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Sample records for treatment called gene

  1. Gene calling and bacterial genome annotation with BG7.

    Science.gov (United States)

    Tobes, Raquel; Pareja-Tobes, Pablo; Manrique, Marina; Pareja-Tobes, Eduardo; Kovach, Evdokim; Alekhin, Alexey; Pareja, Eduardo

    2015-01-01

    New massive sequencing technologies are providing many bacterial genome sequences from diverse taxa but a refined annotation of these genomes is crucial for obtaining scientific findings and new knowledge. Thus, bacterial genome annotation has emerged as a key point to investigate in bacteria. Any efficient tool designed specifically to annotate bacterial genomes sequenced with massively parallel technologies has to consider the specific features of bacterial genomes (absence of introns and scarcity of nonprotein-coding sequence) and of next-generation sequencing (NGS) technologies (presence of errors and not perfectly assembled genomes). These features make it convenient to focus on coding regions and, hence, on protein sequences that are the elements directly related with biological functions. In this chapter we describe how to annotate bacterial genomes with BG7, an open-source tool based on a protein-centered gene calling/annotation paradigm. BG7 is specifically designed for the annotation of bacterial genomes sequenced with NGS. This tool is sequence error tolerant maintaining their capabilities for the annotation of highly fragmented genomes or for annotating mixed sequences coming from several genomes (as those obtained through metagenomics samples). BG7 has been designed with scalability as a requirement, with a computing infrastructure completely based on cloud computing (Amazon Web Services).

  2. Geographic Variation in Advertisement Calls in a Tree Frog Species: Gene Flow and Selection Hypotheses

    Science.gov (United States)

    Jang, Yikweon; Hahm, Eun Hye; Lee, Hyun-Jung; Park, Soyeon; Won, Yong-Jin; Choe, Jae C.

    2011-01-01

    Background In a species with a large distribution relative to its dispersal capacity, geographic variation in traits may be explained by gene flow, selection, or the combined effects of both. Studies of genetic diversity using neutral molecular markers show that patterns of isolation by distance (IBD) or barrier effect may be evident for geographic variation at the molecular level in amphibian species. However, selective factors such as habitat, predator, or interspecific interactions may be critical for geographic variation in sexual traits. We studied geographic variation in advertisement calls in the tree frog Hyla japonica to understand patterns of variation in these traits across Korea and provide clues about the underlying forces for variation. Methodology We recorded calls of H. japonica in three breeding seasons from 17 localities including localities in remote Jeju Island. Call characters analyzed were note repetition rate (NRR), note duration (ND), and dominant frequency (DF), along with snout-to-vent length. Results The findings of a barrier effect on DF and a longitudinal variation in NRR seemed to suggest that an open sea between the mainland and Jeju Island and mountain ranges dominated by the north-south Taebaek Mountains were related to geographic variation in call characters. Furthermore, there was a pattern of IBD in mitochondrial DNA sequences. However, no comparable pattern of IBD was found between geographic distance and call characters. We also failed to detect any effects of habitat or interspecific interaction on call characters. Conclusions Geographic variations in call characters as well as mitochondrial DNA sequences were largely stratified by geographic factors such as distance and barriers in Korean populations of H. japoinca. Although we did not detect effects of habitat or interspecific interaction, some other selective factors such as sexual selection might still be operating on call characters in conjunction with restricted gene

  3. Marketing Residential Treatment Programs for Eating Disorders: A Call for Transparency.

    Science.gov (United States)

    Attia, Evelyn; Blackwood, Kristy L; Guarda, Angela S; Marcus, Marsha D; Rothman, David J

    2016-06-01

    Residential behavioral treatment is a growing sector of the health care industry and is used by a large proportion of adolescent and adult patients with eating disorders. These programs and the organizations that own them have developed extensive marketing strategies that target clinicians and include promotional gifts, meals, travel reimbursement, and continuing education credit. Legislation and policy changes have limited these types of activities when conducted by the pharmaceutical industry, and awareness of conflicts of interest associated with clinician-targeted advertising of drugs and devices has increased. However, similar practices by the behavioral health care industry have evolved without oversight. The authors urge clinicians to consider how marketing strategies by treatment facilities may influence their referral behaviors and call for improved transparency regarding gifts and payments from treatment facilities.

  4. Personalized Medicine: Matching Treatments to Your Genes

    Science.gov (United States)

    ... Issues Subscribe December 2013 Print this issue Personalized Medicine Matching Treatments to Your Genes Send us your ... for disease, and the ways you respond to medicines are also unique. Medicines that work well for ...

  5. Distress call-induced gene expression in the brain of the Indian short-nosed fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Ganesh, Ambigapathy; Raghuram, Hanumanthan; Nathan, Parthasarathy T; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

    2010-02-01

    Individuals in distress emit audible vocalizations to either warn or inform conspecifics. The Indian short-nosed fruit bat, Cynopterus sphinx, emits distress calls soon after becoming entangled in mist nets, which appear to attract conspecifics. Phase I of these distress calls is longer and louder, and includes a secondary peak, compared to phase II. Activity-dependent expression of egr-1 was examined in free-ranging C. sphinx following the emissions and responses to a distress call. We found that the level of expression of egr-1 was higher in bats that emitted a distress call, in adults that responded, and in pups than in silent bats. Up-regulated cDNA was amplified to identify the target gene (TOE1) of the protein Egr-1. The observed expression pattern Toe1 was similar to that of egr-1. These findings suggest that the neuronal activity related to recognition of a distress call and an auditory feedback mechanism induces the expression of Egr-1. Co-expression of egr-1 with Toe1 may play a role in initial triggering of the genetic mechanism that could be involved in the consolidation or stabilization of distress call memories.

  6. Gene expression in periodontal tissues following treatment

    Directory of Open Access Journals (Sweden)

    Eisenacher Martin

    2008-07-01

    Full Text Available Abstract Background In periodontitis, treatment aimed at controlling the periodontal biofilm infection results in a resolution of the clinical and histological signs of inflammation. Although the cell types found in periodontal tissues following treatment have been well described, information on gene expression is limited to few candidate genes. Therefore, the aim of the study was to determine the expression profiles of immune and inflammatory genes in periodontal tissues from sites with severe chronic periodontitis following periodontal therapy in order to identify genes involved in tissue homeostasis. Gingival biopsies from 12 patients with severe chronic periodontitis were taken six to eight weeks following non-surgical periodontal therapy, and from 11 healthy controls. As internal standard, RNA of an immortalized human keratinocyte line (HaCaT was used. Total RNA was subjected to gene expression profiling using a commercially available microarray system focusing on inflammation-related genes. Post-hoc confirmation of selected genes was done by Realtime-PCR. Results Out of the 136 genes analyzed, the 5% most strongly expressed genes compared to healthy controls were Interleukin-12A (IL-12A, Versican (CSPG-2, Matrixmetalloproteinase-1 (MMP-1, Down syndrome critical region protein-1 (DSCR-1, Macrophage inflammatory protein-2β (Cxcl-3, Inhibitor of apoptosis protein-1 (BIRC-1, Cluster of differentiation antigen 38 (CD38, Regulator of G-protein signalling-1 (RGS-1, and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene (C-FOS; the 5% least strongly expressed genes were Receptor-interacting Serine/Threonine Kinase-2 (RIP-2, Complement component 3 (C3, Prostaglandin-endoperoxide synthase-2 (COX-2, Interleukin-8 (IL-8, Endothelin-1 (EDN-1, Plasminogen activator inhibitor type-2 (PAI-2, Matrix-metalloproteinase-14 (MMP-14, and Interferon regulating factor-7 (IRF-7. Conclusion Gene expression profiles found in periodontal tissues following

  7. Opioid Maintenance Treatment--A Call for a Joint European Quality Care Approach.

    Science.gov (United States)

    Brandt, Laura; Unger, Annemarie; Moser, Laura; Fischer, Gabriele; Jagsch, Reinhold

    2016-01-01

    The aim of this exploratory analysis of European Quality Audit of Opioid Treatment data was to identify areas of improvement for current opioid maintenance treatment (OMT) approaches. Factors facilitating treatment entry, retention and refusal were compared between 8 European countries and between OMT patient (OMT-P) and active opioid user (AOU) sample groups. Both groups were divided into those who had never had OMT before (un-experienced OMT-P (n = 573) and AOU (n = 360)) and those who had been maintained at least once prior to this investigation (experienced OMT-P (n = 746) and AOU (n = 377)). The European comparison showed that motives for starting OMT vary distinctly between countries (p ≤ 0.001). Transnationally, experienced AOU reported concerns about their ability to follow treatment rules and negative treatment experiences as decisive reasons for staying out of OMT. Greater flexibility, less pressure to reduce their treatment dose and greater treatment structure were ranked significantly higher by experienced compared to un-experienced OMT-P as factors that might facilitate treatment retention (p ≤ 0.05). Increasing awareness of potential shortcomings of OMT delivery systems is crucial to optimally match treatment approaches to patient needs and also to reduce the considerable economic burden of addiction to society. © 2015 S. Karger AG, Basel.

  8. Westinghouse calls for rethink on Europe's treatment of nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Kraev, Kamen [NucNet The Independent Global Nuclear News Agency, Brussels (Belgium)

    2017-12-15

    US-based nuclear equipment manufacturer Westinghouse Electric Company has called on European Union legislators to adopt a technology-neutral approach when discussing the future of the bloc's low-carbon energy policies. In its 'Clean Energy for All Europeans' legislative package, released in November 2016, the European Commission made no mention of nuclear energy, said Michael Kirst, Westinghouse's vice-president of strategy for the Europe, Middle East and Africa (EMEA) region at a media briefing in Brussels. He said the package did not offer ''a real investment signal'' to developers.

  9. A Call for sting treatment protocol: Case report of a 3 year old with ...

    African Journals Online (AJOL)

    Acute Kidney Injury in children following bee sting envenomation is rare and survival is hinged on early recognition and prompt appropriate management. This report is aimed at raising awareness among healthcare workers, of one of the systemic effects of massive bee sting and the need to develop sting treatment protocol.

  10. Moving Forward in Childhood Obesity Treatment: A Call for Translational Research

    Science.gov (United States)

    Watson, P. M.; Dugdill, L.; Murphy, R.; Knowles, Z.; Cable, N. T.

    2013-01-01

    Childhood obesity is one of the most serious challenges of the 21st century and it is vital that evidence-based treatment approaches can be translated into practice to meet public health needs. Yet policy-makers cannot afford to wait for the results of lengthy trials before "probably efficacious" interventions are made available to the public, and…

  11. Intracranial aneurysms: optimized diagnostic tools call for thorough interdisciplinary treatment strategies.

    Science.gov (United States)

    Mueller, Oliver M; Schlamann, Marc; Mueller, Daniela; Sandalcioglu, I Erol; Forsting, Michael; Sure, Ulrich

    2011-09-01

    Intracranial aneurysms (IAs) require deliberately selected treatment strategies as they are incrementally found prior to rupture and deleterious subarachnoid haemorrhage (SAH). Multiple and recurrent aneurysms necessitate both neurointerventionalists and neurosurgeons to optimize aneurysmal occlusion in an interdisciplinary effort. The present study was conducted to condense essential strategies from a single neurovascular centre with regard to the lessons learned. Medical charts of 321 consecutive patients treated for IAs at our centre from September 2008 until December 2010 were retrospectively analysed for clinical presentation of the aneurysms, multiplicity and treatment pathways. In addition, a selective Medline search was performed. A total of 321 patients with 492 aneurysms underwent occlusion of their symptomatic aneurysm: 132 (41.1%) individuals were treated surgically, 189 (58.2%) interventionally; 138 patients presented with a SAH, of these 44.2% were clipped and 55.8% were coiled. Aneurysms of the middle cerebral artery were primarily occluded surgically (88), whereas most of the aneurysms of the internal carotid artery and anterior communicating artery (114) were treated endovascularly. Multiple aneurysms (range 2-5 aneurysms/individual) were diagnosed in 98 patients (30.2%). During the study period 12 patients with recurrent aneurysms were allocated to another treatment modality (previously clip to coil and vice versa). Our data show that successful interdisciplinary occlusion of IAs is based on both neurosurgical and neurointerventional therapy. In particular, multiple and recurrent aneurysms require tailored individual approaches to aneurysmal occlusion. This is achieved by a consequent interdisciplinary pondering of the optimal strategy to occlude IAs in order to prevent SAH.

  12. A Substance Called Food: Long-Term Psychodynamic Group Treatment for Compulsive Overeating.

    Science.gov (United States)

    Schwartz, Deborah C; Nickow, Marcia S; Arseneau, Ric; Gisslow, Mary T

    2015-07-01

    Obesity has proven difficult to treat. Many approaches neglect to address the deep-rooted underlying psychological issues. This paper describes a psychodynamically oriented approach to treating compulsive overeating as an addiction. Common to all addictions is a compulsion to consume a substance or engage in a behavior, a preoccupation with using behavior and rituals, and a lifestyle marked by an inability to manage the behavior and its harmful consequences. The approach represents a shift away from primarily medical models of intervention to integrated models focusing on the psychological underpinnings of obesity. Long-term psychodynamic group psychotherapy is recommended as a primary treatment.

  13. Racial disparities in bipolar disorder treatment and research: a call to action.

    Science.gov (United States)

    Akinhanmi, Margaret O; Biernacka, Joanna M; Strakowski, Stephen M; McElroy, Susan L; Balls Berry, Joyce E; Merikangas, Kathleen R; Assari, Shervin; McInnis, Melvin G; Schulze, Thomas G; LeBoyer, Marion; Tamminga, Carol; Patten, Christi; Frye, Mark A

    2018-03-12

    Health disparities between individuals of African and European ancestry are well documented. The disparities in bipolar disorder may be driven by racial bias superimposed on established factors contributing to misdiagnosis, including: evolving empirically based diagnostic criteria (International Classification of Diseases [ICD], Research Diagnostic Criteria [RDC] and Diagnostic and Statistical Manual [DSM]), multiple symptom domains (i.e. mania, depression and psychosis), and multimodal medical and additional psychiatric comorbidity. For this paper, we reviewed the phenomenological differences between bipolar individuals of African and European ancestry in the context of diagnostic criteria and clinical factors that may contribute to a potential racial bias. Published data show that bipolar persons of African ancestry, compared with bipolar persons of non-African ancestry, are more often misdiagnosed with a disease other than bipolar disorder (i.e. schizophrenia). Additionally, studies show that there are disparities in recruiting patients of African ancestry to participate in important genomic studies. This gap in biological research in this underrepresented minority may represent a missed opportunity to address potential racial differences in the risk and course of bipolar illness. A concerted effort by the research community to increase inclusion of diverse persons in studies of bipolar disorder through community engagement may facilitate fully addressing these diagnostic and treatment disparities in bipolar individuals of African ancestry. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  14. Clinical effects of specialist and on-call respiratory physiotherapy treatments in mechanically ventilated children: A randomised crossover trial.

    Science.gov (United States)

    Shannon, Harriet; Stocks, Janet; Gregson, Rachael K; Dunne, Catherine; Peters, Mark J; Main, Eleanor

    2015-12-01

    The study investigated treatment outcomes when respiratory physiotherapy was delivered by non-respiratory on-call physiotherapists, compared with specialist respiratory physiotherapists. Prospective, randomised crossover trial. Paediatric, tertiary care hospital in the United Kingdom. Mechanically ventilated children requiring two physiotherapy interventions during a single day were eligible. Twenty two physiotherapists (10 non-respiratory) and 93 patients were recruited. Patients received one treatment from a non-respiratory physiotherapist and another from a respiratory physiotherapist, in a randomised order. Treatments were individualised to the patients' needs, often including re-positioning followed by manual lung inflations, chest wall vibrations and endotracheal suction. The primary outcome was respiratory compliance. Secondary outcomes included adverse physiological events and clinically important respiratory changes (according to an a priori definition). Treatments delivered to 63 patients were analysed. There were significant improvements to respiratory compliance (mean increase [95% confidence intervals], 0.07 and 0.08ml·cmH2O(-1)·kg(-1) [0.01 to 0.14 and 0.04 to 0.13], pphysiotherapy services, both during and outside of normal working hours. Clinicaltrials.gov, NCT01999426. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  15. Calling genotypes from public RNA-sequencing data enables identification of genetic variants that affect gene-expression levels

    NARCIS (Netherlands)

    Deelen, Patrick; Zhernakova, Daria V.; de Haan, Mark; van der Sijde, Marijke; Bonder, Marc Jan; Karjalainen, Juha; van der Velde, K. Joeri; Abbott, Kristin M.; Fu, Jingyuan; Wijmenga, Cisca; Sinke, Richard J.; Swertz, Morris A.; Franke, Lude

    2015-01-01

    Background: RNA-sequencing (RNA-seq) is a powerful technique for the identification of genetic variants that affect gene-expression levels, either through expression quantitative trait locus (eQTL) mapping or through allele-specific expression (ASE) analysis. Given increasing numbers of RNA-seq

  16. Polymeric Gene Delivery for Diabetic Treatment

    Directory of Open Access Journals (Sweden)

    Sung Wan Kim

    2011-08-01

    Full Text Available Several polymers were used to delivery genes to diabetic animals. Polyaminobutyl glycolic acid was utilized to deliver IL-10 plasmid DNA to prevent autoimmune insulitis of non-obese diabetic (NOD mouse. Polyethylene glycol grafted polylysine was combined with antisense glutamic acid decarboxylase (GAD MRNA to represent GAD autoantigene expression. GLP1 and TSTA (SP-EX4 were delivered by bioreducible polymer to stop diabetic progression. Fas siRNA delivery was carried out to treat diabetic NOD mice animal.

  17. Calle Blanco

    Directory of Open Access Journals (Sweden)

    Gonzalo Cerda Brintrup

    1988-06-01

    Full Text Available Importante arteria, que comunica el sector del puerto con la plaza. Las más imponentes construcciones se sucedían de un modo continuo, encaramándose a ambos lados de la empinada calle. Antes del gran incendio de 1936 grandes casonas de madera destacaban en calle Irarrázabal y en la esquina de ésta con calle Blanco, la más hermosa construcción pertenecía a don Alberto Oyarzún y la casa vecina hacia Blanco era de don Mateo Miserda, limitada por arriba con la casa de don Augusto Van Der Steldt y ésta era seguida de la casa de don David Barrientos provista de cuatro cúpulas en las esquinas y de un amplio corredor en el frontis. Todas estas construcciones de madera fueron destruidas en el gran incendio de 1936.

  18. [Study of androgen receptor and phosphoglycerate kinase gene polymorphism in major cellular components of the so-called pulmonary sclerosing hemangioma].

    Science.gov (United States)

    Qi, Feng-jie; Zhang, Xiu-wei; Zhang, Yong-xing; Dai, Shun-dong; Wang, En-hua

    2006-05-01

    To study the clonality of polygonal cells and surface cuboidal cells in the so-called pulmonary sclerosing hemangioma (PSH). 17 female surgically resected PSH were found. The polygonal cells and surface cuboidal cells of the 17 PSH cases were microdissected from routine hematoxylin and eosin-stained sections. Genomic DNA was extracted, pretreated through incubation with methylation-sensitive restrictive endonuclease HhaI or HpaII, and amplified by nested polymerase chain reaction for X chromosome-linked androgen receptor (AR) and phosphoglycerate kinase (PGK) genes. The length polymorphism of AR gene was demonstrated by denaturing polyacrylamide gel electrophoresis and silver staining. The PGK gene products were treated with Bst XI and resolved on agarose gel. Amongst the 17 female cases of PSH, 15 samples were successfully amplified for AR and PGK genes. The rates of polymorphism were 53% (8/15) and 27% (4/15) for AR and PGK genes respectively. Polygonal cells and surface cuboidal cells of 10 cases which were suitable for clonality study, showed the same loss of alleles (clonality ratio = 0) or unbalanced methylation pattern (clonality ratio < 0.25). The polygonal cells and surface cuboidal cells in PSH demonstrate patterns of monoclonal proliferation, indicating that both represent true neoplastic cells.

  19. HEPES activates a MiT/TFE-dependent lysosomal-autophagic gene network in cultured cells: A call for caution.

    Science.gov (United States)

    Tol, Marc J; van der Lienden, Martijn J C; Gabriel, Tanit L; Hagen, Jacob J; Scheij, Saskia; Veenendaal, Tineke; Klumperman, Judith; Donker-Koopman, Wilma E; Verhoeven, Arthur J; Overkleeft, Hermen; Aerts, Johannes M; Argmann, Carmen A; van Eijk, Marco

    2018-01-01

    In recent years, the lysosome has emerged as a highly dynamic, transcriptionally regulated organelle that is integral to nutrient-sensing and metabolic rewiring. This is coordinated by a lysosome-to-nucleus signaling nexus in which MTORC1 controls the subcellular distribution of the microphthalmia-transcription factor E (MiT/TFE) family of "master lysosomal regulators". Yet, despite the importance of the lysosome in cellular metabolism, the impact of traditional in vitro culture media on lysosomal dynamics and/or MiT/TFE localization has not been fully appreciated. Here, we identify HEPES, a chemical buffering agent that is broadly applied in cell culture, as a potent inducer of lysosome biogenesis. Supplementation of HEPES to cell growth media is sufficient to decouple the MiT/TFE family members-TFEB, TFE3 and MITF-from regulatory mechanisms that control their cytosolic retention. Increased MiT/TFE nuclear import in turn drives the expression of a global network of lysosomal-autophagic and innate host-immune response genes, altering lysosomal dynamics, proteolytic capacity, autophagic flux, and inflammatory signaling. In addition, siRNA-mediated MiT/TFE knockdown effectively blunted HEPES-induced lysosome biogenesis and gene expression profiles. Mechanistically, we show that MiT/TFE activation in response to HEPES requires its macropinocytic ingestion and aberrant lysosomal storage/pH, but is independent of MTORC1 signaling. Altogether, our data underscore the cautionary use of chemical buffering agents in cell culture media due to their potentially confounding effects on experimental results.

  20. EMERGENCY CALLS

    CERN Multimedia

    Medical Service

    2001-01-01

    IN URGENT NEED OF A DOCTOR GENEVA EMERGENCY SERVICES GENEVA AND VAUD 144 FIRE BRIGADE 118 POLICE 117 CERN FIREMEN 767-44-44 ANTI-POISONS CENTRE Open 24h/24h 01-251-51-51 Patient not fit to be moved, call family doctor, or: GP AT HOME, open 24h/24h 748-49-50 Association Of Geneva Doctors Emergency Doctors at home 07h-23h 322 20 20 Patient fit to be moved: HOPITAL CANTONAL CENTRAL 24 Micheli-du-Crest 372-33-11 ou 382-33-11 EMERGENCIES 382-33-11 ou 372-33-11 CHILDREN'S HOSPITAL 6 rue Willy-Donzé 372-33-11 MATERNITY 32 bvd.de la Cluse 382-68-16 ou 382-33-11 OPHTHALMOLOGY 22 Alcide Jentzer 382-33-11 ou 372-33-11 MEDICAL CENTRE CORNAVIN 1-3 rue du Jura 345 45 50 HOPITAL DE LA TOUR Meyrin EMERGENCIES 719-61-11 URGENCES PEDIATRIQUES 719-61-00 LA TOUR MEDICAL CENTRE 719-74-00 European Emergency Call 112 FRANCE EMERGENCY SERVICES 15 FIRE BRIGADE 18 POLICE 17 CERN FIREMEN AT HOME 00-41-22-767-44-44 ANTI-POISONS CENTRE Open 24h/24h 04-72-11-69-11 All doctors ...

  1. Gene expression profiles reveal key genes for early diagnosis and treatment of adamantinomatous craniopharyngioma.

    Science.gov (United States)

    Yang, Jun; Hou, Ziming; Wang, Changjiang; Wang, Hao; Zhang, Hongbing

    2018-04-23

    Adamantinomatous craniopharyngioma (ACP) is an aggressive brain tumor that occurs predominantly in the pediatric population. Conventional diagnosis method and standard therapy cannot treat ACPs effectively. In this paper, we aimed to identify key genes for ACP early diagnosis and treatment. Datasets GSE94349 and GSE68015 were obtained from Gene Expression Omnibus database. Consensus clustering was applied to discover the gene clusters in the expression data of GSE94349 and functional enrichment analysis was performed on gene set in each cluster. The protein-protein interaction (PPI) network was built by the Search Tool for the Retrieval of Interacting Genes, and hubs were selected. Support vector machine (SVM) model was built based on the signature genes identified from enrichment analysis and PPI network. Dataset GSE94349 was used for training and testing, and GSE68015 was used for validation. Besides, RT-qPCR analysis was performed to analyze the expression of signature genes in ACP samples compared with normal controls. Seven gene clusters were discovered in the differentially expressed genes identified from GSE94349 dataset. Enrichment analysis of each cluster identified 25 pathways that highly associated with ACP. PPI network was built and 46 hubs were determined. Twenty-five pathway-related genes that overlapped with the hubs in PPI network were used as signatures to establish the SVM diagnosis model for ACP. The prediction accuracy of SVM model for training, testing, and validation data were 94, 85, and 74%, respectively. The expression of CDH1, CCL2, ITGA2, COL8A1, COL6A2, and COL6A3 were significantly upregulated in ACP tumor samples, while CAMK2A, RIMS1, NEFL, SYT1, and STX1A were significantly downregulated, which were consistent with the differentially expressed gene analysis. SVM model is a promising classification tool for screening and early diagnosis of ACP. The ACP-related pathways and signature genes will advance our knowledge of ACP pathogenesis

  2. Vaginal Gene Expression During Treatment With Aromatase Inhibitors.

    Science.gov (United States)

    Kallak, Theodora Kunovac; Baumgart, Juliane; Nilsson, Kerstin; Åkerud, Helena; Poromaa, Inger Sundström; Stavreus-Evers, Anneli

    2015-12-01

    Aromatase inhibitor (AI) treatment suppresses estrogen biosynthesis and causes genitourinary symptoms of menopause such as vaginal symptoms, ultimately affecting the quality of life for many postmenopausal women with breast cancer. Thus, the aim of this study was to examine vaginal gene expression in women during treatment with AIs compared with estrogen-treated women. The secondary aim was to study the presence and localization of vaginal aromatase. Vaginal biopsies were collected from postmenopausal women treated with AIs and from age-matched control women treated with vaginal estrogen therapy. Differential gene expression was studied with the Affymetrix Gene Chip Gene 1.0 ST Array (Affymetrix Inc, Santa Clara, CA) system, Ingenuity pathway analysis, quantitative real-time polymerase chain reaction, and immunohistochemistry. The expression of 279 genes differed between the 2 groups; AI-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion. Some differentially expressed genes were found to interact indirectly with the estrogen receptor alpha. In addition, aromatase protein staining was evident in the basal and the intermediate vaginal epithelium layers, and also in stromal cells with a slightly stronger staining intensity found in AI-treated women. In this study, we demonstrated that genes involved in cell differentiation, proliferation, and cell adhesion are differentially expressed in AI-treated women. The expression of vaginal aromatase suggests that this could be the result of local and systemic inhibition of aromatase. Our results emphasize the role of estrogen for vaginal cell differentiation and proliferation and future drug candidates should be aimed at improving cell differentiation and proliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD

    Directory of Open Access Journals (Sweden)

    Jeong Byung-Hoon

    2011-08-01

    Full Text Available Abstract Background Although polymorphisms of PRNP, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s modulating susceptibility to prion disease. Ribosomal protein SA (RPSA, also called 37 kDa laminin receptor precursor (LRP/67 kDa laminin receptor (LR, acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR. Methods To identify other susceptibility genes involved in prion disease, we performed genetic analysis of RPSA. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on RPSA by direct sequencing or restriction fragment length polymorphism (RFLP analysis. Results We observed four single nucleotide polymorphisms (SNPs, including -8T>C (rs1803893 in the 5'-untranslated region (UTR of exon 2, 134-32C>T (rs3772138 in the intron, 519G>A (rs2269350 in the intron and 793+58C>T (rs2723 in the intron on the RPSA. The 519G>A (at codon 173 is located in the direct PrP binding site. The genotypes and allele frequencies of the RPSA polymorphisms showed no significant differences between the controls and sporadic CJD patients. Conclusion These results suggest that these RPSA polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of RPSA gene with sporadic CJD.

  4. [Validation of the telephone call as a method for measuring compliance to arterial hypertension treatment in Extremadura].

    Science.gov (United States)

    Espinosa-García, J; Cobaleda-Polo, J; González-Velasco, M; Fernández-Bergés, D

    2014-10-01

    Pharmacological non-compliance is a significant problem that can affect patient health. The main aim of this investigation is to validate the telephone call to the patient' home as a self-report method of counting the amount of tablets taken by the patient, as an alternative method to a simple tablet count in the clinic (gold standard). An observational, multicentre, prospective, and longitudinal study was conducted by 25 researchers in different health centres in Extremadura, and which included 125 consecutively enrolled patients with uncontrolled arterial hypertension, 121 ended the study. Three visits were made, including enrollment visit, follow-up visit at 4 weeks, and final visit at 8 weeks. A telephone call was made prior to the enrollment and final visit to remind the patients of the next visit, and to ask at the same time about the number of tablets remaining. A total of 121 patients completed the study. In the final visit, the phone-call method of compliance showed: 100% sensitivity, 86% specificity, 86.8% of overall accuracy, 30.4% PPV, 100% NPV, CP+ 7.13, CP- 0.0, and a kappa index of 0.415 (Pphone call, as a therapeutic compliance method, can be a good alternative due to being almost universal, easy to use, its reduced cost, and without the need of patients to go to the medical centres. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  5. The association of drinking water treatment and distribution network disturbances with Health Call Centre contacts for gastrointestinal illness symptoms.

    Science.gov (United States)

    Malm, Annika; Axelsson, Gösta; Barregard, Lars; Ljungqvist, Jakob; Forsberg, Bertil; Bergstedt, Olof; Pettersson, Thomas J R

    2013-09-01

    There are relatively few studies on the association between disturbances in drinking water services and symptoms of gastrointestinal (GI) illness. Health Call Centres data concerning GI illness may be a useful source of information. This study investigates if there is an increased frequency of contacts with the Health Call Centre (HCC) concerning gastrointestinal symptoms at times when there is a risk of impaired water quality due to disturbances at water works or the distribution network. The study was conducted in Gothenburg, a Swedish city with 0.5 million inhabitants with a surface water source of drinking water and two water works. All HCC contacts due to GI symptoms (diarrhoea, vomiting or abdominal pain) were recorded for a three-year period, including also sex, age, and geocoded location of residence. The number of contacts with the HCC in the affected geographical areas were recorded during eight periods of disturbances in the water works (e.g. short stops of chlorine dosing), six periods of large disturbances in the distribution network (e.g. pumping station failure or pipe breaks with major consequences), and 818 pipe break and leak repairs over a three-year period. For each period of disturbance the observed number of calls was compared with the number of calls during a control period without disturbances in the same geographical area. In total about 55, 000 calls to the HCC due to GI symptoms were recorded over the three-year period, 35 per 1000 inhabitants and year, but much higher (>200) for children water works or in the distribution network. Our results indicate that GI symptoms due to disturbances in water works or the distribution network are rare. The number of serious failures was, however limited, and further studies are needed to be able to assess the risk of GI illness in such cases. The technique of using geocoded HCC data together with geocoded records of disturbances in the drinking water network was feasible. Copyright © 2013 Elsevier

  6. Association between gene variants and response to buprenorphine maintenance treatment.

    Science.gov (United States)

    Gerra, Gilberto; Somaini, Lorenzo; Leonardi, Claudio; Cortese, Elena; Maremmani, Icro; Manfredini, Matteo; Donnini, Claudia

    2014-01-30

    A variety of studies were addressed to differentiate responders and non-responders to substitution treatment among heroin dependent patients, without conclusive findings. In particular, preliminary pharmacogenetic findings have been reported to predict treatment effectiveness in mental health and substance use disorders. Aim of the present study was to investigate the possible association of buprenorphine (BUP) treatment outcome with gene variants that may affect kappa-opioid receptors and dopamine system function. One hundred and seven heroin addicts (West European, Caucasians) who underwent buprenorphine maintenance treatment were genotyped and classified into two groups (A and B) on the basis of treatment outcome. Non-responders to buprenorphine (group B) have been identified taking into account early drop out, continuous use of heroin, severe behavioral or psychiatric problems, misbehavior and diversion during the 6 months treatment period. No difference was evidenced between responders and non-responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP. The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1), allele 10, was evidently much higher in "non-responder" than in "responder" individuals (64.9% vs. 55.93%) whereas the frequency of the category of other alleles (6, 7 and 11) was higher in responder than in non-responder individuals (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene-related changes in kappa-opioid receptor could consistently affect buprenorphine pharmacological action and clinical effectiveness was not confirmed in our study, at least in relation to the single nucleotide polymorphism 36G>T. On the other hand, the possibility that gene-related dopamine changes could have reduced BUP effectiveness and impaired maintenance treatment outcome was cautiously supported by our findings. DAT1 gene variants such as allele 10, previously reported in association with personality and

  7. Gene doping: gene delivery for olympic victory

    OpenAIRE

    Gould, David

    2012-01-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so calledgene doping’. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted...

  8. Id-1 gene and gene products as therapeutic targets for treatment of breast cancer and other types of carcinoma

    Science.gov (United States)

    Desprez, Pierre-Yves; Campisi, Judith

    2014-08-19

    A method for treatment of breast cancer and other types of cancer. The method comprises targeting and modulating Id-1 gene expression, if any, for the Id-1 gene, or gene products in breast or other epithelial cancers in a patient by delivering products that modulate Id-1 gene expression. When expressed, Id-1 gene is a prognostic indicator that cancer cells are invasive and metastatic.

  9. Using mobile phones to ensure that referred tuberculosis patients reach their treatment facilities: a call that makes a difference.

    Science.gov (United States)

    Choun, Kimcheng; Achanta, Shanta; Naik, Balaji; Tripathy, Jaya Prasad; Thai, Sopheak; Lorent, Natalie; Khun, Kim Eam; van Griensven, Johan; Kumar, Ajay M V; Zachariah, Rony

    2017-08-22

    Over the last decade, the availability and use of mobile phones have grown exponentially globally and in Cambodia. In the Sihanouk Hospital Centre of Hope(SHCH) in Cambodia about half of all tuberculosis patients referred out to peripheral health facilities for TB treatment initiation or continuation were lost to contact after referral ranging from 19 to 69% between 2008 and 2013. To address this, we implemented a mobile phone-based patient tracking intervention. Here, we report the number and proportion of referred TB patients who could be contacted through a mobile phone and retained in care after the introduction of mobile phone tracking. A descriptive study involving follow-up of TB patients referred out from SHCH to peripheral health facilities during May-October 2014. Standard operating procedures were used to contact individual patients and/or health facilities using a mobile phone. Among 109 TB patients referred to peripheral health facilities, 107(98%) had access to a mobile phone of whom, 103(97%) could be contacted directly while 5(2%) were contacted through their health care providers. A total of 108(99%) of 109 referred TB patients in intervention period were thus placed on TB treatment. This study provides preliminary, but promising evidence that using mobile phones was accompanied with improved retention of referred TB patients compared to historical cohorts. Given the limitations associated with historical controls, we need better designed studies with larger sample size to strengthen the evidence before national scale-up.

  10. Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

    Science.gov (United States)

    Fischer, Benedikt; Kuganesan, Sharan; Gallassi, Andrea; Malcher-Lopes, Renato; van den Brink, Wim; Wood, Evan

    2015-12-01

    Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for

  11. Fund my treatment!: A call for ethics-focused social science research into the use of crowdfunding for medical care.

    Science.gov (United States)

    Snyder, Jeremy; Mathers, Annalise; Crooks, Valorie A

    2016-11-01

    Crowdfunding involves raising money from large groups of individuals, often through the use of websites dedicated to this purpose. Crowdfunding campaigns aimed at raising money to pay for expenses related to receiving medical treatment are receiving increased media attention and there is evidence that medical crowdfunding websites are heavily used. Nonetheless, virtually no scholarly attention has been paid to these medical crowdfunding campaigns and there is no systematic evidence about how widely they are used and for what reasons, and what effects they have on the provision of medical care and individuals' relationships to their health systems. Ethical concerns have been raised in relation to these campaigns, focusing on issues for campaigners and donors such as exposure to fraudulent campaigns, loss of privacy, and fairness in how medical crowdfunding funds are distributed. Medical crowdfunding websites themselves have not been systematically studied, despite their significant influence on how these campaigns are developed and promoted. In this paper, we identify three very broad and pressing ethical questions regarding medical crowdfunding for social scientists to address and offer some preliminary insights into key issues informing future answers to each: Who benefits the most from medical crowdfunding and how does medical crowdfunding affect access to medical care; How does medical crowdfunding affect our understanding of the causes of inadequate access to medical care; and How are campaigner and donor privacy affected by website design? Our observations indicate the need for increased scholarly attention to the ethical and practical effects of medical crowdfunding for campaigners, recipients, donors, and the health system as a whole. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Call Forecasting for Inbound Call Center

    Directory of Open Access Journals (Sweden)

    Peter Vinje

    2009-01-01

    Full Text Available In a scenario of inbound call center customer service, the ability to forecast calls is a key element and advantage. By forecasting the correct number of calls a company can predict staffing needs, meet service level requirements, improve customer satisfaction, and benefit from many other optimizations. This project will show how elementary statistics can be used to predict calls for a specific company, forecast the rate at which calls are increasing/decreasing, and determine if the calls may stop at some point.

  13. Gene expression analysis of interferon-beta treatment in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F.; Datta, P.; Larsen, J.

    2008-01-01

    by treatment with IFN-beta. We use DNA microarrays to study gene expression in 10 multiple sclerosis (MS) patients who began de novo treatment with IFN-beta. After the first injection of IFN-beta, the expression of 74 out of 3428 genes changed at least two-fold and statistically significantly (after Bonferroni......Treatment with interferon-beta (IFN-beta) induces the expression of hundreds of genes in blood mononuclear cells, and the expression of several genes has been proposed as a marker of the effect of treatment with IFN-beta. However, to date no molecules have been identified that are stably induced...

  14. An Appreciation of The Gene: An Intimate History by Siddhartha Mukherjee and a Call for Expanded Training in the Responsible Conduct of Research.

    Science.gov (United States)

    Morris, Evan D

    2017-12-01

    The Gene: An Intimate History by Siddhartha Mukherjee, first published in 2016, is a comprehensive and fascinating recounting of the discovery of the gene and genetics research from wrinkled peas to CRISPR/Cas9 and all the details in between. In Mukherjee's sweeping history, the science is clearly depicted but also tightly integrated into the political movements and world events that it spawned, both hopeful and detestable. Two stories from The Gene are the central focuses of this article. One story is driven by the desire of Eugenicists in early 20th century America to rid the population of defective traits. The second is driven by the late 20th century promise of gene therapy to rid individuals of fatal inherited diseases. Both stories are tragic and serve as cautionary tales. These and other "case studies" in the role of science in society moved this reader to ask: what level of ethical and professional training is appropriate for today's emerging scientists? In this article, the intent and the limitations of mandated Responsible Conduct of Research (RCR) training for science and engineering graduate students are reviewed and explicated, and the obligations of scientists to themselves and others are discussed. Extrapolating from the stories in the book to the types of events and conflicts that may arise to challenge practicing scientists, a few constructive recommendations are offered for an expansion of the traditional RCR syllabus.

  15. Application of high-resolution capillary array electrophoresis with automated fraction collection for GeneCalling analysis of the yeast genomic DNA

    Czech Academy of Sciences Publication Activity Database

    Berka, J.; Ruiz-Martinez, M. C.; Hammond, R.; Minarik, M.; Foret, František; Sosic, Z.; Klepárník, Karel; Karger, B. L.

    2003-01-01

    Roč. 24, č. 4 (2003), s. 639-647 ISSN 0173-0835 R&D Projects: GA ČR GA203/00/0772; GA ČR GA303/00/0928 Institutional research plan: CEZ:AV0Z4031919 Keywords : capillary array * fraction collection * gene expression profiling Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.040, year: 2003

  16. Host range of antibiotic resistance genes in wastewater treatment plant influent and effluent.

    Science.gov (United States)

    Hultman, Jenni; Tamminen, Manu; Pärnänen, Katariina; Cairns, Johannes; Karkman, Antti; Virta, Marko

    2018-04-01

    Wastewater treatment plants (WWTPs) collect wastewater from various sources for a multi-step treatment process. By mixing a large variety of bacteria and promoting their proximity, WWTPs constitute potential hotspots for the emergence of antibiotic resistant bacteria. Concerns have been expressed regarding the potential of WWTPs to spread antibiotic resistance genes (ARGs) from environmental reservoirs to human pathogens. We utilized epicPCR (Emulsion, Paired Isolation and Concatenation PCR) to detect the bacterial hosts of ARGs in two WWTPs. We identified the host distribution of four resistance-associated genes (tetM, int1, qacEΔ1and blaOXA-58) in influent and effluent. The bacterial hosts of these resistance genes varied between the WWTP influent and effluent, with a generally decreasing host range in the effluent. Through 16S rRNA gene sequencing, it was determined that the resistance gene carrying bacteria include both abundant and rare taxa. Our results suggest that the studied WWTPs mostly succeed in decreasing the host range of the resistance genes during the treatment process. Still, there were instances where effluent contained resistance genes in bacterial groups not carrying these genes in the influent. By permitting exhaustive profiling of resistance-associated gene hosts in WWTP bacterial communities, the application of epicPCR provides a new level of precision to our resistance gene risk estimates.

  17. Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression.

    Science.gov (United States)

    Guilloux, Jean-Philippe; Bassi, Sabrina; Ding, Ying; Walsh, Chris; Turecki, Gustavo; Tseng, George; Cyranowski, Jill M; Sibille, Etienne

    2015-02-01

    Major depressive disorder (MDD) in general, and anxious-depression in particular, are characterized by poor rates of remission with first-line treatments, contributing to the chronic illness burden suffered by many patients. Prospective research is needed to identify the biomarkers predicting nonremission prior to treatment initiation. We collected blood samples from a discovery cohort of 34 adult MDD patients with co-occurring anxiety and 33 matched, nondepressed controls at baseline and after 12 weeks (of citalopram plus psychotherapy treatment for the depressed cohort). Samples were processed on gene arrays and group differences in gene expression were investigated. Exploratory analyses suggest that at pretreatment baseline, nonremitting patients differ from controls with gene function and transcription factor analyses potentially related to elevated inflammation and immune activation. In a second phase, we applied an unbiased machine learning prediction model and corrected for model-selection bias. Results show that baseline gene expression predicted nonremission with 79.4% corrected accuracy with a 13-gene model. The same gene-only model predicted nonremission after 8 weeks of citalopram treatment with 76% corrected accuracy in an independent validation cohort of 63 MDD patients treated with citalopram at another institution. Together, these results demonstrate the potential, but also the limitations, of baseline peripheral blood-based gene expression to predict nonremission after citalopram treatment. These results not only support their use in future prediction tools but also suggest that increased accuracy may be obtained with the inclusion of additional predictors (eg, genetics and clinical scales).

  18. Call Center Capacity Planning

    DEFF Research Database (Denmark)

    Nielsen, Thomas Bang

    in order to relate the results to the service levels used in call centers. Furthermore, the generic nature of the approximation is demonstrated by applying it to a system incorporating a dynamic priority scheme. In the last paper Optimization of overflow policies in call centers, overflows between agent......The main topics of the thesis are theoretical and applied queueing theory within a call center setting. Call centers have in recent years become the main means of communication between customers and companies, and between citizens and public institutions. The extensively computerized infrastructure...... in modern call centers allows for a high level of customization, but also induces complicated operational processes. The size of the industry together with the complex and labor intensive nature of large call centers motivates the research carried out to understand the underlying processes. The customizable...

  19. The effects of antenatal depression and antidepressant treatment on placental gene expression

    Directory of Open Access Journals (Sweden)

    Jocelien DA Olivier

    2015-01-01

    Full Text Available The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy.Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample.In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

  20. Callings and Organizational Behavior

    Science.gov (United States)

    Elangovan, A. R.; Pinder, Craig C.; McLean, Murdith

    2010-01-01

    Current literature on careers, social identity and meaning in work tends to understate the multiplicity, historical significance, and nuances of the concept of calling(s). In this article, we trace the evolution of the concept from its religious roots into secular realms and develop a typology of interpretations using occupation and religious…

  1. Detection of antibiotic resistance genes in samples from acute and chronic endodontic infections and after treatment.

    Science.gov (United States)

    Rôças, Isabela N; Siqueira, José F

    2013-09-01

    The purpose of this study was twofold: survey samples from acute and chronic endodontic infections for the presence of genes encoding resistance to beta-lactams, tetracycline and erythromycin, and evaluate the ability of treatment to eliminate these genes from root canals. DNA extracts from samples of abscess aspirates (n=25) and root canals of teeth with asymptomatic apical periodontitis (n=24) were used as template for direct detection of the genes blaTEM, cfxA, tetM, tetQ, tetW, and ermC using real-time polymerase chain reaction (PCR). Bacterial presence was determined using PCR with universal bacterial primers. Root canals of the asymptomatic cases were also sampled and evaluated after chemomechanical procedures using NiTi instruments with 2.5% NaOCl irrigation. All abscess and initial root canal samples were positive for bacteria. At least one of the target resistance genes was found in 36% of the abscess samples and 67% of the asymptomatic cases. The most prevalent genes in abscesses were blaTEM (24%) and ermC (24%), while tetM (42%) and tetW (29%) prevailed in asymptomatic cases. The blaTEM gene was significantly associated with acute cases (p=0.02). Conversely, tetM was significantly more prevalent in asymptomatic cases (p=0.008). Treatment eliminated resistance genes from most cases. Acute and chronic endodontic infections harboured resistance genes for 3 classes of widely used antibiotics. In most cases, treatment was effective in eliminating these genes, but there were a few cases in which they persisted. The implications of persistence are unknown. Direct detection of resistance genes in abscesses may be a potential method for rapid diagnosis and establishment of proactive antimicrobial therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. MODY in Ukraine: genes, clinical phenotypes and treatment.

    Science.gov (United States)

    Globa, Evgenia; Zelinska, Nataliya; Elblova, Lenka; Dusatkova, Petra; Cinek, Ondrej; Lebl, Jan; Colclough, Kevin; Ellard, Sian; Pruhova, Stepanka

    2017-10-26

    Maturity-onset diabetes of the young (MODY) has not been previously studied in Ukraine. We investigated the genetic etiology in a selected cohort of patients with diabetes diagnosed before 18 years of age, and in their family members. Genetic testing of the most prevalent MODY genes (GCK, HNF1A, HNF4A, HNF1B and INS) was undertaken for 36 families (39 affected individuals) by Sanger or targeted next generation sequencing. A genetic diagnosis of MODY was made in 15/39 affected individuals from 12/36 families (33%). HNF1A and HNF4A MODY were the most common subtypes, accounting for 9/15 of MODY cases. Eight patients with HNF1A or HNF4A MODY and inadequate glycemic control were successfully transferred to sulfonylureas. Median HbA1c decreased from 67 mmol/mol (range 58-69) to 47 mmol/mol (range 43-50) (8.3% [7.5-8.5] to 6.4% [6.1-6.7]) 3 months after transfer (p=0.006). Genetic testing identified pathogenic HNF1A and HNF4A variants as the most common cause of MODY in Ukraine. Transfer to sulfonylureas substantially improved the glycemic control of these patients.

  3. Effects of advanced treatment systems on the removal of antibiotic resistance genes in wastewater treatment plants from Hangzhou, China.

