stock Exchange: Traditional Beta Coefficient Versus Downside Beta Coefficient

    Directory of Open Access Journals (Sweden)

    Gülfen TUNA

    2013-03-01

    Full Text Available The aim of this study is to test the validity of Downside Capital Asset Pricing Model (D-CAPM on the ISE. At the same time, the explanatory power of CAPM's traditional beta and D-CAPM's downside beta on the changes in the average return values are examined comparatively. In this context, the monthly data for seventy three stocks that are continuously traded on the ISE for the period 1991-2009 is used. Regression analysis is applied in this study. The research results have shown that D-CAPM is valid on the ISE. In addition, it is obtained that the power of downside beta coefficient is higher than traditional beta coefficient on explaining the return changes. Therefore, it can be said that the downside beta is superior to traditional beta in the ISE for chosen period.

  16. Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Damstrup, L; Rygaard, K; Spang-Thomsen, M;

    1993-01-01

    A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis...... of the binding data demonstrated that the cells bound between 4.5 and 27.5 fmol mg-1 protein with a KD ranging from 16 to 40 pM. TGF beta 1 binding to the receptors was confirmed by cross-linking TGF beta 1 to the TGF beta-r. Three classes of TGF beta-r were demonstrated, type I and type II receptors with M......(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell...

  17. Neutrino potential for neutrinoless double beta decay

    CERN Document Server

    Iwata, Yoritaka

    2016-01-01

    Neutrino potential for neutrinoless double beta decay is studied with focusing on its statistical property. The statistics provide a gross view of understanding amplitude of constitutional components of the nuclear matrix element.

  18. Phenomenology of neutrinoless double beta decay

    CERN Document Server

    Gómez-Cadenas, J J

    2015-01-01

    This paper reviews the current status and future outlook of neutrinoless double beta decay searches, which try to provide an answer to the fundamental question of whether neutrinos are Dirac or Majorana particles.

  19. Beta cell proliferation and growth factors

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis; Svensson, C; Møldrup, Annette

    1999-01-01

    Formation of new beta cells can take place by two pathways: replication of already differentiated beta cells or neogenesis from putative islet stem cells. Under physiological conditions both processes are most pronounced during the fetal and neonatal development of the pancreas. In adulthood little...... increase in the beta cell number seems to occur. In pregnancy, however, a marked hyperplasia of the beta cells is observed both in rodents and man. Increased mitotic activity has been seen both in vivo and in vitro in islets exposed to placental lactogen (PL), prolactin (PRL) and growth hormone (GH......). Receptors for both GH and PRL are expressed in islet cells and are upregulated during pregnancy. By mutational analysis we have identified different functional domains of the cytoplasmic part of the GH receptor. Thus the mitotic signaling only requires the membrane proximal part of the receptor...

  20. Beta-2 Microglobulin Kidney Disease Test

    Science.gov (United States)

    ... Beta 2 Microglobulin, Serum or Urine Related tests: Albumin , Creatinine , BUN , Heavy Metals Were you looking for ... monitor persons with end-stage renal disease (ESRD) Excess B2M can accumulate in joint spaces ( synovitis ) in ...