    Science.gov (United States)

    Chen, Hong; Zhang, Mingmei

    2013-08-06

    This study aimed at quantifying the concentration and removal of antibiotic resistance genes (ARGs) in three municipal wastewater treatment plants (WWTPs) employing different advanced treatment systems [biological aerated filter, constructed wetland, and ultraviolet (UV) disinfection]. The concentrations of tetM, tetO, tetQ, tetW, sulI, sulII, intI1, and 16S rDNA genes were examined in wastewater and biosolid samples. In municipal WWTPs, ARG reductions of 1-3 orders of magnitude were observed, and no difference was found among the three municipal WWTPs with different treatment processes (p > 0.05). In advanced treatment systems, 1-3 orders of magnitude of reductions in ARGs were observed in constructed wetlands, 0.6-1.2 orders of magnitude of reductions in ARGs were observed in the biological aerated filter, but no apparent decrease by UV disinfection was observed. A significant difference was found between constructed wetlands and biological filter (p removal of ARGs and 16S rDNA genes (R(2) = 0.391-0.866; p removal values with WWTP (p > 0.05) but also have the advantage in ARG relative abundance removal, and it should be given priority to be an advanced treatment system for further ARG attenuation from WWTP.

  4. Transcriptional regulation of the Hansenula polymorpha GSH2 gene in the response to cadmium ion treatment

    Directory of Open Access Journals (Sweden)

    O. V. Blazhenko

    2014-02-01

    Full Text Available In a previous study we cloned GSH2 gene, encoding γ-glutamylcysteine synthetase (γGCS in the yeast Hansenula рolymorpha. In this study an analysis of molecular organisation of the H. рolymorpha GSH2 gene promoter was conducted and the potential binding sites of Yap1, Skn7, Creb/Atf1, and Cbf1 transcription factors were detected. It was established that full regulation of GSH2 gene expression in the response to cadmium and oxidative stress requires the length of GSH2 promoter to be longer than 450 bp from the start of translation initiation. To study the transcriptional regulation of H. polymorpha GSH2 gene recombinant strain, harbouring­ a reporter system, in which 1.832 kb regulatory region of GSH2 gene was fused to structural and terminatory regions of alcohol oxidase gene, was constructed. It was shown that maximum increase in H. polymorpha GSH2 gene transcription by 33% occurs in the rich medium under four-hour incubation with 1 μM concentration of cadmium ions. In the minimal medium the GSH2 gene expression does not correlate with the increased total cellular glutathione levels under cadmium ion treatment. We assume that the increased content of total cellular glutathione under cadmium stress in the yeast H. polymorpha probably is not controlled on the level of GSH2 gene transcription.

  5. [Influence of interleukin-1 beta gene polymorphism and childhood maltreatment on antidepressant treatment].

    Science.gov (United States)

    Chen, Ying; Zhang, Zhijun; Xu, Zhi; Pu, Mengjia; Geng, Leiyu

    2015-12-01

    To explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment. Two hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis. No significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment. The SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

  6. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

    Directory of Open Access Journals (Sweden)

    Tetu Bernard

    2008-02-01

    Full Text Available Abstract Background Chemotherapy (CT resistance in ovarian cancer (OC is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155, following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism, signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes, cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular

  7. Abundance of antibiotic resistance genes in five municipal wastewater treatment plants in the Monastir Governorate, Tunisia.

    Science.gov (United States)

    Rafraf, Ikbel Denden; Lekunberri, Itziar; Sànchez-Melsió, Alexandre; Aouni, Mahjoub; Borrego, Carles M; Balcázar, José Luis

    2016-12-01

    Antimicrobial resistance is a growing and significant threat to global public health, requiring better understanding of the sources and mechanisms involved in its emergence and spread. We investigated the abundance of antibiotic resistance genes (ARGs) before and after treatment in five wastewater treatment plants (WWTPs) located in different areas of the Monastir Governorate (Tunisia). Three of these WWTPs (Frina, Sahline and Zaouiet) use a conventional activated sludge process as secondary treatment, whereas the WWTP located in Beni Hassen applies an ultraviolet disinfection step after the activated sludge process and the WWTP located in Moknine treats wastewater using naturally aerated lagoons as a secondary treatment process. The abundance of six ARGs (bla CTX-M , bla TEM , qnrA, qnrS, sul I and ermB) and the class 1 integron-integrase gene (intI1) were determined by quantitative PCR. All ARGs and the intI1 gene were detected in the wastewater samples, except the bla CTX-M gene, which was not detected in both influent and effluent samples from Sahline and Beni Hassen WWTPs, and the qnrS gene, which was not detected neither in the WWTP influent in Moknine nor in the WWTP effluent in Beni Hassen. Although the relative concentration of ARGs was generally found to be similar between samples collected before and after the wastewater treatment, the abundance of bla CTX-M , bla TEM , and qnrS genes was higher in the effluent of the Frina WWTP which, unlike other WWTPs, not only receives domestic or industrial sewage but also untreated hospital waste. To the best of our knowledge, this study quantified for the first time the abundance of ARGs in different Tunisian WWTPs, and the results agree with previous studies suggesting that conventional wastewater treatment does not efficiently reduce ARGs. Therefore, these findings could be useful to improve the design or operation of WWTPs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Assessing call centers’ success:

    Directory of Open Access Journals (Sweden)

    Hesham A. Baraka

    2013-07-01

    This paper introduces a model to evaluate the performance of call centers based on the Delone and McLean Information Systems success model. A number of indicators are identified to track the call center’s performance. Mapping of the proposed indicators to the six dimensions of the D&M model is presented. A Weighted Call Center Performance Index is proposed to assess the call center performance; the index is used to analyze the effect of the identified indicators. Policy-Weighted approach was used to assume the weights with an analysis of different weights for each dimension. The analysis of the different weights cases gave priority to the User satisfaction and net Benefits dimension as the two outcomes from the system. For the input dimensions, higher priority was given to the system quality and the service quality dimension. Call centers decision makers can use the tool to tune the different weights in order to reach the objectives set by the organization. Multiple linear regression analysis was used in order to provide a linear formula for the User Satisfaction dimension and the Net Benefits dimension in order to be able to forecast the values for these two dimensions as function of the other dimensions

  9. Occurrence of the mcr-1 Colistin Resistance Gene and other Clinically Relevant Antibiotic Resistance Genes in Microbial Populations at Different Municipal Wastewater Treatment Plants in Germany

    Directory of Open Access Journals (Sweden)

    Norman Hembach

    2017-07-01

    Full Text Available Seven wastewater treatment plants (WWTPs with different population equivalents and catchment areas were screened for the prevalence of the colistin resistance gene mcr-1 mediating resistance against last resort antibiotic polymyxin E. The abundance of the plasmid-associated mcr-1 gene in total microbial populations during water treatment processes was quantitatively analyzed by qPCR analyses. The presence of the colistin resistance gene was documented for all of the influent wastewater samples of the seven WWTPs. In some cases the mcr-1 resistance gene was also detected in effluent samples of the WWTPs after conventional treatment reaching the aquatic environment. In addition to the occurrence of mcr-1 gene, CTX-M-32, blaTEM, CTX-M, tetM, CMY-2, and ermB genes coding for clinically relevant antibiotic resistances were quantified in higher abundances in all WWTPs effluents. In parallel, the abundances of Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli were quantified via qPCR using specific taxonomic gene markers which were detected in all influent and effluent wastewaters in significant densities. Hence, opportunistic pathogens and clinically relevant antibiotic resistance genes in wastewaters of the analyzed WWTPs bear a risk of dissemination to the aquatic environment. Since many of the antibiotic resistance gene are associated with mobile genetic elements horizontal gene transfer during wastewater treatment can't be excluded.

  10. 18F-fluorodeoxyglucose positron tomography is useful in evaluating the efficacy of multidisciplinary treatments for so-called borderline unresectable pancreatic head cancers

    International Nuclear Information System (INIS)

    Murakami, Makoto; Katayama, Kanji; Yamaguchi, Akio; Iida, Atsushi; Goi, Takanori; Hirono, Yasuo; Nagano, Hideki; Koneri, Kenji

    2011-01-01

    Currently, computed tomography (CT) is widely used to evaluate the efficacy of treatments on tumor regression in unresectable pancreatic head carcinomas. Recently, 18 F-fluorodeoxyglucose positron emission tomography (PET) examination has been used for the initial diagnosis of pancreatic tumors, for diagnosis of distant metastasis, and for recurrences of pancreatic carcinomas. PET has also been used for the qualitative diagnosis of existing tumors. The current study was designed to observe if PET examination can be used to gauge the efficacy of multidisciplinary treatments, and to estimate the prognosis for unresectable pancreatic head carcinomas in similar clinical stages and during therapy. This was a prospective cohort study and included 18 cases. All cases were unresectable pancreatic head cancers diagnosed as TNM classification stage 3, and had undergone identical multidisciplinary treatment regimens. The level of tumor markers, tumor-size reduction, and maximum standardized uptake values (SUV max ) were correlated with prognosis. Pearson's correlation and Kaplan-Meyer survival rate curves were used for statistical analysis. Tumor-size reduction in CTs and the transition of tumor markers were not related to patient prognosis. Cases in which post-treatment SUV max values were reduced to <3.0 were correlated with a more favorable prognosis and demonstrated extended survival rates. PET examination can be used to estimate the prognosis of unresectable pancreatic head carcinomas which have undergone multidisciplinary treatments. (author)

  11. Care and calls

    DEFF Research Database (Denmark)

    Paasch, Bettina Sletten

    -centred care through the use of tactile resources and embodied orientations while they attend to the phone call. Experienced nurses Thus perform multiactivity by distributing attention towards both the patient and the phone, and the analysis shows that their concrete ways of doing so depend on the complex...... they are telephoned during interactions with patients are not universal. Indeed different strategies have evolved in other hospital departments. Not only does this thesis contribute insights into the way nurses manage phone calls during interactions with patients, but by subscribing to a growing body of embodied...... of human interaction....

  12. Comparative Gene Expression Profiling in Human Cumulus Cells according to Ovarian Gonadotropin Treatments

    Directory of Open Access Journals (Sweden)

    Said Assou

    2013-01-01

    Full Text Available In in vitro fertilization cycles, both HP-hMG and rFSH gonadotropin treatments are widely used to control human follicle development. The objectives of this study are (i to characterize and compare gene expression profiles in cumulus cells (CCs of periovulatory follicles obtained from patients stimulated with HP-hMG or rFSH in a GnRH antagonist cycle and (ii to examine their relationship with in vitro embryo development, using Human Genome U133 Plus 2.0 microarrays. Genes that were upregulated in HP-hMG-treated CCs are involved in lipid metabolism (GM2A and cell-to-cell interactions (GJA5. Conversely, genes upregulated in rFSH-treated CCs are implicated in cell assembly and organization (COL1A1 and COL3A1. Interestingly, some genes specific to each gonadotropin treatment (NPY1R and GM2A for HP-hMG; GREM1 and OSBPL6 for rFSH were associated with day 3 embryo quality and blastocyst grade at day 5, while others (STC2 and PTX3 were related to in vitro embryo quality in both gonadotropin treatments. These genes may prove valuable as biomarkers of in vitro embryo quality.

  13. Promotion of Metastasis-associated Gene Expression in Survived PANC-1 Cells Following Trichostatin A Treatment.

    Science.gov (United States)

    Chen, Zongjing; Yang, Yunxiu; Liu, Biao; Wang, Benquan; Sun, Meng; Zhang, Ling; Chen, Bicheng; You, Heyi; Zhou, Mengtao

    2015-01-01

    Histone deacetylase inhibitors represent a promising class of potential anticancer agents for the treatment of human malignancies. In this study, the effects of trichostatin A (TSA) on apoptosis, metastasis-associated gene expression, and activation of the Notch pathway in human pancreatic cancer cell lines were investigated. After treatment with TSA, cell viability and apoptosis were evaluated using the MTT [3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide] assay, Hoechst 33258 staining, and flow cytometry. Moreover, RT-PCR and western blot analyses were performed to measure the expression levels of apoptosis-associated genes (Bcl-2, Bax, and caspase-3), metastasis-associated genes (E-cadherin, vimentin, and matrix metalloproteinases), and Notch pathway activation (Notch intracellular domain, NICD). The levels of matrix metalloproteinase 2 and NICD were also semi-quantified by immunoassay. Following treatment with TSA for 24 h, PANC-1, SW1990, and MIATACA-2 cells exhibited cell death. The MTT assay revealed that TSA significantly decreased cell viability in a dose-dependent manner in PANC-1 cells. The Hoechst 33258 staining and flow cytometry results evidenced a significant increase in PANC-1 cell apoptosis following TSA treatment. The expression levels of Bax and caspase-3 were increased significantly, whereas Bcl-2 was down-regulated after TSA treatment. In the PANC-1 cells that survived after TSA treatment, the expression levels of vimentin, E-cadherin, and MMP genes were altered by the promotion of potential metastasis and increased expression of NICD. TSA can induce apoptosis of pancreatic cancer cells. In addition, the up-regulation of metastasis-related genes and the activation of the Notch pathway in the survived PANC-1 cells may be associated with a too-low level of TSA or resistance to TSA.

  14. A network-based gene expression signature informs prognosis and treatment for colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Mingguang Shi

    Full Text Available Several studies have reported gene expression signatures that predict recurrence risk in stage II and III colorectal cancer (CRC patients with minimal gene membership overlap and undefined biological relevance. The goal of this study was to investigate biological themes underlying these signatures, to infer genes of potential mechanistic importance to the CRC recurrence phenotype and to test whether accurate prognostic models can be developed using mechanistically important genes.We investigated eight published CRC gene expression signatures and found no functional convergence in Gene Ontology enrichment analysis. Using a random walk-based approach, we integrated these signatures and publicly available somatic mutation data on a protein-protein interaction network and inferred 487 genes that were plausible candidate molecular underpinnings for the CRC recurrence phenotype. We named the list of 487 genes a NEM signature because it integrated information from Network, Expression, and Mutation. The signature showed significant enrichment in four biological processes closely related to cancer pathophysiology and provided good coverage of known oncogenes, tumor suppressors, and CRC-related signaling pathways. A NEM signature-based Survival Support Vector Machine prognostic model was trained using a microarray gene expression dataset and tested on an independent dataset. The model-based scores showed a 75.7% concordance with the real survival data and separated patients into two groups with significantly different relapse-free survival (p = 0.002. Similar results were obtained with reversed training and testing datasets (p = 0.007. Furthermore, adjuvant chemotherapy was significantly associated with prolonged survival of the high-risk patients (p = 0.006, but not beneficial to the low-risk patients (p = 0.491.The NEM signature not only reflects CRC biology but also informs patient prognosis and treatment response. Thus, the network

  15. Treatment planning of electroporation-based medical interventions: electrochemotherapy, gene electrotransfer and irreversible electroporation

    International Nuclear Information System (INIS)

    Zupanic, Anze; Kos, Bor; Miklavcic, Damijan

    2012-01-01

    In recent years, cancer electrochemotherapy (ECT), gene electrotransfer for gene therapy and DNA vaccination (GET) and tissue ablation with irreversible electroporation (IRE) have all entered clinical practice. We present a method for a personalized treatment planning procedure for ECT, GET and IRE, based on medical image analysis, numerical modelling of electroporation and optimization with the genetic algorithm, and several visualization tools for treatment plan assessment. Each treatment plan provides the attending physician with optimal positions of electrodes in the body and electric pulse parameters for optimal electroporation of the target tissues. For the studied case of a deep-seated tumour, the optimal treatment plans for ECT and IRE require at least two electrodes to be inserted into the target tissue, thus lowering the necessary voltage for electroporation and limiting damage to the surrounding healthy tissue. In GET, it is necessary to place the electrodes outside the target tissue to prevent damage to target cells intended to express the transfected genes. The presented treatment planning procedure is a valuable tool for clinical and experimental use and evaluation of electroporation-based treatments. (paper)

  16. Partitioning a call graph

    NARCIS (Netherlands)

    Bisseling, R.H.; Byrka, J.; Cerav-Erbas, S.; Gvozdenovic, N.; Lorenz, M.; Pendavingh, R.A.; Reeves, C.; Röger, M.; Verhoeven, A.; Berg, van den J.B.; Bhulai, S.; Hulshof, J.; Koole, G.; Quant, C.; Williams, J.F.

    2006-01-01

    Splitting a large software system into smaller and more manageable units has become an important problem for many organizations. The basic structure of a software system is given by a directed graph with vertices representing the programs of the system and arcs representing calls from one program to

  17. CALLING AQUARIUM LOVERS...

    CERN Multimedia

    2002-01-01

    CERN's anemones will soon be orphans. We are looking for someone willing to look after the aquarium in the main building, for one year. If you are interested, or if you would like more information, please call 73830. (The anemones living in the aquarium thank you in anticipation.)

  18. A call for surveys

    DEFF Research Database (Denmark)

    Bernstein, Philip A.; Jensen, Christian S.; Tan, Kian-Lee

    2012-01-01

    The database field is experiencing an increasing need for survey papers. We call on more researchers to set aside time for this important writing activity. The database field is growing in population, scope of topics covered, and the number of papers published. Each year, thousands of new papers ...

  19. Call for Research

    International Development Research Centre (IDRC) Digital Library (Canada)

    Marie-Isabelle Beyer

    2014-10-03

    Oct 3, 2014 ... 5.Submission process. 6.Eligibility criteria. 7.Selection Process. 8. Format and requirements. 9.Evaluation criteria. 10.Country clearance requirements. 11. .... It is envisaged that through this call a single consortium will undertake 6-8 projects within a total budget of up to ... principle qualify for IDRC's support.

  20. Too close to call

    DEFF Research Database (Denmark)

    Kurrild-Klitgaard, Peter

    2012-01-01

    a number of other frequent explanations and is found to be quite robust. When augmented with approval ratings for incumbent presidents, the explanatory power increases to 83 pct. and only incorrectly calls one of the last 15 US presidential elections. Applied to the 2012 election as a forecasting model...

  1. Digital Gene Expression Profiling Analysis of Aged Mice under Moxibustion Treatment

    Directory of Open Access Journals (Sweden)

    Nan Liu

    2018-01-01

    Full Text Available Aging is closely connected with death, progressive physiological decline, and increased risk of diseases, such as cancer, arteriosclerosis, heart disease, hypertension, and neurodegenerative diseases. It is reported that moxibustion can treat more than 300 kinds of diseases including aging related problems and can improve immune function and physiological functions. The digital gene expression profiling of aged mice with or without moxibustion treatment was investigated and the mechanisms of moxibustion in aged mice were speculated by gene ontology and pathway analysis in the study. Almost 145 million raw reads were obtained by digital gene expression analysis and about 140 million (96.55% were clean reads. Five differentially expressed genes with an adjusted P value 1 were identified between the control and moxibustion groups. They were Gm6563, Gm8116, Rps26-ps1, Nat8f4, and Igkv3-12. Gene ontology analysis was carried out by the GOseq R package and functional annotations of the differentially expressed genes related to translation, mRNA export from nucleus, mRNA transport, nuclear body, acetyltransferase activity, and so on. Kyoto Encyclopedia of Genes and Genomes database was used for pathway analysis and ribosome was the most significantly enriched pathway term.

  2. Metagenomic profiling of antibiotic resistance genes and mobile genetic elements in a tannery wastewater treatment plant.

    Directory of Open Access Journals (Sweden)

    Zhu Wang

    Full Text Available Antibiotics are often used to prevent sickness and improve production in animal agriculture, and the residues in animal bodies may enter tannery wastewater during leather production. This study aimed to use Illumina high-throughput sequencing to investigate the occurrence, diversity and abundance of antibiotic resistance genes (ARGs and mobile genetic elements (MGEs in aerobic and anaerobic sludge of a full-scale tannery wastewater treatment plant (WWTP. Metagenomic analysis showed that Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria dominated in the WWTP, but the relative abundance of archaea in anaerobic sludge was higher than in aerobic sludge. Sequencing reads from aerobic and anaerobic sludge revealed differences in the abundance of functional genes between both microbial communities. Genes coding for antibiotic resistance were identified in both communities. BLAST analysis against Antibiotic Resistance Genes Database (ARDB further revealed that aerobic and anaerobic sludge contained various ARGs with high abundance, among which sulfonamide resistance gene sul1 had the highest abundance, occupying over 20% of the total ARGs reads. Tetracycline resistance genes (tet were highly rich in the anaerobic sludge, among which tet33 had the highest abundance, but was absent in aerobic sludge. Over 70 types of insertion sequences were detected in each sludge sample, and class 1 integrase genes were prevalent in the WWTP. The results highlighted prevalence of ARGs and MGEs in tannery WWTPs, which may deserve more public health concerns.

  3. ACE gene polymorphism and losartan treatment in type 2 diabetic patients with nephropathy

    NARCIS (Netherlands)

    Parving, Hans-Henrik; de Zeeuw, Dick; Cooper, Mark E.; Remuzzi, Giuseppe; Liu, Nancy; Lunceford, Jared; Shahinfar, Shahnaz; Wong, Peggy H.; Lyle, Paulette A.; Rossing, Peter; Brenner, Barry M.

    Losartan treatment reduced renal outcomes in proteinuric patients with type 2 diabetes in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. It is unknown whether an insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene

  4. Novel liposomal combination treatments using dual genes knockdown in oral cancer treatment

    Science.gov (United States)

    Wu, Jyun-Sian; Yeh, Chia-Hsien; Huang, Leaf; Hsu, Yih-Chih

    2018-02-01

    Small interfering RNA (siRNA) can be used to treat tumor because it can effectively knockdown target oncoprotein expression and it leads to cancer cell death and apoptosis. Hypoxia-inducible factors-1 (HIF-1) is a transcription factor gene. Its high expression of tumor hypoxia cells, activation of transcription factor HIF-1α and angiogenesis found in most cancerous tissues. HIF-1α protein in cancer cells are critical to cell survival, tumor growth and proliferation. Epidermal growth factor receptor (EGFR) gene is another common head and neck oncogene. The dual self-designed siRNA sequences were encapsulated in the lipid-calcium-phosphate (LCP) and targeted to sigma receptors on the surface of cancer cells via binding to amino ethyl anisamide (AEAA). We used human oral cancer cells to establish the xenograft animal model to study the combination therapy for therapeutic results.

  5. Effect of homeopathic treatment on gene expression in Copenhagen rat tumor tissues.

    Science.gov (United States)

    Thangapazham, Rajesh L; Rajeshkumar, N V; Sharma, Anuj; Warren, Jim; Singh, Anoop K; Ives, John A; Gaddipati, Jaya P; Maheshwari, Radha K; Jonas, Wayne B

    2006-12-01

    Increasing evidence suggests that the inability to undergo apoptosis is an important factor in the development and progression of prostate cancer. Agents that induce apoptosis may inhibit tumor growth and provide therapeutic benefit. In a recent study, the authors found that certain homeopathic treatments produced anticancer effects in an animal model. In this study, the authors examined the immunomodulating and apoptotic effects of these remedies. The authors investigated the effect of a homeopathic treatment regimen containing Conium maculatum, Sabal serrulata, Thuja occidentalis, and a MAT-LyLu Carcinosin nosode on the expression of cytokines and genes that regulate apoptosis. This was assessed in prostate cancer tissues, extracted from animals responsive to these drugs, using ribonuclease protection assay or reverse transcription polymerase chain reaction. There were no significant changes in mRNA levels of the apoptotic genes bax, bcl-2, bcl-x, caspase-1, caspase-2, caspase-3, Fas, FasL, or the cytokines interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-beta, IL-3, IL-4, IL-5, IL-6, IL-10, TNF-alpha, IL-2, and interferon-gamma in prostate tumor and lung metastasis after treatment with homeopathic medicines. This study indicates that treatment with the highly diluted homeopathic remedies does not alter the gene expression in primary prostate tumors or in lung metastasis. The therapeutic effect of homeopathic treatments observed in the in vivo experiments cannot be explained by mechanisms based on distinct alterations in gene expression related to apoptosis or cytokines. Future research should explore subtle modulations in the expression of multiple genes in different biological pathways.

  6. Care and Calls

    DEFF Research Database (Denmark)

    Paasch, Bettina Sletten

    on the enactment of care but also on patient safety. Nurses working in various hospital departments have developed different strategies for handling mobile phone calls when with a patient. Additional research into the ways nurses successfully or unsuccessfully enact care and ensure patient safety when they answer......In Danish hospitals, nurses have been equipped with a mobile work phone to improve their availability and efficiency. On the phones nurses receive internal and external phone conversations, patient calls, and alarms from electronic surveillance equipment. For safety reasons the phones cannot...... be switched off or silenced; they consequently ring during all activities and also during interactions with patients. A possible tension thus arises when nurses have to be both caring and sensitive towards the patient and simultaneously be efficient and available and answer their phone. The present paper...

  7. Flight calls and orientation

    DEFF Research Database (Denmark)

    Larsen, Ole Næsbye; Andersen, Bent Bach; Kropp, Wibke

    2008-01-01

    flight calls was simulated by sequential computer controlled activation of five loudspeakers placed in a linear array perpendicular to the bird's migration course. The bird responded to this stimulation by changing its migratory course in the direction of that of the ‘flying conspecifics' but after about......  In a pilot experiment a European Robin, Erithacus rubecula, expressing migratory restlessness with a stable orientation, was video filmed in the dark with an infrared camera and its directional migratory activity was recorded. The flight overhead of migrating conspecifics uttering nocturnal...... 30 minutes it drifted back to its original migration course. The results suggest that songbirds migrating alone at night can use the flight calls from conspecifics as additional cues for orientation and that they may compare this information with other cues to decide what course to keep....

  8. Concentration of facultative pathogenic bacteria and antibiotic resistance genes during sewage treatment and in receiving rivers.

    Science.gov (United States)

    Heß, Stefanie; Lüddeke, Frauke; Gallert, Claudia

    2016-10-01

    Whereas the hygienic condition of drinking and bathing water by law must be monitored by culture-based methods, for quantification of microbes and antibiotic resistance in soil or the aquatic environment, often molecular genetic assays are used. For comparison of both methods, knowledge of their correlation is necessary. Therefore the population of total bacteria, Escherichia coli, enterococci and staphylococci during sewage treatment and in receiving river water was compared by agar plating and quantitative polymerase chain reaction (qPCR) assays. In parallel, all samples were investigated for clinically relevant antibiotic resistance genes. Whereas plating and qPCR data for total bacteria correlated well in sewage after primary treatment, qPCR data of river water indicated higher cell numbers for E. coli. It is unknown if these cells are 'only' not growing under standard conditions or if they are dead. Corresponding to the amount of non-culturable cells, the 'breakpoints' for monitoring water quality should be adapted. The abundances of clinically relevant antibiotic resistance genes in river water were in the same order of magnitude or even higher than in treated sewage. For estimation of the health risk it is important to investigate which species carry respective genes and whether these genes are disseminated via gene transfer.

  9. Gene doping: gene delivery for olympic victory.

    Science.gov (United States)

    Gould, David

    2013-08-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place. © 2012 The Author. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  10. Gene therapy a promising treatment for breast cancer: current scenario in pakistan

    International Nuclear Information System (INIS)

    Muzavir, S.R.; Zahra, S.A.; Ahmad, A.

    2012-01-01

    Breast cancer is one of the most common cancers among women around the world. It accounts for 22.9% of all the cancers and 18% of all female cancers in the world. One million new cases of breast cancer are diagnosed every year. Pakistan has more alarming situation with 90,000 new cases and ending up into 40,000 deaths annually. The risk factor for a female to develop breast cancer as compared with male is 100 : 1. The traditional way of treatment is by surgery, chemotherapy or radiotherapy. Advanced breast cancer is very difficult to treat with any of the traditional treatment options. A new treatment option in the form of gene therapy can be a promising treatment for breast cancer. Gene therapy provides treatment option in the form of targeting mutated gene, expression of cancer markers on the surface of cells, blocking the metastasis and induction of apoptosis, etc. Gene therapy showed very promising results for treatment of various cancers. All this is being trialed, experimented and practiced outside of Pakistan. Therefore, there is an immense need that this kind of work should be started in Pakistan. There are many good research institutes as well as well-reputed hospitals in Pakistan. Presently, there is a need to develop collaboration between research institutes and hospitals, so that the basic work and clinical trials can be done to treat breast cancer patients in the country. This collaboration will prove to be very healthy and will not only strength research institute but also will be very beneficial for cancer patients. (author)

  11. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of 18F-Fluorodeoxyglucose After Radiation Treatment

    International Nuclear Information System (INIS)

    Wilson, George D.; Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L.; Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John; Oliver Wong, Ching Yee; Yan, Di; Marples, Brian; Huang, Jiayi

    2014-01-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm 3 they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: 18 F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism

  12. Cell based-gene delivery approaches for the treatment of spinal cord injury and neurodegenerative disorders.

    Science.gov (United States)

    Taha, Masoumeh Fakhr

    2010-03-01

    Cell based-gene delivery has provided an important therapeutic strategy for different disorders in the recent years. This strategy is based on the transplantation of genetically modified cells to express specific genes and to target the delivery of therapeutic factors, especially for the treatment of cancers and neurological, immunological, cardiovascular and heamatopoietic disorders. Although, preliminary reports are encouraging, and experimental studies indicate functionally and structurally improvements in the animal models of different disorders, universal application of this strategy for human diseases requires more evidence. There are a number of parameters that need to be evaluated, including the optimal cell source, the most effective gene/genes to be delivered, the optimal vector and method of gene delivery into the cells and the most efficient route for the delivery of genetically modified cells into the patient. Also, some obstacles have to be overcome, including the safety and usefulness of the approaches and the stability of the improvements. Here, recent studies concerning with the cell-based gene delivery for spinal cord injury and some neurodegenerative disorders such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease are briefly reviewed, and their exciting consequences are discussed.

  13. Human Mesenchymal Stem Cell Treatment Normalizes Cortical Gene Expression after Traumatic Brain Injury.

    Science.gov (United States)

    Darkazalli, Ali; Vied, Cynthia; Badger, Crystal-Dawn; Levenson, Cathy W

    2017-01-01

    Traumatic brain injury (TBI) results in a progressive disease state with many adverse and long-term neurological consequences. Mesenchymal stem cells (MSCs) have emerged as a promising cytotherapy and have been previously shown to reduce secondary apoptosis and cognitive deficits associated with TBI. Consistent with the established literature, we observed that systemically administered human MSCs (hMSCs) accumulate with high specificity at the TBI lesion boundary zone known as the penumbra. Substantial work has been done to illuminate the mechanisms by which MSCs, and the bioactive molecules they secrete, exert their therapeutic effect. However, no such work has been published to examine the effect of MSC treatment on gene expression in the brain post-TBI. In the present study, we use high-throughput RNA sequencing (RNAseq) of cortical tissue from the TBI penumbra to assess the molecular effects of both TBI and subsequent treatment with intravenously delivered hMSCs. RNAseq revealed that expression of almost 7000 cortical genes in the penumbra were differentially regulated by TBI. Pathway analysis using the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database revealed that TBI regulated a large number of genes belonging to pathways involved in metabolism, receptor-mediated cell signaling, neuronal plasticity, immune cell recruitment and infiltration, and neurodegenerative disease. Remarkably, hMSC treatment was found to normalize 49% of all genes disrupted by TBI, with notably robust normalization of specific pathways within the categories mentioned above, including neuroactive receptor-ligand interactions (57%), glycolysis and gluconeogenesis (81%), and Parkinson's disease (100%). These data provide evidence in support of the multi-mechanistic nature of stem cell therapy and suggest that hMSC treatment is capable of simultaneously normalizing a wide variety of important molecular pathways that are disrupted by brain injury.

  14. Fertility desire and intention of people living with HIV/AIDS in Tanzania: a call for restructuring care and treatment services

    Directory of Open Access Journals (Sweden)

    Mmbaga Elia J

    2013-01-01

    Full Text Available Abstract Background Scaling up of antiretroviral therapy (ART is currently underway in sub-Saharan Africa including, Tanzania, increasing survival of people living with HIV/AIDS (PLWHA. Programmes pay little attention to PLWHA’s reproductive health needs. Information on fertility desire and intention would assist in the integration of sexual and reproductive health in routine care and treatment clinics. Methods A cross-sectional study of all PLWHA aged 15–49 residing in Kahe ward in rural Kilimanjaro Tanzania was conducted. Participants were recruited from the community and a local counselling centre located in the ward. Data on socio-demographic, medical and reproductive characteristics were collected through face-to-face interviews. Data were entered and analysed using STATA statistical software. Results A total of 410 PLWHA with a mean age of 34.2 and constituting 264 (64.4% females participated. Fifty-one per cent reported to be married/cohabiting, 73.9% lived with their partners and 60.5% were sexually active. The rate of unprotected sex was 69.0% with 12.5% of women reporting to be pregnant at the time of the survey. Further biological children were desired by 37.1% of the participants and lifetime fertility intention was 2.4 children. Increased fertility desire was associated with living and having sex with a partner, HIV disclosure, good perceived health status and CD4 count ≥200 cells for both sexes. Reduced desire was associated with havingmore than 2 children among females, divorce or separation, and having a child with the current partner among both males and females. Conclusion Fertility desire and intention of PLWHA was substantially high though lower than that of the general population in Tanzania. Practice of unprotected sexual intercourse with higher pregnancy rate was observed. Fertility desire was determined by individual perceived health and socio-family related factors. With increasing ART coverage and subsequent

  15. Antibiotic resistance genes fate and removal by a technological treatment solution for water reuse in agriculture.

    Science.gov (United States)

    Luprano, Maria Laura; De Sanctis, Marco; Del Moro, Guido; Di Iaconi, Claudio; Lopez, Antonio; Levantesi, Caterina

    2016-11-15

    In order to mitigate the potential effects on the human health which are associated to the use of treated wastewater in agriculture, antibiotic resistance genes (ARGs) are required to be carefully monitored in wastewater reuse processes and their spread should be prevented by the development of efficient treatment technologies. Objective of this study was the assessment of ARGs reduction efficiencies of a novel technological treatment solution for agricultural reuse of municipal wastewaters. The proposed solution comprises an advanced biological treatment (Sequencing Batch Biofilter Granular Reactor, SBBGR), analysed both al laboratory and pilot scale, followed by sand filtration and two different disinfection final stages: ultraviolet light (UV) radiation and peracetic acid (PAA) treatments. By Polymerase Chain Reaction (PCR), the presence of 9 ARGs (ampC, mecA, ermB, sul1, sul2, tetA, tetO, tetW, vanA) were analysed and by quantitative PCR (qPCR) their removal was determined. The obtained results were compared to the reduction of total bacteria (16S rDNA gene) and of a faecal contamination indicator (Escherichia coli uidA gene). Only four of the analysed genes (ermB, sul1, sul2, tetA) were detected in raw wastewater and their abundance was estimated to be 3.4±0.7 x10(4) - 9.6±0.5 x10(9) and 1.0±0.3 x10(3) to 3.0±0.1 x10(7) gene copies/mL in raw and treated wastewaters, respectively. The results show that SBBGR technology is promising for the reduction of ARGs, achieving stable removal performance ranging from 1.0±0.4 to 2.8±0.7 log units, which is comparable to or higher than that reported for conventional activated sludge treatments. No reduction of the ARGs amount normalized to the total bacteria content (16S rDNA), was instead obtained, indicating that these genes are removed together with total bacteria and not specifically eliminated. Enhanced ARGs removal was obtained by sand filtration, while no reduction was achieved by both UV and PAA disinfection

  16. High-throughput profiling of antibiotic resistance genes in drinking water treatment plants and distribution systems.

    Science.gov (United States)

    Xu, Like; Ouyang, Weiying; Qian, Yanyun; Su, Chao; Su, Jianqiang; Chen, Hong

    2016-06-01

    Antibiotic resistance genes (ARGs) are present in surface water and often cannot be completely eliminated by drinking water treatment plants (DWTPs). Improper elimination of the ARG-harboring microorganisms contaminates the water supply and would lead to animal and human disease. Therefore, it is of utmost importance to determine the most effective ways by which DWTPs can eliminate ARGs. Here, we tested water samples from two DWTPs and distribution systems and detected the presence of 285 ARGs, 8 transposases, and intI-1 by utilizing high-throughput qPCR. The prevalence of ARGs differed in the two DWTPs, one of which employed conventional water treatments while the other had advanced treatment processes. The relative abundance of ARGs increased significantly after the treatment with biological activated carbon (BAC), raising the number of detected ARGs from 76 to 150. Furthermore, the final chlorination step enhanced the relative abundance of ARGs in the finished water generated from both DWTPs. The total enrichment of ARGs varied from 6.4-to 109.2-fold in tap water compared to finished water, among which beta-lactam resistance genes displayed the highest enrichment. Six transposase genes were detected in tap water samples, with the transposase gene TnpA-04 showing the greatest enrichment (up to 124.9-fold). We observed significant positive correlations between ARGs and mobile genetic elements (MGEs) during the distribution systems, indicating that transposases and intI-1 may contribute to antibiotic resistance in drinking water. To our knowledge, this is the first study to investigate the diversity and abundance of ARGs in drinking water treatment systems utilizing high-throughput qPCR techniques in China. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. FERMILAB: Call for physics

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    Several hundred physicists attended a special Fermilab 'All Experimenter's Meeting' on November 20 to hear Director John Peoples call for new Tevatron Collider proposals for the years 2000-2005, when the new Main Injector will be complete. At the Tevatron proton-antiproton collider, the CDF and DO experiments are currently completing improvements for Run II to use the Tevatron when the Main Injector is complete later in this decade. New proposals would be aimed at a Collider Run III to follow these CDF and DO efforts

  18. To be called upon

    DEFF Research Database (Denmark)

    Kublitz, Anja

    2015-01-01

    When Danish Muslims explain what made them decide to travel to the Middle East and take up arms in the wake of the Arab Spring, they say that they were called upon. Displayed on videos on social media, women and sometimes children begged them to come to their rescue. In light of some...... to the mass if it is no longer a causal phenomenon that expands from small to big, but rather a simultaneous multitude of one to one relations that are neither local nor global? How are the one and the many related in this specific setting? Furthermore, many of the videos display dead bodies. How can we...

  19. GENE EXPRESSION DYNAMICS IN PATIENTS WITH SEVERE THERAPY-RESISTANT ASTHMA DURING TREATMENT PERIOD

    Directory of Open Access Journals (Sweden)

    Ye. S. Kulikov

    2014-01-01

    Full Text Available Introduction: The leading mechanisms and causes of severe therapy resistant asthma are poorly understood. The aim of this study was to define global patterns of gene expression in adults with severe therapy-resistant asthma in dynamic during treatment period.Methods: Performed 24-week prospective interventional study in parallel groups. Severe asthma patients was aposterior divided at therapy sensitive and resistant patients according to ATS criteria. Global transcriptome profile was characterized using the Affymetrix HuGene ST1.0 chip. Cluster analysis was performed.Results and conclusion: According to our data several mechanisms of therapy resistance may be considered: increased levels of nitric oxide and beta2-agonists nitration, dysregulation of endogenous steroids secretion and involvement in the pathogenesis of Staphylococcus aureus. Absence of suppression of gene expression KEGG-pathway “asthma" may reflect the low efficiency or long period of anti-inflammatory therapy effect realization.

  20. PLGA-Chitosan nanoparticle-mediated gene delivery for oral cancer treatment: A brief review

    Science.gov (United States)

    Bakar, L. M.; Abdullah, M. Z.; Doolaanea, A. A.; Ichwan, S. J. A.

    2017-08-01

    Cancer becomes a serious issue on society with increasing of their growth and proliferation, either in well economic developed countries or not. Recent years, oral cancer is one of the most threatening diseases impairing the quality of life of the patient. Scientists have emphasised on application of gene therapy for oral cancer by using nanoparticle as transportation vectors as a new alternative platform in order to overcome the limitations of conventional approaches. In modern medicine, nanotechnologies’ application, such as nanoparticles-mediated gene delivery, is one of promising tool for therapeutic devices. The objective of this article is to present a brief review summarizes on the current progress of nanotechnology-based gene delivery treatment system targeted for oral cancer.

  1. MEDICAL SERVICE - URGENT CALLS

    CERN Multimedia

    Service Médical

    2000-01-01

    IN URGENT NEED OF A DOCTOR GENEVA: EMERGENCY SERVICES GENEVA AND VAUD 144 FIRE BRIGADE 118 POLICE 117 CERN FIREMEN 767-44-44 ANTI-POISONS CENTRE Open 24h/24h 01-251-51-51 Patient not fit to be moved, call family doctor, or: GP AT HOME: Open 24h/24h 748-49-50 AMG- Association Of Geneva Doctors: Emergency Doctors at home 07h-23h 322 20 20 Patient fit to be moved: HOPITAL CANTONAL CENTRAL 24 Micheli-du-Crest 372-33-11 ou 382-33-11 EMERGENCIES 382-33-11 ou 372-33-11 CHILDREN'S HOSPITAL 6 rue Willy-Donzé 372-33-11 MATERNITY 32 bvd.de la Cluse 382-68-16 ou 382-33-11 OPHTHALMOLOGY 22 Alcide Jentzer 382-33-11 ou 372-33-11 MEDICAL CENTRE CORNAVIN 1-3 rue du Jura 345 45 50 HOPITAL DE LA TOUR Meyrin 719-61-11 EMERGENCIES 719-61-11 CHILDREN'S EMERGENCIES 719-61-00 LA TOUR MEDICAL CENTRE 719-74-00 European Emergency Call 112   FRANCE: EMERGENCY SERVICES 15 FIRE BRIGADE 18 POLICE 17 CERN FIREMEN AT HOME 00-41-22-767-44-44 ...

  2. An Island Called Cuba

    Directory of Open Access Journals (Sweden)

    Jean Stubbs

    2011-06-01

    Full Text Available Review of: An Island Called Home: Returning to Jewish Cuba. Ruth Behar, photographs by Humberto Mayol. New Brunswick NJ: Rutgers University Press, 2007. xiii + 297 pp. (Cloth US$ 29.95 Fidel Castro: My Life: A Spoken Autobiography. Fidel Castro & Ignacio Ramonet. New York: Scribner/Simon & Schuster, 2008. vii + 724 pp. (Paper US$ 22.00, e-book US$ 14.99 Cuba: What Everyone Needs to Know. Julia E. Sweig. New York: Oxford University Press, 2009. xiv + 279 pp. (Paper US$ 16.95 [First paragraph] These three ostensibly very different books tell a compelling story of each author’s approach, as much as the subject matter itself. Fidel Castro: My Life: A Spoken Autobiography is based on a series of long interviews granted by the then-president of Cuba, Fidel Castro, to Spanish-Franco journalist Ignacio Ramonet. Cuba: What Everyone Needs to Know, by U.S. political analyst Julia Sweig, is one of a set country series, and, like Ramonet’s, presented in question/answer format. An Island Called Home: Returning to Jewish Cuba, with a narrative by Cuban-American anthropologist Ruth Behar and photographs by Cuban photographer Humberto Mayol, is a retrospective/introspective account of the Jewish presence in Cuba. While from Ramonet and Sweig we learn much about the revolutionary project, Behar and Mayol convey the lived experience of the small Jewish community against that backdrop.

  3. Call for volunteers

    CERN Document Server

    2008-01-01

    CERN is calling for volunteers from all members of the Laboratory for organizing the two exceptional Open days.CERN is calling for volunteers from all members of the Laboratory’s personnel to help with the organisation of these two exceptional Open Days, for the visits of CERN personnel and their families on the Saturday and above all for the major public Open Day on the Sunday. As for the 50th anniversary in 2004, the success of the Open Days will depend on a large number of volunteers. All those working for CERN as well as retired members of the personnel can contribute to making this event a success. Many guides will be needed at the LHC points, for the activities at the surface and to man the reception and information points. The aim of these major Open Days is to give the local populations the opportunity to discover the fruits of almost 20 years of work carried out at CERN. We are hoping for some 2000 volunteers for the two Open Days, on the Saturday from 9 a.m. to ...

  4. Occurrence of antimicrobials and antimicrobial resistance genes in beef cattle storage ponds and swine treatment lagoons

    International Nuclear Information System (INIS)

    Zhang, Yuping; Zhang, Chiqian; Parker, David B.; Snow, Daniel D.; Zhou, Zhi; Li, Xu

    2013-01-01

    Livestock manure treatment and storage structures are potential environmental sources of antimicrobials and antimicrobial resistance genes (ARGs). In this study, the occurrence of antimicrobials and ARGs was investigated in the water and the sludge compartments of beef cattle storage ponds and swine lagoons. Analysis was focused on two families of antimicrobials (sulfonamide and tetracycline) and the corresponding ARGs (sul1, sul2, tetO, tetQ and tetX). Results showed that the pseudo-partitioning coefficients of tetracyclines were higher than those of sulfonamides, suggesting different distributions of these two classes of antimicrobials between water and sludge. The ARGs tested were detected in nearly all ponds and lagoons, with the highest relative abundance in sul2 at 6.3 × 10 −1 copies per 16S rRNA gene. A positive correlation was observed between total sul genes and total sulfonamides in water while the correlation was negative in sludge. No significant correlation was found between total tet genes and total tetracyclines in either water or sludge, but significant correlations were observed for certain individual tet genes. Ammonia concentrations strongly correlated with all ARGs except tetX. This study provided quantitative information on the occurrence of antimicrobials and ARGs in the liquid and solid compartments of typical manure treatment and storage structures. - Highlights: • Partitioning of antimicrobials between water and sludge is compound specific. • Antimicrobial resistance genes occurred in both water and sludge. • The ARG abundance varied more substantially in swine lagoons than in cattle ponds. • Correlations between ARGs and antimicrobials are system dependent

  5. Gene expression profiling of dendritic cells in different physiological stages under Cordyceps sinensis treatment.

    Directory of Open Access Journals (Sweden)

    Chia-Yang Li

    Full Text Available Cordyceps sinensis (CS has been commonly used as herbal medicine and a health supplement in China for over two thousand years. Although previous studies have demonstrated that CS has benefits in immunoregulation and anti-inflammation, the precise mechanism by which CS affects immunomodulation is still unclear. In this study, we exploited duplicate sets of loop-design microarray experiments to examine two different batches of CS and analyze the effects of CS on dendritic cells (DCs, in different physiology stages: naïve stage and inflammatory stage. Immature DCs were treated with CS, lipopolysaccharide (LPS, or LPS plus CS (LPS/CS for two days, and the gene expression profiles were examined using cDNA microarrays. The results of two loop-design microarray experiments showed good intersection rates. The expression level of common genes found in both loop-design microarray experiments was consistent, and the correlation coefficients (Rs, were higher than 0.96. Through intersection analysis of microarray results, we identified 295 intersecting significantly differentially expressed (SDE genes of the three different treatments (CS, LPS, and LPS/CS, which participated mainly in the adjustment of immune response and the regulation of cell proliferation and death. Genes regulated uniquely by CS treatment were significantly involved in the regulation of focal adhesion pathway, ECM-receptor interaction pathway, and hematopoietic cell lineage pathway. Unique LPS regulated genes were significantly involved in the regulation of Toll-like receptor signaling pathway, systemic lupus erythematosus pathway, and complement and coagulation cascades pathway. Unique LPS/CS regulated genes were significantly involved in the regulation of oxidative phosphorylation pathway. These results could provide useful information in further study of the pharmacological mechanisms of CS. This study also demonstrates that with a rigorous experimental design, the biological effects

  6. Gene expression profiling of dendritic cells in different physiological stages under Cordyceps sinensis treatment.

    Science.gov (United States)

    Li, Chia-Yang; Chiang, Chi-Shiun; Cheng, Wei-Chung; Wang, Shu-Chi; Cheng, Hung-Tsu; Chen, Chaang-Ray; Shu, Wun-Yi; Tsai, Min-Lung; Hseu, Ruey-Shyang; Chang, Cheng-Wei; Huang, Chao-Ying; Fang, Shih-Hua; Hsu, Ian C

    2012-01-01

    Cordyceps sinensis (CS) has been commonly used as herbal medicine and a health supplement in China for over two thousand years. Although previous studies have demonstrated that CS has benefits in immunoregulation and anti-inflammation, the precise mechanism by which CS affects immunomodulation is still unclear. In this study, we exploited duplicate sets of loop-design microarray experiments to examine two different batches of CS and analyze the effects of CS on dendritic cells (DCs), in different physiology stages: naïve stage and inflammatory stage. Immature DCs were treated with CS, lipopolysaccharide (LPS), or LPS plus CS (LPS/CS) for two days, and the gene expression profiles were examined using cDNA microarrays. The results of two loop-design microarray experiments showed good intersection rates. The expression level of common genes found in both loop-design microarray experiments was consistent, and the correlation coefficients (Rs), were higher than 0.96. Through intersection analysis of microarray results, we identified 295 intersecting significantly differentially expressed (SDE) genes of the three different treatments (CS, LPS, and LPS/CS), which participated mainly in the adjustment of immune response and the regulation of cell proliferation and death. Genes regulated uniquely by CS treatment were significantly involved in the regulation of focal adhesion pathway, ECM-receptor interaction pathway, and hematopoietic cell lineage pathway. Unique LPS regulated genes were significantly involved in the regulation of Toll-like receptor signaling pathway, systemic lupus erythematosus pathway, and complement and coagulation cascades pathway. Unique LPS/CS regulated genes were significantly involved in the regulation of oxidative phosphorylation pathway. These results could provide useful information in further study of the pharmacological mechanisms of CS. This study also demonstrates that with a rigorous experimental design, the biological effects of a complex

  7. Occurrence of antimicrobials and antimicrobial resistance genes in beef cattle storage ponds and swine treatment lagoons

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuping; Zhang, Chiqian [Department of Civil Engineering, University of Nebraska-Lincoln, Lincoln, NE (United States); Parker, David B. [USDA Meat Animal Research Center, Clay Center, NE (United States); Snow, Daniel D. [Water Sciences Laboratory, University of Nebraska-Lincoln, Lincoln, NE (United States); Zhou, Zhi [Department of Civil and Environmental Engineering, National University of Singapore (Singapore); Li, Xu, E-mail: xuli@unl.edu [Department of Civil Engineering, University of Nebraska-Lincoln, Lincoln, NE (United States)

    2013-10-01

    Livestock manure treatment and storage structures are potential environmental sources of antimicrobials and antimicrobial resistance genes (ARGs). In this study, the occurrence of antimicrobials and ARGs was investigated in the water and the sludge compartments of beef cattle storage ponds and swine lagoons. Analysis was focused on two families of antimicrobials (sulfonamide and tetracycline) and the corresponding ARGs (sul1, sul2, tetO, tetQ and tetX). Results showed that the pseudo-partitioning coefficients of tetracyclines were higher than those of sulfonamides, suggesting different distributions of these two classes of antimicrobials between water and sludge. The ARGs tested were detected in nearly all ponds and lagoons, with the highest relative abundance in sul2 at 6.3 × 10{sup −1} copies per 16S rRNA gene. A positive correlation was observed between total sul genes and total sulfonamides in water while the correlation was negative in sludge. No significant correlation was found between total tet genes and total tetracyclines in either water or sludge, but significant correlations were observed for certain individual tet genes. Ammonia concentrations strongly correlated with all ARGs except tetX. This study provided quantitative information on the occurrence of antimicrobials and ARGs in the liquid and solid compartments of typical manure treatment and storage structures. - Highlights: • Partitioning of antimicrobials between water and sludge is compound specific. • Antimicrobial resistance genes occurred in both water and sludge. • The ARG abundance varied more substantially in swine lagoons than in cattle ponds. • Correlations between ARGs and antimicrobials are system dependent.

  8. Using Merkel cell polyomavirus specific TCR gene therapy for treatment of Merkel cellcarcinoma

    DEFF Research Database (Denmark)

    Lyngaa, Rikke Birgitte; Pedersen, Natasja Wulff; Linnemann, C.

    2016-01-01

    T cell receptor gene-therapy has entered the clinic and shown potential for successful cancer treatment. However, the clinical evaluation has also highlighted the need for selection of truly cancerspecific targets. Merkel cell carcinoma (MCC) is a highly aggressive skin cancer associated with Mer......T cell receptor gene-therapy has entered the clinic and shown potential for successful cancer treatment. However, the clinical evaluation has also highlighted the need for selection of truly cancerspecific targets. Merkel cell carcinoma (MCC) is a highly aggressive skin cancer associated...... with Merkel cell polyomavirus (MCPyV). Due to the clear viral correlation CD8+ T cells specific for viral epitopes could potentially form cancer-specific targets in MCC patients. We have identified MCPyV specific T cells using a high-throughput platform for T-cell enrichment and combinatorial encoding...

  9. Impact of intramammary treatment on gene expression profiles in bovine Escherichia coli mastitis.

    Directory of Open Access Journals (Sweden)

    Anja Sipka

    Full Text Available Clinical mastitis caused by E. coli accounts for significant production losses and animal welfare concerns on dairy farms worldwide. The benefits of therapeutic intervention in mild to moderate cases are incompletely understood. We investigated the effect of intramammary treatment with cefapirin alone or in combination with prednisolone on gene expression profiles in experimentally-induced E. coli mastitis in six mid-lactating Holstein Friesian cows. Cows were challenged with E. coli in 3 quarters and received 4 doses of 300 mg cefapirin in one quarter and 4 doses of 300 mg cefapirin together with 20 mg prednisolone in another quarter. At 24 h (n = 3 or 48 h (n = 3 post-challenge, tissue samples from control and treated quarters were collected for microarray analysis. Gene expression analysis of challenged, un-treated quarters revealed an up-regulation of transcripts associated with immune response functions compared to un-challenged quarters. Both treatments resulted in down-regulation of these transcripts compared to challenged, un-treated quarters most prominently for genes representing Chemokine and TLR-signaling pathways. Gene expression of Lipopolysaccharide Binding Protein (LBP, CCL2 and CXCL2 were only significantly down-regulated in cefapirin-prednisolone-treated quarters compared to un-treated controls. Down-regulation of chemokines was further confirmed on the basis of protein levels in milk whey for CXCL1, CXCL2 and CXCL8 in both treatments with a greater decrease in cefapirin-prednisolone-treated quarters. The data reveal a significant effect of treatment on cell recruitment with a more pronounced effect in cefapirin-prednisolone treated quarters. Provided a rapid bacteriological clearance, combination therapy may prevent neutrophil-induced tissue damage and promote recovery of the gland.

  10. Impact of intramammary treatment on gene expression profiles in bovine Escherichia coli mastitis.

    Science.gov (United States)

    Sipka, Anja; Klaessig, Suzanne; Duhamel, Gerald E; Swinkels, Jantijn; Rainard, Pascal; Schukken, Ynte

    2014-01-01

    Clinical mastitis caused by E. coli accounts for significant production losses and animal welfare concerns on dairy farms worldwide. The benefits of therapeutic intervention in mild to moderate cases are incompletely understood. We investigated the effect of intramammary treatment with cefapirin alone or in combination with prednisolone on gene expression profiles in experimentally-induced E. coli mastitis in six mid-lactating Holstein Friesian cows. Cows were challenged with E. coli in 3 quarters and received 4 doses of 300 mg cefapirin in one quarter and 4 doses of 300 mg cefapirin together with 20 mg prednisolone in another quarter. At 24 h (n = 3) or 48 h (n = 3) post-challenge, tissue samples from control and treated quarters were collected for microarray analysis. Gene expression analysis of challenged, un-treated quarters revealed an up-regulation of transcripts associated with immune response functions compared to un-challenged quarters. Both treatments resulted in down-regulation of these transcripts compared to challenged, un-treated quarters most prominently for genes representing Chemokine and TLR-signaling pathways. Gene expression of Lipopolysaccharide Binding Protein (LBP), CCL2 and CXCL2 were only significantly down-regulated in cefapirin-prednisolone-treated quarters compared to un-treated controls. Down-regulation of chemokines was further confirmed on the basis of protein levels in milk whey for CXCL1, CXCL2 and CXCL8 in both treatments with a greater decrease in cefapirin-prednisolone-treated quarters. The data reveal a significant effect of treatment on cell recruitment with a more pronounced effect in cefapirin-prednisolone treated quarters. Provided a rapid bacteriological clearance, combination therapy may prevent neutrophil-induced tissue damage and promote recovery of the gland.

  11. Fate of antibiotic resistance genes within the microbial communities of three waste water treatment plants

    OpenAIRE

    Di Cesare, Andrea; Eckert, Ester; D'Urso, Silvia; Doppelbauer, Julia; Corno, Gianluca

    2016-01-01

    Although Waste Water Treatment Plant (WWTP) are designed to reduce the biological pollution of urban waters, they lack a specific action against antibiotic resistance bacteria (ARB) or antibiotic resistance genes (ARGs). Nowadays, it is well documented that WWTPs constitute a reservoir of antibiotic resistances and, in some cases, they can be a favorable environment for the selection of ARB. This represent a serious concern for the public health, because the effluents of the WWTPs can be reus...

  12. Maternal uterine artery VEGF gene therapy for treatment of intrauterine growth restriction.

    Science.gov (United States)

    David, Anna L

    2017-11-01

    Intrauterine growth restriction (IUGR) is a serious pregnancy complication affecting approximately 8% of all pregnancies. The aetiology is believed to be insufficient maternal uteroplacental perfusion which prevents adequate nutrient and oxygen availability for the fetus. There is no treatment that can improve uteroplacental perfusion and thereby increase fetal growth in the uterus. Maternal uterine artery gene therapy presents a promising treatment strategy for IUGR, with the use of adenoviral vectors encoding for proteins such as Vascular Endothelial Growth Factor (VEGF) demonstrating improvements in fetal growth and neonatal outcome in preclinical studies. Mechanistically, maternal VEGF gene therapy delivered to the uterine arteries increases uterine blood flow and enhances vascular relaxation short term, while reducing vascular contractility long term. It also leads to vascular remodeling with increased endothelial cell proliferation in the perivascular adventitia of uterine arteries. Safety assessments suggest no vector spread to the fetus and no adverse risk to the mother or fetus; a clinical trial is in development. This article assesses research into VEGF maternal uterine artery directed gene therapy for IUGR, investigating the use of transgenes and vectors, their route of administration in obstetrics, and the steps that will be needed to take this treatment modality into the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Blended call center with idling times during the call service

    NARCIS (Netherlands)

    Legros, Benjamin; Jouini, Oualid; Koole, Ger

    We consider a blended call center with calls arriving over time and an infinitely backlogged amount of outbound jobs. Inbound calls have a non-preemptive priority over outbound jobs. The inbound call service is characterized by three successive stages where the second one is a break; i.e., there is

  14. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Yang, Shuo; Ma, Si-Qi; Wan, Xing; He, Heng; Pei, Han; Zhao, Min-Jian; Chen, Chen; Wang, Dao-Wen; Dong, Xiao-Yan; Yuan, Jia-Jia; Li, Bin

    2016-08-01

    Leber's hereditary optic neuropathy (LHON) is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP), optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2-9) received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8) and untreated eyes (Patients 2, 3, 4, 6 and 8). Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1) who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains stable in the

  15. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Shuo Yang

    2016-08-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a disease that leads to blindness. Gene therapy has been investigated with some success, and could lead to important advancements in treating LHON. This was a prospective, open-label trial involving 9 LHON patients at Tongji Hospital, Wuhan, China, from August 2011 to December 2015. The purpose of this study was to evaluate the long-term outcomes of gene therapy for LHON. Nine LHON patients voluntarily received an intravitreal injection of rAAV2-ND4. Systemic examinations and visual function tests were performed during the 36-month follow-up period to determine the safety and efficacy of this gene therapy. Based on successful experiments in an animal model of LHON, 1 subject also received an rAAV2-ND4 injection in the second eye 12 months after gene therapy was administered in the first eye. Recovery of visual acuity was defined as the primary outcome of this study. Changes in the visual field, visual evoked potential (VEP, optical coherence tomography findings, liver and kidney function, and antibodies against AAV2 were defined as secondary endpoints. Eight patients (Patients 2–9 received unilateral gene therapy and visual function improvement was observed in both treated eyes (Patients 4, 6, 7, and 8 and untreated eyes (Patients 2, 3, 4, 6 and 8. Visual regression fluctuations, defined as changes in visual acuity greater than or equal to 0.3 logMAR, were observed in Patients 2 and 9. Age at disease onset, disease duration, and the amount of remaining optic nerve fibers did not have a significant effect on the visual function improvement. The visual field and pattern reversal VEP also improved. The patient (Patient 1 who received gene therapy in both eyes had improved visual acuity in the injected eye after the first treatment. Unfortunately, visual acuity in this eye decreased 3 months after he received gene therapy in the second eye. Animal experiments suggested that ND4 expression remains

  16. The Role of Gene Therapy in the Treatment of Retinal Diseases: A Review.

    Science.gov (United States)

    Campa, C; Gallenga, C E; Bolletta, E; Perri, P

    2017-01-01

    Gene therapy represents the therapeutic delivery of nucleic acid polymers into patient cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ. It is not surprising therefore that several clinical trials are now ongoing in this field. The purpose of this review was to provide an update on gene therapy for retinal diseases, discussing differences in treatment strategies, vector designs and surgical techniques. Research was performed on PubMed, ClinicalTrials.gov, and Home Genetic Reference. We additionally utilized the internet database for genetics of retinal diseases, the portal for rare diseases and orphan drugs and the NCBI database Online Mendelian Inheritance in Man. No restriction was applied on the language of publications. We present the available results of current active clinical trials for inherited retinal disease such as Leber's congenital amaurosis type 2, choroideremia, Stargardt disease, achromatopsia and juvenile X-linked retinoschisis. We also illustrate a new approach of this therapy for the treatment of much more common ocular diseases such as age-related macular degeneration and diabetic retinopathy. Gene therapy represents an emerging and promising therapeutic approach for the treatment not only of rare inherited retinal diseases but also much more common retinal pathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Functional pathway analysis of genes associated with response to treatment for chronic hepatitis C.

    Science.gov (United States)

    Birerdinc, A; Afendy, A; Stepanova, M; Younossi, I; Manyam, G; Baranova, A; Younossi, Z M

    2010-10-01

    Chronic hepatitis C (CH-C) is among the most common causes of chronic liver disease. Approximately 50% of patients with CH-C treated with pegylated interferon-α and ribavirin (PEG-IFN-α + RBV) achieve a sustained virological response (SVR). Several factors such as genotype 1, African American (AA) race, obesity and the absence of an early virological response (EVR) are associated with low SVR. This study elucidates molecular pathways deregulated in patients with CH-C with negative predictors of response to antiviral therapy. Sixty-eight patients with CH-C who underwent a full course of treatment with PEG-IFN-α + RBV were included in the study. Pretreatment blood samples were collected in PAXgene™ RNA tubes. EVR, complete EVR (cEVR), and SVR rates were 76%, 57% and 41%, respectively. Total RNA was extracted from pretreatment peripheral blood mononuclear cells, quantified and used for one-step RT-PCR to profile 154 mRNAs. The expression of mRNAs was normalized with six 'housekeeping' genes. Differentially expressed genes were separated into up and downregulated gene lists according to the presence or absence of a risk factor and subjected to KEGG Pathway Painter which allows high-throughput visualization of the pathway-specific changes in expression profiles. The genes were consolidated into the networks associated with known predictors of response. Before treatment, various genes associated with core components of the JAK/STAT pathway were activated in the cohorts least likely to achieve SVR. Genes related to focal adhesion and TGF-β pathways were activated in some patients with negative predictors of response. Pathway-centred analysis of gene expression profiles from treated patients with CH-C points to the Janus kinase-signal transducers and activators of transcription signalling cascade as the major pathogenetic component responsible for not achieving SVR. In addition, focal adhesion and TGF-β pathways are associated with some predictors of response.

  18. Validation of potential reference genes for qPCR in maize across abiotic stresses, hormone treatments, and tissue types.

    Directory of Open Access Journals (Sweden)

    Yueai Lin

    Full Text Available The reverse transcription quantitative polymerase chain reaction (RT-qPCR is a powerful and widely used technique for the measurement of gene expression. Reference genes, which serve as endogenous controls ensure that the results are accurate and reproducible, are vital for data normalization. To bolster the literature on reference gene selection in maize, ten candidate reference genes, including eight traditionally used internal control genes and two potential candidate genes from our microarray datasets, were evaluated for expression level in maize across abiotic stresses (cold, heat, salinity, and PEG, phytohormone treatments (abscisic acid, salicylic acid, jasmonic acid, ethylene, and gibberellins, and different tissue types. Three analytical software packages, geNorm, NormFinder, and Bestkeeper, were used to assess the stability of reference gene expression. The results revealed that elongation factor 1 alpha (EF1α, tubulin beta (β-TUB, cyclophilin (CYP, and eukaryotic initiation factor 4A (EIF4A were the most reliable reference genes for overall gene expression normalization in maize, while GRP (Glycine-rich RNA-binding protein, GLU1(beta-glucosidase, and UBQ9 (ubiquitin 9 were the least stable and most unsuitable genes. In addition, the suitability of EF1α, β-TUB, and their combination as reference genes was confirmed by validating the expression of WRKY50 in various samples. The current study indicates the appropriate reference genes for the urgent requirement of gene expression normalization in maize across certain abiotic stresses, hormones, and tissue types.

  19. Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-L-carnitine treatment.

    Directory of Open Access Journals (Sweden)

    Giuseppe Federighi

    Full Text Available Acetyl-L-carnitine (ALC is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.

  20. Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-L-carnitine treatment.

    Science.gov (United States)

    Federighi, Giuseppe; Macchi, Monica; Bernardi, Rodolfo; Scuri, Rossana; Brunelli, Marcello; Durante, Mauro; Traina, Giovanna

    2013-01-01

    Acetyl-L-carnitine (ALC) is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.

  1. Antibiotic Resistant Bacteria And Their Associated Resistance Genes in a Conventional Municipal Wastewater Treatment Plant

    KAUST Repository

    Aljassim, Nada I.

    2013-12-01

    With water scarcity as a pressing issue in Saudi Arabia and other Middle Eastern countries, the treatment and reuse of municipal wastewater is increasingly being used as an alternative water source to supplement country water needs. Standards are in place to ensure a safe treated wastewater quality, however they do not regulate pathogenic bacteria and emerging contaminants. Information is lacking on the levels of risk to public health associated with these factors, the efficiency of conventional treatment strategies in removing them, and on wastewater treatment in Saudi Arabia in general. In this study, a municipal wastewater treatment plant in Saudi Arabia is investigated to assess the efficiency of conventional treatment in meeting regulations and removing pathogens and emerging contaminants. The study found pathogenic bacterial genera, antibiotic resistance genes and antibiotic resistant bacteria, many of which were multi-resistant in plant discharges. It was found that although the treatments are able to meet traditional quality guidelines, there remains a risk from the discussed contaminants with wastewater reuse. A deeper understanding of this risk, and suggestions for more thorough guidelines and monitoring are needed.

  2. Ultrasound-Mediated Drug/Gene Delivery in Solid Tumor Treatment

    Directory of Open Access Journals (Sweden)

    Yufeng Zhou

    2013-01-01

    Full Text Available Ultrasound is an emerging modality for drug delivery in chemotherapy. This paper reviews this novel technology by first introducing the designs and characteristics of three classes of drug/gene vehicles, microbubble (including nanoemulsion, liposomes, and micelles. In comparison to conventional free drug, the targeted drug-release and delivery through vessel wall and interstitial space to cancerous cells can be activated and enhanced under certain sonication conditions. In the acoustic field, there are several reactions of these drug vehicles, including hyperthermia, bubble cavitation, sonoporation, and sonodynamics, whose physical properties are illustrated for better understanding of this approach. In vitro and in vivo results are summarized, and future directions are discussed. Altogether, ultrasound-mediated drug/gene delivery under imaging guidance provides a promising option in cancer treatment with enhanced agent release and site specificity and reduced toxicity.

  3. Progress on gene therapy, cell therapy, and pharmacological strategies toward the treatment of oculopharyngeal muscular dystrophy.

    Science.gov (United States)

    Harish, Pradeep; Malerba, Alberto; Dickson, George; Bachtarzi, Houria

    2015-05-01

    Oculopharyngeal muscular dystrophy (OPMD) is a muscle-specific, late-onset degenerative disorder whereby muscles of the eyes (causing ptosis), throat (leading to dysphagia), and limbs (causing proximal limb weakness) are mostly affected. The disease is characterized by a mutation in the poly(A)-binding protein nuclear-1 (PABPN1) gene, resulting in a short GCG expansion in the polyalanine tract of PABPN1 protein. Accumulation of filamentous intranuclear inclusions in affected skeletal muscle cells constitutes the pathological hallmark of OPMD. This review highlights the current translational research advances in the treatment of OPMD. In vitro and in vivo disease models are described. Conventional and experimental therapeutic approaches are discussed with emphasis on novel molecular therapies including the use of intrabodies, gene therapy, and myoblast transfer therapy.

  4. Understanding Autoimmune Mechanisms in Multiple Sclerosis Using Gene Expression Microarrays: Treatment Effect and Cytokine-related Pathways

    Directory of Open Access Journals (Sweden)

    A. Achiron

    2004-01-01

    Full Text Available Multiple sclerosis (MS is a central nervous system disease in which activated autoreactive T-cells invade the blood brain barrier and initiate an inflammatory response that leads to myelin destruction and axonal loss. The etiology of MS, as well as the mechanisms associated with its unexpected onset, the unpredictable clinical course spanning decades, and the different rates of progression leading to disability over time, remains an enigma. We have applied gene expression microarrays technology in peripheral blood mononuclear cells (PBMC to better understand MS pathogenesis and better target treatment approaches. A signature of 535 genes were found to distinguish immunomodulatory treatment effects between 13 treated and 13 untreated MS patients. In addition, the expression pattern of 1109 gene transcripts that were previously reported to significantly differentiate between MS patients and healthy subjects were further analyzed to study the effect of cytokine-related pathways on disease pathogenesis. When relative gene expression for 26 MS patients was compared to 18 healthy controls, 30 genes related to various cytokine-associated pathways were identified. These genes belong to a variety of families such as interleukins, small inducible cytokine subfamily and tumor necrosis factor ligand and receptor. Further analysis disclosed seven cytokine-associated genes within the immunomodulatory treatment signature, and two cytokine-associated genes SCYA4 (small inducible cytokine A4 and FCAR (Fc fragment of IgA, CD89 that were common to both the MS gene expression signature and the immunomodulatory treatment gene expression signature. Our results indicate that cytokine-associated genes are involved in various pathogenic pathways in MS and also related to immunomodulatory treatment effects.

  5. Investigation of Endogenous Retrovirus Sequences in the Neighborhood of Genes Up-regulated in a Neuroblastoma Model after Treatment with Hypoxia-Mimetic Cobalt Chloride.

    Science.gov (United States)

    Brütting, Christine; Narasimhan, Harini; Hoffmann, Frank; Kornhuber, Malte E; Staege, Martin S; Emmer, Alexander

    2018-01-01

    Human endogenous retroviruses (ERVs) have been found to be associated with different diseases, e.g., multiple sclerosis (MS). Most human ERVs integrated in our genome are not competent to replicate and these sequences are presumably silent. However, transcription of human ERVs can be reactivated, e.g., by hypoxia. Interestingly, MS has been linked to hypoxia since decades. As some patterns of demyelination are similar to white matter ischemia, hypoxic damage is discussed. Therefore, we are interested in the association between hypoxia and ERVs. As a model, we used human SH-SY5Y neuroblastoma cells after treatment with the hypoxia-mimetic cobalt chloride and analyzed differences in the gene expression profiles in comparison to untreated cells. The vicinity of up-regulated genes was scanned for endogenous retrovirus-derived sequences. Five genes were found to be strongly up-regulated in SH-SY5Y cells after treatment with cobalt chloride: clusterin, glutathione peroxidase 3, insulin-like growth factor 2, solute carrier family 7 member 11, and neural precursor cell expressed developmentally down-regulated protein 9. In the vicinity of these genes we identified large (>1,000 bp) open reading frames (ORFs). Most of these ORFs showed only low similarities to proteins from retro-transcribing viruses. However, we found very high similarity between retrovirus envelope sequences and a sequence in the vicinity of neural precursor cell expressed developmentally down-regulated protein 9. This sequence encodes the human endogenous retrovirus group FRD member 1, the encoded protein product is called syncytin 2. Transfection of syncytin 2 into the well-characterized Ewing sarcoma cell line A673 was not able to modulate the low immunostimulatory activity of this cell line. Future research is needed to determine whether the identified genes and the human endogenous retrovirus group FRD member 1 might play a role in the etiology of MS.

  6. Multicomponent nanoparticles as nonviral vectors for the treatment of Fabry disease by gene therapy

    Directory of Open Access Journals (Sweden)

    Ruiz de Garibay AP

    2012-10-01

    Full Text Available Aritz Pérez Ruiz de Garibay, Diego Delgado, Ana del Pozo-Rodríguez, María Ángeles Solinís, Alicia Rodríguez GascónPharmacokinetics, Nanotechnology and Gene Therapy Group, Pharmacy Faculty, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, SpainPurpose: Gene-mediated enzyme replacement is a reasonable and highly promising approach for the treatment of Fabry disease (FD. The objective of the present study was to demonstrate the potential applications of solid lipid nanoparticle (SLN-based nonviral vectors for the treatment of FD.Methods: SLNs containing the pR-M10-αGal A plasmid that encodes the α-Galactosidase A (α-Gal A enzyme were prepared and their in vitro transfection efficacy was studied in Hep G2 cells. We also studied the cellular uptake of the vectors and the intracellular disposition of the plasmid.Results: The enzymatic activity of the cells treated with the vectors increased significantly relative to the untreated cells, regardless of the formulation assayed. When the SLNs were prepared with protamine or dextran and protamine, the activity of the α-Gal A enzyme by the transfected Hep G2 cells increased up to 12-fold compared to that of untreated cells.Conclusion: With this work we have revealed in Hep G2 cells the ability of a multicomponent system based on SLNs to act as efficient nonviral vectors to potentially correct low α-Gal A activity levels in FD with gene therapy.Keywords: solid lipid nanoparticles, Fabry disease, nonviral vectors, gene therapy

  7. Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian Tamil Rheumatoid Arthritis patients.

    Science.gov (United States)

    Muralidharan, Niveditha; Gulati, Reena; Misra, Durga Prasanna; Negi, Vir S

    2018-02-01

    The aim of the study was to look for any association of MTR 2756A>G and MTRR 66A>G gene polymorphisms with clinical phenotype, methotrexate (MTX) treatment response, and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). A total of 335 patients with RA were investigated. MTR 2756A>G gene polymorphism was analyzed by PCR-RFLP, and MTRR 66A>G SNP was analyzed by TaqMan 5' nuclease assay. The allele frequencies were compared with HapMap groups. MTR 2756G allele was found to be associated with risk of developing RA. The allele frequencies of MTR 2756A>G and MTRR 66A>G SNPs in controls differed significantly when compared with HapMap groups. Neither of the SNPs influenced the MTX treatment outcome and adverse effects. Neither of the SNPs seems to be associated with MTX treatment outcome and adverse events in South Indian Tamil patients with RA.

  8. Bioaerosol emissions and detection of airborne antibiotic resistance genes from a wastewater treatment plant

    Science.gov (United States)

    Li, Jing; Zhou, Liantong; Zhang, Xiangyu; Xu, Caijia; Dong, Liming; Yao, Maosheng

    2016-01-01

    Air samples from twelve sampling sites (including seven intra-plant sites, one upwind site and four downwind sites) from a wastewater treatment plant (WWTP) in Beijing were collected using a Reuter Centrifugal Sampler High Flow (RCS); and their microbial fractions were studied using culturing and high throughput gene sequence. In addition, the viable (fluorescent) bioaerosol concentrations for 7 intra-plant sites were also monitored for 30 min each using an ultraviolet aerodynamic particle sizer (UV-APS). Both air and water samples collected from the plant were investigated for possible bacterial antibiotic resistance genes and integrons using polymerase chain reaction (PCR) coupled with gel electrophoresis. The results showed that the air near sludge thickening basin was detected to have the highest level of culturable bacterial aerosols (up to 1697 CFU/m3) and fungal aerosols (up to 930 CFU/m3). For most sampling sites, fluorescent peaks were observed at around 3-4 μm, except the office building with a peak at 1.5 μm, with a number concentration level up to 1233-6533 Particles/m3. About 300 unique bacterial species, including human opportunistic pathogens, such as Comamonas Testosteroni and Moraxella Osloensis, were detected from the air samples collected over the biological reaction basin. In addition, we have detected the sul2 gene resistant to cotrimoxazole (also known as septra, bactrim and TMP-SMX) and class 1 integrase gene from the air samples collected from the screen room and the biological reaction basin. Overall, the screen room, sludge thickening basin and biological reaction basin imposed significant microbial exposure risks, including those from airborne antibiotic resistance genes.

  9. Effects of nickel treatment on H3K4 trimethylation and gene expression.

    Directory of Open Access Journals (Sweden)

    Kam-Meng Tchou-Wong

    Full Text Available Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl(2 for 24 hr significantly increased global levels of trimethylated H3K4 (H3K4me3, a transcriptional activating mark that maps to the promoters of transcribed genes. To further understand the potential epigenetic mechanism(s underlying nickel carcinogenesis, we performed genome-wide mapping of H3K4me3 by chromatin immunoprecipitation and direct genome sequencing (ChIP-seq and correlated with transcriptome genome-wide mapping of RNA transcripts by massive parallel sequencing of cDNA (RNA-seq. The effect of NiCl(2 treatment on H3K4me3 peaks within 5,000 bp of transcription start sites (TSSs on a set of genes highly induced by nickel in both A549 cells and human peripheral blood mononuclear cells were analyzed. Nickel exposure increased the level of H3K4 trimethylation in both the promoters and coding regions of several genes including CA9 and NDRG1 that were increased in expression in A549 cells. We have also compared the extent of the H3K4 trimethylation in the absence and presence of formaldehyde crosslinking and observed that crosslinking of chromatin was required to observe H3K4 trimethylation in the coding regions immediately downstream of TSSs of some nickel-induced genes including ADM and IGFBP3. This is the first genome-wide mapping of trimethylated H3K4 in the promoter and coding regions of genes induced after exposure to NiCl(2. This study may provide insights into the epigenetic mechanism(s underlying the carcinogenicity of nickel compounds.

  10. Genes that are involved in high hydrostatic pressure treatments in a Listeria monocytogenes Scott A ctsR deletion mutant

    Science.gov (United States)

    Listeria monocytogenes is a food-borne pathogen of significant threat to public health. High Hydrostatic Pressure (HHP) treatment can be used to control L. monocytogenes in food. The CtsR (class three stress gene repressor) protein negatively regulates the expression of class III heat shock genes....

  11. The association of polymorphisms in 5-fluorouracil metabolism genes with outcome in adjuvant treatment of colorectal cancer

    DEFF Research Database (Denmark)

    Shoaib, Afzal; Gusella, Milena; Jensen, Søren Astrup

    2011-01-01

    The purpose of this study was to investigate whether specific combinations of polymorphisms in 5-fluorouracil (5-FU) metabolism-related genes were associated with outcome in 5-FU-based adjuvant treatment of colorectal cancer....

  12. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  13. Induction of specific Escherichia coli genes by sublethal treatments with alkylating agents.

    OpenAIRE

    Volkert, M R; Nguyen, D C

    1984-01-01

    Fusions of the lac operon to genes induced by treatment with sublethal levels of alkylating agents have been selected from random insertions of the Mu-dl(ApRlac) phage by screening for induction of beta-galactosidase activity in the presence of methyl methanesulfonate. Genetic analysis reveals that these fusions resulted from insertion of Mu-dl(ApRlac) into two regions of the chromosome. One region (aidA) is near his and, based on phenotypic effects, appears to represent insertion into the al...

  14. Removal of bacterial cells, antibiotic resistance genes and integrase genes by on-site hospital wastewater treatment plants: surveillance of treated hospital effluent quality

    KAUST Repository

    Timraz, Kenda Hussain Hassan

    2016-12-15

    This study aims to evaluate the removal efficiency of microbial contaminants, including total cell counts, antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs, e.g. tetO, tetZ, sul1 and sul2) and integrase genes (e.g. intl1 and intl2), by wastewater treatment plants (WWTPs) operated on-site of two hospitals (i.e., SH WWTP and IH WWTP). Both SH and IH WWTPs utilize the conventional activated sludge process but differences in the removal efficiencies were observed. Over the 2 week sampling period, IH WWTP outperformed SH WWTP, and achieved an approximate 0.388 to 2.49-log log removal values (LRVs) for total cell counts compared to the 0.010 to 0.162-log removal in SH WWTP. Although ARB were present in the hospital influent, the treatment process of both hospitals effectively removed ARB from most of the effluent samples. In instances where ARB were recovered in the effluent, none of the viable isolates were identified to be opportunistic pathogenic species based on 16S rRNA gene sequencing. However, sul1 and intl1 genes remained detectable at up to 105 copies per mL or 8 x 10(-1) copies per 16S rRNA gene in the treated effluent, with an LRV of less than 1.2. When the treated effluent is discharged from hospital WWTPs into the public sewer for further treatment as per requirement in many countries, the detected amount of ARGs and integrase genes in the hospital effluent can become a potential source of horizontal gene dissemination in the municipal WWTP. Proper on-site wastewater treatment and surveillance of the effluent quality for emerging contaminants are therefore highly recommended.

  15. Radioactive cDNA microarray (II): Gene expression profiling of antidepressant treatment by human cDNA microarray

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hye; Kang, Rhee Hun; Ham, Byung Joo; Lee, Min Su; Shin, Kyung Ho; Choe, Jae Gol; Kim, Meyoung Kon [College of Medicine, Univ. of Korea, Seoul (Korea, Republic of)

    2003-07-01

    Major depressive disorder is a prevalent psychiatric disorder in primary care, associated with impaired patient functioning and well-being. Fluoxetine is a selective serotonin-reuptake inhibitors (SSRIs) and is a commonly prescribed antidepressant compound. Its action is primarily attributed to selective inhibition of the reuptake of serotonin (5-hydroxytryptamine) in the central nervous system. Objectives ; the aims of this study were two-fold: (1) to determine the usefulness for investigation of the transcription profiles in depression patients, and (2) to assess the differences in gene expression profiles between positive response group and negative response groups by fluoxetine treatment. This study included 53 patients with major depression (26 in positive response group with antidepressant treatment, 27 in negative response group with antidepressant treatment), and 53 healthy controls. To examine the difference of gene expression profile in depression patients, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 genes in total. Using 33p-labeled probes, this method provided highly sensitive gene expression profiles including brain receptors, drug metabolism, and cellular signaling. Gene transcription profiles were classified into several categories in accordance with the antidepressant gene-regulation. The gene profiles were significantly up-(22 genes) and down-(16 genes) regulated in the positive response group when compared to the control group. Also, in the negative response group, 35 genes were up-regulated and 8 genes were down-regulated when compared to the control group. Consequently, we demonstrated that radioactive human cDNA microarray is highly likely to be an efficient technology for evaluating the gene regulation of antidepressants, such as selective serotonin-reuptake inhibitors (SSRIs), by using high-throughput biotechnology.

  16. Radioactive cDNA microarray (II): Gene expression profiling of antidepressant treatment by human cDNA microarray

    International Nuclear Information System (INIS)

    Lee, Ji Hye; Kang, Rhee Hun; Ham, Byung Joo; Lee, Min Su; Shin, Kyung Ho; Choe, Jae Gol; Kim, Meyoung Kon

    2003-01-01

    Major depressive disorder is a prevalent psychiatric disorder in primary care, associated with impaired patient functioning and well-being. Fluoxetine is a selective serotonin-reuptake inhibitors (SSRIs) and is a commonly prescribed antidepressant compound. Its action is primarily attributed to selective inhibition of the reuptake of serotonin (5-hydroxytryptamine) in the central nervous system. Objectives ; the aims of this study were two-fold: (1) to determine the usefulness for investigation of the transcription profiles in depression patients, and (2) to assess the differences in gene expression profiles between positive response group and negative response groups by fluoxetine treatment. This study included 53 patients with major depression (26 in positive response group with antidepressant treatment, 27 in negative response group with antidepressant treatment), and 53 healthy controls. To examine the difference of gene expression profile in depression patients, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 genes in total. Using 33p-labeled probes, this method provided highly sensitive gene expression profiles including brain receptors, drug metabolism, and cellular signaling. Gene transcription profiles were classified into several categories in accordance with the antidepressant gene-regulation. The gene profiles were significantly up-(22 genes) and down-(16 genes) regulated in the positive response group when compared to the control group. Also, in the negative response group, 35 genes were up-regulated and 8 genes were down-regulated when compared to the control group. Consequently, we demonstrated that radioactive human cDNA microarray is highly likely to be an efficient technology for evaluating the gene regulation of antidepressants, such as selective serotonin-reuptake inhibitors (SSRIs), by using high-throughput biotechnology

  17. Brugia malayi gene expression in response to the targeting of the Wolbachia endosymbiont by tetracycline treatment.

    Directory of Open Access Journals (Sweden)

    Elodie Ghedin

    2009-10-01

    Full Text Available Brugia malayi, like most human filarial parasite species, harbors an endosymbiotic bacterium of the genus Wolbachia. Elimination of the endosymbiont leads to sterilization of the adult female. Previous biochemical and genetic studies have established that communication with its endobacterium is essential for survival of the worm.We used electron microscopy to examine the effects of antibiotic treatment on Wolbachia cell structure. We have also used microarray and quantitative RT-PCR analyses to examine the regulation of the B. malayi transcripts altered in response to the anti-Wolbachia treatment. Microscopy of worms taken from animals treated with tetracycline for 14 and 21 days (14 d and 21 d demonstrated substantial morphologic effects on the Wolbachia endobacterium by 14 d and complete degeneration of the endobacterial structures by 21 d. We observed upregulation of transcripts primarily encoding proteins involved in amino acid synthesis and protein translation, and downregulation of transcripts involved in cuticle biosynthesis after both 7 d and 14 d of treatment. In worms exposed to tetracycline in culture, substantial effects on endobacteria morphology were evident by day 3, and extensive death of the endobacteria was observed by day 5. In a detailed examination of the expression kinetics of selected signaling genes carried out on such cultured worms, a bimodal pattern of regulation was observed. The selected genes were upregulated during the early phase of antibiotic treatment and quickly downregulated in the following days. These same genes were upregulated once more at 6 days post-treatment.Upregulation of protein translation and amino acid synthesis may indicate a generalized stress response induced in B. malayi due to a shortage of essential nutrients/factors that are otherwise supplied by Wolbachia. Downregulation of transcripts involved in cuticle biosynthesis perhaps reflects a disruption in the normal embryogenic program. This is

  18. Molecular cloning and functional characterization of a mouse gene upregulated by lipopolysaccharide treatment reveals alternative splicing

    Energy Technology Data Exchange (ETDEWEB)

    Du, Kejun; Chen, Yaoming; Dai, Zongming; Bi, Yuan; Cai, Tongjian [Department of Occupational and Environmental Health, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China); Hou, Lichao [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China); Chai, Yubo; Song, Qinghe; Chen, Sumin [Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health, Fourth Military Medical University, Xi' an 710032, Shaanxi Province (China)

    2010-01-01

    Treatment of mouse cells with lipopolysaccharide (LPS) potently initiates an inflammatory response, but the underlying mechanisms are unclear. We therefore sought to characterize cDNA sequences of a new mouse LPS-responsive gene, and to evaluate the effects of MLrg. Full-length cDNAs were obtained from LPS-treated NIH3T3 cells. We report that the MLrg gene produces two alternative splice products (GenBank Accession Nos. (DQ316984) and (DQ320011)), respectively, encoding MLrgW and MLrgS polypeptides. Both proteins contain zinc finger and leucine zipper domains and are thus potential regulators of transcription. Expression of MLrgW and MLrgS were robustly upregulated following LPS treatment, and the proteins were localized predominantly in the nuclear membrane and cytoplasm. In stable transfectants over-expressing MLrgW the proportion of cells in G1 phase was significantly reduced, while in cells over-expressing MLrgS the proportion of cells in G2 was significantly increased; both proteins are thus potential regulators of cell cycle progression. Upregulation of MLrgW and MLrgS may be an important component of the LPS inflammatory pathway and of the host response to infection with GNB.

  19. Systematic Evaluation of Promising Clinical Trials-Gene Silencing for the Treatment of Glioblastoma.

    Science.gov (United States)

    Karaarslan, Numan; Yilmaz, Ibrahim; Ozbek, Hanefi; Caliskan, Tezcan; Topuk, Savas; Sirin, Duygu Yasar; Ates, Ozkan

    2018-04-06

    The aim of this study was to systematically investigate the role of artificial small interfering RNA (siRNA) molecules in glioblastoma treatment and to give a detailed overview of the literature concerning studies performed in this field worldwide in the last 31 years. Articles about clinical trials conducted between December 1, 1949 and November 8, 2017, were identified from the Cochrane Collaboration, the Cochrane Library, Ovid MEDLINE, ProQuest, the National Library of Medicine, and PubMed electronic databases, using the terms "post transcriptional gene silencing," "small interfering RNA," "siRNA," and "glioblastoma," either individually or combined (\\"OR\\" and \\"AND"), without language and country restrictions. Articles that met the examination criteria were included in the study. After descriptive statistical evaluation, the results were reported in frequency (%). After scanning 2.752 articles, five articles were found that met the research criteria. Examination of full texts of the five identified articles provided no sufficient evidence for research conducted with regard to the use of gene silencing via siRNAs in glioblastoma treatment. To be able to evaluate the clinical use of siRNAs, there is an urgent need for in-vivo studies and for trials with randomized, controlled, and clinical designs that provide long-term functional outcomes.

  20. Gene x environment interactions in conduct disorder: Implications for future treatments.

    Science.gov (United States)

    Holz, Nathalie E; Zohsel, Katrin; Laucht, Manfred; Banaschewski, Tobias; Hohmann, Sarah; Brandeis, Daniel

    2016-08-18

    Conduct disorder (CD) causes high financial and social costs, not only in affected families but across society, with only moderately effective treatments so far. There is consensus that CD is likely caused by the convergence of many different factors, including genetic and adverse environmental factors. There is ample evidence of gene-environment interactions in the etiology of CD on a behavioral level regarding genetically sensitive designs and candidate gene-driven approaches, most prominently and consistently represented by MAOA. However, conclusive indications of causal GxE patterns are largely lacking. Inconsistent findings, lack of replication and methodological limitations remain a major challenge. Likewise, research addressing the identification of affected brain pathways which reflect plausible biological mechanisms underlying GxE is still very sparse. Future research will have to take multilevel approaches into account, which combine genetic, environmental, epigenetic, personality, neural and hormone perspectives. A better understanding of relevant GxE patterns in the etiology of CD might enable researchers to design customized treatment options (e.g. biofeedback interventions) for specific subgroups of patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Alterations in Gene Expression in Depression: Prospects for Personalize Patient Treatment.

    Science.gov (United States)

    Donev, Rossen; Alawam, Khaled

    2015-01-01

    The number of people around the world suffering from depression has dramatically increased in last few decades. It has been predicted that by 2020 depression will become the second most common cause of disability. Furthermore, depression is often misdiagnosed and confused with other psychiatric disorders showing similar symptoms, i.e., anxiety and bipolar disorder, due to the fact that diagnosing is often carried out by medical workers who are not psychiatrically trained. These facts prompt us to prepare this review which focuses on alterations in gene expression in depression. We believe that an in-depth knowledge of molecular bases of behavior in depression and other mood disorders would be of a great benefit for the correct diagnosing of these disorders, as well as for prescribing a treatment that best suits each individual depending on expression alterations in depression-related genes. Therefore, the main aim of this review is to promote further translational research on the biochemistry of mood disorders and take the results further for the design of new targeted therapeutics that can be used for personalized treatment with minimal adverse effects. © 2015 Elsevier Inc. All rights reserved.

  2. Call Centre- Computer Telephone Integration

    Directory of Open Access Journals (Sweden)

    Dražen Kovačević

    2012-10-01

    Full Text Available Call centre largely came into being as a result of consumerneeds converging with enabling technology- and by the companiesrecognising the revenue opportunities generated by meetingthose needs thereby increasing customer satisfaction. Regardlessof the specific application or activity of a Call centre, customersatisfaction with the interaction is critical to the revenuegenerated or protected by the Call centre. Physical(v, Call centreset up is a place that includes computer, telephone and supervisorstation. Call centre can be available 24 hours a day - whenthe customer wants to make a purchase, needs information, orsimply wishes to register a complaint.

  3. GSTM1 Gene Expression Correlates to Leiomyoma Volume Regression in Response to Mifepristone Treatment

    Science.gov (United States)

    Engman, Mikael; Varghese, Suby; Lagerstedt Robinson, Kristina; Malmgren, Helena; Hammarsjö, Anna; Byström, Birgitta; L Lalitkumar, Parameswaran Grace; Gemzell-Danielsson, Kristina

    2013-01-01

    Progesterone receptor modulators, such as mifepristone are useful and well tolerated in reducing leiomyoma volume although with large individual variation. The objective of this study was to investigate the molecular basis for the observed leiomyoma volume reduction, in response to mifepristone treatment and explore a possible molecular marker for the selective usage of mifepristone in leiomyoma patients. Premenopausal women (N = 14) were treated with mifepristone 50 mg, every other day for 12 weeks prior to surgery. Women were arbitrarily sub-grouped as good (N = 4), poor (N = 4) responders to treatment or intermediate respondents (N = 3). Total RNA was extracted from leiomyoma tissue, after surgical removal of the tumour and the differential expression of genes were analysed by microarray. The results were analysed using Ingenuity Pathway Analysis software. The glutathione pathway was the most significantly altered canonical pathway in which the glutathione-s transferase mu 1 (GSTM1) gene was significantly over expressed (+8.03 folds) among the good responders compared to non responders. This was further confirmed by Real time PCR (p = 0.024). Correlation of immunoreactive scores (IRS) for GSTM1 accumulation in leiomyoma tissue was seen with base line volume change of leiomyoma R = −0.8 (p = 0.011). Furthermore the accumulation of protein GSTM1 analysed by Western Blot correlated significantly with the percentual leiomyoma volume change R = −0.82 (p = 0.004). Deletion of the GSTM1 gene in leiomyoma biopsies was found in 50% of the mifepristone treated cases, with lower presence of the GSTM1 protein. The findings support a significant role for GSTM1 in leiomyoma volume reduction induced by mifepristone and explain the observed individual variation in this response. Furthermore the finding could be useful to further explore GSTM1 as a biomarker for tailoring medical treatment of uterine leiomyomas for optimizing the response

  4. Prevalence and proliferation of antibiotic resistance genes in two municipal wastewater treatment plants.

    Science.gov (United States)

    Mao, Daqing; Yu, Shuai; Rysz, Michal; Luo, Yi; Yang, Fengxia; Li, Fengxiang; Hou, Jie; Mu, Quanhua; Alvarez, P J J

    2015-11-15

    The propagation of antibiotic resistance genes (ARGs) is an emerging health concern worldwide. Thus, it is important to understand and mitigate their occurrence in different systems. In this study, 30 ARGs that confer resistance to tetracyclines, sulfonamides, quinolones or macrolides were detected in two activated sludge wastewater treatment plants (WWTPs) in northern China. Bacteria harboring ARGs persisted through all treatment units, and survived disinfection by chlorination in greater percentages than total Bacteria (assessed by 16S rRNA genes). Although the absolute abundances of ARGs were reduced from the raw influent to the effluent by 89.0%-99.8%, considerable ARG levels [(1.0 ± 0.2) × 10(3) to (9.5 ± 1.8) × 10(5) copies/mL)] were found in WWTP effluent samples. ARGs were concentrated in the waste sludge (through settling of bacteria and sludge dewatering) at (1.5 ± 2.3) × 10(9) to (2.2 ± 2.8) × 10(11) copies/g dry weight. Twelve ARGs (tetA, tetB, tetE, tetG, tetH, tetS, tetT, tetX, sul1, sul2, qnrB, ermC) were discharged through the dewatered sludge and plant effluent at higher rates than influent values, indicating overall proliferation of resistant bacteria. Significant antibiotic concentrations (2%-50% of raw influent concentrations) remained throughout all treatment units. This apparently contributed selective pressure for ARG replication since the relative abundance of resistant bacteria (assessed by ARG/16S rRNA gene ratios) was significantly correlated to the corresponding effluent antibiotic concentrations. Similarly, the concentrations of various heavy metals (which induce a similar bacterial resistance mechanism as antibiotics - efflux pumps) were also correlated to the enrichment of some ARGs. Thus, curtailing the release of antibiotics and heavy metals to sewage systems (or enhancing their removal in pre-treatment units) may alleviate their selective pressure and mitigate ARG proliferation in WWTPs. Copyright © 2015 Elsevier Ltd. All

  5. Preclinical evaluation of gene delivery methods for the treatment of loco-regional disease in breast cancer.

    LENUS (Irish Health Repository)

    Rajendran, Simon

    2011-04-01

    Preclinical results with various gene therapy strategies indicate significant potential for new cancer treatments. However, many therapeutics fail at clinical trial, often due to differences in tissue physiology between animal models and humans, and tumor phenotype variation. Clinical data relevant to treatment strategies may be generated prior to clinical trial through experimentation using intact patient tissue ex vivo. We developed a novel tumor slice model culture system that is universally applicable to gene delivery methods, using a realtime luminescence detection method to assess gene delivery. Methods investigated include viruses (adenovirus [Ad] and adeno-associated virus), lipofection, ultrasound (US), electroporation and naked DNA. Viability and tumor populations within the slices were well maintained for seven days, and gene delivery was qualitatively and quantitatively examinable for all vectors. Ad was the most efficient gene delivery vector with transduction efficiency >50%. US proved the optimal non-viral gene delivery method in human tumor slices. The nature of the ex vivo culture system permitted examination of specific elements. Parameters shown to diminish Ad gene delivery included blood, regions of low viability and secondary disease. US gene delivery was significantly reduced by blood and skin, while tissue hyperthermia improved gene delivery. US achieved improved efficacy for secondary disease. The ex vivo model was also suitable for examination of tissue-specific effects on vector expression, with Ad expression mediated by the CXCR4 promoter shown to provide a tumor selective advantage over the ubiquitously active cytomegalovirus promoter. In conclusion, this is the first study incorporating patient tissue models in comparing gene delivery from various vectors, providing knowledge on cell-type specificity and examining the crucial biological factors determining successful gene delivery. The results highlight the importance of in

  6. Preclinical evaluation of gene delivery methods for the treatment of loco-regional disease in breast cancer.

    LENUS (Irish Health Repository)

    Rajendran, Simon

    2012-01-31

    Preclinical results with various gene therapy strategies indicate significant potential for new cancer treatments. However, many therapeutics fail at clinical trial, often due to differences in tissue physiology between animal models and humans, and tumor phenotype variation. Clinical data relevant to treatment strategies may be generated prior to clinical trial through experimentation using intact patient tissue ex vivo. We developed a novel tumor slice model culture system that is universally applicable to gene delivery methods, using a realtime luminescence detection method to assess gene delivery. Methods investigated include viruses (adenovirus [Ad] and adeno-associated virus), lipofection, ultrasound (US), electroporation and naked DNA. Viability and tumor populations within the slices were well maintained for seven days, and gene delivery was qualitatively and quantitatively examinable for all vectors. Ad was the most efficient gene delivery vector with transduction efficiency >50%. US proved the optimal non-viral gene delivery method in human tumor slices. The nature of the ex vivo culture system permitted examination of specific elements. Parameters shown to diminish Ad gene delivery included blood, regions of low viability and secondary disease. US gene delivery was significantly reduced by blood and skin, while tissue hyperthermia improved gene delivery. US achieved improved efficacy for secondary disease. The ex vivo model was also suitable for examination of tissue-specific effects on vector expression, with Ad expression mediated by the CXCR4 promoter shown to provide a tumor selective advantage over the ubiquitously active cytomegalovirus promoter. In conclusion, this is the first study incorporating patient tissue models in comparing gene delivery from various vectors, providing knowledge on cell-type specificity and examining the crucial biological factors determining successful gene delivery. The results highlight the importance of in

  7. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment

    Science.gov (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  8. An ethanolic extract of Artemisia dracunculus L. regulates gene expression of ubiquitin-proteasome system enzymes in skeletal muscle: potential role in the treatment of sarcopenic obesity.

    Science.gov (United States)

    Kirk-Ballard, Heather; Kilroy, Gail; Day, Britton C; Wang, Zhong Q; Ribnicky, David M; Cefalu, William T; Floyd, Z Elizabeth

    2014-01-01

    Obesity is linked to insulin resistance, a primary component of metabolic syndrome and type 2 diabetes. The problem of obesity-related insulin resistance is compounded when age-related skeletal muscle loss, called sarcopenia, occurs with obesity. Skeletal muscle loss results from elevated levels of protein degradation and prevention of obesity-related sarcopenic muscle loss will depend on strategies that target pathways involved in protein degradation. An extract from Artemisia dracunculus, termed PMI 5011, improves insulin signaling and increases skeletal muscle myofiber size in a rodent model of obesity-related insulin resistance. The aim of this study was to examine the effect of PMI 5011 on the ubiquitin-proteasome system, a central regulator of muscle protein degradation. Gastrocnemius and vastus lateralis skeletal muscle was obtained from KK-A(y) obese diabetic mice fed a control or 1% (w/w) PMI 5011-supplemented diet. Regulation of genes encoding enzymes of the ubiquitin-proteasome system was determined using real-time quantitative reverse transcriptase polymerase chain reaction. Although MuRF-1 ubiquitin ligase gene expression is consistently down-regulated in skeletal muscle, atrogin-1, Fbxo40, and Traf6 expression is differentially regulated by PMI 5011. Genes encoding other enzymes of the ubiquitin-proteasome system ranging from ubiquitin to ubiquitin-specific proteases are also regulated by PMI 5011. Additionally, expression of the gene encoding the microtubule-associated protein-1 light chain 3 (LC3), a ubiquitin-like protein pivotal to autophagy-mediated protein degradation, is down-regulated by PMI 5011 in the vastus lateralis. PMI 5011 alters the gene expression of ubiquitin-proteasome system enzymes that are essential regulators of skeletal muscle mass. This suggests that PMI 5011 has therapeutic potential in the treatment of obesity-linked sarcopenia by regulating ubiquitin-proteasome-mediated protein degradation. Copyright © 2014 Elsevier Inc

  9. Evaluation of the reliability and durability of some chemical treatments proposed for consolidation of so called-marble decoration used in 19th century cemetery (Hosh Al Basha, Cairo, Egypt

    Directory of Open Access Journals (Sweden)

    dr.Amany Bakr

    2011-01-01

    Full Text Available The conservation of so called-marble ornaments is a very important cultural heritage issue, since this kind of decoration was widely use for casing stone buildings during 19th and beginning of 20th centuries in Egypt. The wide variation of materials and techniques used for imitating natural marble is a really big challenge for conservators. Actually most of so called- marble decorations are subjected to several degradation agents which can lead to the loss of material cohesion mostly caused by alteration phenomena that often produce the detachment of large areas of imitated marble ornaments. Surface consolidation, directed to achieve cohesion and stability, is based on the use of materials with aggregating properties. This study started with characterization of the yellow veined imitated marble stucco used in Hosh Al Basha courtyard dating back to Mohammed Ali's family period (1805-1952 in Egypt. The imitated marble stucco consists of two main layers. The outer finishing layer, yellow paint veined with brown color, composed mainly of yellow zincite (ZnO. Gypsum (CaSO4.2H2O, halite (NaCl and calcite (CaCo3 were detected in this layer also. The mineral composition of the subsurface layer (prime layer shows the presence of gypsum (major mineral, zincite (ZnO, anhydrite (CaSO4 and halite (NaCl were also detected. Two products (Paraloid B-72 and SILRES® BS OH 100 were selected to evaluate their efficiency for consolidation treatments of imitated marble stucco. The selected products were tested under thermal ageing. Polarizing microscope (PLM, scanning electron microscopy with the energy dispersive X-ray (SEM-EDX, X-ray diffraction (XRD, Fourier-transform infrared spectroscopy (FTIR-ATR and colorimetric measurements were used in performing the study

  10. Expression responses of five cold tolerant related genes to two temperature dropping treatments in sea cucumber Apostichopus japonicus

    Science.gov (United States)

    Li, Chengze; Chang, Yaqing; Pang, Zhenguo; Ding, Jun; Ji, Nanjing

    2015-03-01

    Environmental conditions, including ambient temperature, play important roles in survival, growth development, and reproduction of the Japanese sea cucumber, Apostichopus japonicus. Low temperatures result in slowed growth and skin ulceration disease. In a previous study, we investigated the effect of low temperature on gene expression profiles in A. japonicus by suppression subtractive hybridization (SSH). Genes encoding Ferritin, Lysozyme, Hsp70, gp96, and AjToll were selected from a subtracted cDNA library of A. japonicus under acute cold stress. The transcriptional expression profiles of these genes were investigated in different tissues (coelomocyte, respiratory tree, intestine, longitudinal muscle) after exposure to acute and mild temperature dropping treatments. The results show that (1) the five cold-tolerance-related genes were found in all four tissues and the highest mRNA levels were observed in coelomocyte and respiratory tree; (2) under the temperature dropping treatments, three types of transcriptional regulation patterns were observed: primary suppression followed by up-regulation at -2°C, suppressed expression throughout the two treatments, and more rarely an initial stimulation followed by suppression; and (3) gene expression suppression was more severe under acute temperature dropping than under mild temperature dropping treatment. The five cold-tolerance-related genes that were distributed mainly in coelomocyte and respiratory tissues were generally down-regulated by low temperature stress but an inverse up-regulation event was found at the extreme temperature (-2°C).

  11. Acupuncture as Treatment of Hot Flashes and the Possible Role of Calcitonin Gene-Related Peptide

    Directory of Open Access Journals (Sweden)

    Anna-Clara E. Spetz Holm

    2012-01-01

    Full Text Available The mechanisms behind hot flashes in menopausal women are not fully understood. The flashes in women are probably preceded by and actually initiated by a sudden downward shift in the set point for the core body temperature in the thermoregulatory center that is affected by sex steroids, β-endorphins, and other central neurotransmitters. Treatments that influence these factors may be expected to reduce hot flashes. Since therapy with sex steroids for hot flashes has appeared to cause a number of side effects and risks and women with hot flashes and breast cancer as well as men with prostate cancer and hot flashes are prevented from sex steroid therapy there is a great need for alternative therapies. Acupuncture affecting the opioid system has been suggested as an alternative treatment option for hot flashes in menopausal women and castrated men. The heat loss during hot flashes may be mediated by the potent vasodilator and sweat gland activator calcitonin gene-related peptide (CGRP the concentration of which increases in plasma during flashes in menopausal women and, according to one study, in castrated men with flushes. There is also evidence for connections between the opioid system and the release of CGRP. In this paper we discuss acupuncture as a treatment alternative for hot flashes and the role of CGRP in this context.

  12. Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles.

    Science.gov (United States)

    Peccate, Cécile; Mollard, Amédée; Le Hir, Maëva; Julien, Laura; McClorey, Graham; Jarmin, Susan; Le Heron, Anita; Dickson, George; Benkhelifa-Ziyyat, Sofia; Piétri-Rouxel, France; Wood, Matthew J; Voit, Thomas; Lorain, Stéphanie

    2016-08-15

    In preclinical models for Duchenne muscular dystrophy, dystrophin restoration during adeno-associated virus (AAV)-U7-mediated exon-skipping therapy was shown to decrease drastically after six months in treated muscles. This decline in efficacy is strongly correlated with the loss of the therapeutic AAV genomes, probably due to alterations of the dystrophic myofiber membranes. To improve the membrane integrity of the dystrophic myofibers at the time of AAV-U7 injection, mdx muscles were pre-treated with a single dose of the peptide-phosphorodiamidate morpholino (PPMO) antisense oligonucleotides that induced temporary dystrophin expression at the sarcolemma. The PPMO pre-treatment allowed efficient maintenance of AAV genomes in mdx muscles and enhanced the AAV-U7 therapy effect with a ten-fold increase of the protein level after 6 months. PPMO pre-treatment was also beneficial to AAV-mediated gene therapy with transfer of micro-dystrophin cDNA into muscles. Therefore, avoiding vector genome loss after AAV injection by PPMO pre-treatment would allow efficient long-term restoration of dystrophin and the use of lower and thus safer vector doses for Duchenne patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Gene Expression in Hair Follicle Dermal Papilla Cells after Treatment with Stanozolol

    Directory of Open Access Journals (Sweden)

    M. Reiter

    2009-01-01

    Full Text Available Doping with anabolic agents is a topic in sports where strength is crucial, e.g. sprinting, weight lifting and many more. Testosterone and its functional analogs are the drugs of choice taken as pills, creams, tape or injections to increase muscle mass and body performance, and to reduce body fat. Stanozolol (17β-hydroxy-17α-methyl-5α-androst- 2-eno[3,2c]pyrazol is a testosterone analogue with the same anabolic effect like testosterone but its ring structure makes it possible to take it orally. Therefore, stanozolol is one of the most frequently used anabolic steroids. Common verification methods for anabolic drugs exist, identifying the chemicals in tissues, like hair or blood samples. The idea of this feasibility study was to search for specific gene expression regulations induced by stanozolol to identify the possible influence of the synthetically hormone on different metabolic pathways. Finding biomarkers for anabolic drugs could be supportive of the existing methods and an additional proof for illegal drug abuse. In two separate cell cultures, human HFDPC (hair follicle dermal papilla cells from a female and a male donor were treated with stanozolol. In the female cell culture treatment concentrations of 0 nM (control, 1 nM, 10 nM and 100 nM were chosen. Cells were taken 0 h, 6 h, 24 h and 48 h after stimulation and totalRNA was extracted. Learning from the results of the pilot experiment, the male cell culture was treated in 10 nM and 100 nM concentrations and taken after 0 h, 6 h, 24 h and 72 h. Using quantitative real-time RT-PCR expression of characteristics of different target genes were analysed. Totally 13 genes were selected according to their functionality by screening the actual literature and composed to functional groups: factors of apoptosis regulation were Fas Ligand (FasL, its receptor (FasR, Caspase 8 and Bcl-2. Androgen receptor (AR and both estrogen receptors (ERα, ERβ were summarized in the steroid receptor group

  14. Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment

    Directory of Open Access Journals (Sweden)

    Li Qingdi

    2012-06-01

    Full Text Available Abstract Background The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The present study aimed to identify reference genes as internal controls for gene expression studies by RT-qPCR in azole-stimulated Candida glabrata. Results The expression stability of 16 reference genes under fluconazole stress was evaluated using fold change and standard deviation computations with the hkgFinder tool. Our data revealed that the mRNA expression levels of three ribosomal RNAs (RDN5.8, RDN18, and RDN25 remained stable in response to fluconazole, while PGK1, UBC7, and UBC13 mRNAs showed only approximately 2.9-, 3.0-, and 2.5-fold induction by azole, respectively. By contrast, mRNA levels of the other 10 reference genes (ACT1, EF1α, GAPDH, PPIA, RPL2A, RPL10, RPL13A, SDHA, TUB1, and UBC4 were dramatically increased in C. glabrata following antifungal treatment, exhibiting changes ranging from 4.5- to 32.7-fold. We also assessed the expression stability of these reference genes using the 2-ΔΔCT method and three other software packages. The stability rankings of the reference genes by geNorm and the 2-ΔΔCT method were identical to those by hkgFinder, whereas the stability rankings by BestKeeper and NormFinder were notably different. We then validated the suitability of six candidate reference genes (ACT1, PGK1, RDN5.8, RDN18, UBC7, and UBC13 as internal controls for ten target genes in this system using the comparative CT method. Our validation experiments passed for all six reference genes analyzed except RDN18, where the amplification efficiency of RDN18 was different from that of the ten target genes. Finally, we demonstrated that the relative quantification of target gene expression varied according to the endogenous control used, highlighting the importance of the choice of internal controls in such

  15. Developmental programming: gestational bisphenol-A treatment alters trajectory of fetal ovarian gene expression.

    Science.gov (United States)

    Veiga-Lopez, Almudena; Luense, Lacey J; Christenson, Lane K; Padmanabhan, Vasantha

    2013-05-01

    Bisphenol-A (BPA), a ubiquitous environmental endocrine disrupting chemical, is a component of polycarbonate plastic and epoxy resins. Because of its estrogenic properties, there is increasing concern relative to risks from exposures during critical periods of early organ differentiation. Prenatal BPA treatment in sheep results in low birth weight, hypergonadotropism, and ovarian cycle disruptions. This study tested the hypothesis that gestational exposure to bisphenol A, at an environmentally relevant dose, induces early perturbations in the ovarian transcriptome (mRNA and microRNA). Pregnant Suffolk ewes were treated with bisphenol A (0.5 mg/kg, sc, daily, produced ∼2.6 ng/mL of unconjugated BPA in umbilical arterial samples of BPA treated fetuses approaching median levels of BPA measured in maternal circulation) from days 30 to 90 of gestation. Expression of steroidogenic enzymes, steroid/gonadotropin receptors, key ovarian regulators, and microRNA biogenesis components were measured by RT-PCR using RNA derived from fetal ovaries collected on gestational days 65 and 90. An age-dependent effect was evident in most steroidogenic enzymes, steroid receptors, and key ovarian regulators. Prenatal BPA increased Cyp19 and 5α-reductase expression in day 65, but not day 90, ovaries. Fetal ovarian microRNA expression was altered by prenatal BPA with 45 down-regulated (>1.5-fold) at day 65 and 11 down-regulated at day 90 of gestation. These included microRNAs targeting Sry-related high-mobility-group box (SOX) family genes, kit ligand, and insulin-related genes. The results of this study demonstrate that exposure to BPA at an environmentally relevant dose alters fetal ovarian steroidogenic gene and microRNA expression of relevance to gonadal differentiation, folliculogenesis, and insulin homeostasis.

  16. Differential expression of the klf6 tumor suppressor gene upon cell damaging treatments in cancer cells

    International Nuclear Information System (INIS)

    Gehrau, Ricardo C.; D'Astolfo, Diego S.; Andreoli, Veronica; Bocco, Jose L.; Koritschoner, Nicolas P.

    2011-01-01

    The mammalian Krueppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Also, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several cell-damaging stimuli. DNA damaging agents at lethal concentrations induce a p53-independent down-regulation of the klf6 gene. To investigate the impact of external stimuli on human klf6 gene expression, its mRNA level was analyzed using a cancer cell line profiling array system, consisting in an assortment of immobilized cDNAs from multiple cell lines treated with several cell-damaging agents at growth inhibitory concentrations (IC 50 ). Cell-damaging agents affected the klf6 expression in 62% of the cDNA samples, though the expression pattern was not dependent on the cell origin type. Interestingly, significant differences (p 50 concentrations of physical and chemical stimuli in a p53-dependent manner. Most of these agents are frequently used in cancer therapy. Induction of klf6 expression in the absence of functional p53 directly correlates with cell death triggered by these compounds, whereas it is down-regulated in p53+/+ cells. Hence, klf6 expression level could represent a valuable marker for the efficiency of cell death upon cancer treatment.

  17. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury.

    Science.gov (United States)

    Pachori, Alok S; Melo, Luis G; Hart, Melanie L; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D; Stahl, Gregory L; Pratt, Richard E; Dzau, Victor J

    2004-08-17

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  18. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

    Science.gov (United States)

    Pachori, Alok S.; Melo, Luis G.; Hart, Melanie L.; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D.; Stahl, Gregory L.; Pratt, Richard E.; Dzau, Victor J.

    2004-08-01

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  19. A searchable cross-platform gene expression database reveals connections between drug treatments and disease

    Directory of Open Access Journals (Sweden)

    Williams Gareth

    2012-01-01

    Full Text Available Abstract Background Transcriptional data covering multiple platforms and species is collected and processed into a searchable platform independent expression database (SPIED. SPIED consists of over 100,000 expression fold profiles defined independently of control/treatment assignment and mapped to non-redundant gene lists. The database is thus searchable with query profiles defined over genes alone. The motivation behind SPIED is that transcriptional profiles can be quantitatively compared and ranked and thus serve as effective surrogates for comparing the underlying biological states across multiple experiments. Results Drug perturbation, cancer and neurodegenerative disease derived transcriptional profiles are shown to be effective descriptors of the underlying biology as they return related drugs and pathologies from SPIED. In the case of Alzheimer's disease there is high transcriptional overlap with other neurodegenerative conditions and rodent models of neurodegeneration and nerve injury. Combining the query signature with correlating profiles allows for the definition of a tight neurodegeneration signature that successfully highlights many neuroprotective drugs in the Broad connectivity map. Conclusions Quantitative querying of expression data from across the totality of deposited experiments is an effective way of discovering connections between different biological systems and in particular that between drug action and biological disease state. Examples in cancer and neurodegenerative conditions validate the utility of SPIED.

  20. Antibiotic resistance genes in municipal wastewater treatment systems and receiving waters in Arctic Canada

    DEFF Research Database (Denmark)

    Neudorf, Kara D.; Huang, Yan Nan; Ragush, Colin M.

    2017-01-01

    Domestic wastewater discharges may adversely impact arctic ecosystems and local indigenous people, who rely on being able to hunt and harvest food from their local environment. Therefore, there is a need to develop efficient wastewater treatment plants (WWTPs), which can be operated in remote...... communities under extreme climatic conditions. WWTPs have been identified as reservoirs of antibiotic resistance genes (ARGs). The objective of this work was to quantify the presence of nine different ARG markers (int1, sul1, sul2, tet(O), erm(B), mecA, blaCTX-M, blaTEM, and qnr(S)) in two passive systems...... (waste stabilization ponds [WSPs]) and one mechanical filtration plant operating in two smaller and one large community, respectively, in Nunavut, Canada. Measurement of water quality parameters (carbonaceous oxygen demand, ammonia, total suspended solids, Escherichia coli and total coliforms) showed...

  1. ACE gene polymorphism and losartan treatment in type 2 diabetic patients with nephropathy

    DEFF Research Database (Denmark)

    de, Zeeuw D.; Cooper, M.E.; Remuzzi, G.

    2008-01-01

    Losartan treatment reduced renal outcomes in proteinuric patients with type 2 diabetes in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. It is unknown whether an insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE......) gene predicts renal outcomes and death and influences the effect of losartan in these patients. Pharmacogenetic analyses were performed comparing losartan with placebo administered with conventional blood pressure-lowering therapy in 1435 (95%) of the 1513 RENAAL study patients. The primary endpoint......, losartan reduced the risk of reaching the composite endpoint by 5.8% (95% confidence interval, -23.3, 28.0), 17.6% (3.8, 29.4), and 27.9% (7.0, 44.1) among those with the II, ID, and DD genotypes, respectively. Similar trends were demonstrated for the individual endpoints. In conclusion, proteinuric type 2...

  2. The Composition and Spatial Patterns of Bacterial Virulence Factors and Antibiotic Resistance Genes in 19 Wastewater Treatment Plants.

    Directory of Open Access Journals (Sweden)

    Bing Zhang

    Full Text Available Bacterial pathogenicity and antibiotic resistance are of concern for environmental safety and public health. Accumulating evidence suggests that wastewater treatment plants (WWTPs are as an important sink and source of pathogens and antibiotic resistance genes (ARGs. Virulence genes (encoding virulence factors are good indicators for bacterial pathogenic potentials. To achieve a comprehensive understanding of bacterial pathogenic potentials and antibiotic resistance in WWTPs, bacterial virulence genes and ARGs in 19 WWTPs covering a majority of latitudinal zones of China were surveyed by using GeoChip 4.2. A total of 1610 genes covering 13 virulence factors and 1903 genes belonging to 11 ARG families were detected respectively. The bacterial virulence genes exhibited significant spatial distribution patterns of a latitudinal biodiversity gradient and a distance-decay relationship across China. Moreover, virulence genes tended to coexist with ARGs as shown by their strongly positive associations. In addition, key environmental factors shaping the overall virulence gene structure were identified. This study profiles the occurrence, composition and distribution of virulence genes and ARGs in current WWTPs in China, and uncovers spatial patterns and important environmental variables shaping their structure, which may provide the basis for further studies of bacterial virulence factors and antibiotic resistance in WWTPs.

  3. Potential of Gene Editing and Induced Pluripotent Stem Cells (iPSCs) in Treatment of Retinal Diseases.

    Science.gov (United States)

    Chuang, Katherine; Fields, Mark A; Del Priore, Lucian V

    2017-12-01

    The advent of gene editing has introduced the ability to make changes to the genome of cells, thus allowing for correction of genetic mutations in patients with monogenic diseases. Retinal diseases are particularly suitable for the application of this new technology because many retinal diseases, such as Stargardt disease, retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA), are monogenic. Moreover, gene delivery techniques such as the use of adeno-associated virus (AAV) vectors have been optimized for intraocular use, and phase III trials are well underway to treat LCA, a severe form of inherited retinal degeneration, with gene therapy. This review focuses on the use of gene editing techniques and another relatively recent advent, induced pluripotent stem cells (iPSCs), and their potential for the study and treatment of retinal disease. Investment in these technologies, including overcoming challenges such as off-target mutations and low transplanted cell integration, may allow for future treatment of many debilitating inherited retinal diseases.

  4. An update on gene therapy for the treatment of lipoprotein lipase deficiency

    Directory of Open Access Journals (Sweden)

    Libby AE

    2014-05-01

    Full Text Available Andrew E Libby, Hong Wang Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado at Denver, Aurora, CO, USA Abstract: Lipoprotein lipase (LPL is responsible for clearance of triglyceride-rich lipoproteins from the blood. Deficiency or defects in this enzyme result in profound hypertriglyceridemia and susceptibility to chronic, life-threatening pancreatitis. Management of LPL deficiency has traditionally been restricted to palliative care and strategies to reduce the risk of pancreatitis, including severe dietary restrictions of fat. Recently, the European Commission approved the first gene therapy treatment in the West to treat this rare disease. Alipogene tiparvovec (Glybera® was granted marketing authorization in November 2012 to treat LPL deficiency in a subset of patients that are at increased risk for pancreatitis. Designed as a one-time treatment, the drug uses adeno-associated virus (AAV1 delivery of transgenic LPL to muscle in patients lacking functional enzyme. Although statistically significant reduction of serum triglycerides was initially observed in trial subjects, this effect was found to be transient, with triglyceride levels eventually rebounding to basal levels by 26 weeks in all participants. Nevertheless, despite the return of triglycerides to pretreatment levels, alipogene tiparvovec was found to have a long-term impact on postprandial chylomicron metabolism by lowering the fraction of triglyceride found in this subset of lipoproteins. Furthermore, the drug led to a clinically significant reduction in the incidence of pancreatitis in LPL-deficient patients. The regulatory approval of alipogene tiparvovec was a historic process and serves as an example of the challenges that future orphan drugs will face. Keywords: lipoprotein lipase deficiency, gene therapy, AAV, chylomicron, pancreatitis

  5. Effect of GA3 treatment on seed development and seed-related gene expression in grape.

    Directory of Open Access Journals (Sweden)

    Chenxia Cheng

    Full Text Available The phytohormone gibberellic acid (GA3 is widely used in the table grape industry to induce seedlessness in seeded varieties. However, there is a paucity of information concerning the mechanisms by which GAs induce seedlessness in grapes.In an effort to systematically analyze the cause of this GA3-induced seed abortion, we conducted an in depth characterization of two seeded grape cultivars ('Kyoho' and 'Red Globe', along with a seedless cultivar ('Thompson Seedless', following treatment with GA3. In a similar fashion to the seedless control, which exhibited GA3-induced abortion of the seeds 9 days after full bloom (DAF, both 'Kyoho' and 'Red Globe' seeded varieties exhibited complete abortion of the seeds 15 DAF when treated with GA3. Morphological analyses indicated that while fertilization appeared to occur normally following GA3 treatment, as well as in the untreated seedless control cultivar, seed growth eventually ceased. In addition, we found that GA3 application had an effect on redox homeostasis, which could potentially cause cell damage and subsequent seed abortion. Furthermore, we carried out an analysis of antioxidant enzyme activities, as well as transcript levels from various genes believed to be involved in seed development, and found several differences between GA3-treated and untreated controls.Therefore, it seems that the mechanisms driving GA3-induced seedlessness are similar in both seeded and seedless cultivars, and that the observed abortion of seeds may result at least in part from a GA3-induced increase in cell damage caused by reactive oxygen species, a decrease in antioxidant enzymatic activities, and an alteration of the expression of genes related to seed development.

  6. Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer.

    Science.gov (United States)

    Wang, Haiying; Molina, Julian; Jiang, John; Ferber, Matthew; Pruthi, Sandhya; Jatkoe, Timothy; Derecho, Carlo; Rajpurohit, Yashoda; Zheng, Jian; Wang, Yixin

    2013-11-01

    Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and

  7. Occurrence of antibiotics and antibiotic resistance genes in a sewage treatment plant and its effluent-receiving river.

    Science.gov (United States)

    Xu, Jian; Xu, Yan; Wang, Hongmei; Guo, Changsheng; Qiu, Huiyun; He, Yan; Zhang, Yuan; Li, Xiaochen; Meng, Wei

    2015-01-01

    The extensive use of antibiotics has caused the contamination of both antibiotics and antibiotic resistance genes (ARGs) in the environment. In this study, the abundance and distribution of antibiotics and ARGs from a sewage treatment plant (STP) and its effluent-receiving river in Beijing China were characterized. Three classes of antibiotics including tetracycline, sulfonamide and quinolone were quantified by LC-MS/MS. In the secondary effluent they were detected at 195, 2001 and 3866 ng L(-1), respectively, which were higher than in the receiving river water. A total of 13 ARGs (6 tet genes: tetA, tetB, tetE, tetW, tetM and tetZ, 3 sulfonamide genes: sul1, sul2 and sul3, and 4 quinolone genes: gryA, parC, qnrC and qnrD) were determined by quantitative PCR. For all ARGs, sulfonamide resistance genes were present at relatively high concentrations in all samples, with the highest ARG concentration above 10(-1). ARGs remained relatively stable along each sewage treatment process. The abundances of detected ARGs from the STP were also higher than its receiving river. Bivariate correlation analysis showed that relative tet gene copies (tetB/16S-rRNA and tetW/16S-rRNA) were strongly correlated with the concentrations of tetracycline residues (r(2)>0.8, pgenes. A negative correlation between the relative abundance of quinolone resistance gene (qnrC/16S-rRNA) and the concentrations of enrofloxacin (ENR) was also determined. The difference of ARGs levels in the raw influent and secondary effluent suggested that the STP treatment process may induce to increase the abundance of resistance genes. The results showed that the sewage was an important repository of the resistance genes, which need to be effectively treated before discharge into the natural water body. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Differential expression of the klf6 tumor suppressor gene upon cell damaging treatments in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Gehrau, Ricardo C.; D' Astolfo, Diego S.; Andreoli, Veronica [Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina); Bocco, Jose L., E-mail: jbocco@fcq.unc.edu.ar [Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina); Koritschoner, Nicolas P. [Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)

    2011-02-10

    The mammalian Krueppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Also, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several cell-damaging stimuli. DNA damaging agents at lethal concentrations induce a p53-independent down-regulation of the klf6 gene. To investigate the impact of external stimuli on human klf6 gene expression, its mRNA level was analyzed using a cancer cell line profiling array system, consisting in an assortment of immobilized cDNAs from multiple cell lines treated with several cell-damaging agents at growth inhibitory concentrations (IC{sub 50}). Cell-damaging agents affected the klf6 expression in 62% of the cDNA samples, though the expression pattern was not dependent on the cell origin type. Interestingly, significant differences (p < 0.0001) in KLF6 mRNA levels were observed depending on the cellular p53 status upon cell damage. KLF6 expression was significantly increased in 63% of p53-deficient cells (122/195). Conversely, KLF6 mRNA level decreased nearly 4 fold in more than 70% of p53+/+ cells. In addition, klf6 gene promoter activity was down-regulated by DNA damaging agents in cells expressing the functional p53 protein whereas it was moderately increased in the absence of functional p53. Consistent results were obtained for the endogenous KLF6 protein level. Results indicate that human klf6 gene expression is responsive to external cell damage mediated by IC{sub 50} concentrations of physical and chemical stimuli in a p53-dependent manner. Most of these agents are frequently used in cancer therapy. Induction of klf6 expression in the absence of functional p53 directly correlates with cell death triggered by these compounds, whereas it is down-regulated in p53+/+ cells. Hence, klf6 expression level could represent a valuable

  9. Multifuntional Nanotherapeutics for the Combinatorial Drug and Gene Therapy in the Treatment of Glioblastoma Multiforme

    Science.gov (United States)

    Hourigan, Breanne

    Glioblastoma multiforme (GBM), a grade IV glioma, is the most common primary brain tumor, affecting about 3 out of 100,000 persons per year in the United States. GBM accounts for about 80% of primary malignant brain tumors, and is also the most aggressive of malignant brain tumors. With exhaustive treatment, survival only averages between 12 and 15 months, with a 2-year survival rate less than 25%. New therapeutic strategies are necessary to improve the outcomes of this disease. Chemotherapy with temozolomide (TMZ), a DNA alkylating agent, is used as a first-line of treatment for GBM. However, GBM tumors develop resistance to TMZ over time due to increased expression of O6-methylguanine-DNA methyltransferase (MGMT), a gene responsible for DNA repair. We previously developed cationic, amphiphilic copolymer poly(lactide-co-glycolide)-g-polyethylenimine (PgP) and demonstrated its utility for nucleic acid delivery. Here, we examine the ability of PgP polyplexes to overcome TMZ resistance and improve therapeutic efficacy through combination drug and gene therapy for GBM treatment. In this study, we evaluated the ability of PgP to deliver siRNA targeting to MGMT (siMGMT), a gene responsible for drug resistance in GBM. Our results demonstrated that PgP effectively forms stable complex with siRNA and protects siRNAs from heparin competition assay, serum- and ribonuclease-mediated degradation, confirming the potential of the polyplex for in vivo delivery. Results from MTT assays showed that PgP/siRNA polyplexes exhibited minimal cytotoxicity compared to untreated cells when incubated with T98G human GBM cells. We also demonstrated that PgP/siMGMT polyplexes mediate knockdown of MGMT protein as well as a significant ˜56% and ˜68% knockdown of MGMT mRNA in T98G GBM cells compared to cells treated with PgP complexed with non-targeting siRNA (siNT) at a 60:1 and 80:1 nitrogen:phosphate (N:P) ratio, respectively. Further, co-incubation of PgP/siMGMT polyplexes with TMZ

  10. Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep.

    Science.gov (United States)

    Nuruddin, Syed; Krogenæs, Anette; Brynildsrud, Ola Brønstad; Verhaegen, Steven; Evans, Neil P; Robinson, Jane E; Haraldsen, Ira Ronit Hebold; Ropstad, Erik

    2013-12-01

    The nature of hormonal involvement in pubertal brain development has attracted wide interest. Structural changes within the brain that occur during pubertal development appear mainly in regions closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors, results in exaggerated sex-differences in cognitive executive function and emotional control, as well as sex and hemisphere specific patterns of expression of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explored effects of this treatment regime on the gene expression profile of the ovine amygdala. The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until approximately 50 weeks of age. Gene expression profiles of the left and right amygdala were measured using 8×15 K Agilent ovine microarrays. Differential expression of selected genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with Ingenuity Pathway Analysis (IPA), version 7.5 and DAVID (Database for Annotation, Visualization and integrated Discovery) version 6.7 software packages, respectively. GnRHa treatment was associated with significant sex- and hemisphere-specific differential patterns of gene expression. GnRHa treatment was associated with differential expression of 432 (|logFC|>0.3, adj. p value expressed as a result of GnRHa treatment in the male animals. The results indicated that GnRH may, directly and/or indirectly, be involved in the regulation of sex- and hemisphere-specific differential expression of genes in the amygdala. This finding should be considered when long-term peri-pubertal GnRHa treatment is used in children. Copyright

  11. Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice

    Directory of Open Access Journals (Sweden)

    Chunming Jia

    2015-05-01

    Full Text Available Pioglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARγ, is an insulin sensitizer drug that is being used in a number of insulin-resistant conditions, including non-alcoholic fatty liver disease (NAFLD. However, there is a discrepancy between preclinical and clinical data in the literature and the benefits of pioglitazone treatment as well as the precise mechanism of action remain unclear. In the present study, we determined the effect of chronic pioglitazone treatment on hepatic gene expression profile in diet-induced obesity (DIO C57BL/6J mice in order to understand the mechanisms of NAFLD induced by PPARγ agonists. DIO mice were treated with pioglitazone (25 mg/kg/day for 38 days, the gene expression profile in liver was evaluated using Affymetrix Mouse GeneChip 1.0 ST array. Pioglitazone treatment resulted in exacerbated hepatic steatosis and increased hepatic triglyceride and free fatty acids concentrations, though significantly increased the glucose infusion rate in hyperinsulinemic-euglycemic clamp test. The differentially expressed genes in liver of pioglitazone treated vs. untreated mice include 260 upregulated and 86 downregulated genes. Gene Ontology based enrichment analysis suggests that inflammation response is transcriptionally downregulated, while lipid metabolism is transcriptionally upregulated. This may underlie the observed aggravating liver steatosis and ameliorated systemic insulin resistance in DIO mice.

  12. The difficult medical emergency call

    DEFF Research Database (Denmark)

    Møller, Thea Palsgaard; Kjærulff, Thora Majlund; Viereck, Søren

    2017-01-01

    BACKGROUND: Pre-hospital emergency care requires proper categorization of emergency calls and assessment of emergency priority levels by the medical dispatchers. We investigated predictors for emergency call categorization as "unclear problem" in contrast to "symptom-specific" categories and the ......BACKGROUND: Pre-hospital emergency care requires proper categorization of emergency calls and assessment of emergency priority levels by the medical dispatchers. We investigated predictors for emergency call categorization as "unclear problem" in contrast to "symptom-specific" categories...... and the effect of categorization on mortality. METHODS: Register-based study in a 2-year period based on emergency call data from the emergency medical dispatch center in Copenhagen combined with nationwide register data. Logistic regression analysis (N = 78,040 individuals) was used for identification...

  13. A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide

    Directory of Open Access Journals (Sweden)

    Paiva Renata T

    2012-06-01

    Full Text Available Abstract Background Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide. Results We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR. Conclusions The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.

  14. Interferon-γ gene polymorphisms at +874T/A loci associated with response to treatment with hepatitis C virus

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    Hosein Norozian

    2016-02-01

    Full Text Available Background: Hepatitis C virus (HCV is a worldwide health problem, which associated with cirrhosis and hepatocellular carcinoma. Interferon-α and Ribavirin are only acceptable treatment regimen for these patients. These regimen are effective only on 50% of the patients. The aim of this study was to evaluate the response to treatment with interferon gamma gene polymorphism in patients with hepatitis C. Materials and Methods: In this study, a cross - sectional study, response or lack of response to treatment in 78 patients treated with interferon gamma gene polymorphism were studied at Shiraz Namazi Hospital from 2011-2012 . DNA samples extract by salt (salting out and interferon gamma gene polymorphism (+874T/A IFN–gamma was evaluate with ARMS-PCR technique. Data were analyzed using EPI Info2000 and SPSS 16 software (chi-square test. Results: Results showed that 39 patients (50% out of 78 studied patients had TT alleles, 11 patients (1.14% had AA alleles and 28 patients (9.39% had TA alleles. 49 patients (62.82% responded to treatment. TT genotype and allele frequencies between the studied groups showed significant differencey (P=0.002. Conclusion: Interferon gamma is a key cytokine in the immune response against hepatitis C. Polymorphism in the interferon-gamma gene is (+874T/AIFN–gamma One of the most important factors interferes with treatment response in hepatitis C patients.

  15. Characterization of housekeeping genes in zebrafish: male-female differences and effects of tissue type, developmental stage and chemical treatment

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    Callard Gloria V

    2008-11-01

    Full Text Available Abstract Background Research using the zebrafish model has experienced a rapid growth in recent years. Although real-time reverse transcription PCR (QPCR, normalized to an internal reference ("housekeeping" gene, is a frequently used method for quantifying gene expression changes in zebrafish, many commonly used housekeeping genes are known to vary with experimental conditions. To identify housekeeping genes that are stably expressed under different experimental conditions, and thus suitable as normalizers for QPCR in zebrafish, the present study evaluated the expression of eight commonly used housekeeping genes as a function of stage and hormone/toxicant exposure during development, and by tissue type and sex in adult fish. Results QPCR analysis was used to quantify mRNA levels of bactin1, tubulin alpha 1(tuba1, glyceraldehyde-3-phosphate dehydrogenase (gapdh, glucose-6-phosphate dehydrogenase (g6pd, TATA-box binding protein (tbp, beta-2-microglobulin (b2m, elongation factor 1 alpha (elfa, and 18s ribosomal RNA (18s during development (2 – 120 hr postfertilization, hpf; in different tissue types (brain, eye, liver, heart, muscle, gonads of adult males and females; and after treatment of embryos/larvae (24 – 96 hpf with commonly used vehicles for administration and agents that represent known environmental endocrine disruptors. All genes were found to have some degree of variability under the conditions tested here. Rank ordering of expression stability using geNorm analysis identified 18s, b2m, and elfa as most stable during development and across tissue types, while gapdh, tuba1, and tpb were the most variable. Following chemical treatment, tuba1, bactin1, and elfa were the most stably expressed whereas tbp, 18s, and b2m were the least stable. Data also revealed sex differences that are gene- and tissue-specific, and treatment effects that are gene-, vehicle- and ligand-specific. When the accuracy of QPCR analysis was tested using

  16. Response to methadone maintenance treatment is associated with the MYOCD and GRM6 genes.

    Science.gov (United States)

    Fonseca, Francina; Gratacòs, Mònica; Escaramís, Geòrgia; De Cid, Rafael; Martín-Santos, Rocío; Fernández-Espejo, Emilio; Estivill, Xavier; Torrens, Marta

    2010-06-01

    There is increasing interest in the pharmacogenetic basis for explaining differences between patients in treatment outcome among methadone-treated subjects. Most studies have focused on genetic polymorphisms related to methadone pharmacokinetics and, to a lesser extent, those genes implicated in the pharmacodynamics of methadone. This study aimed to investigate the associations between response to methadone maintenance treatment (MMT) and polymorphisms in genes coding for the OPRM1 opioid receptor, the metabotropic glutamate receptors GRM6 and GRM8, the nuclear receptor NR4A2, the photolyase enzyme cryptochrome 1 (CRY1), and the transcription factor myocardin (MYOCD), which have previously been associated with the risk of opioid dependence disorder. The study used an association, case-control design, conducted in the setting of an MMT program in a drug abuse outpatient center in Barcelona, Spain. We recruited 169 opioid-dependent patients (diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders [4th Edition] criteria) receiving MMT. The inclusion criteria included Caucasian ethnicity, being enrolled in MMT for at least 6 months, and receiving a stable methadone dose for the previous 2 months. The exclusion criteria included language-related barriers, severe cognitive impairment, or any medical disorder that would interfere with the research assessments. Single nucleotide polymorphism (SNP) variants in several candidate genes and regions were genotyped: MYOCD (rs1714984), GRM8 (rs1034576), CRY1 (rs1861591), GRM6 (rs953741), OPRM1 (rs1074287), NR4A2 (rs1405735), and the intergenic variants rs965972 (1q31.2) and rs1867898 (2q21.2). MMT response status was assessed by the number of opioid-positive controls detected by random urinalysis in the previous 2 months. We used the chi-squared test and p-value for the allele frequencies of the eight SNPs in responders versus nonresponders, and multivariate logistic regression analyses to examine

  17. House Calls in Private Practice.

    Science.gov (United States)

    Whittington, Ronaele

    1985-01-01

    Relates the experiences of a social worker in private practice who offered house calls as an ongoing setting for counseling and psychotherapy to individuals and families. Describes advantages and disadvantages, liability, and target populations. (JAC)

  18. Acute and repeated ECS treatment increases CRF, POMC and PENK gene expression in selected regions of the rat hypothalamus.

    Science.gov (United States)

    Garcia-Garcia, L; Llewellyn-Jones, V; Fernandez Fernandez, I; Fuentes, J A; Manzanares, J

    1998-01-05

    The purpose of this study was to investigate the effects of acute and repeated electroconvulsive shock (ECS) on corticotropin releasing factor (CRF), proopiomelanocortin (POMC) and proenkephalin (PENK) gene expression in selected regions of the brain and pituitary of the rat. Acute ECS increased CRF gene expression in the paraventricular nucleus (PVN) by 20%, an effect that was further enhanced to 38% when rats received repeated ECS treatment. Acute and repeated ECS increased POMC gene expression in the arcuate nucleus (ARC) by 49-59% but failed to alter these mRNA levels in the anterior lobe (AL) of the pituitary gland. PENK gene expression was increased by 35% in the nucleus accumbens (NA) and by 180% the ventromedial nucleus (VMN) after acute or repeated ECS treatment but no significant changes were found in the PVN or striatum (ST). Taken together, these results indicate a differential CRF and opioid gene expression regulation after acute or repeated ECS treatment that may be relevant to their therapeutic or side effects in depression.

  19. Evaluation of five antibiotic resistance genes in wastewater treatment systems of swine farms by real-time PCR.

    Science.gov (United States)

    Tao, Chi-Wei; Hsu, Bing-Mu; Ji, Wen-Tsai; Hsu, Tsui-Kang; Kao, Po-Min; Hsu, Chun-Po; Shen, Shu-Min; Shen, Tzung-Yu; Wan, Terng-Jou; Huang, Yu-Li

    2014-10-15

    Antibiotics are widely used in livestock for infection treatment and growth promotion. Wastes from animal husbandry are a potential environmental source of antibiotic-insensitive pathogens, and the removal efficiency of the resistance genotypes in current wastewater treatment plants (WWTPs) is unknown. In this study, quantitative PCR was used for evaluating antibiotic resistance genes in wastewater treatment processes. Six wastewater treatment plants in different swine farms were included in this study, and five antibiotic resistance genes (ARGs) were tested for each treatment procedure. All of the tested ARGs including tetA, tetW, sulI, sulII, and blaTEM genes were detected in six swine farms with considerable amounts. The results showed that antibiotic resistance is prevalent in livestock farming. The ARG levels were varied by wastewater treatment procedure, frequently with the highest level at anaerobic treatment tank and lowest in the activated sludge unit and the effluents. After normalizing the ARG levels to 16S rRNA gene copies, the results showed that ARGs in WWTP units fluctuated partly with the quantity of bacteria. Regardless of its importance in biodegradation, the anaerobic procedure may facilitate bacterial growth thus increasing the sustainability of the antibiotic resistance genotypes. After comparing the copy numbers in influx and efflux samples, the mean removal efficiency of ARGs ranged between 33.30 and 97.56%. The results suggested that treatments in the WWTP could partially reduce the spread of antibiotic-resistant bacteria, and additional procedures such as sedimentation may not critically affect the removal efficiency. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Quantification and characterization of β-lactam resistance genes in 15 sewage treatment plants from East Asia and North America.

    Science.gov (United States)

    Yang, Ying; Zhang, Tong; Zhang, Xu-Xiang; Liang, Da-Wei; Zhang, Ming; Gao, Da-Wen; Zhu, He-Guang; Huang, Qing-Guo; Fang, Herbert H P

    2012-09-01

    The emerging antibiotic resistance genes in the aquatic environment have aroused public concern. As β-lactam is the most widely used group of antibiotics, β-lactam resistance genes were selected to investigate their distribution and diversity in the activated sludge from 15 geographically different sewage treatment plants (STPs) of China, Singapore, USA, and Canada. Specific PCR and quantitative real-time PCR (q-PCR) were used to investigate the occurrence and abundance of nine β-lactam resistance genes. Five genes (OXA-1, OXA-2, OXA-10, ampC, and TEM-1) were detected in most of the sludge collected, while three genes (mecA, CTX-M-1, and SME) were not found in any sludge sample. The total abundances of the six detected β-lactam resistance genes in the 15 STPs varied from 5.34 × 10(1) copies/ng DNA (ampC) to 5.49 × 10(4) copies/ng DNA (OXA-1). Overall, OXA-1 had the highest total concentration, followed by IMP and OXA-10. Noticeably, the abundances of TEM-1 in Chinese STPs were generally higher than those in the STPs of other countries, while the abundances of OXA-2 and IMP in the STPs of North America were much greater than those of East Asia. A total of 78 clones carrying β-lactam resistance genes were randomly selected from six clone libraries for phylogenetic diversity analysis; the similarity of these cloned genes to known β-lactam resistance genes with sequence identities ranged from 96% to 100%. Furthermore, OXA-1, ampC, and IMP were found to be more diverse than the other β-lactam resistance genes.

  1. Differential expression of bean chitinase genes by virus infection, chemical treatment and UV irradiation

    International Nuclear Information System (INIS)

    Margis-Pinheiro, M.; Martin, C.; Didierjean, L.; Burkard, G.

    1993-01-01

    Three chitinases have been shown previously to be induced upon various stresses of bean leaves. Time course studies of mRNA accumulation of two of them (P3- and P4-chitinases) have been studied upon virus infection, mercuric chloride treatment and UV irradiation. In alfalfa mosaic virus (AlMV)-infected plants both mRNAs, absent in uninfected bean leaves, become detectable 36 h after inoculation. A maximum level of mRNAs is reached 84 h after inoculation and, whereas the amount of P3-ch mRNA decreases soon after having reached the maximum, the amount of P4-ch mRNA remains at high levels for several days. In mercuric chloride-treated leaves P4-ch mRNA becomes detectable 1-1.5 h after onset of treatment and a maximum level is observed between 6 h and 24 h after treatment; P3-ch mRNA becomes detectable later than P4-ch mRNA in treated leaves and reaches a maximum as late as 18 h after treatment has been applied. UV light also induces the synthesis of both mRNAs but, here again, important differences are observed in the accumulation rate of the two transcripts. The relative amounts of each mRNA induced by the different stresses have been compared. The most effective inducer of P3-ch mRNA is AlMV. In contrast, mercuric chloride induces P4-ch mRNA more efficiently than AlMV or UV light. We have also determined the complete nucleotide sequence of the cDNA encoding P3-chitinase that has been isolated from a cDNA library by using the cucumber lysozyme-chitinase cDNA as a probe. The 1072 bp P3-ch cDNA encodes a mature protein of 268 amino acid residues and the 25 residue NH2-terminal signal peptide of the precursor. Because of its high structural homology to the cucumber and Arabidopsis acidic chitinases as well as to the N-terminal amino acid sequence of the bifunctional lysozyme-chitinase from P. quinquifolia, bean P3-chitinase can be considered to belong to the class III chitinases. Southern blot analysis of bean genomic DNA revealed that P3-chitinase is encoded by a

  2. Variation of antibiotic resistance genes in municipal wastewater treatment plant with A(2)O-MBR system.

    Science.gov (United States)

    Du, Jing; Geng, Jinju; Ren, Hongqiang; Ding, Lili; Xu, Ke; Zhang, Yan

    2015-03-01

    The variation of five antibiotic resistance genes (ARGs)-tetG, tetW, tetX, sul1, and intI1-in a full-scale municipal wastewater treatment plant with A(2)O-MBR system was studied. The concentrations of five resistance genes both in influent and in membrane bioreactor (MBR) effluent decreased as sul1 > intI1 > tetX > tetG > tetW, and an abundance of sul1 was statistically higher than three other tetracycline resistance genes (tetG, tetW, and tetX) (p MBR effluent. The reduction of tetW, intI1, and sul1 was all significantly positively correlated with the reduction of 16S ribosomal DNA (rDNA) in the wastewater treatment process (p MBR was observed for all ARGs.

  3. Identification of Potentially Neuroprotective Genes Upregulated by Neurotrophin Treatment of CA3 Neurons in the Injured Brain

    Science.gov (United States)

    Malik, Saafan Z.; Motamedi, Shahab; Royo, Nicolas C.; LeBold, David

    2011-01-01

    Abstract Specific neurotrophic factors mediate histological and/or functional improvement in animal models of traumatic brain injury (TBI). In previous work, several lines of evidence indicated that the mammalian neurotrophin NT-4/5 is neuroprotective for hippocampal CA3 pyramidal neurons after experimental TBI. We hypothesized that NT-4/5 neuroprotection is mediated by changes in the expression of specific sets of genes, and that NT-4/5-regulated genes are potential therapeutic targets for blocking delayed neuronal death after TBI. In this study, we performed transcription profiling analysis of CA3 neurons to identify genes regulated by lateral fluid percussion injury, or by treatment with the trkB ligands NT-4/5 or brain-derived neurotrophic factor (BDNF). The results indicate extensive overlap between genes upregulated by neurotrophins and genes upregulated by injury, suggesting that the mechanism behind neurotrophin neuroprotection may mimic the brain's endogenous protective response. A subset of genes selected for further study in vitro exhibited neuroprotection against glutamate excitotoxicity. The neuroprotective genes identified in this study were upregulated at 30 h post-injury, and are thus expected to act during a clinically useful time frame of hours to days after injury. Modulation of these factors and pathways by genetic manipulation or small molecules may confer hippocampal neuroprotection in vivo in preclinical models of TBI. PMID:21083427

  4. Application of HSVtk suicide gene to X-SCID gene therapy: Ganciclovir treatment offsets gene corrected X-SCID B cells

    International Nuclear Information System (INIS)

    Uchiyama, Toru; Kumaki, Satoru; Ishikawa, Yoshinori; Onodera, Masafumi; Sato, Miki; Du, Wei; Sasahara, Yoji; Tanaka, Nobuyuki; Sugamura, Kazuo; Tsuchiya, Shigeru

    2006-01-01

    Recently, a serious adverse effect of uncontrolled clonal T cell proliferation due to insertional mutagenesis of retroviral vector was reported in X-SCID gene therapy clinical trial. To offset the side effect, we have incorporated a suicide gene into therapeutic retroviral vector for selective elimination of transduced cells. In this study, B-cell lines from two X-SCID patients were transduced with bicistronic retroviral vector carrying human γc chain cDNA and Herpes simplex virus thymidine kinase gene. After confirmation of functional reconstitution of the γc chain, the cells were treated with ganciclovir (GCV). The γc chain positive cells were eliminated under low concentration without cytotoxicity on untransduced cells and have not reappeared at least for 5 months. Furthermore, the γc chain transduced cells were still sensitive to GCV after five months. These results demonstrated the efficacy of the suicide gene therapy although further in vivo studies are required to assess feasibility of this approach in clinical trial

  5. Imágenes y narración: análisis de un espacio pedagógico con niñas y niños en situación de calle

    Directory of Open Access Journals (Sweden)

    María Amalia Miano

    2015-01-01

    Full Text Available Analizamos un proceso de aprendizaje en un espacio pedagógico para niñas y niños en situación de calle, orientado a proveer herramientas para la alfabetización en dife-rentes lenguajes (visual, teatral, musical, oral. Desde el concepto de aprendizaje en interacción, analizamos los distintos productos realizados en el marco del taller (un cuento, dibujos, maquetas y collages como una compleja trama de recursos diferen-tes, que consideramos posibles por las situaciones de interacción (con otros, con el medio, con diferentes tipos de textos que produjeron oportunidades de aprendizaje sobre la alfabetización y, específicamente, sobre cómo narrar. Finalmente, evaluamos las posibilidades y limitaciones de estas propuestas y mencionamos algunos aprendi-zajes de eventual utilidad para equipos de trabajo deseosos de encarar experiencias pedagógicas similares.

  6. Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate.

    Science.gov (United States)

    Dhabaan, Ghulam Nasser; AbuBakar, Sazaly; Cerqueira, Gustavo Maia; Al-Haroni, Mohammed; Pang, Sui Ping; Hassan, Hamimah

    2015-12-14

    Acinetobacter baumannii has emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential for A. baumannii adherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Imp(r)) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imp(s)) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imp(r) but not in the Imp(s) isolate. Notably, this finding is corroborated by an increase in the motility of the Imp(r) strain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage to A. baumannii and may contribute to clinical success. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Differential gene expression in liver tissues of streptozotocin-induced diabetic rats in response to resveratrol treatment.

    Directory of Open Access Journals (Sweden)

    Gökhan Sadi

    Full Text Available This study was conducted to elucidate the genome-wide gene expression profile in streptozotocin induced diabetic rat liver tissues in response to resveratrol treatment and to establish differentially expressed transcription regulation networks with microarray technology. In addition to measure the expression levels of several antioxidant and detoxification genes, real-time quantitative polymerase chain reaction (qRT-PCR was also used to verify the microarray results. Moreover, gene and protein expressions as well as enzymatic activities of main antioxidant enzymes; superoxide dismutase (SOD-1 and SOD-2 and glutathione S-transferase (GST-Mu were analyzed. Diabetes altered 273 genes significantly and 90 of which were categorized functionally which suggested that genes in cellular catalytic activities, oxidation-reduction reactions, co-enzyme binding and terpenoid biosynthesis were dominated by up-regulated expression in diabetes. Whereas; genes responsible from cellular carbohydrate metabolism, regulation of transcription, cell signal transduction, calcium independent cell-to-cell adhesion and lipid catabolism were down-regulated. Resveratrol increased the expression of 186 and decreased the expression of 494 genes in control groups. While cellular and extracellular components, positive regulation of biological processes, biological response to stress and biotic stimulants, and immune response genes were up-regulated, genes responsible from proteins present in nucleus and nucleolus were mainly down-regulated. The enzyme assays showed a significant decrease in diabetic SOD-1 and GST-Mu activities. The qRT-PCR and Western-blot results demonstrated that decrease in activity is regulated at gene expression level as both mRNA and protein expressions were also suppressed. Resveratrol treatment normalized the GST activities towards the control values reflecting a post-translational effect. As a conclusion, global gene expression in the liver tissues is

  8. Correction of gene expression data: Performance-dependency on inter-replicate and inter-treatment biases.

    Science.gov (United States)

    Darbani, Behrooz; Stewart, C Neal; Noeparvar, Shahin; Borg, Søren

    2014-10-20

    This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies. For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce an analytical approach to examine the suitability of correction methods by considering the inter-treatment bias as well as the inter-replicate variance, which allows use of the best correction method with minimum residual bias. Analyses of RNA sequencing and microarray data showed that the efficiencies of correction methods are influenced by the inter-treatment bias as well as the inter-replicate variance. Therefore, we recommend inspecting both of the bias sources in order to apply the most efficient correction method. As an alternative correction strategy, sequential application of different correction approaches is also advised. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. [Clinical significance of calcitonin gene-related peptide level before and after treatment in patients with chronic periodontitis].

    Science.gov (United States)

    Yan, Ying; Xiang, Xue-Rong; Wang, Chun; Ye, Guo; Fan, Xiao-Ping

    2016-08-01

    To explore the clinical significance of calcitonin gene-related peptide (CGRP) levels in patients with chronic periodontitis before and after treatment, and to detect the calcitonin gene-related peptide content in human venous blood. Thirty healthy controls and thirty patients with mild, moderate, severe periodontitis were enrolled from August 2014 to June 2015.CGRP level in the patients' peripheral blood was detected by ELISA. Three months after periodontal treatment, CGRP level in mild, moderate, severe periodontitis patients' peripheral blood was re-examined by ELISA. Then the correlation between calcitonin gene-related peptide and inflammation of chronic periodontitis was analyzed with SPSS 22.0 software package. The content of CGRP in healthy controls was significantly higher than that in patients with periodontitis. With the aggravation of periodontal inflammation, blood level of CGRP decreased gradually, and the lowest was in patients with severe periodontitis (Pperiodontal treatment, CGRP content was significantly higher compared with that before treatment (Pperiodontitis (P>0.05). The level of CGRP in venous blood decreased with the increasing severity of chronic periodontitis, and CGRP was negatively correlated with the degree of inflammation of chronic periodontitis. CGRP may be involved in the occurrence and development of chronic periodontitis. CGRP content in serum of patients with chronic periodontitis after treatment was significantly increased, CGRP may be used as the basis for clinical detection of chronic periodontitis.

  10. Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hermann, Thomas S; Li, Weijie; Dominguez, Helena

    2005-01-01

    OBJECTIVE: Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects...... and simultaneously increase the expression of genes that are pertinent for endothelial function and metabolism. METHODS: Twenty-four type 2 diabetic subjects were randomized to receive 2 months of quinapril 20 mg daily or no treatment in an open parallel study. Endothelium-dependent and -independent vasodilation...... occlusion plethysmography. Gene expression was measured by real-time PCR. RESULTS: Quinapril treatment increased insulin-stimulated endothelial function in the type 2 diabetic subjects (P = 0.005), whereas forearm glucose uptake was unchanged. Endothelial function was also increased by quinapril (P = 0...

  11. Stress-related gene expression changes in rainbow trout hepatocytes exposed to various municipal wastewater treatment influents and effluents.

    Science.gov (United States)

    Gagné, F; Smyth, S A; André, C; Douville, M; Gélinas, M; Barclay, K

    2013-03-01

    The present study sought to examine the performance of six different wastewater treatment processes from 12 wastewater treatment plants using a toxicogenomic approach in rainbow trout hepatocytes. Freshly prepared rainbow trout hepatocytes were exposed to increasing concentrations of influent (untreated wastewaters) and effluent (C(18)) extracts for 48 h at 15 °C. A test battery of eight genes was selected to track changes in xenobiotic biotransformation, estrogenicity, heavy metal detoxification, and oxidative stress. The wastewaters were processed by six different treatment systems: facultative and aerated lagoons, activated sludge, biological aerated filter, biological nutrient removal, chemically assisted primary treated, and trickling filter/solids contact. Based on the chemical characteristics of the effluents, the treatment plants were generally effective in removing total suspended solids and chemical oxygen demand, but less so for ammonia and alkalinity. The 12 influents differed markedly with each other, which makes the comparison among treatment processes difficult. For the influents, both population size and flow rate influenced the increase in the following mRNA levels in exposed hepatocytes: metallothionein (MT), cytochrome P4503A4 (CYP3A4), and vitellogenin (VTG). Gene expression of glutathione S-transferase (GST) and the estrogen receptor (ER), were influenced only by population size in exposed cells to the influent extracts. The remaining genes-superoxide dismutase (SOD) and multidrug resistance transporter (MDR)-were not influenced by either population size or flow rate in exposed cells. It is noteworthy that the changes in MT, ER, and VTG in cells exposed to the effluents were significantly affected by the influents across the 12 cities examined. However, SOD, CYP1A1, CYP3A4, GST, and MDR gene expression were the least influenced by the incoming influents. The data also suggest that wastewater treatments involving biological or aeration

  12. The Wireless Nursing Call System

    DEFF Research Database (Denmark)

    Jensen, Casper Bruun

    2006-01-01

    This paper discusses a research project in which social scientists were involved both as analysts and supporters during a pilot with a new wireless nursing call system. The case thus exemplifies an attempt to participate in developing dependable health care systems and offers insight into the cha......This paper discusses a research project in which social scientists were involved both as analysts and supporters during a pilot with a new wireless nursing call system. The case thus exemplifies an attempt to participate in developing dependable health care systems and offers insight...

  13. Perpetual Cancellable American Call Option

    OpenAIRE

    Emmerling, Thomas J.

    2010-01-01

    This paper examines the valuation of a generalized American-style option known as a Game-style call option in an infinite time horizon setting. The specifications of this contract allow the writer to terminate the call option at any point in time for a fixed penalty amount paid directly to the holder. Valuation of a perpetual Game-style put option was addressed by Kyprianou (2004) in a Black-Scholes setting on a non-dividend paying asset. Here, we undertake a similar analysis for the perpetua...

  14. Integrating heterogeneous healthcare call centers.

    Science.gov (United States)

    Peschel, K M; Reed, W C; Salter, K

    1998-01-01

    In a relatively short period, OHS has absorbed multiple call centers supporting different LOBs from various acquisitions, functioning with diverse standards, processes, and technologies. However, customer and employee satisfaction is predicated on OHS's ability to thoroughly integrate these heterogeneous call centers. The integration was initiated and has successfully progressed through a balanced program of focused leadership and a defined strategy which includes site consolidation, sound performance management philosophies, and enabling technology. Benefits have already been achieved with even more substantive ones to occur as the integration continues to evolve.

  15. Dehydration-induced WRKY genes from tobacco and soybean respond to jasmonic acid treatments in BY-2 cell culture.

    Science.gov (United States)

    Rabara, Roel C; Tripathi, Prateek; Lin, Jun; Rushton, Paul J

    2013-02-15

    Drought is one of the important environmental factors affecting crop production worldwide and therefore understanding the molecular response of plant to stress is an important step in crop improvement. WRKY transcription factors are one of the 10 largest transcription factor families across the green lineage. In this study, highly upregulated dehydration-induced WRKY and enzyme-coding genes from tobacco and soybean were selected from microarray data for promoter analyses. Putative stress-related cis-regulatory elements such as TGACG motif, ABRE-like elements; W and G-like sequences were identified by an in silico analyses of promoter region of the selected genes. GFP quantification of transgenic BY-2 cell culture showed these promoters direct higher expression in-response to 100 μM JA treatment compared to 100 μM ABA, 10% PEG and 85 mM NaCl treatments. Thus promoter activity upon JA treatment and enrichment of MeJA-responsive elements in the promoter of the selected genes provides insights for these genes to be jasmonic acid responsive with potential of mediating cross-talk during dehydration responses. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Global hepatic gene expression in rainbow trout exposed to sewage effluents: A comparison of different sewage treatment technologies

    Energy Technology Data Exchange (ETDEWEB)

    Cuklev, Filip, E-mail: filip.cuklev@neuro.gu.se [Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, Box 434, SE-405 30 Goeteborg (Sweden); Gunnarsson, Lina, E-mail: lina.gunnarsson@fysiologi.gu.se [Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, Box 434, SE-405 30 Goeteborg (Sweden); Cvijovic, Marija, E-mail: marija.cvijovic@chalmers.se [Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, Box 434, SE-405 30 Goeteborg (Sweden); Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, SE-412 96 Goeteborg (Sweden); Kristiansson, Erik, E-mail: erik.kristiansson@chalmers.se [Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, SE-412 96 Goeteborg (Sweden); Rutgersson, Carolin [Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, Box 434, SE-405 30 Goeteborg (Sweden); Bjoerlenius, Berndt, E-mail: berndtb@kth.se [Stockholm Water Company, Vaermdoevaegen 23, SE-131 55 Stockholm (Sweden); Larsson, D.G. Joakim, E-mail: joakim.larsson@fysiologi.gu.se [Institute of Neuroscience and Physiology, Department of Physiology, The Sahlgrenska Academy at the University of Gothenburg, Box 434, SE-405 30 Goeteborg (Sweden)

    2012-06-15

    Effluents from sewage treatment plants contain a mixture of micropollutants with the potential of harming aquatic organisms. Thus, addition of advanced treatment techniques to complement existing conventional methods has been proposed. Some of the advanced techniques could, however, potentially produce additional compounds affecting exposed organisms by unknown modes of action. In the present study the aim was to improve our understanding of how exposure to different sewage effluents affects fish. This was achieved by explorative microarray and quantitative PCR analyses of hepatic gene expression, as well as relative organ sizes of rainbow trout exposed to different sewage effluents (conventionally treated, granular activated carbon, ozonation (5 or 15 mg/L), 5 mg/L ozone plus a moving bed biofilm reactor, or UV-light treatment in combination with hydrogen peroxide). Exposure to the conventionally treated effluent caused a significant increase in liver and heart somatic indexes, an effect removed by all other treatments. Genes connected to xenobiotic metabolism, including cytochrome p450 1A, were differentially expressed in the fish exposed to the conventionally treated effluents, though only effluent treatment with granular activated carbon or ozone at 15 mg/L completely removed this response. The mRNA expression of heat shock protein 70 kDa was induced in all three groups exposed to ozone-treated effluents, suggesting some form of added stress in these fish. The induction of estrogen-responsive genes in the fish exposed to the conventionally treated effluent was effectively reduced by all investigated advanced treatment technologies, although the moving bed biofilm reactor was least efficient. Taken together, granular activated carbon showed the highest potential of reducing responses in fish induced by exposure to sewage effluents. - Highlights: Black-Right-Pointing-Pointer Livers of trout exposed to different sewage effluents were analysed by microarray. Black

  17. Global hepatic gene expression in rainbow trout exposed to sewage effluents: A comparison of different sewage treatment technologies

    International Nuclear Information System (INIS)

    Cuklev, Filip; Gunnarsson, Lina; Cvijovic, Marija; Kristiansson, Erik; Rutgersson, Carolin; Björlenius, Berndt; Larsson, D.G. Joakim

    2012-01-01

    Effluents from sewage treatment plants contain a mixture of micropollutants with the potential of harming aquatic organisms. Thus, addition of advanced treatment techniques to complement existing conventional methods has been proposed. Some of the advanced techniques could, however, potentially produce additional compounds affecting exposed organisms by unknown modes of action. In the present study the aim was to improve our understanding of how exposure to different sewage effluents affects fish. This was achieved by explorative microarray and quantitative PCR analyses of hepatic gene expression, as well as relative organ sizes of rainbow trout exposed to different sewage effluents (conventionally treated, granular activated carbon, ozonation (5 or 15 mg/L), 5 mg/L ozone plus a moving bed biofilm reactor, or UV-light treatment in combination with hydrogen peroxide). Exposure to the conventionally treated effluent caused a significant increase in liver and heart somatic indexes, an effect removed by all other treatments. Genes connected to xenobiotic metabolism, including cytochrome p450 1A, were differentially expressed in the fish exposed to the conventionally treated effluents, though only effluent treatment with granular activated carbon or ozone at 15 mg/L completely removed this response. The mRNA expression of heat shock protein 70 kDa was induced in all three groups exposed to ozone-treated effluents, suggesting some form of added stress in these fish. The induction of estrogen-responsive genes in the fish exposed to the conventionally treated effluent was effectively reduced by all investigated advanced treatment technologies, although the moving bed biofilm reactor was least efficient. Taken together, granular activated carbon showed the highest potential of reducing responses in fish induced by exposure to sewage effluents. - Highlights: ► Livers of trout exposed to different sewage effluents were analysed by microarray. ► Exposure to conventionally

  18. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of {sup 18}F-Fluorodeoxyglucose After Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, George D., E-mail: george.wilson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L. [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Oliver Wong, Ching Yee [Department of Diagnostic Radiology and Molecular Imaging Medicine, William Beaumont Hospital, Royal Oak, Michigan (United States); Yan, Di; Marples, Brian [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Huang, Jiayi [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-11-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm{sup 3} they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: {sup 18}F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism.

  19. Relabeling the Medications We Call Antidepressants

    Directory of Open Access Journals (Sweden)

    David Antonuccio

    2012-01-01

    Full Text Available This paper raises the question about whether the data on the medications we call antidepressants justify the label of antidepressant. The authors argue that a true antidepressant should be clearly superior to placebo, should offer a risk/benefit balance that exceeds that of alternative treatments, should not increase suicidality, should not increase anxiety and agitation, should not interfere with sexual functioning, and should not increase depression chronicity. Unfortunately, these medications appear to fall short on all of these dimensions. Many of the “side effects” of these medications have larger effect sizes than the antidepressant effect size. To call these medications antidepressants may make sense from a marketing standpoint but may be misleading from a scientific perspective. Consumers deserve a label that more accurately reflects the data on the largest effects and helps them understand the range of effects from these medications. In other words, it may make just as much sense to call these medications antiaphrodisiacs as antidepressants because the negative effects on libido and sexual functioning are so common. It can be argued that a misleading label may interfere with our commitment to informed consent. Therefore, it may be time to stop calling these medications antidepressants.

  20. Calling to Nursing: Concept Analysis.

    Science.gov (United States)

    Emerson, Christie

    The aims of this article are (a) to analyze the concept of a calling as it relates nursing and (b) to develop a definition of calling to nursing with the detail and clarity needed to guide reliable and valid research. The classic steps described by Walker and Avant are used for the analysis. Literature from several disciplines is reviewed including vocational psychology, Christian career counseling, sociology, organizational management, and nursing. The analysis provides an operational definition of a calling to nursing and establishes 3 defining attributes of the concept: (a) a passionate intrinsic motivation or desire (perhaps with a religious component), (b) an aspiration to engage in nursing practice, as a means of fulfilling one's purpose in life, and (c) the desire to help others as one's purpose in life. Antecedents to the concept are personal introspection and cognitive awareness. Positive consequences to the concept are improved work meaningfulness, work engagement, career commitment, personal well-being, and satisfaction. Negative consequences of having a calling might include willingness to sacrifice well-being for work and problems with work-life balance. Following the concept analysis, philosophical assumptions, contextual factors, interdisciplinary work, research opportunities, and practice implications are discussed.

  1. An Evaluation Framework for CALL

    Science.gov (United States)

    McMurry, Benjamin L.; Williams, David Dwayne; Rich, Peter J.; Hartshorn, K. James

    2016-01-01

    Searching prestigious Computer-assisted Language Learning (CALL) journals for references to key publications and authors in the field of evaluation yields a short list. The "American Journal of Evaluation"--the flagship journal of the American Evaluation Association--is only cited once in both the "CALICO Journal and Language…

  2. Concurrent AURKA and MYCN Gene Amplifications Are Harbingers of Lethal TreatmentRelated Neuroendocrine Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Juan Miguel Mosquera

    2013-01-01

    Full Text Available Neuroendocrine prostate cancer (NEPC, also referred to as anaplastic prostate cancer, is a lethal tumor that most commonly arises in late stages of prostate adenocarcinoma (PCA with predilection to metastasize to visceral organs. In the current study, we explore for evidence that Aurora kinase A (AURKA and N-myc (MYCN gene abnormalities are harbingers of treatment-related NEPC (t-NEPC. We studied primary prostate tissue from 15 hormone naïve PCAs, 51 castration-resistant prostate cancers, and 15 metastatic tumors from 72 patients at different stages of disease progression to t-NEPC, some with multiple specimens. Histologic evaluation, immunohistochemistry, and fluorescence in situ hybridization were performed and correlated with clinical variables. AURKA amplification was identified in overall 65% of PCAs (hormone naïve and treated from patients that developed t-NEPC and in 86% of metastases. Concurrent amplification of MYCN was present in 70% of primary PCAs, 69% of treated PCAs, and 83% of metastases. In contrast, in an unselected PCA cohort, AURKA and MYCN amplifications were identified in only 5% of 169 cases. When metastatic t-NEPC was compared to primary PCA from the same patients, there was 100% concordance of ERG rearrangement, 100% concordance of AURKA amplification, and 60% concordance of MYCN amplification. In tumors with mixed features, there was also 100% concordance of ERG rearrangement and 94% concordance of AURKA and MYCN co-amplification between areas of NEPC and adenocarcinoma. AURKA and MYCN amplifications may be prognostic and predictive biomarkers, as they are harbingers of tumors at risk of progressing to t-NEPC after hormonal therapy.

  3. Differential gene expression in response to juvenile hormone analog treatment in the damp-wood termite Hodotermopsis sjostedti (Isoptera, Archotermopsidae).

    Science.gov (United States)

    Cornette, Richard; Hayashi, Yoshinobu; Koshikawa, Shigeyuki; Miura, Toru

    2013-04-01

    Termite societies are characterized by a highly organized division of labor among conspicuous castes, groups of individuals with various morphological specializations. Termite caste differentiation is under control of juvenile hormone (JH), but the molecular mechanism underlying the response to JH and early events triggering caste differentiation are still poorly understood. In order to profile candidate gene expression during early soldier caste differentiation of the damp-wood termite, Hodotermopsis sjostedti, we treated pseudergates (workers) with a juvenile hormone analog (JHA) to induce soldier caste differentiation. We then used Suppressive Subtractive Hybridization to create two cDNA libraries enriched for transcripts that were either up- or downregulated at 24h after treatment. Finally, we used quantitative PCR to confirm temporal expression patterns. Hexamerins represent a large proportion of the genes upregulated following JHA treatment and have an expression pattern that shows roughly an inverse correlation to intrinsic JH titers. This data is consistent with the role of a JH "sink", which was demonstrated for hexamerins in another termite, Reticulitermes flavipes. A putative nuclear protein was also upregulated a few hours after JHA treatment, which suggests a role in the early response to JH and subsequent regulation of transcriptional events associated with soldier caste differentiation. Some digestive enzymes, such as endogenous beta-endoglucanase and chymotrypsin, as well as a protein associated to digestion were identified among genes downregulated after JHA treatment. This suggests that JH may directly influence the pseudergate-specific digestive system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Identification of Genes and Genetic Variants Associated with Poor Treatment Response in Patients with Prostate Cancer

    Science.gov (United States)

    2012-10-01

    gene DAL-1 (Jiang and Newsham, 2006). The gene NELL1 ( Homo sapiens NEL-like 1) may be involved in cell growth regulation and differentiation by...interval for the pedigree linked to chromosome 11 occurs approximately 34-46 cM. This region contains 13 currently documented genomic features , several

  5. Reducing juvenile delinquency with automated cell phone calls.

    Science.gov (United States)

    Burraston, Bert O; Bahr, Stephen J; Cherrington, David J

    2014-05-01

    Using a sample of 70 juvenile probationers (39 treatment and 31 controls), we evaluated the effectiveness of a rehabilitation program that combined cognitive-behavioral training and automated phone calls. The cognitive-behavioral training contained six 90-min sessions, one per week, and the phone calls occurred twice per day for the year following treatment. Recidivism was measured by whether they were rearrested and the total number of rearrests during the 1st year. To test the impact of the phone calls, those who received phone calls were divided into high and low groups depending on whether they answered more or less than half of their phone calls. Those who completed the class and answered at least half of their phone calls were less likely to have been arrested and had fewer total arrests.

  6. Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healing-associated genes

    Directory of Open Access Journals (Sweden)

    Matt C Danzi

    2016-01-01

    Full Text Available Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion (DRG sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.

  7. Calle y Saberes en Movimiento

    Directory of Open Access Journals (Sweden)

    Laura Daniela Aguirre Aguilar

    2010-01-01

    Full Text Available En México el rezago, el ausentismo, la deserción escolar, el trabajo a temprana edad y el inicio de una vida en la calle, en repetidas ocasiones son consecuencia de un núcleo familiar desarticulado o de una débil relación intrafamiliar, así como de una condición socioeconómica en desventaja. Ante esta problemática, la Secretaría de Educación Pública, instancia gubernamental encargada de garantizar una educación de calidad para la población, trabaja coordinadamente con organizaciones de la sociedad civil e instancias públicas, para la reintegración a los espacios educativos de los niños, niñas y jóvenes en situación de calle.

  8. Global hepatic gene expression in rainbow trout exposed to sewage effluents: a comparison of different sewage treatment technologies.

    Science.gov (United States)

    Cuklev, Filip; Gunnarsson, Lina; Cvijovic, Marija; Kristiansson, Erik; Rutgersson, Carolin; Björlenius, Berndt; Larsson, D G Joakim

    2012-06-15

    Effluents from sewage treatment plants contain a mixture of micropollutants with the potential of harming aquatic organisms. Thus, addition of advanced treatment techniques to complement existing conventional methods has been proposed. Some of the advanced techniques could, however, potentially produce additional compounds affecting exposed organisms by unknown modes of action. In the present study the aim was to improve our understanding of how exposure to different sewage effluents affects fish. This was achieved by explorative microarray and quantitative PCR analyses of hepatic gene expression, as well as relative organ sizes of rainbow trout exposed to different sewage effluents (conventionally treated, granular activated carbon, ozonation (5 or 15 mg/L), 5 mg/L ozone plus a moving bed biofilm reactor, or UV-light treatment in combination with hydrogen peroxide). Exposure to the conventionally treated effluent caused a significant increase in liver and heart somatic indexes, an effect removed by all other treatments. Genes connected to xenobiotic metabolism, including cytochrome p450 1A, were differentially expressed in the fish exposed to the conventionally treated effluents, though only effluent treatment with granular activated carbon or ozone at 15 mg/L completely removed this response. The mRNA expression of heat shock protein 70 kDa was induced in all three groups exposed to ozone-treated effluents, suggesting some form of added stress in these fish. The induction of estrogen-responsive genes in the fish exposed to the conventionally treated effluent was effectively reduced by all investigated advanced treatment technologies, although the moving bed biofilm reactor was least efficient. Taken together, granular activated carbon showed the highest potential of reducing responses in fish induced by exposure to sewage effluents. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Amoxicillin effects on functional microbial community and spread of antibiotic resistance genes in amoxicillin manufacture wastewater treatment system.

    Science.gov (United States)

    Meng, Lingwei; Li, Xiangkun; Wang, Xinran; Ma, Kaili; Liu, Gaige; Zhang, Jie

    2017-11-01

    This study aimed to reveal how amoxicillin (AMX) affected the microbial community and the spread mechanism of antibiotic resistance genes (ARGs) in the AMX manufacture wastewater treatment system. For this purpose, a 1.47 L expanded granular sludge bed (EGSB) reactor was designed and run for 241days treating artificial AMX manufacture wastewater. 454 pyrosequencing was applied to analyze functional microorganisms in the system. The antibiotic genes OXA- 1 , OXA -2 , OXA -10 , TEM -1 , CTX-M -1 , class I integrons (intI1) and 16S rRNA genes were also examined in sludge samples. The results showed that the genera Ignavibacterium, Phocoenobacter, Spirochaeta, Aminobacterium and Cloacibacillus contributed to the degradation of different organic compounds (such as various sugars and amines). And the relative quantification of each β-lactam resistance gene in the study was changed with the increasing of AMX concentration. Furthermore the vertical gene transfer was the main driver for the spread of ARGs rather than horizontal transfer pathways in the system. Copyright © 2017. Published by Elsevier B.V.

  10. Ultrasound call detection in capybara

    Directory of Open Access Journals (Sweden)

    Selene S.C. Nogueira

    2012-07-01

    Full Text Available The vocal repertoire of some animal species has been considered a non-invasive tool to predict distress reactivity. In rats ultrasound emissions were reported as distress indicator. Capybaras[ vocal repertoire was reported recently and seems to have ultrasound calls, but this has not yet been confirmed. Thus, in order to check if a poor state of welfare was linked to ultrasound calls in the capybara vocal repertoire, the aim of this study was to track the presence of ultrasound emissions in 11 animals under three conditions: 1 unrestrained; 2 intermediately restrained, and 3 highly restrained. The ultrasound track identified frequencies in the range of 31.8±3.5 kHz in adults and 33.2±8.5 kHz in juveniles. These ultrasound frequencies occurred only when animals were highly restrained, physically restrained or injured during handling. We concluded that these calls with ultrasound components are related to pain and restraint because they did not occur when animals were free of restraint. Thus we suggest that this vocalization may be used as an additional tool to assess capybaras[ welfare.

  11. A Gene Expression Signature Associated With Overall Survival in Patients With Hepatocellular Carcinoma Suggests a New Treatment Strategy

    DEFF Research Database (Denmark)

    Gillet, Jean-Pierre; Andersen, Jesper B; Madigan, James P

    2015-01-01

    Despite improvements in the management of liver cancer, the survival rate for individuals with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure...... are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance-associated genes in two independent cohorts of patients with advanced hepatocellular carcinoma, with the aim of finding ways to improve survival in this poor-prognosis cancer...

  12. Lipopolyplex for therapeutic gene delivery and its application for the treatment of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Wei eChen

    2016-04-01

    Full Text Available Abstract: Lipopolyplex is a core-shell structure composed of nucleic acid, polycation and lipid. As a non-viral gene delivery vector, lipopolyplex combining the advantages of polyplex and lipoplex has shown superior colloidal stability, reduced cytotoxicity, extremely high gene transfection efficiency. Following intravenous administration, there are many strategies based on lipopolyplex to overcome the complex biological barriers in systemic gene delivery including condensation of nucleic acids into nanoparticles, long circulation, cell targeting, endosomal escape, release to cytoplasm and entry into cell nucleus. Parkinson’s disease is the second most common neurodegenerative disorder and severely influences the patients’ life quality. Current gene therapy clinical trials for Parkinson’s disease employing viral vectors didn’t achieve satisfactory efficacy. However, lipopolyplex may become a promising alternative approach owing to its stability in blood, ability to cross the blood-brain barrier and specific targeting to diseased brain cells.

  13. A theoretical treatment of interval mapping of a disease gene using ...

    Indian Academy of Sciences (India)

    SEARCHU

    increases with the decrease in recombination probability and that it is higher for a lower frequency of the disease gene. ... based methods could be employed to develop statistics for ..... for phase inference, which can handle data on related.

  14. Targeting pancreatic expressed PAX genes for the treatment of diabetes mellitus and pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Martin-Montalvo, Alejandro; Lorenzo, Petra I; López-Noriega, Livia; Gauthier, Benoit R

    2017-01-01

    Four members of the PAX family, PAX2, PAX4, PAX6 and PAX8 are known to be expressed in the pancreas. Accumulated evidences indicate that several pancreatic expressed PAX genes play a significant role in pancreatic development/functionality and alterations in these genes are involved in the pathogenesis of pancreatic diseases. Areas covered: In this review, we summarize the ongoing research related to pancreatic PAX genes in diabetes mellitus and pancreatic neuroendocrine tumors. We dissect the current knowledge at different levels; from mechanistic studies in cell lines performed to understand the molecular processes controlled by pancreatic PAX genes, to in vivo studies using rodent models that over-express or lack specific PAX genes. Finally, we describe human studies associating variants on pancreatic-expressed PAX genes with pancreatic diseases. Expert opinion: Based on the current literature, we propose that future interventions to treat pancreatic neuroendocrine tumors and diabetes mellitus could be developed via the modulation of PAX4 and/or PAX6 regulated pathways.

  15. A L-type lectin gene is involved in the response to hormonal treatment and water deficit in Volkamer lemon.

    Science.gov (United States)

    Vieira, Dayse Drielly Sousa Santana; Emiliani, Giovanni; Bartolini, Paola; Podda, Alessandra; Centritto, Mauro; Luro, François; Carratore, Renata Del; Morillon, Raphaël; Gesteira, Abelmon; Maserti, Biancaelena

    2017-11-01

    Combination of biotic and abiotic stress is a major challenge for crop and fruit production. Thus, identification of genes involved in cross-response to abiotic and biotic stress is of great importance for breeding superior genotypes. Lectins are glycan-binding proteins with a functions in the developmental processes as well as in the response to biotic and abiotic stress. In this work, a lectin like gene, namely ClLectin1, was characterized in Volkamer lemon and its expression was studied in plants exposed to either water stress, hormonal elicitors (JA, SA, ABA) or wounding to understand whether this gene may have a function in the response to multiple stress combination. Results showed that ClLectin1 has 100% homology with a L-type lectin gene from C. sinensis and the in silico study of the 5'UTR region showed the presence of cis-responsive elements to SA, DRE2 and ABA. ClLectin1 was rapidly induced by hormonal treatments and wounding, at local and systemic levels, suggesting an involvement in defence signalling pathways and a possible role as fast detection biomarker of biotic stress. On the other hand, the induction of ClLectin1 by water stress pointed out a role of the gene in the response to drought. The simultaneous response of ClLectin1 expression to water stress and SA treatment could be further investigated to assess whether a moderate drought stress may be useful to improve citrus performance by stimulating the SA-dependent response to biotic stress. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Reciprocity of mobile phone calls

    OpenAIRE

    Kovanen, Lauri; Saramaki, Jari; Kaski, Kimmo

    2010-01-01

    We present a study of the reciprocity of human behaviour based on mobile phone usage records. The underlying question is whether human relationships are mutual, in the sense that both are equally active in keeping up the relationship, or is it on the contrary typical that relationships are lopsided, with one party being significantly more active than the other. We study this question with the help of a mobile phone data set consisting of all mobile phone calls between 5.3 million customers of...

  17. What Do Monkey Calls Mean?

    Science.gov (United States)

    Schlenker, Philippe; Chemla, Emmanuel; Zuberbühler, Klaus

    2016-12-01

    A field of primate linguistics is gradually emerging. It combines general questions and tools from theoretical linguistics with rich data gathered in experimental primatology. Analyses of several monkey systems have uncovered very simple morphological and syntactic rules and have led to the development of a primate semantics that asks new questions about the division of semantic labor between the literal meaning of monkey calls, additional mechanisms of pragmatic enrichment, and the environmental context. We show that comparative studies across species may validate this program and may in some cases help in reconstructing the evolution of monkey communication over millions of years. Copyright © 2016. Published by Elsevier Ltd.

  18. Gene Expression Differences Predict Treatment Outcome of Merkel Cell Carcinoma Patients

    Directory of Open Access Journals (Sweden)

    Loren Masterson

    2014-01-01

    Full Text Available Due to the rarity of Merkel cell carcinoma (MCC, prospective clinical trials have not been practical. This study aimed to identify biomarkers with prognostic significance. While sixty-two patients were identified who were treated for MCC at our institution, only seventeen patients had adequate formalin-fixed paraffin-embedded archival tissue and followup to be included in the study. Patients were stratified into good, moderate, or poor prognosis. Laser capture microdissection was used to isolate tumor cells for subsequent RNA isolation and gene expression analysis with Affymetrix GeneChip Human Exon 1.0 ST arrays. Among the 191 genes demonstrating significant differential expression between prognostic groups, keratin 20 and neurofilament protein have previously been identified in studies of MCC and were significantly upregulated in tumors from patients with a poor prognosis. Immunohistochemistry further established that keratin 20 was overexpressed in the poor prognosis tumors. In addition, novel genes of interest such as phospholipase A2 group X, kinesin family member 3A, tumor protein D52, mucin 1, and KIT were upregulated in specimens from patients with poor prognosis. Our pilot study identified several gene expression differences which could be used in the future as prognostic biomarkers in MCC patients.

  19. Impact of blue, red, and far-red light treatments on gene expression and steviol glycoside accumulation in Stevia rebaudiana.

    Science.gov (United States)

    Yoneda, Yuki; Nakashima, Hiroshi; Miyasaka, Juro; Ohdoi, Katsuaki; Shimizu, Hiroshi

    2017-05-01

    Stevia rebaudiana (Bertoni) Bertoni is a plant that biosynthesizes a group of natural sweeteners that are up to approximately 400 times sweeter than sucrose. The sweetening components of S. rebaudiana are steviol glycosides (SGs) that partially share their biosynthesis pathway with gibberellins (GAs). However, the molecular mechanisms through which SGs levels can be improved have not been studied. Therefore, transcription levels of several SG biosynthesis-related genes were analyzed under several light treatments involved in GA biosynthesis. We detected higher transcription of UGT85C2, which is one of the UDP-glycosyltransferases (UGTs) involved in catalyzing the sugar-transfer reaction, under red/far-red (R/FR) 1.22 light-emitting diodes (LEDs) and blue LEDs treatment. In this study, it was demonstrated that transcription levels of SG-related genes and the SGs content are affected by light treatments known to affect the GA contents. It is expected that this approach could serve as a practical way to increase SG contents using specific light treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Neonatal Diabetes: An Expanding List of Genes Allows for Improved Diagnosis and Treatment

    Science.gov (United States)

    Naylor, Rochelle N.; Philipson, Louis H.; Bell, Graeme I.

    2011-01-01

    There has been major progress in recent years uncovering the genetic causes of diabetes presenting in the first year of life. Twenty genes have been identified to date. The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel (KATP), KCNJ11 and ABCC8, and the insulin gene (INS), as well as abnormalities in chromosome 6q24. Patients with activating mutations in KCNJ11 and ABCC8 can be treated with oral sulfonylureas in lieu of insulin injections. This compelling example of personalized genetic medicine leading to improved glucose regulation and quality of life may—with continued research—be repeated for other forms of neonatal diabetes in the future. PMID:21993633

  1. When gene medication is also genetic modification--regulating DNA treatment.

    Science.gov (United States)

    Foss, Grethe S; Rogne, Sissel

    2007-07-26

    The molecular methods used in DNA vaccination and gene therapy resemble in many ways the methods applied in genetic modification of organisms. In some regulatory regimes, this creates an overlap between 'gene medication' and genetic modification. In Norway, an animal injected with plasmid DNA, in the form of DNA vaccine or gene therapy, currently is viewed as being genetically modified for as long as the added DNA is present in the animal. However, regulating a DNA-vaccinated animal as genetically modified creates both regulatory and practical challenges. It is also counter-intuitive to many biologists. Since immune responses can be elicited also to alter traits, the borderline between vaccination and the modification of properties is no longer distinct. In this paper, we discuss the background for the Norwegian interpretation and ways in which the regulatory challenge can be handled.

  2. Identification of Genes Differentially Expressed During Heat Shock Treatment in Aedes aegypti

    Science.gov (United States)

    2009-01-01

    Chan, C. W. Cheng, and R. S. Wu. 2003. Cloning of theHSP70 gene in barnacle larvae and its expression under hypoxic conditions. Mar. Pollut. Bull. 46...665Ð671. Chuang, K. H., S. H. Ho, and Y. L. Song. 2007. Cloning and expression analysis of heat shock cognate 70 gene pro- moter in tiger shrimp ...in larvae , but not adults, of a polar insect. Proc. Natl. Acad. Sci. U.S.A. 103: 14223Ð14227. Robich, R. M., J. P. Rinehart, L. J. Kitchen, and D. L

  3. Treatment of rat gliomas with recombinant retrovirus harboring Herpes simplex virus thymidine kinase suicide gene

    International Nuclear Information System (INIS)

    Hlavaty, J.; Hlubinova, K.; Altanerova, V.; Liska, J.; Altaner, C.

    1997-01-01

    The retrovirus vector containing Herpes simplex virus type 1 thymidine kinase (HSVtk) gene was constructed. The vector was transfected into the packaging cell line PG13. It was shown that individual transfected cells differ in the production of recombinant retrovirus and in their susceptibility to be killed by ganciclovir. Recombinant retrovirus with a gibbon envelope was able to transduced the HSVtk gene into rat glioma cells. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to influence subcutaneous and intracerebral tumors developed after injection of C 6 rat glioma cells with subsequent injection of HSVtk retrovirus producing cells. (author)

  4. Short- and long-term changes in sugarbeet (Beta vulgaris L. gene expression due to postharvest jasmonic acid treatment - Data

    Directory of Open Access Journals (Sweden)

    Lucilene Silva de Oliveira

    2017-04-01

    Full Text Available Jasmonic acid is a natural plant hormone that induces native defense responses in plants. Sugarbeet (Beta vulgaris L. root unigenes that were differentially expressed 2 and 60 days after a postharvest jasmonic acid treatment are presented. Data include changes in unigene expression relative to water-treated controls, unigene annotations against nonredundant (Nr, Swiss-Prot, Clusters of Orthologous Groups (COG, and Kyoto Encyclopedia of Genes and Genomes (KEGG protein databases, and unigene annotations with Gene Ontology (GO terms. Putative defense unigenes are compiled and annotated against the sugarbeet genome. Differential gene expression data were generated by RNA sequencing. Interpretation of the data is available in the research article, “Jasmonic acid causes short- and long-term alterations to the transcriptome and the expression of defense genes in sugarbeet roots” (K.K. Fugate, L.S. Oliveira, J.P. Ferrareze, M.D. Bolton, E.L. Deckard, F.L. Finger, 2017 [1]. Public dissemination of this dataset will allow further analyses of the data.

  5. Altered Gene Expression in Three Plant Species in Response to Treatment with Nep1, a Fungal Protein That Causes Necrosis

    Science.gov (United States)

    Keates, Sarah E.; Kostman, Todd A.; Anderson, James D.; Bailey, Bryan A.

    2003-01-01

    Nep1 is an extracellular fungal protein that causes necrosis when applied to many dicotyledonous plants, including invasive weed species. Using transmission electron microscopy, it was determined that application of Nep1 (1.0 μg mL–1, 0.1% [v/v] Silwet-L77) to Arabidopsis and two invasive weed species, spotted knapweed (Centaurea maculosa) and dandelion (Taraxacum officinale), caused a reduction in the thickness of the cuticle and a breakdown of chloroplasts 1 to 4 h after treatment. Membrane breakdown was most severe in cells closest to the surface of application. Differential display was used to isolate cDNA clones from the three species showing differential expression in response to Nep1 treatment. Differential gene expression was observed for a putative serpin (CmSER-1) and a calmodulin-like (CmCAL-1) protein from spotted knapweed, and a putative protein phosphatase 2C (ToPP2C-1) and cytochrome P-450 (ToCYP-1) protein from dandelion. In addition, differential expression was observed for genes coding for a putative protein kinase (AtPK-1), a homolog (AtWI-12) of wound-induced WI12, a homolog (AtLEA-1) of late embryogenesis abundant LEA-5, a WRKY-18 DNA-binding protein (AtWRKY-18), and a phospholipase D (AtPLD-1) from Arabidopsis. Genes showing elevated mRNA levels in Nep1-treated (5 μg mL–1, 0.1% [v/v] Silwet-L77) leaves 15 min after Nep1 treatment included CmSER-1 and CmCAL-1 for spotted knapweed, ToCYP-1 and CmCAL-1 for dandelion, and AtPK-1, AtWRKY-18, AtWI-12, and AtLEA-1 for Arabidopsis. Levels of mRNA for AtPLD-1 (Arabidopsis) and ToPP2C-1 (dandelion) decreased rapidly in Silwet-l77-treated plants between 15 min and 4 h of treatment, but were maintained or decreased more slowly over time in Nep1-treated (5 μg mL–1, 0.1% [v/v] Silwet-L77) leaves. In general, increases in mRNA band intensities were in the range of two to five times, with only ToCYP-1 in dandelion exceeding an increase of 10 times. The identified genes have been shown to be involved

  6. Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53

    Directory of Open Access Journals (Sweden)

    Arindam Datta

    2016-06-01

    Full Text Available Mutation in TP53 is a common genetic alteration in human cancers. Certain tumor associated p53 missense mutants acquire gain-of-function (GOF properties and confer oncogenic phenotypes including enhanced chemoresistance. The colorectal cancers (CRC harboring mutant p53 are generally aggressive in nature and difficult to treat. To identify a potential gene expression signature of GOF mutant p53-driven acquired chemoresistance in CRC, we performed transcriptome profiling of floxuridine (FUdR treated SW480 cells expressing mutant p53R273H (GEO#: GSE77533. We obtained several genes differentially regulated between FUdR treated and untreated cells. Further, functional characterization and pathway analysis revealed significant enrichment of crucial biological processes and pathways upon FUdR treatment in SW480 cells. Our data suggest that in response to chemotherapeutics treatment, cancer cells with GOF mutant p53 can modulate key cellular pathways to withstand the cytotoxic effect of the drugs. The genes and pathways identified in the present study can be further validated and targeted for better chemotherapy response in colorectal cancer patients harboring mutant p53.

  7. N-acetyltransferase 2 (NAT2 Gene Polymorphisms and the Effectiveness of Infertility Treatment in Patients with Peritoneal Endometriosis

    Directory of Open Access Journals (Sweden)

    Ekaterina D. Dubinskaya

    2014-03-01

    Full Text Available Today, infertility has become a global issue. WHO ranks it the fifth among the major diseases of those below 60 years, after alcoholism, depression, injuries and eyesight disorders. Numerous studies conducted on the problems of infertility in endometriosis still do not offer clear answers regarding the pathogenesis and mechanisms of this disease and its influences on fertility. According to the survey results, point mutations of the NAT2 gene (NAT2*5 and NAT2*6 have been identified in 75.6% of the patients with infertility problems and the peritoneal form of endometriosis, that create “slow” allelic variants, which exceed the average index in the population. The peculiarities of the NAT2 gene polymorphisms have been proven to be associated with the effectiveness of the infertility treatment of female patients with peritoneal endometriosis. In the group of non-pregnant patients, the presence of с.341Т>C, c.481C>T, c.590G>A and c.803A>G heterozygous point mutations are 73.2, 73.2, 5.4, and 62.5%, respectively. The significant difference in the comparison of the allelic polymorphism during the various stages of the endometriosis was not identified. At stage III-IV endometriosis the frequency of three and more point substitutions was significantly higher. NAT2 gene polymorphisms can find use as an additional criterion for predicting the effectiveness of the infertility treatment of patients with peritoneal endometriosis.

  8. Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

    Science.gov (United States)

    BANERJI, JULIAN

    2015-01-01

    The present treatment of childhood T-cell leukemias involves the systemic administration of prokary-otic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity. PMID:26178806

  9. Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).

    Science.gov (United States)

    Banerji, Julian

    2015-09-01

    The present treatment of childhood T-cell leukemias involves the systemic administration of prokaryotic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity.

  10. Distribution of tetracycline resistance genes in anaerobic treatment of waste sludge: The role of pH in regulating tetracycline resistant bacteria and horizontal gene transfer.

    Science.gov (United States)

    Huang, Haining; Chen, Yinguang; Zheng, Xiong; Su, Yinglong; Wan, Rui; Yang, Shouye

    2016-10-01

    Although pH value has been widely regarded as an important factor that affects resource recovery of waste sludge, the potential influence of diverse pHs on the distribution of tetracycline resistance genes (TRGs) during sludge anaerobic treatment is largely unknown. Here we reported that in the range of pH 4-10, 0.58-1.18 log unit increase of target TRGs was observed at pH 4, compared with that at pH 7, while 0.70-1.31 log unit further removal were obtained at pH 10. Mechanism study revealed that varied pHs not only altered the community structures of tetracycline resistant bacteria (TRB), but also changed their relative abundances, benefitting the propagation (acidic pHs) or attenuation (alkaline pHs) of TRB. Further investigation indicated that the amount and gene-possessing abilities of key genetic vectors for horizontal TRGs transfer were greatly promoted at acidic pHs but restricted under alkaline conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Gene amplification in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lucimari Bizari

    2006-01-01

    Full Text Available Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM and homogeneously staining regions (HSR, both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

  12. Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs) with different waste load

    DEFF Research Database (Denmark)

    Laht, Mailis; Karkman, Antti; Voolaid, Veiko

    2014-01-01

    Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs), an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs) were quantified using qPCR in three WWTPs of decreasing capacity located...... abundances with 16S rRNA gene abundances while assessing if the respective genes increased or decreased during treatment. ARGs were detected in most samples; sul1, sul2, and tetM were detected in all samples. Statistically significant differences (adjusted p... in the relative abundance of resistance genes, while the raw abundances fell by several orders of magnitude. Standard water quality variables (biological oxygen demand, total phosphorus and nitrogen, etc.) were weakly related or unrelated to the relative abundance of resistance genes. Based on our results we...

  13. Gene therapies that restore dystrophin expression for the treatment of Duchenne muscular dystrophy

    Science.gov (United States)

    Robinson-Hamm, Jacqueline N.; Gersbach, Charles A.

    2016-01-01

    Duchenne muscular dystrophy is one of the most common inherited genetic diseases and is caused by mutations to the DMD gene that encodes the dystrophin protein. Recent advances in genome editing and gene therapy offer hope for the development of potential therapeutics. Truncated versions of the DMD gene can be delivered to the affected tissues with viral vectors and show promising results in a variety of animal models. Genome editing with the CRISPR/Cas9 system has recently been used to restore dystrophin expression by deleting one or more exons of the DMD gene in patient cells and in a mouse model that led to functional improvement of muscle strength. Exon skipping with oligonucleotides has been successful in several animal models and evaluated in multiple clinical trials. Next-generation oligonucleotide formulations offer significant promise to build on these results. All these approaches to restoring dystrophin expression are encouraging, but many hurdles remain. This review summarizes the current state of these technologies and summarizes considerations for their future development. PMID:27542949

  14. A theoretical treatment of interval mapping of a disease gene using ...

    Indian Academy of Sciences (India)

    The genetic basis of the transmission disequilibrium test (TDT) for two-marker loci is explored from first principles. In this case, parents doubly heterozygous for a given haplotype at the pair of marker loci that are each in linkage disequilibrium with the disease gene with the further possibility of a second-order linkage ...

  15. Combinatorial RNA-based gene therapy for the treatment of HIV/AIDS.

    Science.gov (United States)

    Chung, Janet; DiGiusto, David L; Rossi, John J

    2013-03-01

    HIV/AIDS continues to be a worldwide health problem and viral eradication has been an elusive goal. HIV+ patients are currently treated with combination antiretroviral therapy (cART) which is not curative. For many patients, cART is inaccessible, intolerable or unaffordable. Therefore, a new class of therapeutics for HIV is required to overcome these limitations. Cell and gene therapy for HIV has been proposed as a way to provide a functional cure for HIV in the form of a virus/infection resistant immune system. In this review, the authors describe the standard therapy for HIV/AIDS, its limitations, current areas of investigation and the potential of hematopoietic stem cells modified with anti-HIV RNAs as a means to affect a functional cure for HIV. Cell and gene therapy for HIV/AIDS is a promising alternative to antiviral drug therapy and may provide a functional cure. In order to show clinical benefit, multiple mechanisms of inhibition of HIV entry and lifecycle are likely to be required. Among the most promising antiviral strategies is the use of transgenic RNA molecules that provide protection from HIV infection. When these molecules are delivered as gene-modified hematopoietic stem and progenitor cells, long-term repopulation of the patient's immune system with gene-modified progeny has been observed.

  16. Fate of antibiotic resistance genes in mesophilic and thermophilic anaerobic digestion of chemically enhanced primary treatment (CEPT) sludge.

    Science.gov (United States)

    Jang, Hyun Min; Shin, Jingyeong; Choi, Sangki; Shin, Seung Gu; Park, Ki Young; Cho, Jinwoo; Kim, Young Mo

    2017-11-01

    Anaerobic digestion (AD) of chemically enhanced primary treatment (CEPT) sludge and non-CEPT (conventional sedimentation) sludge were comparatively operated under mesophilic and thermophilic conditions. The highest methane yield (692.46±0.46mL CH 4 /g VS removed in CEPT sludge) was observed in mesophilic AD of CEPT sludge. Meanwhile, thermophilic conditions were more favorable for the removal of total antibiotic resistance genes (ARGs). In this study, no measurable difference in the fates and removal of ARGs and class 1 integrin-integrase gene (intI1) was observed between treated non-CEPT and CEPT sludge. However, redundancy analysis indicated that shifts in bacterial community were primarily accountable for the variations in ARGs and intI1. Network analysis further revealed potential host bacteria for ARGs and intI1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. HDAC gene expression in pancreatic tumor cell lines following treatment with the HDAC inhibitors panobinostat (LBH589) and trichostatine (TSA).

    Science.gov (United States)

    Mehdi, Ouaïssi; Françoise, Silvy; Sofia, Costa Lima; Urs, Giger; Kevin, Zemmour; Bernard, Sastre; Igor, Sielezneff; Anabela, Cordeiro-da-Silva; Dominique, Lombardo; Eric, Mas; Ali, Ouaïssi

    2012-01-01

    In this study, the effect of LBH589 and trichostatin (TSA), a standard histone deacetylase inhibitor (HDACi) toward the growth of pancreatic cancer cell lines was studied. Thus, we examined for the first time, the HDAC family gene expression levels before and after drug treatment. Several human pancreatic cancer cell lines (Panc-1, BxPC-3, SOJ-6) and a normal human pancreatic duct immortalized epithelial cell line (HPDE/E6E7) were used as target cells. The cell growth was measured by MTT assay, cell cycle alteration, membrane phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane potential loss, RT-PCR and Western blots were done using standard methods. The effect of drugs on tumor growth in vivo was studied using subcutaneous xenograft model. Except in the case of certain HDAC gene/tumor cell line couples: (SIRT1/HPDE-SOJ6/TSA- or LBH589-treated cells; LBH589-treated Panc-1 Cells; HDAC2/BxPC-3/LBH589-treated cells or TSA-treated SOJ-6-1 cells), there were no major significant changes of HDACs genes transcription in cells upon drug treatment. However, significant variation in HDACs and SIRTs protein expression levels could be seen among individual cell samples. The in vivo results showed that LBH589 formulation exhibited similar tumor reduction efficacy as the commercial drug gemcitabine. Our data demonstrate that LBH589 induced the death of pancreatic tumor cell by apoptosis. In line with its in vitro activity, LBH589 achieved a significant reduction in tumor growth in BxPC-3 pancreatic tumor cell line subcutaneous xenograft mouse model. Furthermore, exploring the impact of LBH589 on HDACs encoding genes expression revealed for the first time that some of them, depending on the cell line considered, seem to be regulated during translation. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  18. Effects of non-ablative fractional erbium glass laser treatment on gene regulation in human three-dimensional skin models.

    Science.gov (United States)

    Amann, Philipp M; Marquardt, Yvonne; Steiner, Timm; Hölzle, Frank; Skazik-Voogt, Claudia; Heise, Ruth; Baron, Jens M

    2016-04-01

    Clinical experiences with non-ablative fractional erbium glass laser therapy have demonstrated promising results for dermal remodelling and for the indications of striae, surgical scars and acne scars. So far, molecular effects on human skin following treatment with these laser systems have not been elucidated. Our aim was to investigate laser-induced effects on skin morphology and to analyse molecular effects on gene regulation. Therefore, human three-dimensional (3D) organotypic skin models were irradiated with non-ablative fractional erbium glass laser systems enabling qRT-PCR, microarray and histological studies at same and different time points. A decreased mRNA expression of matrix metalloproteinases (MMPs) 3 and 9 was observed 3 days after treatment. MMP3 also remained downregulated on protein level, whereas the expression of other MMPs like MMP9 was recovered or even upregulated 5 days after irradiation. Inflammatory gene regulatory responses measured by the expression of chemokine (C-X-C motif) ligands (CXCL1, 2, 5, 6) and interleukin expression (IL8) were predominantly reduced. Epidermal differentiation markers such as loricrin, filaggrin-1 and filaggrin-2 were upregulated by both tested laser optics, indicating a potential epidermal involvement. These effects were also shown on protein level in the immunofluorescence analysis. This novel standardised laser-treated human 3D skin model proves useful for monitoring time-dependent ex vivo effects of various laser systems on gene expression and human skin morphology. Our study reveals erbium glass laser-induced regulations of MMP and interleukin expression. We speculate that these alterations on gene expression level could play a role for dermal remodelling, anti-inflammatory effects and increased epidermal differentiation. Our finding may have implications for further understanding of the molecular mechanism of erbium glass laser-induced effects on human skin.

  19. Identification of Genes and Genetic Variants Associated with Poor Treatment Response in Patients with Prostate Cancer

    Science.gov (United States)

    2014-12-01

    relatives affected, paternal versus maternal family history, and age at first PC diagnosis. Results: 3,921 individuals in UPDB were diagnosed with...not appear to affect LPC RR. Higher risks of LPC were associated with the maternal compared to the paternal lineages. Conclusions: Examination of...genes identi- fied in Utah are represented similarly in other studies in terms of frequency, penetrance, and interactions with risk factors and

  20. Occurrence and Variety of β-Lactamase Genes among Aeromonas spp. Isolated from Urban Wastewater Treatment Plant

    Directory of Open Access Journals (Sweden)

    Marta Piotrowska

    2017-05-01

    Full Text Available Members of the genus Aeromonas that commonly occur in various aquatic ecosystems are taken into account as vectors spreading antibiotic resistance genes (ARGs in the environment. In our study strains of Aeromonas spp. (n = 104 not susceptible to ampicillin were isolated from municipal sewage of different levels of purification – raw sewage, activated sludge and treated wastewater. The crucial step of the study was the identification of β-lactamase resistance genes. The identified genes encode β-lactamases from 14 families – blaTEM, blaOXA, blaSHV, blaCTX-M, blaMOX, blaACC, blaFOX, blaGES, blaPER, blaV EB, blaKPC, cphA, imiH, and cepH. There were no significant differences in number of identified ARGs between isolation points. BlaOXA, blaFOX variants and, characteristic for Aeromonas genus, metallo-β-lactamase cphA-related genes were the most commonly identified types of β-lactam resistance determinants. Moreover, we found four extended-spectrum β-lactamases (blaSHV -11, blaCTX-M-27, blaCTX-M-98, and blaPER-4 – and seven AmpC (blaACC, blaFOX-2-like, blaFOX-3, blaFOX-4-like, blaFOX-9, blaFOX-10-like, and blaFOX-13-like types and variants of genes that had never been found among Aeromonas spp. before. Five of the β-lactamases families (blaTEM, blaOXA, blaFOX, blaV EB, and cphA were identified in all three isolation sites, which supports the hypothesis that wastewater treatment plants (WWTPs are hot spots of ARGs dissemination. The obtained ARGs sequences share high identity with previously described β-lactamases, but new variants of those genes have to be considered as well. Characterization of antibiotic susceptibility was performed using disk the diffusion method with 12 different antibiotics according to CLSI guidelines. Over 60% of the strains are unsusceptible to cefepime and chloramphenicol and the majority of the strains have a multidrug resistance phenotype (68%. Finally, analysis of plasmid profiles among the resistant strains

  1. Metagenomics shows that low-energy anaerobic-aerobic treatment reactors reduce antibiotic resistance gene levels from domestic wastewater.

    Science.gov (United States)

    Christgen, Beate; Yang, Ying; Ahammad, S Z; Li, Bing; Rodriquez, D Catalina; Zhang, Tong; Graham, David W

    2015-02-17

    Effective domestic wastewater treatment is among our primary defenses against the dissemination of infectious waterborne disease. However, reducing the amount of energy used in treatment processes has become essential for the future. One low-energy treatment option is anaerobic-aerobic sequence (AAS) bioreactors, which use an anaerobic pretreatment step (e.g., anaerobic hybrid reactors) to reduce carbon levels, followed by some form of aerobic treatment. Although AAS is common in warm climates, it is not known how its compares to other treatment options relative to disease transmission, including its influence on antibiotic resistance (AR) in treated effluents. Here, we used metagenomic approaches to contrast the fate of antibiotic-resistant genes (ARG) in anaerobic, aerobic, and AAS bioreactors treating domestic wastewater. Five reactor configurations were monitored for 6 months, and treatment performance, energy use, and ARG abundance and diversity were compared in influents and effluents. AAS and aerobic reactors were superior to anaerobic units in reducing ARG-like sequence abundances, with effluent ARG levels of 29, 34, and 74 ppm (198 ppm influent), respectively. AAS and aerobic systems especially reduced aminoglycoside, tetracycline, and β-lactam ARG levels relative to anaerobic units, although 63 persistent ARG subtypes were detected in effluents from all systems (of 234 assessed). Sulfonamide and chloramphenicol ARG levels were largely unaffected by treatment, whereas a broad shift from target-specific ARGs to ARGs associated with multi-drug resistance was seen across influents and effluents. AAS reactors show promise for future applications because they can reduce more ARGs for less energy (32% less energy here), but all three treatment options have limitations and need further study.

  2. Your Wake-Up Call

    Science.gov (United States)

    ... way to help your doctor determine if you need help with your sleep is to create a sleep diary for a ... whether there are subgroups of children who may need additional treatment to improve their sleep apnea. The researchers also will see if improvement ...

  3. Comprehensive gene expression analysis of the NAC gene family under normal growth conditions, hormone treatment, and drought stress conditions in rice using near-isogenic lines (NILs) generated from crossing Aday Selection (drought tolerant) and IR64.

    Science.gov (United States)

    Nuruzzaman, Mohammed; Sharoni, Akhter Most; Satoh, Kouji; Moumeni, Ali; Venuprasad, Ramiah; Serraj, Rachid; Kumar, Arvind; Leung, Hei; Attia, Kotb; Kikuchi, Shoshi

    2012-05-01

    The NAC (NAM, ATAF1/2 and CUC2) genes are plant-specific transcriptional factors known to play diverse roles in various plant developmental processes. We describe the rice (Oryza sativa) OsNAC genes expression profiles (GEPs) under normal and water-deficit treatments (WDTs). The GEPs of the OsNAC genes were analyzed in 25 tissues covering the entire life cycle of Minghui 63. High expression levels of 17 genes were demonstrated in certain tissues under normal conditions suggesting that these genes may play important roles in specific organs. We determined that 16 genes were differentially expressed under at least 1 phytohormone (NAA, GA3, KT, SA, ABA, and JA) treatment. To investigate the GEPs in the root, leaf, and panicle of three rice genotypes [e.g., 2 near-isogenic lines (NILs) and IR64], we used two NILs from a common genetic combination backcross developed by Aday Selection and IR64. WDTs were applied using the fraction of transpirable soil water at severe, mild, and control conditions. Transcriptomic analysis using a 44K oligoarray from Agilent was performed on all the tissue samples. We identified common and specific genes in all tissues from the two NILs under both WDTs, and the majority of the OsNAC genes that were activated were in the drought-tolerant IR77298-14-1-2-B-10 line compared with the drought-susceptible IR77298-14-1-2-B-13 or IR64. In IR77298-14-1-2-B-10, seventeen genes were very specific in their expression levels. Approximately 70 % of the genes from subgroups SNAC and NAM/CUC3 were activated in the leaf, but 37 % genes from subgroup SND were inactivated in the root compared with the control under severe stress conditions. These results provide a useful reference for the cloning of candidate genes from the specific subgroup for further functional analysis.

  4. BUFO PARDALIS (ANURA: BUFONIDAE): MATING CALL AND ...

    African Journals Online (AJOL)

    the calls of one of these species, Bufo pardalis. Hewitt, were not analysed by Tandy & Keith. (1972). Furthennore there is some confusion in the literature regarding the mating call of this species. For these reasons this mating call is here clarified. The mating call of B. pardaiis was first described by Ranger (in Hewitt 1935) as ...

  5. 78 FR 76218 - Rural Call Completion

    Science.gov (United States)

    2013-12-17

    ... calls to rural areas, and enforce restrictions against blocking, choking, reducing, or restricting calls... to alert the Commission of systemic problems receiving calls from a particular originating long... associated with completing calls to rural areas. These rules will also enhance our ability to enforce...

  6. Non-Thermal Plasma Treatment Diminishes Fungal Viability and Up-Regulates Resistance Genes in a Plant Host

    Science.gov (United States)

    Panngom, Kamonporn; Lee, Sang Hark; Park, Dae Hoon; Sim, Geon Bo; Kim, Yong Hee; Uhm, Han Sup; Park, Gyungsoon; Choi, Eun Ha

    2014-01-01

    Reactive oxygen and nitrogen species can have either harmful or beneficial effects on biological systems depending on the dose administered and the species of organism exposed, suggesting that application of reactive species can possibly produce contradictory effects in disease control, pathogen inactivation and activation of host resistance. A novel technology known as atmospheric-pressure non-thermal plasma represents a means of generating various reactive species that adversely affect pathogens (inactivation) while simultaneously up-regulating host defense genes. The anti-microbial efficacy of this technology was tested on the plant fungal pathogen Fusarium oxysporum f.sp. lycopersici and its susceptible host plant species Solanum lycopercicum. Germination of fungal spores suspended in saline was decreased over time after exposed to argon (Ar) plasma for 10 min. Although the majority of treated spores exhibited necrotic death, apoptosis was also observed along with the up-regulation of apoptosis related genes. Increases in the levels of peroxynitrite and nitrite in saline following plasma treatment may have been responsible for the observed spore death. In addition, increased transcription of pathogenesis related (PR) genes was observed in the roots of the susceptible tomato cultivar (S. lycopercicum) after exposure to the same Ar plasma dose used in fungal inactivation. These data suggest that atmospheric-pressure non-thermal plasma can be efficiently used to control plant fungal diseases by inactivating fungal pathogens and up-regulating mechanisms of host resistance. PMID:24911947

  7. Non-thermal plasma treatment diminishes fungal viability and up-regulates resistance genes in a plant host.

    Science.gov (United States)

    Panngom, Kamonporn; Lee, Sang Hark; Park, Dae Hoon; Sim, Geon Bo; Kim, Yong Hee; Uhm, Han Sup; Park, Gyungsoon; Choi, Eun Ha

    2014-01-01

    Reactive oxygen and nitrogen species can have either harmful or beneficial effects on biological systems depending on the dose administered and the species of organism exposed, suggesting that application of reactive species can possibly produce contradictory effects in disease control, pathogen inactivation and activation of host resistance. A novel technology known as atmospheric-pressure non-thermal plasma represents a means of generating various reactive species that adversely affect pathogens (inactivation) while simultaneously up-regulating host defense genes. The anti-microbial efficacy of this technology was tested on the plant fungal pathogen Fusarium oxysporum f.sp. lycopersici and its susceptible host plant species Solanum lycopercicum. Germination of fungal spores suspended in saline was decreased over time after exposed to argon (Ar) plasma for 10 min. Although the majority of treated spores exhibited necrotic death, apoptosis was also observed along with the up-regulation of apoptosis related genes. Increases in the levels of peroxynitrite and nitrite in saline following plasma treatment may have been responsible for the observed spore death. In addition, increased transcription of pathogenesis related (PR) genes was observed in the roots of the susceptible tomato cultivar (S. lycopercicum) after exposure to the same Ar plasma dose used in fungal inactivation. These data suggest that atmospheric-pressure non-thermal plasma can be efficiently used to control plant fungal diseases by inactivating fungal pathogens and up-regulating mechanisms of host resistance.

  8. Non-thermal plasma treatment diminishes fungal viability and up-regulates resistance genes in a plant host.

    Directory of Open Access Journals (Sweden)

    Kamonporn Panngom

    Full Text Available Reactive oxygen and nitrogen species can have either harmful or beneficial effects on biological systems depending on the dose administered and the species of organism exposed, suggesting that application of reactive species can possibly produce contradictory effects in disease control, pathogen inactivation and activation of host resistance. A novel technology known as atmospheric-pressure non-thermal plasma represents a means of generating various reactive species that adversely affect pathogens (inactivation while simultaneously up-regulating host defense genes. The anti-microbial efficacy of this technology was tested on the plant fungal pathogen Fusarium oxysporum f.sp. lycopersici and its susceptible host plant species Solanum lycopercicum. Germination of fungal spores suspended in saline was decreased over time after exposed to argon (Ar plasma for 10 min. Although the majority of treated spores exhibited necrotic death, apoptosis was also observed along with the up-regulation of apoptosis related genes. Increases in the levels of peroxynitrite and nitrite in saline following plasma treatment may have been responsible for the observed spore death. In addition, increased transcription of pathogenesis related (PR genes was observed in the roots of the susceptible tomato cultivar (S. lycopercicum after exposure to the same Ar plasma dose used in fungal inactivation. These data suggest that atmospheric-pressure non-thermal plasma can be efficiently used to control plant fungal diseases by inactivating fungal pathogens and up-regulating mechanisms of host resistance.

  9. Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

    Science.gov (United States)

    Ehrlich, David E.; Neigh, Gretchen N.; Bourke, Chase H.; Nemeth, Christina L.; Hazra, Rimi; Ryan, Steven J.; Rowson, Sydney; Jairam, Nesha; Sholar, Courtney; Rainnie, Donald G.; Stowe, Zachary N.; Owens, Michael J.

    2015-01-01

    Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure. PMID:26032436

  10. Sequential treatment of icotinib after first-line pemetrexed in advanced lung adenocarcinoma with unknown EGFR gene status.

    Science.gov (United States)

    Zheng, Yulong; Fang, Weijia; Deng, Jing; Zhao, Peng; Xu, Nong; Zhou, Jianying

    2014-07-01

    In non-small cell lung cancer (NSCLC), the well-developed epidermal growth factor receptor (EGFR) is an important therapeutic target. EGFR activating gene mutations have been proved strongly predictive of response to EGFR-tyrosine kinase inhibitors (TKI) in NSCLC. However, both in daily clinical practice and clinical trials, patients with unknown EGFR gene status (UN-EGFR-GS) are very common. In this study, we assessed efficacy and tolerability of sequential treatment of first-line pemetrexed followed by icotinib in Chinese advanced lung adenocarcinoma with UN-EGFR-GS. We analyzed 38 patients with advanced lung adenocarcinoma with UN-EGFR-GS treated with first-line pemetrexed-based chemotherapy followed by icotinib as maintenance or second-line therapy. The response rates to pemetrexed and icotinib were 21.1% and 42.1%, respectively. The median overall survival was 27.0 months (95% CI, 19.7-34.2 months). The 12-month overall survival probability was 68.4%. The most common toxicities observed in icotinib phase were rashes, diarrheas, and elevated aminotransferase. Subgroup analysis indicated that the overall survival is correlated with response to icotinib. The sequence of first-line pemetrexed-based chemotherapy followed by icotinib treatment is a promising option for advanced lung adenocarcinoma with UN-EGFR-GS in China.

  11. Monitoring and evaluation of antibiotic resistance genes in four municipal wastewater treatment plants in Harbin, Northeast China.

    Science.gov (United States)

    Wen, Qinxue; Yang, Lian; Duan, Ruan; Chen, Zhiqiang

    2016-05-01

    The development and proliferation of antibiotic resistance in pathogenic and environmental microorganisms is of great concern for public health. In this study, the distribution and removal efficiency of intI1 and eight subtypes of antibiotic resistance genes (ARGs) for tetracycline, sulfonamides, beta-lactams resistance in four municipal wastewater treatment plants (WWTPs) in Harbin, which locates in Songhua River basin in cold areas of China, were monitored by real-time fluorescent quantitative PCR. The results showed that intI1 and 6 ARGs except for blaTEM and blaSHV were detected in wastewater and sludge samples and 0.3-2.7 orders of magnitude of ARGs removal efficiency in the four WWTPs were observed. The investigation on the removal of ARGs of different treatment units in one WWTP showed that the biological treatment unit played the most important role in ARGs removal (1.2-1.8 orders of magnitude), followed by UV disinfection, while primary physical treatment units can hardly remove any ARGs. Although all the WWTPs can remove ARGs effectively, ARGs concentrations are still relatively high in the effluent, their further attenuation should be investigated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Fate and proliferation of typical antibiotic resistance genes in five full-scale pharmaceutical wastewater treatment plants

    International Nuclear Information System (INIS)

    Wang, Jilu; Mao, Daqing; Mu, Quanhua; Luo, Yi

    2015-01-01

    This study investigated the characteristics of 10 subtypes of antibiotic resistance genes (ARGs) for sulfonamide, tetracycline, β-lactam and macrolide resistance and the class 1 integrase gene (intI1). In total, these genes were monitored in 24 samples across each stage of five full-scale pharmaceutical wastewater treatment plants (PWWTPs) using qualitative and real-time quantitative polymerase chain reactions (PCRs). The levels of typical ARG subtypes in the final effluents ranged from (2.08 ± 0.16) × 10 3 to (3.68 ± 0.27) × 10 6 copies/mL. The absolute abundance of ARGs in effluents accounted for only 0.6%–59.8% of influents of the five PWWTPs, while the majority of the ARGs were transported to the dewatered sludge with concentrations from (9.38 ± 0.73) × 10 7 to (4.30 ± 0.81) × 10 10 copies/g dry weight (dw). The total loads of ARGs discharged through dewatered sludge was 7–308 folds higher than that in the raw influents and 16–638 folds higher than that in the final effluents. The proliferation of ARGs mainly occurs in the biological treatment processes, such as conventional activated sludge, cyclic activated sludge system (CASS) and membrane bio-reactor (MBR), implying that significant replication of certain subtypes of ARGs may be attributable to microbial growth. High concentrations of antibiotic residues (ranging from 0.14 to 92.2 mg/L) were detected in the influents of selected wastewater treatment systems and they still remain high residues in the effluents. Partial correlation analysis showed significant correlations between the antibiotic concentrations and the associated relative abundance of ARG subtypes in the effluent. Although correlation does not prove causation, this study demonstrates that in addition to bacterial growth, the high antibiotic residues within the pharmaceutical WWTPs may influence the proliferation and fate of the associated ARG subtypes. - Highlights: • The ARGs in final discharges were 7–308 times higher than

  13. Fate and proliferation of typical antibiotic resistance genes in five full-scale pharmaceutical wastewater treatment plants

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jilu [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China); Mao, Daqing, E-mail: mao@tju.edu.cn [School of Environmental Science and Engineering, Tianjin University, Tianjin 300072 (China); Mu, Quanhua [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China); Luo, Yi, E-mail: luoy@nankai.edu.cn [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China)

    2015-09-01

    This study investigated the characteristics of 10 subtypes of antibiotic resistance genes (ARGs) for sulfonamide, tetracycline, β-lactam and macrolide resistance and the class 1 integrase gene (intI1). In total, these genes were monitored in 24 samples across each stage of five full-scale pharmaceutical wastewater treatment plants (PWWTPs) using qualitative and real-time quantitative polymerase chain reactions (PCRs). The levels of typical ARG subtypes in the final effluents ranged from (2.08 ± 0.16) × 10{sup 3} to (3.68 ± 0.27) × 10{sup 6} copies/mL. The absolute abundance of ARGs in effluents accounted for only 0.6%–59.8% of influents of the five PWWTPs, while the majority of the ARGs were transported to the dewatered sludge with concentrations from (9.38 ± 0.73) × 10{sup 7} to (4.30 ± 0.81) × 10{sup 10} copies/g dry weight (dw). The total loads of ARGs discharged through dewatered sludge was 7–308 folds higher than that in the raw influents and 16–638 folds higher than that in the final effluents. The proliferation of ARGs mainly occurs in the biological treatment processes, such as conventional activated sludge, cyclic activated sludge system (CASS) and membrane bio-reactor (MBR), implying that significant replication of certain subtypes of ARGs may be attributable to microbial growth. High concentrations of antibiotic residues (ranging from 0.14 to 92.2 mg/L) were detected in the influents of selected wastewater treatment systems and they still remain high residues in the effluents. Partial correlation analysis showed significant correlations between the antibiotic concentrations and the associated relative abundance of ARG subtypes in the effluent. Although correlation does not prove causation, this study demonstrates that in addition to bacterial growth, the high antibiotic residues within the pharmaceutical WWTPs may influence the proliferation and fate of the associated ARG subtypes. - Highlights: • The ARGs in final discharges were 7

  14. Monitoring and evaluation of antibiotic resistance genes in four municipal wastewater treatment plants in Harbin, Northeast China

    International Nuclear Information System (INIS)

    Wen, Qinxue; Yang, Lian; Duan, Ruan; Chen, Zhiqiang

    2016-01-01

    The development and proliferation of antibiotic resistance in pathogenic and environmental microorganisms is of great concern for public health. In this study, the distribution and removal efficiency of intI1 and eight subtypes of antibiotic resistance genes (ARGs) for tetracycline, sulfonamides, beta-lactams resistance in four municipal wastewater treatment plants (WWTPs) in Harbin, which locates in Songhua River basin in cold areas of China, were monitored by real-time fluorescent quantitative PCR. The results showed that intI1 and 6 ARGs except for bla_T_E_M and bla_S_H_V were detected in wastewater and sludge samples and 0.3–2.7 orders of magnitude of ARGs removal efficiency in the four WWTPs were observed. The investigation on the removal of ARGs of different treatment units in one WWTP showed that the biological treatment unit played the most important role in ARGs removal (1.2–1.8 orders of magnitude), followed by UV disinfection, while primary physical treatment units can hardly remove any ARGs. Although all the WWTPs can remove ARGs effectively, ARGs concentrations are still relatively high in the effluent, their further attenuation should be investigated. - Highlights: • The distribution of 8 ARGs and intI1 in WWTPs in Harbin in winter were monitored. • ARGs removal in 4 WWTPs with different processes were investigated. • Biological treatment process plays the most important role in ARGs removal. • A relatively high level of ARGs is still present in the effluent after wastewater treatment. • Regional uses of antibiotics other than season temperature affects the fate of ARGs in WWTPs.

  15. Nifedipine treatment reduces resting calcium concentration, oxidative and apoptotic gene expression, and improves muscle function in dystrophic mdx mice.

    Directory of Open Access Journals (Sweden)

    Francisco Altamirano

    Full Text Available Duchenne Muscular Dystrophy (DMD is a recessive X-linked genetic disease, caused by mutations in the gene encoding dystrophin. DMD is characterized in humans and in mdx mice by a severe and progressive destruction of muscle fibers, inflammation, oxidative/nitrosative stress, and cell death. In mdx muscle fibers, we have shown that basal ATP release is increased and that extracellular ATP stimulation is pro-apoptotic. In normal fibers, depolarization-induced ATP release is blocked by nifedipine, leading us to study the potential therapeutic effect of nifedipine in mdx muscles and its relation with extracellular ATP signaling. Acute exposure to nifedipine (10 µM decreased [Ca(2+]r, NF-κB activity and iNOS expression in mdx myotubes. In addition, 6-week-old mdx mice were treated with daily intraperitoneal injections of nifedipine, 1 mg/Kg for 1 week. This treatment lowered the [Ca(2+]r measured in vivo in the mdx vastus lateralis. We demonstrated that extracellular ATP levels were higher in adult mdx flexor digitorum brevis (FDB fibers and can be significantly reduced after 1 week of treatment with nifedipine. Interestingly, acute treatment of mdx FDB fibers with apyrase, an enzyme that completely degrades extracellular ATP to AMP, reduced [Ca(2+]r to a similar extent as was seen in FDB fibers after 1-week of nifedipine treatment. Moreover, we demonstrated that nifedipine treatment reduced mRNA levels of pro-oxidative/nitrosative (iNOS and gp91(phox/p47(phox NOX2 subunits and pro-apoptotic (Bax genes in mdx diaphragm muscles and lowered serum creatine kinase (CK levels. In addition, nifedipine treatment increased muscle strength assessed by the inverted grip-hanging test and exercise tolerance measured with forced swimming test in mdx mice. We hypothesize that nifedipine reduces basal ATP release, thereby decreasing purinergic receptor activation, which in turn reduces [Ca(2+]r in mdx skeletal muscle cells. The results in this work open new

  16. Dysregulated genes and their functional pathways in luteinized granulosa cells from PCOS patients after cabergoline treatment.

    Science.gov (United States)

    Ferrero, H; Díaz-Gimeno, P; Sebastián-León, P; Faus, A; Gómez, R; Pellicer, A

    2018-04-01

    Polycystic ovarian syndrome (PCOS) is a common reproductive disorder frequently associated with a substantial risk factor for ovarian hyperstimulation syndrome (OHSS). Dopamine receptor 2 (D2) agonists, like cabergoline (Cb2), have been used to reduce the OHSS risk. However, lutein granulosa cells (LGCs) from PCOS patients treated with Cb2 still show a deregulated dopaminergic tone (decreased D2 expression and low dopamine production) and increased vascularization compared to non-PCOS LGCs. Therefore, to understand the PCOS ovarian physiology, it is important to explore the mechanisms that underlie syndrome based on the therapeutic effects of Cb2. Here, LGCs from non-PCOS and PCOS patients were cultured with hCG in the absence/presence of Cb2 ( n  = 12). Subsequently, a transcriptomic-paired design that compared untreated vs treated LGCs within each patient was performed. After transcriptomic analysis, functions and genes were prioritized by systems biology approaches and validated by RT-qPCR. We identified that similar functions were altered in both PCOS and non-PCOS LGCs treated with Cb2; however, PCOS-treated LGCs exhibited more significant changes than non-PCOS. Among the prioritized functions, dopaminergic synapse, vascular endothelial growth factor (VEGF) signaling, apoptosis and ovarian steroidogenesis were highlighted. Finally, network modeling showed CASP9 , VEGFA , AKT1 , CREB , AIF , MAOA , MAPK14 and BMAL1 as key genes implicated in these pathways in Cb2 response, which might be potential biomarkers for further studies in PCOS. © 2018 Society for Reproduction and Fertility.

  17. Leaf Volatile Compounds and Associated Gene Expression during Short-Term Nitrogen Deficient Treatments in Cucumis Seedlings

    Directory of Open Access Journals (Sweden)

    Jie Deng

    2016-11-01

    Full Text Available Nitrogen (N is an important macronutrient for plant growth and development, but the regulatory mechanism of volatile compounds in response to N deficiency is not well understood, especially in cucumber, which consumes excessive N during growth. In this study, the major volatile compounds from cucumber leaves subjected to N deficiency were analyzed by GC-MS. A total of 24 volatile components were identified including 15 aldehydes, two ketones, two alkenes, and five other volatile compounds in 9930 leaves. Principal component analysis using volatile compounds from cucumber leaves provided good separation between N-sufficient and N-deficient treatments. The main volatiles in cucumber leaves were found to be C6 and C9 aldehydes, especially (E-2-hexanal and (E,Z-2,6-nonadienal. (E-2-hexanal belonged to the C6 aldehyde and was the most abundant compound, whereas (E,Z-2,6-nonadienal was the chief component of C9 aldehydes. During N-deficient treatment, short-chain volatile content was significantly improved at 5 day, other volatiles displayed significant reduction or no significantly changes in all sampling points. Improvement of short-chain volatiles was confirmed in the six other inbred lines at 5 day after N-deficient treatments. The expression analysis of 12 cucumber LOX genes and two HPL genes revealed that CsLOX19, CsLOX20, and CsLOX22 had common up-regulated expression patterns in response to N-deficient stress in most inbred lines; meanwhile, most sample points of CsHPL1 also had significant up-regulated expression patterns. This research focused on the relationship between volatiles in cucumber and different nitrogen environments to provide valuable insight into the effect of cultivation and management of the quality of cucumber and contributes to further research on volatile metabolism in cucumber.

  18. The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484.

    Science.gov (United States)

    Bradshaw, Nicholas J; Ukkola-Vuoti, Liisa; Pankakoski, Maiju; Zheutlin, Amanda B; Ortega-Alonso, Alfredo; Torniainen-Holm, Minna; Sinha, Vishal; Therman, Sebastian; Paunio, Tiina; Suvisaari, Jaana; Lönnqvist, Jouko; Cannon, Tyrone D; Haukka, Jari; Hennah, William

    2017-11-01

    Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1 , NDE1 , NDEL1 , PDE4B and PDE4D , the 'DISC1 network'. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 ( p = 3.0 × 10 -8 ), located on a non-coding exon of NDE1 Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment. © 2017 The Authors.

  19. A Novel Combination of Thermal Ablation and Heat-Inducible Gene therapy for Breast Cancer Treatment

    Science.gov (United States)

    2009-04-01

    11. Khokhlova, V.A., et al., Effects of nonlinear propagation, cavitation , and boiling in lesion formation by high intensity focused ultrasound in...intensity focused ultrasound (HIFU) has been developed as an emerging non-invasive strategy for cancer treatment by thermal ablation of tumor tissue. The...Concepts, Seattle, WA) operating at its fundamental frequency (1.1 MHz) or its third harmonics (3.3 MHz). The ultrasound imaging system was a 5/7

  20. What does addiction medicine expect from neuroscience? From genes and neurons to treatment responses.

    Science.gov (United States)

    Le Foll, Bernard

    2016-01-01

    The field of neuroscience is rapidly growing as evidenced by the mapping of the human genome, the progress in brain imaging technologies, and the refinement of sophisticated molecular tools that can be combined with innovative preclinical models. With these advances, it seems that our understanding of processes underlying addiction has never been so great. In comparison, the clinical domain has evolved at a much slower pace. Nonetheless, the addiction medical field has seen some gradual improvements in clinical care with the availability of a larger range of pharmacological options. Notably, several therapeutic alternatives are now offered for the treatment of nicotine, alcohol, and opioid use disorders. Some of these developments in treatment regimens have directly emerged from basic neuroscience research and represent a success story for the bench to beside translational approach. However, the clinical and research needs in addiction medicine are huge. There are still no pharmacological interventions available for psychostimulant and cannabis use disorders. Further, major questions remain unanswered: Would a better understanding of the neurocircuitry of addiction lead to therapeutic intervention? Would a better understanding of the neurochemical signature of addiction lead to the validation of a therapeutic target? Will pharmacogenetics hold its promise as a personalized medicine treatment approach? Using recent research developments, we will illustrate the potential of neuroscience to address some of the pressing questions in Addiction Medicine. © 2016 Elsevier B.V. All rights reserved.

  1. Characterization and Quantitation of a Novel β-Lactamase Gene Found in a Wastewater Treatment Facility and the Surrounding Coastal Ecosystem▿

    Science.gov (United States)

    Uyaguari, Miguel I.; Fichot, Erin B.; Scott, Geoffrey I.; Norman, R. Sean

    2011-01-01

    Wastewater treatment plants (WWTPs) are engineered structures that collect, concentrate, and treat human waste, ultimately releasing treated wastewater into local environments. While WWTPs efficiently remove most biosolids, it has been shown that many antibiotics and antibiotic-resistant bacteria can survive the treatment process. To determine how WWTPs influence the concentration and dissemination of antibiotic-resistant genes into the environment, a functional metagenomic approach was used to identify a novel antibiotic resistance gene within a WWTP, and quantitative PCR (qPCR) was used to determine gene copy numbers within the facility and the local coastal ecosystem. From the WWTP metagenomic library, the fosmid insert contained in one highly resistant clone (MIC, ∼416 μg ml−1 ampicillin) was sequenced and annotated, revealing 33 putative genes, including a 927-bp gene that is 42% identical to a functionally characterized β-lactamase from Staphylococcus aureus PC1. Isolation and subcloning of this gene, referred to as blaM-1, conferred ampicillin resistance to its Escherichia coli host. When normalized to volume, qPCR showed increased concentrations of blaM-1 during initial treatment stages but 2-fold-decreased concentrations during the final treatment stage. The concentration ng−1 DNA increased throughout the WWTP process from influent to effluent, suggesting that blaM-1 makes up a significant proportion of the overall genetic material being released into the coastal ecosystem. Average discharge was estimated to be 3.9 × 1014 copies of the blaM-1 gene released daily into this coastal ecosystem. Furthermore, the gene was observed in all sampled coastal water and sediment samples surrounding the facility. Our results suggest that WWTPs may be a pathway for the dissemination of novel antibiotic resistance genes into the environment. PMID:21965412

  2. Hornbills can distinguish between primate alarm calls.

    Science.gov (United States)

    Rainey, Hugo J.; Zuberbühler, Klaus; Slater, Peter J. B.

    2004-01-01

    Some mammals distinguish between and respond appropriately to the alarm calls of other mammal and bird species. However, the ability of birds to distinguish between mammal alarm calls has not been investigated. Diana monkeys (Cercopithecus diana) produce different alarm calls to two predators: crowned eagles (Stephanoaetus coronatus) and leopards (Panthera pardus). Yellow-casqued hornbills (Ceratogymna elata) are vulnerable to predation by crowned eagles but are not preyed on by leopards and might therefore be expected to respond to the Diana monkey eagle alarm call but not to the leopard alarm call. We compared responses of hornbills to playback of eagle shrieks, leopard growls, Diana monkey eagle alarm calls and Diana monkey leopard alarm calls and found that they distinguished appropriately between the two predator vocalizations as well as between the two Diana monkey alarm calls. We discuss possible mechanisms leading to these responses. PMID:15209110

  3. Fitness and Recovery of Bacterial Communities and Antibiotic Resistance Genes in Urban Wastewaters Exposed to Classical Disinfection Treatments.

    Science.gov (United States)

    Di Cesare, Andrea; Fontaneto, Diego; Doppelbauer, Julia; Corno, Gianluca

    2016-09-20

    Antibiotic resistance genes (ARGs) are increasingly appreciated to be important as micropollutants. Indirectly produced by human activities, they are released into the environment, as they are untargeted by conventional wastewater treatments. In order to understand the fate of ARGs and of other resistant forms (e.g., phenotypical adaptations) in urban wastewater treatment plants (WWTPs), we monitored three WWTPs with different disinfection processes (chlorine, peracetic acid (PAA), and ultraviolet light (UV)). We monitored WWTPs influx and pre- and postdisinfection effluent over 24 h, followed by incubation experiments lasting for 96 h. We measured bacterial abundance, size distribution and aggregational behavior, the proportion of intact (active) cells, and the abundances of four ARGs and of the mobile element integron1. While all the predisinfection treatments of all WWTPs removed the majority of bacteria and of associated ARGs, of the disinfection processes only PAA efficiently removed bacterial cells. However, the stress imposed by PAA selected for bacterial aggregates and, similarly to chlorine, stimulated the selection of ARGs during the incubation experiment. This suggests disinfections based on chemically aggressive destruction of bacterial cell structures can promote a residual microbial community that is more resistant to antibiotics and, given the altered aggregational behavior, to competitive stress in nature.

  4. The role of the gene SERPINH1 as a pharmacogenetic biomarker for choroidal neovascularization (CNV) responses to anti vascular endothelial growth factor (VEGF) treatment in clinical practice

    OpenAIRE

    Pierce, Charles

    2015-01-01

    Age related macular degeneration is the commonest cause of blindness in the western world and current treatment regimens represent a significant output for national health services. The disease process is multifactorial in origin and has a variable progression and response to current methods of treatment. A targeted approach with individualized therapy based on recognized biomarkers to predict disease outcome would be the ideal treatment modality.We plan to investigate the role of genes known...

  5. Calling in Work: Secular or Sacred?

    Science.gov (United States)

    Steger, Michael F.; Pickering, N. K.; Shin, J. Y.; Dik, B. J.

    2010-01-01

    Recent scholarship indicates that people who view their work as a calling are more satisfied with their work and their lives. Historically, calling has been regarded as a religious experience, although modern researchers frequently have adopted a more expansive and secular conceptualization of calling, emphasizing meaning and personal fulfillment…

  6. Indico CONFERENCE: Define the Call for Abstracts

    CERN Multimedia

    CERN. Geneva; Ferreira, Pedro

    2017-01-01

    In this tutorial, you will learn how to define and open a call for abstracts. When defining a call for abstracts, you will be able to define settings related to the type of questions asked during a review of an abstract, select the users who will review the abstracts, decide when to open the call for abstracts, and more.

  7. Do market participants learn from conference calls?

    NARCIS (Netherlands)

    Roelofsen, E.; Verbeeten, F.; Mertens, G.

    2014-01-01

    We examine whether market participants learn from the information that is disseminated during the Q-and-A section of conference calls. Specifically, we investigate whether stock prices react to information on intangible assets provided during conference calls, and whether conference calls

  8. HOW TO CALL THE CERN FIRE BRIGADE

    CERN Multimedia

    2001-01-01

    The telephone numbers of the CERN Fire Brigade are: 74444 for emergency calls 74848 for other calls Note The number 112 will stay in use for emergency calls from 'wired' telephones, however, from mobile phones it leads to non-CERN emergency services.

  9. HOW TO CALL THE CERN FIRE BRIGADE

    CERN Multimedia

    2001-01-01

    The telephone numbers of the CERN Fire Brigade are: 74444 for emergency calls 74848 for other calls Note: the number 112 will stay in use for emergency calls from 'wired' telephones, however, from mobile phones it leads to non-CERN emergency services.

  10. How to call the Fire Brigade

    CERN Multimedia

    2003-01-01

    The telephone numbers for the CERN Fire Brigade are: 74444 for emergency calls 74848 for other calls Note The number 112 will stay in use for emergency calls from "wired" telephones, however, from mobile phones it leads to non-CERN emergency services.

  11. HOW TO CALL THE CERN FIRE BRIGADE

    CERN Multimedia

    2002-01-01

    The telephone numbers of the CERN Fire Brigade are: 74444 for emergency calls 74848 for other calls Note The number 112 will stay in use for emergency calls from 'wired' telephones, however, from mobile phones it leads to non-CERN emergency services.  

  12. HOW TO CALL THE CERN FIRE BRIGADE

    CERN Multimedia

    2002-01-01

    The telephone numbers of the CERN Fire Brigade are: 74444 for emergency calls 74848 for other calls Note The number 112 will stay in use for emergency calls from 'wired' telephones, however, from mobile phones it leads to non-CERN emergency services.

  13. Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex

    OpenAIRE

    He, Zhi-Yao; Deng, Feng; Wei, Xia-Wei; Ma, Cui-Cui; Luo, Min; Zhang, Ping; Sang, Ya-Xiong; Liang, Xiao; Liu, Li; Qin, Han-Xiao; Shen, Ya-Li; Liu, Ting; Liu, Yan-Tong; Wang, Wei; Wen, Yan-Jun

    2016-01-01

    Overexpression of folate receptor alpha (FR?) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FR?-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in ...

  14. Dynamic call center routing policies using call waiting and agent idle times

    NARCIS (Netherlands)

    Chan, W.; Koole, G.M.; L'Ecuyer, P.

    2014-01-01

    We study call routing policies for call centers with multiple call types and multiple agent groups. We introduce new weight-based routing policies where each pair (call type, agent group) is given a matching priority defined as an affine combination of the longest waiting time for that call type and

  15. Perceiving a Calling, Living a Calling, and Job Satisfaction: Testing a Moderated, Multiple Mediator Model

    Science.gov (United States)

    Duffy, Ryan D.; Bott, Elizabeth M.; Allan, Blake A.; Torrey, Carrie L.; Dik, Bryan J.

    2012-01-01

    The current study examined the relation between perceiving a calling, living a calling, and job satisfaction among a diverse group of employed adults who completed an online survey (N = 201). Perceiving a calling and living a calling were positively correlated with career commitment, work meaning, and job satisfaction. Living a calling moderated…

  16. Prevalence of antibiotic resistance genes and bacterial community composition in a river influenced by a wastewater treatment plant.

    Directory of Open Access Journals (Sweden)

    Elisabet Marti

    Full Text Available Antibiotic resistance represents a global health problem, requiring better understanding of the ecology of antibiotic resistance genes (ARGs, their selection and their spread in the environment. Antibiotics are constantly released to the environment through wastewater treatment plant (WWTP effluents. We investigated, therefore, the effect of these discharges on the prevalence of ARGs and bacterial community composition in biofilm and sediment samples of a receiving river. We used culture-independent approaches such as quantitative PCR to determine the prevalence of eleven ARGs and 16S rRNA gene-based pyrosequencing to examine the composition of bacterial communities. Concentration of antibiotics in WWTP influent and effluent were also determined. ARGs such as qnrS, bla TEM, bla CTX-M, bla SHV, erm(B, sul(I, sul(II, tet(O and tet(W were detected in all biofilm and sediment samples analyzed. Moreover, we observed a significant increase in the relative abundance of ARGs in biofilm samples collected downstream of the WWTP discharge. We also found significant differences with respect to community structure and composition between upstream and downstream samples. Therefore, our results indicate that WWTP discharges may contribute to the spread of ARGs into the environment and may also impact on the bacterial communities of the receiving river.

  17. Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment.

    Directory of Open Access Journals (Sweden)

    Naoto Tanaka

    Full Text Available Cyclic nucleotide-gated (CNG ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM. ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients.

  18. Importance of pharmacogenetic markers in the methylenetetrahydrofolate reductase gene during methotrexate treatment in pediatric patients with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2017-01-01

    Full Text Available Despite remarkable progress in survival of children with acute lymphoblastic leukemia (ALL which has reached about 85%, early toxicity and relapse rate remain issues that need to to be resolved. Genetic variants are important factors influencing the metabolism of cytotoxic drugs in ALL treatment. Variants in genes coding for methotrexate (MTX-metabolizing enzymes are under constant scientific interest due to their potential impact on drug toxicity and relapse rate. We investigated methylenetetrahydrofolate reductase (MTHFR c.677C>T and MTHFR c.1298A>C variants as pharmacogenetic markers of MTX toxicity and predictors of relapse. The study enrolled 161 children with ALL, treated according to the current International Berlin-Frankfurt-Munster group (BFM for diagnostics and treatment of leukemia and lymphoma protocols. Genotyping was performed using PCRRFLP and allele-specific PCR assays. Our results revealed similar distributions of MTHFR c.677C>T and MTHFR c.1298A>C genotypes among 104 healthy individuals as compared to pediatric ALL patients. A lower incidence of early MTX toxicity was noted in the MTHFR c.677TT genotype (p=0.017, while MTHFR c.1298A>C genotypes were not associated with MTX toxicity. Carriers of any MTHFR c.677C>T and MTHFR c.1298A>C genotypes did not experience decreased overall survival (OAS or higher relapse rates. Genetic variants in the MTHFR gene are not involved in leukemogenesis in pediatric ALL. The presence of the MTHFR c.677TT genotype was recognized as a predictive factor for decreased MTX toxicity during the intensification phase of therapy. Neither MTHFR c.677C>T nor MTHFR c.1298A>C genotypes correlated with an increased number of toxic deaths or relapse rate. Our study emphasizes the importance of implementing pharmacogenetic markers in order to optimize pediatric ALL therapy. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III 41004

  19. Mortality and need of surgical treatment in acute upper gastrointestinal bleeding: a one year study in a tertiary center with a 24 hours / day-7 days / week endoscopy call. Has anything changed?

    Science.gov (United States)

    Botianu, Am; Matei, D; Tantau, M; Acalovschi, M

    2013-01-01

    Acute upper gastrointestinal bleeding, previously often a surgical problem, is now the most common gastroenterological emergency. To evaluate the current situation in terms of mortality and need of surgery. Retrospective non-randomised clinical study performed between 1st January-31st December 2011, at "Professor Dr. Octavian Fodor" Regional Institute of Gastroenterology and Hepatology in Cluj Napoca. 757 patients with upper gastrointestinal bleeding were endoscopically examined within 24 hours from presentation in the emergency unit. Data were collected from admission charts and Hospital Manager programme. Statistical analysis was performed with GraphPad 2004, using the following tests: chi square, Spearman, Kruskall-Wallis, Mann-Whitney, area under receiver operating curve. Non-variceal etiology was predominant, the main cause was bleeding being peptic ulcer. In hospital global mortality was of 10.43%, global rebleeding rate was 12.02%, surgery was performed in 7.66% of patients. Urgent haemostatic surgery was needed in 3.68% of patients with nonvariceal bleeding. The need for surgery correlated with the postendoscopic Rockall score (p=0.0425). In peptic ulcer, the need for surgery was not influenced by time to endoscopy or type of treatment (p=0.1452). Weekend (p=0.996) or night (p=0.5414) admission were not correlated with a higher need for surgery. Over the last decade, the need for urgent surgery in upper gastrointestinal bleeding has decreased by half, but mortality has remained unchanged. Celsius.

  20. MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment.

    Science.gov (United States)

    Huang, Xiao; Qin, Xianhui; Yang, Wenbin; Liu, Lishun; Jiang, Chongfei; Zhang, Xianglin; Jiang, Shanqun; Bao, Huihui; Su, Hai; Li, Ping; He, Mingli; Song, Yun; Zhao, Min; Yin, Delu; Wang, Yu; Zhang, Yan; Li, Jianping; Yang, Renqang; Wu, Yanqing; Hong, Kui; Wu, Qinhua; Chen, Yundai; Sun, Ningling; Li, Xiaoying; Tang, Genfu; Wang, Binyan; Cai, Yefeng; Hou, Fan Fan; Huo, Yong; Wang, Hong; Wang, Xiaobin; Cheng, Xiaoshu

    2018-03-01

    This post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial) assessed the individual variation in total homocysteine (tHcy)-lowering response after an average 4.5 years of 0.8 mg daily folic acid therapy in Chinese hypertensive adults and evaluated effect modification by methylenetetrahydrofolate reductase ( MTHFR ) C677T genotypes and serum folate levels. This analysis included 16 413 participants from the CSPPT, who were randomly assigned to 2 double-blind treatment groups: either 10-mg enalapril+0.8-mg folic acid or 10-mg enalapril, daily and had individual measurements of serum folate and tHcy levels at baseline and exit visits and MTHFR C677T genotypes. Mean baseline tHcy levels were comparable between the 2 treatment groups (14.5±8.5 versus 14.4±8.1 μmol/L; P =0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7±6.1 μmol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4±7.9 μmol/L, group difference: 1.61 μmol/L; 11% reduction). More importantly, tHcy lowering varied by MTHFR genotypes and serum folate levels. Compared with CC and CT genotypes, participants with the TT genotype had a more prominent L-shaped curve between tHcy and serum folate levels and required higher folate levels (at least 15 ng/mL) to eliminate the differences in tHcy by genotypes. Compared with CC or CT, tHcy in the TT group manifested a heightened L-shaped curve from low to high folate levels, but this difference in tHcy by genotype was eliminated when plasma folate levels reach ≈15 ng/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual MTHFR C677T genotype and folate status. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2018 American Heart Association, Inc.

  1. The fecal presence of enterotoxin and F4 genes as an indicator of efficacy of treatment with colistin sulfate in pigs.

    Science.gov (United States)

    Rhouma, Mohamed; Fairbrother, John Morris; Thériault, William; Beaudry, Francis; Bergeron, Nadia; Laurent-Lewandowski, Sylvette; Letellier, Ann

    2017-01-05

    Enterotoxigenic Escherichia coli (ETEC) strains producing multiple enterotoxins are important causes of post-weaning diarrhea (PWD) in pigs. The aim of the present study was to investigate the fecal presence of ETEC enterotoxin as well as F4 and F18 genes as an indicator of colistin sulfate (CS) efficacy for treatment of PWD in pigs. Forty-eight piglets were weaned at the age of 21 days, and were divided into four groups: challenged treated, challenged untreated, unchallenged treated, and unchallenged untreated. Challenge was performed using 10 9  CFU of an ETEC: F4 strain, and treatment was conducted using oral CS at the dose of 50,000 IU/kg. The fecal presence of genes encoding for STa, STb, LT, F4 and F18 was detected using PCR. The PCR amplification of ETEC virulence genes showed that nearly 100% of pigs excreted genes encoding for STa and STb toxins in the feces before the challenge. These genes, in the absence of the gene encoding F4, were considered as a marker for F4-negative ETEC. One day after ETEC: F4 oral challenge pigs in the two challenged groups excreted the genes encoding LT and F4 in the feces. These genes were considered as a marker for F4-positive ETEC. However, the gene encoding F18 was not detected in any fecal samples of the 4 groups throughout the experiment. After only 3 days of successive oral treatment with CS, a significant reduction in both the F4-positive and negative ETEC populations was observed in the challenged treated group compared to the challenged untreated group (p F4-positive and F4-negative ETEC in pigs. However, CS clinical efficiency was correlated with non-detection of F4-positive ETEC in the feces. Furthermore the fecal presence of F4-negative ETEC was not associated with clinical symptoms of post-weaning diarrhea in pigs.

  2. Short stature caused by isolated SHOX gene haploinsufficiency: update on the diagnosis and treatment.

    Science.gov (United States)

    Jorge, Alexander A L; Funari, Mariana Fa; Nishi, Mirian Y; Mendonca, Berenice B

    2010-12-01

    Heterozygous SHOX defects are observed in about 50 to 90% of patients with Leri-Weill dyschondrosteosis (LWD), a common dominant inherited skeletal dysplasia; and in 2 to 15% of children with idiopathic short stature (ISS), indicating that SHOX defects are the most important monogenetic cause of short stature. In addition, children selected by disproportionate idiopathic short stature had a higher frequency of SHOX mutations (22%). A careful clinical evaluation of family members with short stature is recommended since it usually revealed LWD patients in families first classified as having ISS or familial short stature. SHOX-molecular analysis is indicated in families with LWD and ISS children with disproportionate short stature. Treatment with recombinant human growth hormone is considered an accepted approach to treat short stature associated with isolated SHOX defect. Here we review clinical, molecular and therapeutic aspects of SHOX haploinsufficiency.

  3. Removal of bacterial cells, antibiotic resistance genes and integrase genes by on-site hospital wastewater treatment plants: surveillance of treated hospital effluent quality

    KAUST Repository

    Timraz, Kenda Hussain Hassan; Xiong, Yanghui; Al Qarni, Hamed; Hong, Pei-Ying

    2016-01-01

    This study aims to evaluate the removal efficiency of microbial contaminants, including total cell counts, antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs, e.g. tetO, tetZ, sul1 and sul2) and integrase genes (e.g. intl1

  4. Gene therapy by electroporation for the treatment of chronic renal failure in companion animals

    Directory of Open Access Journals (Sweden)

    Pope Melissa A

    2009-01-01

    Full Text Available Abstract Background Growth hormone-releasing hormone (GHRH plasmid-based therapy for the treatment of chronic renal failure and its complications was examined. Companion dogs (13.1 ± 0.8 years, 29.4 ± 5.01 kg and cats (13.2 ± 0.9 years, 8.5 ± 0.37 kg received a single 0.4 mg or 0.1 mg species-specific plasmid injection, respectively, intramuscularly followed by electroporation, and analyzed up to 75 days post-treatment; controls underwent electroporation without plasmid administration. Results Plasmid-treated animals showed an increase in body weight (dogs 22.5% and cats 3.2% compared to control animals, and displayed improved quality of life parameters including significant increases in appetite, activity, mentation and exercise tolerance levels. Insulin-like growth factor I (IGF-I, the downstream effector of GHRH levels were increased in the plasmid treated animals. Hematological parameters were also significantly improved. Protein metabolism changes were observed suggesting a shift from a catabolic to an anabolic state in the treated animals. Blood urea nitrogen and creatinine did not show any significant changes suggesting maintenance of kidney function whereas the control animal's renal function deteriorated. Treated animals survived longer than control animals with 70% of dogs and 80% of cats surviving until study day 75. Only 17% and 40% of the control dogs and cats, respectively, survived to day 75. Conclusion Improved quality of life, survival and general well-being indicate that further investigation is warranted, and show the potential of a plasmid-based therapy by electroporation in preventing and managing complications of renal insufficiency.

  5. Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs with different waste load.

    Directory of Open Access Journals (Sweden)

    Mailis Laht

    Full Text Available Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs, an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs were quantified using qPCR in three WWTPs of decreasing capacity located in Helsinki, Tallinn, and Tartu, respectively: sulphonamide resistance genes (sul1 and sul2, tetracycline resistance genes (tetM and tetC, and resistance genes for extended spectrum beta-lactams (blaoxa-58, blashv-34, and blactx-m-32. To avoid inconsistencies among qPCR assays we normalised the ARG abundances with 16S rRNA gene abundances while assessing if the respective genes increased or decreased during treatment. ARGs were detected in most samples; sul1, sul2, and tetM were detected in all samples. Statistically significant differences (adjusted p<0.01 between the inflow and effluent were detected in only four cases. Effluent values for blaoxa-58 and tetC decreased in the two larger plants while tetM decreased in the medium-sized plant. Only blashv-34 increased in the effluent from the medium-sized plant. In all other cases the purification process caused no significant change in the relative abundance of resistance genes, while the raw abundances fell by several orders of magnitude. Standard water quality variables (biological oxygen demand, total phosphorus and nitrogen, etc. were weakly related or unrelated to the relative abundance of resistance genes. Based on our results we conclude that there is neither considerable enrichment nor purification of antibiotic resistance genes in studied conventional WWTPs.

  6. Cloning and characterization of WRKY gene homologs in Chieh-qua (Benincasa hispida Cogn. var. Chieh-qua How) and their expression in response to fusaric acid treatment.

    Science.gov (United States)

    Mao, Yizhou; Jiang, Biao; Peng, Qingwu; Liu, Wenrui; Lin, Yue; Xie, Dasen; He, Xiaoming; Li, Shaoshan

    2017-05-01

    The WRKY transcription factors play an important role in plant resistance for biotic and abiotic stresses. In the present study, we cloned 10 WRKY gene homologs (CqWRKY) in Chieh-qua (Benincasa hispida Cogn. var. Chieh-qua) using the rapid-amplification of cDNA ends (RACE) or homology-based cloning methods. We characterized the structure of these CqWRKY genes. Phylogenetic analysis of these sequences with cucumber homologs suggested possible structural conservation of these genes among cucurbit crops. We examined the expression levels of these genes in response to fusaric acid (FA) treatment between resistant and susceptible Chieh-qua lines with quantitative real-time PCR. All genes could be upregulated upon FA treatment, but four CqWRKY genes exhibited differential expression between resistant and susceptible lines before and after FA application. CqWRKY31 seemed to be a positive regulator while CqWRKY1, CqWRKY23 and CqWRKY53 were negative regulators of fusaric resistance. This is the first report of characterization of WRKY family genes in Chieh-qua. The results may also be useful in breeding Chieh-qua for Fusarium wilt resistance.

  7. Clinical study of Gene-Eden-VIR/Novirin in genital herpes: suppressive treatment safely decreases the duration of outbreaks in both severe and mild cases.

    Science.gov (United States)

    Polansky, Hanan; Itzkovitz, Edan; Javaherian, Adrian

    2016-12-01

    We conducted a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on genital herpes. Our previous paper showed that the treatment decreased the number of genital herpes outbreaks without any side effects. It also showed that the clinical effects of Gene-Eden-VIR/Novirin are mostly better than those reported in the studies that tested acyclovir, valacyclovir, and famciclovir. The current paper reports the effect of suppressive treatment with Gene-Eden-VIR/Novirin on the duration of outbreaks, in severe and mild genital herpes cases. The framework was a retrospective chart review. The population included 137 participants. The treatment was 1-4 capsules per day. The duration of treatment was 2-48 months. The study included three controls: baseline, no-treatment, and dose-response. The treatment decreased the duration of outbreaks in 87 % of participants and decreased the mean duration of outbreaks from 8.77 days and 6.7 days in the control groups to 2.87 days in the treatment group (P genital herpes outbreaks, in both severe and mild cases, without any side effects. Based on the results reported in this and our previous paper, we recommend suppressive treatment with Gene-Eden-VIR/Novirin as a natural alternative to both suppressive and episodic treatments with current drugs, in both severe and mild genital herpes cases. Trial registration ClinicalTrials.gov NCT02715752 Registered 17 March 2016 Retrospectively Registered.

  8. A candidate gene study of serotonergic pathway genes and pain relief during treatment with escitalopram in patients with neuropathic pain shows significant association to serotonin receptor2C (HTR2C)

    DEFF Research Database (Denmark)

    Brasch-Andersen, Charlotte; Møller, Malik U; Christiansen, Lene

    2011-01-01

    the association between polymorphisms in genes involved in the serotonergic pathway and the effect of escitalopram on peripheral neuropathic pain. METHODS: We genotyped 34 participants from a placebo-controlled trial of escitalopram in peripheral neuropathic pain for polymorphisms in five genes: the serotonin.......047), with 75% carrying the C allele being responders. The same tendency was seen in women. Similarly, carriership of the C allele at rs6318 was associated with better pain relief during treatment with escitalopram [odds ratio (OR) 15.5, p = 0.014)] Furthermore, there was a tendency of better relief...... with increasing number of short alleles for the 5-HTTLPR polymorphism of the serotonin transporter (OR 5.7, p = 0.057). None of the other polymorphisms showed a significant association with treatment response to escitalopram. CONCLUSION: This study indicates that variation in the HTR2C gene is associated...

  9. Occurrence and removal of antibiotics and the corresponding resistance genes in wastewater treatment plants: effluents' influence to downstream water environment.

    Science.gov (United States)

    Li, Jianan; Cheng, Weixiao; Xu, Like; Jiao, Yanan; Baig, Shams Ali; Chen, Hong

    2016-04-01

    In this study, the occurrence of 8 antibiotics [3 tetracyclines (TCs), 4 sulfonamides, and 1 trimethoprim (TMP)], 12 antibiotic resistance genes (ARGs) (10 tet, 2 sul), 4 types of bacteria [no antibiotics, anti-TC, anti-sulfamethoxazole (SMX), and anti-double], and intI1 in two wastewater treatment plants (WWTPs) were assessed and their influences in downstream lake were investigated. Both WWTPs' effluent demonstrated some similarities, but the abundance and removal rate varied significantly. Results revealed that biological treatment mainly removed antibiotics and ARGs, whereas physical techniques were found to eliminate antibiotic resistance bacteria (ARBs) abundance (about 1 log for each one). UV disinfection did not significantly enhance the removal efficiency, and the release of the abundantly available target contaminants from the excess sludge may pose threats to human and the environment. Different antibiotics showed diverse influences on the downstream lake, and the concentrations of sulfamethazine (SM2) and SMX were observed to increase enormously. The total ARG abundance ascended about 0.1 log and some ARGs (e.g., tetC, intI1, tetA) increased due to the high input of the effluent. In addition, the abundance of ARB variation in the lake also changed, but the abundance of four types of bacteria remained stable in the downstream sampling sites.

  10. Height outcome of the recombinant human growth hormone treatment in patients with SHOX gene haploinsufficiency: a meta-analysis.

    Science.gov (United States)

    Massart, Francesco; Bizzi, Martina; Baggiani, Angelo; Miccoli, Mario

    2013-04-01

    Patients with mutations or deletions of the SHOX gene present variable growth impairment, with or without mesomelic skeletal dysplasia. If untreated, short patients with SHOX haplodeficiency (SHOXD) remain short into adulthood. Although recombinant human growth hormone (rhGH) treatment improves short-term linear growth, there are episodic data on the final height of treated SHOXD subjects. After a thorough search of the published literature for pertinent studies, we undertook a meta-analysis evaluation of the efficacy and safety of rhGH treatment in SHOXD patients. In SHOXD patients, administration of rhGH progressively improved the height deficit from baseline to 24 months, although the major catch-up growth was detected after 12 months. The rhGH-induced growth appeared constant until final height. Our meta-analysis suggested rhGH therapy improves height outcome of SHOXD patients, though future studies using carefully titrated rhGH protocols are needed. Original submitted 29 October 2012; Revision submitted 22 February 2013.

  11. Metagenomic analysis of bacterial community composition and antibiotic resistance genes in a wastewater treatment plant and its receiving surface water.

    Science.gov (United States)

    Tang, Junying; Bu, Yuanqing; Zhang, Xu-Xiang; Huang, Kailong; He, Xiwei; Ye, Lin; Shan, Zhengjun; Ren, Hongqiang

    2016-10-01

    The presence of pathogenic bacteria and the dissemination of antibiotic resistance genes (ARGs) may pose big risks to the rivers that receive the effluent from municipal wastewater treatment plants (WWTPs). In this study, we investigated the changes of bacterial community and ARGs along treatment processes of one WWTP, and examined the effects of the effluent discharge on the bacterial community and ARGs in the receiving river. Pyrosequencing was applied to reveal bacterial community composition including potential bacterial pathogen, and Illumina high-throughput sequencing was used for profiling ARGs. The results showed that the WWTP had good removal efficiency on potential pathogenic bacteria (especially Arcobacter butzleri) and ARGs. Moreover, the bacterial communities of downstream and upstream of the river showed no significant difference. However, the increase in the abundance of potential pathogens and ARGs at effluent outfall was observed, indicating that WWTP effluent might contribute to the dissemination of potential pathogenic bacteria and ARGs in the receiving river. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Rena Watanabe

    2018-02-01

    Full Text Available Tumor necrosis factor-stimulated gene-6 (TSG-6 is a 35-kDa glycoprotein that has been shown to exert anti-inflammatory effects in experimental models of arthritis, acute myocardial infarction, and acute cerebral infarction. Several lines of evidence have shed light on the pathophysiological roles of TSG-6 in atherosclerosis. TSG-6 suppresses inflammatory responses of endothelial cells, neutrophils, and macrophages as well as macrophage foam cell formation and vascular smooth muscle cell (VSMC migration and proliferation. Exogenous TSG-6 infusion and endogenous TSG-6 attenuation with a neutralizing antibody for four weeks retards and accelerates, respectively, the development of aortic atherosclerotic lesions in ApoE-deficient mice. TSG-6 also decreases the macrophage/VSMC ratio (a marker of plaque instability and promotes collagen fibers in atheromatous plaques. In patients with coronary artery disease (CAD, plasma TSG-6 levels are increased and TSG-6 is abundantly expressed in the fibrous cap within coronary atheromatous plaques, indicating that TSG-6 increases to counteract the progression of atherosclerosis and stabilize the plaque. These findings indicate that endogenous TSG-6 enhancement and exogenous TSG-6 replacement treatments are expected to emerge as new lines of therapy against atherosclerosis and related CAD. Therefore, this review provides support for the clinical utility of TSG-6 in the diagnosis and treatment of atherosclerotic cardiovascular diseases.

  13. Long-distance calls in Neotropical primates

    Directory of Open Access Journals (Sweden)

    Oliveira Dilmar A.G.

    2004-01-01

    Full Text Available Long-distance calls are widespread among primates. Several studies concentrate on such calls in just one or in few species, while few studies have treated more general trends within the order. The common features that usually characterize these vocalizations are related to long-distance propagation of sounds. The proposed functions of primate long-distance calls can be divided into extragroup and intragroup ones. Extragroup functions relate to mate defense, mate attraction or resource defense, while intragroup functions involve group coordination or alarm. Among Neotropical primates, several species perform long-distance calls that seem more related to intragroup coordination, markedly in atelines. Callitrichids present long-distance calls that are employed both in intragroup coordination and intergroup contests or spacing. Examples of extragroup directed long-distance calls are the duets of titi monkeys and the roars and barks of howler monkeys. Considerable complexity and gradation exist in the long-distance call repertoires of some Neotropical primates, and female long-distance calls are probably more important in non-duetting species than usually thought. Future research must focus on larger trends in the evolution of primate long-distance calls, including the phylogeny of calling repertoires and the relationships between form and function in these signals.

  14. Transcriptome-based analysis of kidney gene expression changes associated with diabetes in OVE26 mice, in the presence and absence of losartan treatment.

    Directory of Open Access Journals (Sweden)

    Radko Komers

    Full Text Available Diabetes is among the most common causes of end-stage renal disease, although its pathophysiology is incompletely understood. We performed next-generation sequencing-based transcriptome analysis of renal gene expression changes in the OVE26 murine model of diabetes (age 15 weeks, relative to non-diabetic control, in the presence and absence of short-term (seven-day treatment with the angiotensin receptor blocker, losartan (n = 3-6 biological replicates per condition. We detected 1438 statistically significant changes in gene expression across conditions. Of the 638 genes dysregulated in diabetes relative to the non-diabetic state, >70% were downregulation events. Unbiased functional annotation of genes up- and down-regulated by diabetes strongly associated (p52-fold, encoded by the cationic amino acid transporter Slc7a12, and the gene product most highly downregulated by diabetes (>99%--encoded by the "pseudogene" Gm6300--are adjacent in the murine genome, are members of the SLC7 gene family, and are likely paralogous. Therefore, diabetes activates a near-total genetic switch between these two paralogs. Other individual-level changes in gene expression are potentially relevant to diabetic pathophysiology, and novel pathways are suggested. Genes unaffected by diabetes alone but exhibiting increased renal expression with losartan produced a signature consistent with malignant potential.

  15. A comprehensive view of expression profiles dynamics of capsaicinoid biosynthesis-related genes during pepper fruit development and under meja treatment

    International Nuclear Information System (INIS)

    Deng, M.; Huo, J.; Zhu, H.; Zhang, Z.

    2018-01-01

    Capsaicinoids are a group of secondary plant metabolites which are synthesized and accumulated only in the fruits of peppers (Capsicum annuum L.). In this paper, the fruits of nadao chili peppers were used as experiment materials and the mechanism of capsaicinoid biosynthesis was studied. HPLC studies revealed that capsaicinoid accumulation in the developing fruits initially occurred at 24 days after pollination (DAP), was increasing at 36 DAP, and peaked at 48 DAP. Eleven genes that encoded enzymes involved in capsaicinoid biosynthesis were isolated and characterized. Gene expression with quantitative reverse-transcription polymerase chain reaction analysis demonstrated that capsaicin synthase (CaCS) was expressed only in the placenta of the fruit, while the other ten genes were expressed in all tissues tested, with nine of the eleven genes (with the exception of cinnamic acid-4-hydroxylase [CaCa4H] and p-coumaric acid-3-hydroxylase [CaCa3H]) being strongly expressed in placenta tissue. Spatial expression analysis demonstrated that the 11 genes could be grouped into four categories, based on the patterns of relative expression of the genes during fruit development. Category I contained two genes, which displayed a bell-shaped expression pattern, with peak expression at 24 DAP. Category II contained five genes, the expression of which increased steadily from 0 to 36 DAP, peaking at 36 DAP. Category III comprises two genes, expression of which peaked at 48 DAP. Category IV consists of two genes, which were not expressed from 0 to 12 DAP, but then showed a high level of expression at 36 and 48 DAP. Treatment of the developing fruit with methyl jasmonate (MeJA) resulted in upregulation of the expression of each of the 11 genes. These results provide the first information on capsaicinoid biosynthesis and regulation during pepper fruit development. (author)

  16. Common genetic variation in the indoleamine-2,3-dioxygenase genes and antidepressant treatment outcome in major depressive disorder.

    Science.gov (United States)

    Cutler, Jessica A; Rush, A John; McMahon, Francis J; Laje, Gonzalo

    2012-03-01

    The essential amino acid tryptophan is the precursor to serotonin, but it can also be metabolized into kynurenine through indoleamine-2,3-dioxygenase (IDO). Increased immune activation has long been associated with symptoms of depression and has been shown to upregulate the expression of IDO. The presence of additional IDO directs more tryptophan down the kynurenine pathway, leaving less available for synthesis of serotonin and its metabolites. Kynurenine can be metabolized through a series of enzymes to quinolinic acid, a potent N-methyl-D-aspartate receptor agonist with demonstrated neurotoxic effects. We tested the hypothesis that IDO plays a role in outcome of treatment with the selective serotonin reuptake inhibitor, citalopram. Patients consisted of 1953 participants enrolled in the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D). Genotypes corresponding to 94 single nucleotide polymorphisms (SNPs) in the genes IDO1 and IDO2, which encode IDO and IDO2, were extracted from a larger genome-wide set and analyzed using single marker tests to look for association with previously defined response, remission and QIDS-C score change phenotypes, with adequate correction for racial stratification and multiple testing. One SNP, rs2929115, showed evidence of association with citalopram response (OR = 0.64, p = 0.0005) after experiment-wide correction for multiple testing. Another closely associated marker, rs2929116 (OR = 0.64, p = 0.0006) had an experiment-wide significant result. Both implicated SNPs are located between 26 kb and 28 kb downstream of IDO2. We conclude that common genetic variation in IDO1 and IDO2 may play a role in antidepressant treatment outcome. These results are modest in a genome-wide context and need to be replicated in an independent sample.

  17. Transferrin Level Before Treatment and Genetic Polymorphism in HFE Gene as Predictive Markers for Response to Adalimumab in Crohn's Disease Patients.

    Science.gov (United States)

    Repnik, Katja; Koder, Silvo; Skok, Pavel; Ferkolj, Ivan; Potočnik, Uroš

    2016-08-01

    Tumor necrosis factor α inhibitors (anti-TNF) have improved treatment of several complex diseases, including Crohn's disease (CD). However, the effect varies and approximately one-third of the patients do not respond. Since blood parameters as well as genetic factors have shown a great potential to predict response during treatment, the aim of the study was to evaluate response to anti-TNF treatment with adalimumab (ADA) between genes HFE and TF and haematological parameters in Slovenian refractory CD patients. Single nucleotide polymorphisms (SNPs) rs1799852 in gene TF and rs2071303 in gene HFE were genotyped in 68 refractory CD patients for which response has been measured using inflammatory bowel disease questionnaire (IBDQ) index. Haematological parameters and IBDQ index were determined before therapy and after 4, 12, 20 and 30 weeks. We found novel strong association between SNP rs2071303 in gene HFE and response to ADA treatment, particularly patients with G allele comparing to A allele had better response after 20 weeks (p = 0.008). Further, we found strong association between transferrin level at baseline and treatment response after 12, 20 and 30 weeks, where average transferrin level before therapy was lower in responders (2.38 g/L) compared to non-responders (2.89 g/L, p = 0.005). Association was found between transferrin level in week 30 and SNP rs1799852 (p = 0.023), and between MCHC level before treatment and SNP rs2071303 (p = 0.007). Our results suggest that SNP in gene HFE as well as haematological markers serve as promising prognostic markers of response to anti-TNF treatment in CD patients.

  18. Influence of IL15 gene variations on the clinical features, treatment response and risk of developing childhood acute lymphoblastic leukemia in Latvian population.

    Science.gov (United States)

    Rots, Dmitrijs; Kreile, Madara; Nikulshin, Sergejs; Kovalova, Zhanna; Gailite, Linda

    2018-02-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Modern treatment protocols allow achievement of long-term event-free survival rates in up to 85% of cases, although the treatment response varies among different patient groups. It is hypothesized that treatment response is influenced by the IL15 gene variations, although research results are conflicting. To analyze IL15 gene variations influence treatment response, clinical course and the risk of developing ALL we performed a case-control and family-based study. The study included 81 patients with childhood ALL. DNA samples of both or one biological parent were available for 62 of ALL patients and 130 age and gender adjusted healthy samples were used as a control group. Analyzed IL15 gene variations: rs10519612, rs10519613 and rs17007695 were genotyped using PCR-RFLP assay. Our results shows that IL15 gene variations haplotypes are associated with the risk of developing childhood ALL (p variations separately. The variations rs10519612 and rs1059613 in a recessive pattern of inheritance were associated with hyperdiploidy (p = 0.048). Analyzed genetic variations had no impact on other clinical features and treatment response (assessed by the minimal residual disease) in our study.

  19. REMINDER: In a medical emergency call 74444

    CERN Multimedia

    2005-01-01

    What happened? A CERN colleague, complaining of pains that might indicate serious heart problem, went to the ?infirmary' on the Prévessin site for medical aid. He was unaware that the ?infirmary' was in fact no such thing, but the office of the French contractors' medical practitioner, and, on top of that, it was closed. He therefore took his own car and went to the CERN Fire Station on the Meyrin Site (Building 65). The firemen and the CERN medical team took care of him and requested helicopter transport to the Geneva cantonal hospital, where he responded well to medical treatment. What do we learn from this event? You must call the CERN internal number 74444 in the event of serious and acute illness, and do not have to present yourself in person or get somebody to go with you. This number is not reserved exclusively for accident, pollution, fire etc. The Firemen can prodice professional assistance at all times as required: first aid on the spot, amulance transport and medical assistance as necessary. ...

  20. Outsourcing an Effective Postdischarge Call Program

    Science.gov (United States)

    Meek, Kevin L.; Williams, Paula; Unterschuetz, Caryn J.

    2018-01-01

    To improve patient satisfaction ratings and decrease readmissions, many organizations utilize internal staff to complete postdischarge calls to recently released patients. Developing, implementing, monitoring, and sustaining an effective call program can be challenging and have eluded some of the renowned medical centers in the country. Using collaboration with an outsourced vendor to bring state-of-the-art call technology and staffed with specially trained callers, health systems can achieve elevated levels of engagement and satisfaction for their patients postdischarge. PMID:29494453

  1. Call Duration Characteristics based on Customers Location

    Directory of Open Access Journals (Sweden)

    Žvinys Karolis

    2014-05-01

    Full Text Available Nowadays a lot of different researches are performed based on call duration distributions (CDD analysis. However, the majority of studies are linked with social relationships between the people. Therefore the scarcity of information, how the call duration is associated with a user's location, is appreciable. The goal of this paper is to reveal the ties between user's voice call duration and the location of call. For this reason we analyzed more than 5 million calls from real mobile network, which were made over the base stations located in rural areas, roads, small towns, business and entertainment centers, residential districts. According to these site types CDD’s and characteristic features for call durations are given and discussed. Submitted analysis presents the users habits and behavior as a group (not an individual. The research showed that CDD’s of customers being them in different locations are not equal. It has been found that users at entertainment, business centers are tend to talk much shortly, than people being at home. Even more CDD can be distorted strongly, when machinery calls are evaluated. Hence to apply a common CDD for a whole network it is not recommended. The study also deals with specific parameters of call duration for distinguished user groups, the influence of network technology for call duration is considered.

  2. Experimental Gene Therapy with Serine-Histogranin and Endomorphin 1 for the Treatment of Chronic Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Stanislava Jergova

    2017-12-01

    Full Text Available The insufficient pain relief provided by current pharmacotherapy for chronic neuropathic pain is a serious medical problem. The enhanced glutamate signaling via NMDA receptors appears to be one of the key events in the development of chronic pain. Although effective, clinical use of systemic NMDA antagonists is limited by adverse effects such as hallucinations and motor dysfunction. Opioids are also potent analgesics but their chronic use is accompanied by tolerance and risk of addiction. However, combination of NMDA antagonists and opioids seems to provide a stable pain relieve at subthreshold doses of both substances, eliminating development of side effects. Our previous research showed that combined delivery of NMDA antagonist Serine histrogranin (SHG and endomorphin1 (EM1 leads to attenuation of acute and chronic pain. The aim of this study was to design and evaluate an analgesic potency of the gene construct encoding SHG and EM1. Constructs with 1SHG copy in combination with EM1, 1SHG/EM1, and 6SHG/EM1 were intraspinally injected to animals with peripheral nerve injury-induced pain (chronic constriction injury, CCI or spinal cord injury induced pain (clip compression model, SCI and tactile and cold allodynia were evaluated. AAV2/8 particles were used for gene delivery. The results demonstrated 6SHG/EM1 as the most efficient for alleviation of pain-related behavior. The effect was observed up to 8 weeks in SCI animals, suggesting the lack of tolerance of possible synergistic effect between SHG and EM1. Intrathecal injection of SHG antibody or naloxone attenuated the analgesic effect in treated animals. Biochemical and histochemical evaluation confirmed the presence of both peptides in the spinal tissue. The results of this study showed that the injection of AAV vectors encoding combined SHG/EM constructs can provide long term attenuation of pain without overt adverse side effects. This approach may provide better treatment options for

  3. 47 CFR 22.921 - 911 call processing procedures; 911-only calling mode.

    Science.gov (United States)

    2010-10-01

    ... programming in the mobile unit that determines the handling of a non-911 call and permit the call to be... CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.921 911 call processing procedures; 911-only calling mode. Mobile telephones manufactured after February 13, 2000 that are capable of...

  4. Expression analysis of nine small heat shock protein genes from Tamarix hispida in response to different abiotic stresses and abscisic acid treatment.

    Science.gov (United States)

    Yang, Guiyan; Wang, Yucheng; Zhang, Kaimin; Gao, Caiqiu

    2014-03-01

    Heat shock proteins (HSPs) play important roles in protecting plants against environmental stresses. Furthermore, small heat shock proteins (sHSPs) are the most ubiquitous HSP subgroup with molecular weights ranging from 15 to 42 kDa. In this study, nine sHSP genes (designated as ThsHSP1-9) were cloned from Tamarix hispida. Their expression patterns in response to cold, heat shock, NaCl, PEG and abscisic acid (ABA) treatments were investigated in the roots and leaves of T. hispida by real-time RT-PCR analysis. The results showed that most of the nine ThsHSP genes were expressed at higher levels in roots than in leaves under normal growth condition. All of ThsHSP genes were highly induced under conditions of cold (4 °C) and different heat shocks (36, 40, 44, 48 and 52 °C). Under NaCl stress, all nine ThsHSPs genes were up-regulated at least one stress time-point in both roots and leaves. Under PEG and ABA treatments, the nine ThsHSPs showed various expression patterns, indicating a complex regulation pathway among these genes. This study represents an important basis for the elucidation of ThsHSP gene function and provides essential information that can be used for stress tolerance genetic engineering in future studies.

  5. Increasing Power by Sharing Information from Genetic Background and Treatment in Clustering of Gene Expression Time Series

    OpenAIRE

    Sura Zaki Alrashid; Muhammad Arifur Rahman; Nabeel H Al-Aaraji; Neil D Lawrence; Paul R Heath

    2018-01-01

    Clustering of gene expression time series gives insight into which genes may be co-regulated, allowing us to discern the activity of pathways in a given microarray experiment. Of particular interest is how a given group of genes varies with different conditions or genetic background. This paper develops
a new clustering method that allows each cluster to be parameterised according to whether the behaviour of the genes across conditions is correlated or anti-correlated. By specifying correlati...

  6. Thiopurine treatment in patients with Crohn's disease leads to a selective reduction of an effector cytotoxic gene expression signature revealed by whole-genome expression profiling.

    Science.gov (United States)

    Bouma, G; Baggen, J M; van Bodegraven, A A; Mulder, C J J; Kraal, G; Zwiers, A; Horrevoets, A J; van der Pouw Kraan, C T M

    2013-07-01

    Crohn's disease (CD) is characterized by chronic inflammation of the gastrointestinal tract, as a result of aberrant activation of the innate immune system through TLR stimulation by bacterial products. The conventional immunosuppressive thiopurine derivatives (azathioprine and mercaptopurine) are used to treat CD. The effects of thiopurines on circulating immune cells and TLR responsiveness are unknown. To obtain a global view of affected gene expression of the immune system in CD patients and the treatment effect of thiopurine derivatives, we performed genome-wide transcriptome analysis on whole blood samples from 20 CD patients in remission, of which 10 patients received thiopurine treatment, compared to 16 healthy controls, before and after TLR4 stimulation with LPS. Several immune abnormalities were observed, including increased baseline interferon activity, while baseline expression of ribosomal genes was reduced. After LPS stimulation, CD patients showed reduced cytokine and chemokine expression. None of these effects were related to treatment. Strikingly, only one highly correlated set of 69 genes was affected by treatment, not influenced by LPS stimulation and consisted of genes reminiscent of effector cytotoxic NK cells. The most reduced cytotoxicity-related gene in CD was the cell surface marker CD160. Concordantly, we could demonstrate an in vivo reduction of circulating CD160(+)CD3(-)CD8(-) cells in CD patients after treatment with thiopurine derivatives in an independent cohort. In conclusion, using genome-wide profiling, we identified a disturbed immune activation status in peripheral blood cells from CD patients and a clear treatment effect of thiopurine derivatives selectively affecting effector cytotoxic CD160-positive cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Help Options in CALL: A Systematic Review

    Science.gov (United States)

    Cardenas-Claros, Monica S.; Gruba, Paul A.

    2009-01-01

    This paper is a systematic review of research investigating help options in the different language skills in computer-assisted language learning (CALL). In this review, emerging themes along with is-sues affecting help option research are identified and discussed. We argue that help options in CALL are application resources that do not only seem…

  8. Coaching "Callings" throughout the Adult Life Cycle.

    Science.gov (United States)

    Hudson, Frederic M.

    2001-01-01

    The process of "callings" continues throughout life. Coaching can connect the present to the future in a meaningful way. Callings represent a value shift requiring revision of the nature and scope of one's central purpose in life and meaningful activities. (JOW)

  9. Performance indicators for call centers with impatience

    NARCIS (Netherlands)

    Jouini, O.; Koole, G.M.; Roubos, A.

    2013-01-01

    An important feature of call center modeling is the presence of impatient customers. This article considers single-skill call centers including customer abandonments. A number of different service-level definitions are structured, including all those used in practice, and the explicit computation of

  10. Call centers with a postponed callback offer

    NARCIS (Netherlands)

    B. Legros (Benjamin); S. Ding (Sihan); R.D. van der Mei (Rob); O. Jouini (Oualid)

    2017-01-01

    textabstractWe study a call center model with a postponed callback option. A customer at the head of the queue whose elapsed waiting time achieves a given threshold receives a voice message mentioning the option to be called back later. This callback option differs from the traditional ones found in

  11. Peafowl antipredator calls encode information about signalers.

    Science.gov (United States)

    Yorzinski, Jessica L

    2014-02-01

    Animals emit vocalizations that convey information about external events. Many of these vocalizations, including those emitted in response to predators, also encode information about the individual that produced the call. The relationship between acoustic features of antipredator calls and information relating to signalers (including sex, identity, body size, and social rank) were examined in peafowl (Pavo cristatus). The "bu-girk" antipredator calls of male and female peafowl were recorded and 20 acoustic parameters were automatically extracted from each call. Both the bu and girk elements of the antipredator call were individually distinctive and calls were classified to the correct signaler with over 90% and 70% accuracy in females and males, respectively. Females produced calls with a higher fundamental frequency (F0) than males. In both females and males, body size was negatively correlated with F0. In addition, peahen rank was related to the duration, end mean frequency, and start harmonicity of the bu element. Peafowl antipredator calls contain detailed information about the signaler and can potentially be used by receivers to respond to dangerous situations.

  12. Calling, is there anything special about it?

    African Journals Online (AJOL)

    2016-07-15

    Jul 15, 2016 ... when a pastor is installed or a new candidate is ordained, 'The one who calls you is faithful .... extension to secular work of the dignity of a calling' (Fowler ... For Luther, therefore, the private life of devotion exercised in the.

  13. The Call to Teach and Teacher Hopefulness

    Science.gov (United States)

    Bullough, Robert V., Jr.; Hall-Kenyon, Kendra M.

    2011-01-01

    The purpose of this paper is to explore teacher motivation and well-being. Our analysis focuses on two central concepts, the notion of a "calling to teach" and of teacher "hopefulness." Data from 205 preservice and inservice teachers were collected to determine teachers' sense of calling and level of hope. Results indicate that overwhelmingly,…

  14. Call center performance with direct response advertising

    NARCIS (Netherlands)

    M. Kiygi Calli (Meltem); M. Weverbergh (Marcel); Ph.H.B.F. Franses (Philip Hans)

    2017-01-01

    textabstractThis study investigates the manpower planning and the performance of a national call center dealing with car repairs and on the road interventions. We model the impact of advertising on the capacity required. The starting point is a forecasting model for the incoming calls, where we take

  15. Gene expression analysis of the rat testis after treatment with di(2-ethylhexyl) phthalate using cDNA microarray and real-time RT-PCR

    International Nuclear Information System (INIS)

    Kijima, Kazuyasu; Toyosawa, Kaoru; Yasuba, Masashi; Matsuoka, Nobuo; Adachi, Tetsuya; Komiyama, Masatoshi; Mori, Chisato

    2004-01-01

    To investigate the effects of di(2-ethylhexyl) phthalate (DEHP) on gene expression in rat testis, 6-week-old male Sprague-Dawley rats were given a single oral dose of 20 or 2000 mg/kg and euthanized 3, 6, 24, or 72 h thereafter. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells were significantly increased in the testis at 24 and 72 h after the exposure to 2000 mg/kg of DEHP. On cDNA microarray analysis, in addition to apoptosis-related genes, genes associated with atrophy, APEX nuclease, MutS homologue (E. coli), testosterone-repressed-prostatic-message-2 (TRPM-2), connective tissue growth factor, collagen alpha 2 type V, and cell adhesion kinase were differentially expressed. To investigate the relationship between histopathological alteration and gene expression, we selected genes associated with apoptosis and analyzed their expression by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). With 20 mg/kg of DEHP treatment, bcl-2, key gene related to apoptosis, was increased. Up-regulation of bcl-2, inhibitor of Apaf-1/caspase-9/caspase-2 cascade of apoptosis, may be related to the fact that no morphological apoptotic change was induced after dosing of 20 mg/kg DEHP. With 2000 mg/kg of DEHP treatment, the apoptotic activator cascade, Fas/FasL, FADD/caspase-8/caspase-3 cascade, and Apaf-1/caspase-9/caspase-2 cascade were increased and bcl-2 was decreased. Thus, these gene regulations might lead the cells into apoptosis in the case of high exposure to DEHP. In contrast, FADD/caspase-10/caspase-6 cascade and caspase-11/caspase-3 cascade were not increased. These results indicate that the cascades of FADD/caspase-10/caspase-6 and caspase-11/caspase-3 are not related to apoptosis with DEHP treatment

  16. Clinical Predictors of Response to Cognitive-Behavioral Therapy in Pediatric Anxiety Disorders : The Genes for Treatment (GxT) Study

    NARCIS (Netherlands)

    Hudson, Jennifer L.; Keers, Robert; Roberts, Susanna; Coleman, Jonathan R. I.; Breen, Gerome; Arendt, Kristian; Boegels, Susan; Cooper, Peter; Creswell, Cathy; Hartman, Catharina; Heiervang, Einar R.; Hoetzel, Katrin; In-Albon, Tina; Lavallee, Kristen; Lyne-Ham, Heidi J.; Marin, Carla E.; McKinnon, Anna; Meiser-Stedman, Richard; Morris, Talia; Nauta, Maaike; Rapee, Ronald M.; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Wergeland, Gro Janne; Lester, Kathryn J.; Eley, Thalia C.

    Objective: The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined

  17. Clinical predictors of response to Cognitive-Behavioral Therapy in pediatric anxiety disorders: The genes for treatment (GxT) study

    NARCIS (Netherlands)

    Hudson, J.L.; Keers, R.; Roberts, S.; Coleman, J.R.I.; Breen, G.; Arendt, K.; Cooper, P.; Bögels, S.; Creswell, C.; Hartman, C.; Heiervang, E.R.; Hötzel, K.; In-Albon, T.; Lavallee, K.; Lyneham, H.J.; Marin, C.E.; McKinnon, A.; Meiser-Stedman, R.; Morris, T.; Nauta, M.

    2015-01-01

    Objective The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined

  18. Id-1 and Id-2 genes and products as therapeutic targets for treatment of breast cancer and other types of carcinoma

    Science.gov (United States)

    Desprez, Pierre-Yves; Campisi, Judith

    2014-09-30

    A method for treatment and amelioration of breast, cervical, ovarian, endometrial, squamous cells, prostate cancer and melanoma in a patient comprising targeting Id-1 or Id-2 gene expression with a delivery vehicle comprising a product which modulates Id-1 or Id-2 expression.

  19. Perceived Calling and Work Engagement Among Nurses.

    Science.gov (United States)

    Ziedelis, Arunas

    2018-03-01

    The purpose of this study was to explore the relationship of perceived calling and work engagement in nursing over and above major work environment factors. In all, 351 nurses from various health care institutions completed the survey. Data were collected about the most demanding aspects of nursing, major job resources, the degree to which nursing is perceived as a meaningful calling, work engagement, and main demographic information. Hierarchical linear regression was applied to assess the relation between perceived calling and work engagement, while controlling for demographic and work environment factors, and perceived calling was significantly related to two out of three components of nurses' work engagement. The highest association was found with dedication component, and vigor component was related insignificantly. Results have shown that perceived calling might motivate nurses to engage in their work even in burdensome environment, although possible implications for the occupational well-being of nurses themselves remains unclear.

  20. Haplotype of platelet receptor P2RY12 gene is associated with residual clopidogrel on-treatment platelet reactivity.

    Science.gov (United States)

    Nie, Xiao-Yan; Li, Jun-Lei; Zhang, Yong; Xu, Yang; Yang, Xue-Li; Fu, Yu; Liang, Guang-Kai; Lu, Yun; Liu, Jian; Shi, Lu-Wen

    To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboelastography (TEG). One hundred and eighty patients with acute coronary syndrome (ACS) treated with clopidogrel and aspirin were included and platelet function was assessed by TEG. Five selected P2RY12 single nucleotide polymorphisms (SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934), which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs ( * 2, * 3, * 17) were genotyped and possible haplotypes were analyzed. The high on-treatment platelet reactivity (HTPR) prevalence defined by a platelet inhibition rate <30% by TEG in adenosine diphosphate (ADP)-channel was 69 (38.33%). Six common haplotypes were inferred from four of the selected P2RY12 SNPs (denoted H 0 to H 5 ) according to the linkage disequilibrium R square (except for rs2046934). Haplotype H 1 showed a significantly lower incidence of HTPR than the reference haplotype (H 0 ) in the total study population while haplotypes H 1 and H 2 showed significantly lower incidences of HTPR than H 0 in the nonsmoker subgroup after adjusting for CYP2C19 effects and demographic characteristics. rs2046934 (T744C) did not show any significant association with HTPR. The combination of common P2RY12 variations including regulatory regions rather than rs2046934 (T744C) that related to pharmacodynamics of clopidogrel in patients with ACS was independently associated with residual on-clopidogrel platelet reactivity. This is apart from the established association of the CYP2C19. This association seemed more important in the subgroup defined by smoking.

  1. Call cultures in orang-utans?

    Directory of Open Access Journals (Sweden)

    Serge A Wich

    Full Text Available BACKGROUND: Several studies suggested great ape cultures, arguing that human cumulative culture presumably evolved from such a foundation. These focused on conspicuous behaviours, and showed rich geographic variation, which could not be attributed to known ecological or genetic differences. Although geographic variation within call types (accents has previously been reported for orang-utans and other primate species, we examine geographic variation in the presence/absence of discrete call types (dialects. Because orang-utans have been shown to have geographic variation that is not completely explicable by genetic or ecological factors we hypothesized that this will be similar in the call domain and predict that discrete call type variation between populations will be found. METHODOLOGY/PRINCIPAL FINDINGS: We examined long-term behavioural data from five orang-utan populations and collected fecal samples for genetic analyses. We show that there is geographic variation in the presence of discrete types of calls. In exactly the same behavioural context (nest building and infant retrieval, individuals in different wild populations customarily emit either qualitatively different calls or calls in some but not in others. By comparing patterns in call-type and genetic similarity, we suggest that the observed variation is not likely to be explained by genetic or ecological differences. CONCLUSION/SIGNIFICANCE: These results are consistent with the potential presence of 'call cultures' and suggest that wild orang-utans possess the ability to invent arbitrary calls, which spread through social learning. These findings differ substantially from those that have been reported for primates before. First, the results reported here are on dialect and not on accent. Second, this study presents cases of production learning whereas most primate studies on vocal learning were cases of contextual learning. We conclude with speculating on how these findings might

  2. HPV has left the building – the absence of detectable HPV DNA and the presence of r allele/s for the P72R polymorphism in the TP53 gene may call for more aggressive therapeutic approach in HPV-associated tumours

    International Nuclear Information System (INIS)

    Petkova, Rumena; Chelenkova, Pavlina; Yemendzhiev, Husein; Tsekov, Iliya; Kalvatchev, Zlatko; Chakarov, Stoyan

    2013-01-01

    HPV infection is a major pathogenetic factor in cervical carcinoma as well as in many of the squamous cancers of head and neck and other epithelial cancers. Persistence of HPV DNA detectable by routine methods is considered to be a risk factor for advanced CIN and, in patients treated by surgery or non-surgical treatment modalities (radiotherapy, chemotherapy), HPV persistence is believed to be associated with increased risk for local recurrence. In terms of survival, however, it has been repeatedly proven that patients with cervical cancer and other HPV-associated cancers with detectable HPV DNA tend to have better outcomes than patients with HPV-negative tumours. The P72R polymorphism in the human TP53 gene has been contemplated as an independent phenotype modifier in cancers, especially the R allele which has been shown to confer higher pro-apoptotic properties to the resultant p53 protein. It has been demonstrated, however, that RR homozygotes were much more common in study groups with HPV-associated tumours than the other two genotypes and that the P allele in P/R heterozygotes was preferentially lost while the R allele was preferentially retained and mutated. It is possible that HPV-dependent carcinogenesis strictly relies on the presence of HPV and the expression of the E6 and E7 onco proteins only in the initial phases of transformation of infected cells (e.g. CIN). It may be associated with activation of latent HPV that would create a background of decreased control over the integrity of the genome of the host cell. The process can develop further by mechanisms independent of the presence of HPV and if the virus clears at some later point, that would not halt the already ongoing neoplastic transformation. Absence of HPV DNA in cervical tumours, whether before or after treatment, is not a reason to decrease vigilant monitoring and rule out the need for further treatment, as it may be quite possible that the TP53 gene of the infected cells has already been

  3. Preparation by alkaline treatment and detailed characterisation of empty hepatitis B virus core particles for vaccine and gene therapy applications

    Science.gov (United States)

    Strods, Arnis; Ose, Velta; Bogans, Janis; Cielens, Indulis; Kalnins, Gints; Radovica, Ilze; Kazaks, Andris; Pumpens, Paul; Renhofa, Regina

    2015-06-01

    Hepatitis B virus (HBV) core (HBc) virus-like particles (VLPs) are one of the most powerful protein engineering tools utilised to expose immunological epitopes and/or cell-targeting signals and for the packaging of genetic material and immune stimulatory sequences. Although HBc VLPs and their numerous derivatives are produced in highly efficient bacterial and yeast expression systems, the existing purification and packaging protocols are not sufficiently optimised and standardised. Here, a simple alkaline treatment method was employed for the complete removal of internal RNA from bacteria- and yeast-produced HBc VLPs and for the conversion of these VLPs into empty particles, without any damage to the VLP structure. The empty HBc VLPs were able to effectively package the added DNA and RNA sequences. Furthermore, the alkaline hydrolysis technology appeared efficient for the purification and packaging of four different HBc variants carrying lysine residues on the HBc VLP spikes. Utilising the introduced lysine residues and the intrinsic aspartic and glutamic acid residues exposed on the tips of the HBc spikes for chemical coupling of the chosen peptide and/or nucleic acid sequences ensured a standard and easy protocol for the further development of versatile HBc VLP-based vaccine and gene therapy applications.

  4. Ageing genes

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2018-01-01

    The idea of gerontogenes is in line with the evolutionary explanation of ageing as being an emergent phenomenon as a result of the imperfect maintenance and repair systems. Although evolutionary processes did not select for any specific ageing genes that restrict and determine the lifespan...... of an individual, the term ‘gerontogenes’ primarily refers to any genes that may seem to influence ageing and longevity, without being specifically selected for that role. Such genes can also be called ‘virtual gerontogenes’ by virtue of their indirect influence on the rate and process of ageing. More than 1000...... virtual gerontogenes have been associated with ageing and longevity in model organisms and humans. The ‘real’ genes, which do influence the essential lifespan of a species, and have been selected for in accordance with the evolutionary life history of the species, are known as the longevity assurance...

  5. External GSM phone calls now made simpler

    CERN Multimedia

    2007-01-01

    On 2 July, the IT/CS Telecom Service introduced a new service making external calls from CERN GSM phones easier. A specific prefix is no longer needed for calls outside CERN. External calls from CERN GSM phones are to be simplified. It is no longer necessary to use a special prefix to call an external number from the CERN GSM network.The Telecom Section of the IT/CS Group is introducing a new system that will make life easier for GSM users. It is no longer necessary to use a special prefix (333) to call an external number from the CERN GSM network. Simply dial the number directly like any other Swiss GSM customer. CERN currently has its own private GSM network with the Swiss mobile operator, Sunrise, covering the whole of Switzerland. This network was initially intended exclusively for calls between CERN numbers (replacing the old beeper system). A special system was later introduced for external calls, allowing them to pass thr...

  6. Attitude of Farmers towards Kisan Call Centres

    Directory of Open Access Journals (Sweden)

    Shely Mary Koshy

    2017-09-01

    Full Text Available The present study was conducted to measure the attitude of farmers in Kerala, India towards Kisan Call Centre (KCC. Kisan Call Centre provides free agricultural advisory services to every citizen involved in agriculture through a toll free number. One hundred and fifty farmers who have utilized the Kisan Call Centre service were selected from the database of KCC. The results showed that the respondents had moderately favourable attitude towards KCC followed by highly favourable attitude. The variables digital divide, temporal awareness on KCC, satisfaction towards KCC and utilization of KCC were found to have a positive correlation with the attitude of respondents towards KCC.

  7. Lunar phases and crisis center telephone calls.

    Science.gov (United States)

    Wilson, J E; Tobacyk, J J

    1990-02-01

    The lunar hypothesis, that is, the notion that lunar phases can directly affect human behavior, was tested by time-series analysis of 4,575 crisis center telephone calls (all calls recorded for a 6-month interval). As expected, the lunar hypothesis was not supported. The 28-day lunar cycle accounted for less than 1% of the variance of the frequency of crisis center calls. Also, as hypothesized from an attribution theory framework, crisis center workers reported significantly greater belief in lunar effects than a non-crisis-center-worker comparison group.

  8. Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

    Directory of Open Access Journals (Sweden)

    Torres-Trejo Alejandro

    2007-12-01

    received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-γ post-vaccine responses or prolonged progression-free survival in these participants. Conclusion Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines.

  9. Perceiving a calling, living a calling, and job satisfaction: testing a moderated, multiple mediator model.

    Science.gov (United States)

    Duffy, Ryan D; Bott, Elizabeth M; Allan, Blake A; Torrey, Carrie L; Dik, Bryan J

    2012-01-01

    The current study examined the relation between perceiving a calling, living a calling, and job satisfaction among a diverse group of employed adults who completed an online survey (N = 201). Perceiving a calling and living a calling were positively correlated with career commitment, work meaning, and job satisfaction. Living a calling moderated the relations of perceiving a calling with career commitment and work meaning, such that these relations were more robust for those with a stronger sense they were living their calling. Additionally, a moderated, multiple mediator model was run to examine the mediating role of career commitment and work meaning in the relation of perceiving a calling and job satisfaction, while accounting for the moderating role of living a calling. Results indicated that work meaning and career commitment fully mediated the relation between perceiving a calling and job satisfaction. However, the indirect effects of work meaning and career commitment were only significant for individuals with high levels of living a calling, indicating the importance of living a calling in the link between perceiving a calling and job satisfaction. Implications for research and practice are discussed. (c) 2012 APA, all rights reserved.

  10. Short communication: relationship of call rate and accuracy of single nucleotide polymorphism genotypes in dairy cattle.

    Science.gov (United States)

    Cooper, T A; Wiggans, G R; VanRaden, P M

    2013-05-01

    Call rates on both a single nucleotide polymorphism (SNP) basis and an animal basis are used as measures of data quality and as screening tools for genomic studies and evaluations of dairy cattle. To investigate the relationship of SNP call rate and genotype accuracy for individual SNP, the correlation between percentages of missing genotypes and parent-progeny conflicts for each SNP was calculated for 103,313 Holsteins. Correlations ranged from 0.14 to 0.38 for the BovineSNP50 and BovineLD (Illumina Inc., San Diego, CA) and GeneSeek Genomic Profiler (Neogen Corp., Lincoln, NE) chips, with lower correlations for newer chips. For US genomic evaluations, genotypes are excluded for animals with a call rate of call rate for 220,175 Holstein, Jersey, and Brown Swiss genotypes was 99.6%. Animal genotypes with a call rate of ≤99% were examined from the US Department of Agriculture genotype database to determine how genotype call rate is related to accuracy of calls on an animal basis. Animal call rate was determined from SNP used in genomic evaluation and is the number of called autosomal and X-specific SNP genotypes divided by the number of SNP from that type of chip. To investigate the relationship of animal call rate and parentage validation, conflicts between a genotyped animal and its sire or dam were determined through a duo test (opposite homozygous SNP genotypes between sire and progeny; 1,374 animal genotypes) and a trio test (also including conflicts with dam and heterozygous SNP genotype for the animal when both parents are the same homozygote; 482 animal genotypes). When animal call rate was ≤ 80%, parentage validation was no longer reliable with the duo test. With the trio test, parentage validation was no longer reliable when animal call rate was ≤ 90%. To investigate how animal call rate was related to genotyping accuracy for animals with multiple genotypes, concordance between genotypes for 1,216 animals that had a genotype with a call rate of ≤ 99

  11. DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol-induced cell growth and restores expression of DNA repair genes in human breast cancer cells.

    Science.gov (United States)

    Singh, Kamaleshwar P; Treas, Justin; Tyagi, Tulika; Gao, Weimin

    2012-03-01

    Prolonged exposure to elevated levels of estrogen is a risk factor for breast cancer. Though increased cell growth and loss of DNA repair capacity is one of the proposed mechanisms for estrogen-induced cancers, the mechanism through which estrogen induces cell growth and decreases DNA repair capacity is not clear. DNA hypermethylation is known to inactivate DNA repair genes and apoptotic response in cancer cells. Therefore, the objective of this study was to determine the role of DNA hypermethylation in estrogen-induced cell growth and regulation of DNA repair genes expression in breast cancer cells. To achieve this objective, the estrogen-responsive MCF-7 cells either pretreated with 5-aza-2-deoxycytidine (5-aza-dC) or untreated (as control) were exposed to 17 beta-estradiol (E2), and its effect on cell growth and expression of DNA repair genes were measured. The result revealed that 5-aza-dC abrogates the E2-induced growth in MCF-7 cells. An increased expression of OGG1, MSH4, and MLH1 by 5-aza-dC treatment alone, suggest the DNA hypermethylation as a potential cause for decreased expression of these genes in MCF-7 cells. The decreased expression of ERCC1, XPC, OGG1, and MLH1 by E2 alone and its restoration by co-treatment with 5-aza-dC further suggest that E2 reduces the expression of these DNA repair genes potentially through promoter hypermethylation. Reactivation of mismatch repair (MMR) gene MLH1 and abrogation of E2-induced cell growth by 5-aza-dC treatment suggest that estrogen causes increased growth in breast cancer cells potentially through the inhibition of MMR-mediated apoptotic response. In summary, this study suggests that estrogen increases cell growth and decreases the DNA repair capacity in breast cancer cells, at least in part, through epigenetic mechanism. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. The Microbiota and Abundance of the Class 1 Integron-Integrase Gene in Tropical Sewage Treatment Plant Influent and Activated Sludge.

    Directory of Open Access Journals (Sweden)

    Magna C Paiva

    Full Text Available Bacteria are assumed to efficiently remove organic pollutants from sewage in sewage treatment plants, where antibiotic-resistance genes can move between species via mobile genetic elements known as integrons. Nevertheless, few studies have addressed bacterial diversity and class 1 integron abundance in tropical sewage. Here, we describe the extant microbiota, using V6 tag sequencing, and quantify the class 1 integron-integrase gene (intI1 in raw sewage (RS and activated sludge (AS. The analysis of 1,174,486 quality-filtered reads obtained from RS and AS samples revealed complex and distinct bacterial diversity in these samples. The RS sample, with 3,074 operational taxonomic units, exhibited the highest alpha-diversity indices. Among the 25 phyla, Proteobacteria, Bacteroidetes and Firmicutes represented 85% (AS and 92% (RS of all reads. Increased relative abundance of Micrococcales, Myxococcales, and Sphingobacteriales and reduced pathogen abundance were noted in AS. At the genus level, differences were observed for the dominant genera Simplicispira and Diaphorobacter (AS as well as for Enhydrobacter (RS. The activated sludge process decreased (55% the amount of bacteria harboring the intI1 gene in the RS sample. Altogether, our results emphasize the importance of biological treatment for diminishing pathogenic bacteria and those bearing the intI1 gene that arrive at a sewage treatment plant.

  13. The function of migratory bird calls

    DEFF Research Database (Denmark)

    Reichl, Thomas; Andersen, Bent Bach; Larsen, Ole Næsbye

    The function of migratory bird calls: do they influence orientation and navigation?   Thomas Reichl1, Bent Bach Andersen2, Ole Naesbye Larsen2, Henrik Mouritsen1   1Institute of Biology, University of Oldenburg, Oldenburg, D-26111 Oldenburg, Germany 2Institute of Biology, University of Southern...... migration and to stimulate migratory restlessness in conspecifics. We wished to test if conspecific flight calls influence the flight direction of a nocturnal migrant, the European Robin (Erithacus rubecula), i.e. if flight calls help migrants keeping course. Wild caught birds showing migratory restlessness...... the experimental bird could be activated successively to simulate a migrating Robin cruising E-W, W-E, S-N or N-S at a chosen height (mostly about 40 m), at 10 m/s and emitting Robin flight calls of 80 dB(A) at 1 m. The simulated flight of a "ding" sound served as a control. During an experiment the bird was first...

  14. 76 FR 4896 - Call for Candidates

    Science.gov (United States)

    2011-01-27

    ... designated to establish generally accepted accounting principles for federal government entities. Generally, non-federal Board members are selected from the general financial community, the accounting and... FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Call for Candidates AGENCY: Federal Accounting...

  15. Reflections … they called it 'restructuring'[1

    African Journals Online (AJOL)

    turnaround strategy with the appointment of a CEO to implement such strategy in ... found herself accepting so-called 'native' advertising (the practice of publishing an ... preferring to receive their reading 'lite' on mobile platforms. According.

  16. Application of Adoptive T-Cell Therapy Using Tumor Antigen-Specific T-Cell Receptor Gene Transfer for the Treatment of Human Leukemia

    Directory of Open Access Journals (Sweden)

    Toshiki Ochi

    2010-01-01

    Full Text Available The last decade has seen great strides in the field of cancer immunotherapy, especially the treatment of melanoma. Beginning with the identification of cancer antigens, followed by the clinical application of anti-cancer peptide vaccination, it has now been proven that adoptive T-cell therapy (ACT using cancer antigen-specific T cells is the most effective option. Despite the apparent clinical efficacy of ACT, the timely preparation of a sufficient number of cancer antigen-specific T cells for each patient has been recognized as its biggest limitation. Currently, therefore, attention is being focused on ACT with engineered T cells produced using cancer antigen-specific T-cell receptor (TCR gene transfer. With regard to human leukemia, ACT using engineered T cells bearing the leukemia antigen-specific TCR gene still remains in its infancy. However, several reports have provided preclinical data on TCR gene transfer using Wilms' tumor gene product 1 (WT1, and also preclinical and clinical data on TCR gene transfer involving minor histocompatibility antigen, both of which have been suggested to provide additional clinical benefit. In this review, we examine the current status of anti-leukemia ACT with engineered T cells carrying the leukemia antigen-specific TCR gene, and discuss the existing barriers to progress in this area.

  17. Antibiotic-resistant genes and antibiotic-resistant bacteria in the effluent of urban residential areas, hospitals, and a municipal wastewater treatment plant system.

    Science.gov (United States)

    Li, Jianan; Cheng, Weixiao; Xu, Like; Strong, P J; Chen, Hong

    2015-03-01

    In this study, we determined the abundance of 8 antibiotics (3 tetracyclines, 4 sulfonamides, and 1 trimethoprim), 12 antibiotic-resistant genes (10 tet, 2 sul), 4 antibiotic-resistant bacteria (tetracycline, sulfamethoxazole, and combined resistance), and class 1 integron integrase gene (intI1) in the effluent of residential areas, hospitals, and municipal wastewater treatment plant (WWTP) systems. The concentrations of total/individual targets (antibiotics, genes, and bacteria) varied remarkably among different samples, but the hospital samples generally had a lower abundance than the residential area samples. The WWTP demonstrated removal efficiencies of 50.8% tetracyclines, 66.8% sulfonamides, 0.5 logs to 2.5 logs tet genes, and less than 1 log of sul and intI1 genes, as well as 0.5 log to 1 log removal for target bacteria. Except for the total tetracycline concentration and the proportion of tetracycline-resistant bacteria (R (2) = 0.330, P antibiotics and the corresponding resistant bacteria (P > 0.05). In contrast, various relationships were identified between antibiotics and antibiotic resistance genes (P antibiotic-resistant bacteria (P < 0.01).

  18. Gene expression and gene therapy imaging

    International Nuclear Information System (INIS)

    Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

    2007-01-01

    The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

  19. Early effects of FOLFOX treatment of colorectal tumour in an animal model: assessment of changes in gene expression and FDG kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, Ludwig G. [German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center, Medical PET Group - Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Hoffend, Johannes [Klinikum Ludwigshafen, Institute of Diagnostic and Interventional Radiology, Ludwigshafen (Germany); Koczan, Dirk [University of Rostock, Institute of Immunology, Rostock (Germany); Pan, Leyun; Dimitrakopoulou-Strauss, Antonia [German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Haberkorn, Uwe [German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany)

    2009-08-15

    The very early chemotherapeutic effects of the FOLFOX (fluorouracil, folinic acid, oxaliplatin) protocol were assessed in mice implanted with a human colorectal cell line. The aim of this study was to identify changes in gene expression patterns and to detect combinations of PET parameters that may be helpful in identifying treated tumours early after chemotherapy using dynamic PET studies. A human colorectal cell line (HCT 116) was used in nude mice. Dynamic PET studies were performed in untreated (n=13) and treated (n=12) animals. The data were assessed using compartmental and noncompartmental analysis. The removed tumour specimens were assessed by gene array analysis to obtain quantitative information on gene expression. One chemotherapeutic treatment using the FOLFOX protocol resulted in an upregulation of 2,078 gene probes by more than 25%, while 2,254 probes were downregulated following treatment. The gene array data demonstrated primarily an enhancement of genes related to apoptosis. In particular, the apoptosis antigen 1 (APO-1), p21 and the G protein-coupled receptor 87 (G-87) were 2.6- to 3.3-fold upregulated as compared to the expression in untreated animals. There was a 100% separation of untreated and treated animals on the basis of these three genes. The SUV and the FDG kinetic parameters obtained by compartmental and noncompartmental fitting were not significantly different when individual parameters were compared between groups. However, classification analysis of the combination of the PET parameters VB, K1, k3, and influx revealed an overall accuracy of 84%. We were able to identify 91.7% (11/12) of the treated animals and 76.9% (10/13) of the untreated animals correctly using the classification analysis of PET data. Even one chemotherapeutic treatment using FOLFOX has an impact on gene expression and significantly modulates FDG kinetics. Quantitative assessment of the tracer kinetics and the application of classification analysis to the data are

  20. Identification and expression analysis of WRKY transcription factor genes in canola (Brassica napus L. in response to fungal pathogens and hormone treatments

    Directory of Open Access Journals (Sweden)

    Deyholos Michael K

    2009-06-01

    expression patterns. Conclusion We identified a set of 13 BnWRKY genes from among 16 BnWRKY genes assayed, that are responsive to both fungal pathogens and hormone treatments, suggesting shared signaling mechanisms for these responses. This study suggests that a large number of BnWRKY proteins are involved in the transcriptional regulation of defense-related genes in response to fungal pathogens and hormone stimuli.

  1. The Role of Calling in Military Engagement

    Science.gov (United States)

    2017-06-01

    depression , hopelessness, emotional and behavior problems , and have lower levels of neuroticism (Oladipo et al., 2013; Suldo & Huebner, 2004; Gilman...retention? Data from surveys of Naval Postgraduate School students reveal many work-related correlations with calling and calling’s positive effects. My...retention? Data from surveys of Naval Postgraduate School students reveal many work-related correlations with calling and calling’s positive effects

  2. Molecular determination of extended spectrum b-lactamases antibiotics resistance genes in E.coli isolated from diarrhea in cattle

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    Ghassan Khudhair Ismaeel

    2017-07-01

    Full Text Available None response to the treatment by an antibiotic called antibiotics resistance result from some genes called resistance genes .This mechanism is widespread in most of the bacteria, like E.coli . All of the extended resistance genes called (ESBIS is a typical example for study of some genes that resistance beta-lactam antibiotic is subject of this research. Fifty feces sample were collected from cattle suffering from diarrhea in alqaissiyah city were cultured on selective media for E.coli , then DNA was extracted from all E.coli isolates for antibiotic resistance gene detection by PCR ; The results of this study revealed the prevalence of B-lactamase gene four B-lactamases genes in E.coli blaAmpc gene were (91.4%, the blactx-m gene were (80%, blaTem were (62.8% and finally and blaSHV gene were (22% among isolates E.coli ; blaAMPC gene has high prevalence than others genes while blaSHV was a lower percentage than other genes

  3. Behavioral Preferences for Individual Securities : The Case for Call Warrants and Call Options

    NARCIS (Netherlands)

    Ter Horst, J.R.; Veld, C.H.

    2002-01-01

    Since 1998, large investment banks have flooded the European capital markets with issues of call warrants.This has led to a unique situation in the Netherlands, where now call warrants, traded on the stock exchange, and long-term call options, traded on the options exchange, exist.Both entitle their

  4. Increasing Power by Sharing Information from Genetic Background and Treatment in Clustering of Gene Expression Time Series

    Directory of Open Access Journals (Sweden)

    Sura Zaki Alrashid

    2018-02-01

    Full Text Available Clustering of gene expression time series gives insight into which genes may be co-regulated, allowing us to discern the activity of pathways in a given microarray experiment. Of particular interest is how a given group of genes varies with different conditions or genetic background. This paper develops
a new clustering method that allows each cluster to be parameterised according to whether the behaviour of the genes across conditions is correlated or anti-correlated. By specifying correlation between such genes,more information is gain within the cluster about how the genes interrelate. Amyotrophic lateral sclerosis (ALS is an irreversible neurodegenerative disorder that kills the motor neurons and results in death within 2 to 3 years from the symptom onset. Speed of progression for different patients are heterogeneous with significant variability. The SOD1G93A transgenic mice from different backgrounds (129Sv and C57 showed consistent phenotypic differences for disease progression. A hierarchy of Gaussian isused processes to model condition-specific and gene-specific temporal co-variances. This study demonstrated about finding some significant gene expression profiles and clusters of associated or co-regulated gene expressions together from four groups of data (SOD1G93A and Ntg from 129Sv and C57 backgrounds. Our study shows the effectiveness of sharing information between replicates and different model conditions when modelling gene expression time series. Further gene enrichment score analysis and ontology pathway analysis of some specified clusters for a particular group may lead toward identifying features underlying the differential speed of disease progression.

  5. 17α-Ethinylestradiol (EE2) treatment of wild roach (Rutilus rutilus) during early life development disrupts expression of genes directly involved in the feedback cycle of estrogen.

    Science.gov (United States)

    Nikoleris, Lina; Hultin, Cecilia L; Hallgren, Per; Hansson, Maria C

    2016-02-01

    Fish are more sensitive to introduced disturbances from synthetic endocrine disrupting compounds during early life phases compared with mature stages. 17α-Ethinylestradiol (EE2), which is the active compound in human oral contraceptives and hormone replacement therapies, is today ever present in the effluents from sewage treatment plants. EE2 targets and interacts with the endogenous biological systems of exposed vertebrates resulting in to large extents unknown short- and long-term effects. We investigated how EE2 exposure affects expression profiles of a large number of target genes during early life of roach (Rutilus rutilus). We exposed fertilized roach eggs collected from a lake in Southern Sweden to EE2 for 12weeks together with 1+-year-old roach in aquaria. We measured the gene expression of the estrogen receptor (esr)1/2a/2b, androgen receptor (ar), vitellogenin, cytochrome P450 (cyp)19a1a/1b in fertilized eggs; newly hatched larvae; 12-week-old fry; and juvenile wild roach (1+-year-old). Results shows that an EE2 concentration as low as 0.5ng/L significantly affects gene expression during early development. Gene expression responses vary both among life stages and molecular receptors. We also show that the gene profile of the estrogen feedback cycle to a large extent depends on the relationship between the three esr genes and the two cyp19a1 genes, which are all up-regulated with age. Results indicate that a disruption of the natural activity of the dominant esr gene could lead to detrimental biological effects if EE2 exposure occurs during development, even if this exposure occurred for only a short period. Copyright © 2015. Published by Elsevier Inc.

  6. Human anti-CCR4 minibody gene transfer for the treatment of cutaneous T-cell lymphoma.

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    Thomas Han

    Full Text Available Although several therapeutic options have become available for patients with Cutaneous T-cell Lymphoma (CTCL, no therapy has been curative. Recent studies have demonstrated that CTCL cells overexpress the CC chemokine receptor 4 (CCR4.In this study, a xenograft model of CTCL was established and a recombinant adeno-associated viral serotype 8 (AAV8 vector expressing a humanized single-chain variable fragment (scFv-Fc fusion (scFvFc or "minibody" of anti-CCR4 monoclonal antibody (mAb h1567 was evaluated for curative treatment. Human CCR4+ tumor-bearing mice treated once with intravenous infusion of AAV8 virions encoding the h1567 (AAV8-h1567 minibody showed anti-tumor activity in vivo and increased survival. The AAV8-h1567 minibody notably increased the number of tumor-infiltrating Ly-6G+ FcγRIIIa(CD16A+ murine neutrophils in the tumor xenografts over that of AAV8-control minibody treated mice. Furthermore, in CCR4+ tumor-bearing mice co-treated with AAV8-h1567 minibody and infused with human peripheral blood mononuclear cells (PBMCs, marked tumor infiltration of human CD16A+ CD56+ NK cells was observed. The h1567 minibody also induced in vitro ADCC activity through both mouse neutrophils and human NK cells.Overall, our data demonstrate that the in vivo anti-tumor activity of h1567 minibody is mediated, at least in part, through CD16A+ immune effector cell ADCC mechanisms. These data further demonstrate the utility of the AAV-minibody gene transfer system in the rapid evaluation of candidate anti-tumor mAbs and the potency of h1567 as a potential novel therapy for CTCL.

  7. Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance.

    Science.gov (United States)

    Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun; Jakobsen, Marianne Antonius; Brusgaard, Klaus; Tan, Qihua; Gaster, Michael

    2014-09-05

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls. Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin sensitivity and if testosterone is implicated in muscular insulin resistance in PCOS, this is by and indirect mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Does prior traumatization affect the treatment outcome of CBT for panic disorder? The potential role of the MAOA gene and depression symptoms.

    Science.gov (United States)

    Trautmann, Sebastian; Richter, Jan; Muehlhan, Markus; Höfler, Michael; Wittchen, Hans-Ulrich; Domschke, Katharina; Ströhle, Andreas; Hamm, Alfons O; Weber, Heike; Kircher, Tilo; Arolt, Volker; Gerlach, Alexander L; Alpers, Georg W; Fydrich, Thomas; Lang, Thomas; Reif, Andreas

    2017-07-15

    Although cognitive behavioral therapy (CBT) is highly effective in the treatment of anxiety disorders, many patients still do not benefit. This study investigates whether a history of traumatic event experience is negatively associated with outcomes of CBT for panic disorder. The moderating role of the monoamine oxidase A (MAOA) gene and depression symptoms as well as the association between trauma history and fear reactivity as a potential mechanism are further analyzed. We conducted a post-hoc analysis of 172 male and 60 female patients with panic disorder treated with CBT in a multi-center study. Treatment outcome was assessed at post-treatment using self-report and clinician rating scales. Fear reactivity before treatment was assessed via heart rate and self-reported anxiety during a behavioral avoidance test. Among females, we did not find any differences in treatment response between traumatized and non-traumatized individuals or any two-way interaction trauma history × MAOA genotype. There was a significant three-way interaction trauma history × MAOA genotype × depression symptoms on all treatment outcomes indicating that in traumatized female patients carrying the low-activity allele, treatment effect sizes decreased with increasing depression symptoms at baseline. No such effects were observed for males. In conclusion, we found no evidence for a differential treatment response in traumatized and non-traumatized individuals. There is preliminary evidence for poorer treatment outcomes in a subgroup of female traumatized individuals carrying the low-active variant of the MAOA gene. These patients also report more symptoms of depression symptomatology and exhibit a dampened fear response before treatment which warrants further investigation.

  9. Modification of the association between antipsychotic treatment response and childhood adversity by MMP9 gene variants in a first-episode schizophrenia cohort.

    Science.gov (United States)

    McGregor, Nathaniel; Thompson, Nicole; O'Connell, Kevin Sean; Emsley, Robin; van der Merwe, Lize; Warnich, Louise

    2018-04-01

    Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity. This study investigated the role of variants in matrix metallopeptidase 9 (MMP9), a gene involved in synaptic plasticity, with treatment outcome considering the severity of childhood trauma as an interacting variable. The cohort comprised South African first episode schizophrenia patients treated with a single injectable antipsychotic, flupenthixol decanoate, monitored over 12 months. Relationships between novel and previously described variants, and haplotypes, with antipsychotic treatment response were found to be modified when considering childhood trauma as an interacting variable. This study provides the first evidence for the involvement of polymorphisms within MMP9 and the severity of childhood trauma in antipsychotic treatment response, and warrants further investigation into the role gene-environment interactions may play in the betterment of antipsychotic treatment strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Telephone calls by individuals with cancer.

    Science.gov (United States)

    Flannery, Marie; McAndrews, Leanne; Stein, Karen F

    2013-09-01

    To describe symptom type and reporting patterns found in spontaneously initiated telephone calls placed to an ambulatory cancer center practice. Retrospective, descriptive. Adult hematology oncology cancer center. 563 individuals with a wide range of oncology diagnoses who initiated 1,229 telephone calls to report symptoms. Raw data were extracted from telephone forms using a data collection sheet with 23 variables obtained for each phone call, using pre-established coding criteria. A literature-based, investigator-developed instrument was used for the coding criteria and selection of which variables to extract. Symptom reporting, telephone calls, pain, and symptoms. A total of 2,378 symptoms were reported by telephone during the four months. At least 10% of the sample reported pain (38%), fatigue (16%), nausea (16%), swelling (12%), diarrhea (12%), dyspnea (10%), and anorexia (10%). The modal response was to call only one time and to report only one symptom (55%). Pain emerged as the symptom that most often prompted an individual to pick up the telephone and call. Although variation was seen in symptom reporting, an interesting pattern emerged with an individual reporting on a solitary symptom in a single telephone call. The emergence of pain as the primary symptom reported by telephone prompted educational efforts for both in-person clinic visit management of pain and prioritizing nursing education and protocol management of pain reported by telephone. Report of symptoms by telephone can provide nurses unique insight into patient-centered needs. Although pain has been an important focus of education and research for decades, it remains a priority for individuals with cancer. A wide range in symptom reporting by telephone was evident.

  11. Identification of Novel Signal Transduction, Immune Function, and Oxidative Stress Genes and Pathways by Topiramate for Treatment of Methamphetamine Dependence Based on Secondary Outcomes

    Directory of Open Access Journals (Sweden)

    Tianhua Niu

    2017-12-01

    Full Text Available BackgroundTopiramate (TPM is suggested to be a promising medication for treatment of methamphetamine (METH dependence, but the molecular basis remains to be elucidated.MethodsAmong 140 METH-dependent participants randomly assigned to receive either TPM (N = 69 or placebo (N = 71 in a previously conducted randomized controlled trial, 50 TPM- and 49 placebo-treated participants had a total 212 RNA samples available at baseline, week 8, and week 12 time points. Following our primary analysis of gene expression data, we reanalyzed the microarray expression data based on a latent class analysis of binary secondary outcomes during weeks 1–12 that provided a classification of 21 responders and 31 non-responders with consistent responses at both time points.ResultsBased on secondary outcomes, 1,381, 576, 905, and 711 differentially expressed genes at nominal P values < 0.05 were identified in responders versus non-responders for week 8 TPM, week 8 placebo, week 12 TPM, and week 12 placebo groups, respectively. Among 1,381 genes identified in week 8 TPM responders, 359 genes were identified in both week 8 and week 12 TPM groups, of which 300 genes were exclusively detected in TPM responders. Of them, 32 genes had nominal P values < 5 × 10−3 at either week 8 or week 12 and false discovery rates < 0.15 at both time points with consistent directions of gene expression changes, which include GABARAPL1, GPR155, and IL15RA in GABA receptor signaling that represent direct targets for TPM. Analyses of these 300 genes revealed 7 enriched pathways belonging to neuronal function/synaptic plasticity, signal transduction, inflammation/immune function, and oxidative stress response categories. No pathways were enriched for 72 genes exclusively detected in both week 8 and week 12 placebo groups.ConclusionThis secondary analysis study of gene expression data from a TPM clinical trial not only yielded consistent results with those of primary

  12. The dynamics of gene expression changes in a mouse model of oral tumorigenesis may help refine prevention and treatment strategies in patients with oral cancer.

    Science.gov (United States)

    Foy, Jean-Philippe; Tortereau, Antonin; Caulin, Carlos; Le Texier, Vincent; Lavergne, Emilie; Thomas, Emilie; Chabaud, Sylvie; Perol, David; Lachuer, Joël; Lang, Wenhua; Hong, Waun Ki; Goudot, Patrick; Lippman, Scott M; Bertolus, Chloé; Saintigny, Pierre

    2016-06-14

    A better understanding of the dynamics of molecular changes occurring during the early stages of oral tumorigenesis may help refine prevention and treatment strategies. We generated genome-wide expression profiles of microdissected normal mucosa, hyperplasia, dysplasia and tumors derived from the 4-NQO mouse model of oral tumorigenesis. Genes differentially expressed between tumor and normal mucosa defined the "tumor gene set" (TGS), including 4 non-overlapping gene subsets that characterize the dynamics of gene expression changes through different stages of disease progression. The majority of gene expression changes occurred early or progressively. The relevance of these mouse gene sets to human disease was tested in multiple datasets including the TCGA and the Genomics of Drug Sensitivity in Cancer project. The TGS was able to discriminate oral squamous cell carcinoma (OSCC) from normal oral mucosa in 3 independent datasets. The OSCC samples enriched in the mouse TGS displayed high frequency of CASP8 mutations, 11q13.3 amplifications and low frequency of PIK3CA mutations. Early changes observed in the 4-NQO model were associated with a trend toward a shorter oral cancer-free survival in patients with oral preneoplasia that was not seen in multivariate analysis. Progressive changes observed in the 4-NQO model were associated with an increased sensitivity to 4 different MEK inhibitors in a panel of 51 squamous cell carcinoma cell lines of the areodigestive tract. In conclusion, the dynamics of molecular changes in the 4-NQO model reveal that MEK inhibition may be relevant to prevention and treatment of a specific molecularly-defined subgroup of OSCC.

  13. Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

    Science.gov (United States)

    Candotti, Fabio; Shaw, Kit L; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F; Weinberg, Kenneth I; Crooks, Gay M; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S; Rosenblatt, Howard M; Davis, Carla M; Hanson, Celine; Rishi, Radha G; Wang, Xiaoyan; Gjertson, David; Yang, Otto O; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A; Engel, Barbara C; Podsakoff, Gregory M; Hershfield, Michael S; Blaese, R Michael; Parkman, Robertson; Kohn, Donald B

    2012-11-01

    We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.

  14. Gene therapy for adenosine deaminase–deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans

    Science.gov (United States)

    Candotti, Fabio; Shaw, Kit L.; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H.; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G. Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F.; Weinberg, Kenneth I.; Crooks, Gay M.; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S.; Rosenblatt, Howard M.; Davis, Carla M.; Hanson, Celine; Rishi, Radha G.; Wang, Xiaoyan; Gjertson, David; Yang, Otto O.; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A.; Engel, Barbara C.; Podsakoff, Gregory M.; Hershfield, Michael S.; Blaese, R. Michael; Parkman, Robertson

    2012-01-01

    We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)–deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34+ cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m2). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency. PMID:22968453

  15. Identification and expression analysis of ERF transcription factor genes in petunia during flower senescence and in response to hormone treatments.

    Science.gov (United States)

    Liu, Juanxu; Li, Jingyu; Wang, Huinan; Fu, Zhaodi; Liu, Juan; Yu, Yixun

    2011-01-01

    Ethylene-responsive element-binding factor (ERF) genes constitute one of the largest transcription factor gene families in plants. In Arabidopsis and rice, only a few ERF genes have been characterized so far. Flower senescence is associated with increased ethylene production in many flowers. However, the characterization of ERF genes in flower senescence has not been reported. In this study, 13 ERF cDNAs were cloned from petunia. Based on the sequence characterization, these PhERFs could be classified into four of the 12 known ERF families. Their predicted amino acid sequences exhibited similarities to ERFs from other plant species. Expression analyses of PhERF mRNAs were performed in corollas and gynoecia of petunia flower. The 13 PhERF genes displayed differential expression patterns and levels during natural flower senescence. Exogenous ethylene accelerates the transcription of the various PhERF genes, and silver thiosulphate (STS) decreased the transcription of several PhERF genes in corollas and gynoecia. PhERF genes of group VII showed a strong association with the rise in ethylene production in both petals and gynoecia, and might be associated particularly with flower senescence in petunia. The effect of sugar, methyl jasmonate, and the plant hormones abscisic acid, salicylic acid, and 6-benzyladenine in regulating the different PhERF transcripts was investigated. Functional nuclear localization signal analyses of two PhERF proteins (PhERF2 and PhERF3) were carried out using fluorescence microscopy. These results supported a role for petunia PhERF genes in transcriptional regulation of petunia flower senescence processes.

  16. Identification of a gene expression core signature for Duchenne Muscular Dystrophy (DMD) via integrative analysis reveals novel potential compounds for treatment

    KAUST Repository

    Ichim-Moreno, Norú

    2010-05-01

    Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy and one of the most prevalent genetic disorders of childhood. DMD is characterized by rapid progression of muscle degeneration, and ultimately death. Currently, glucocorticoids are the only available treatment for DMD, but they have been shown to result in serious side effects. The purpose of this research was to define a core signature of gene expression related to DMD via integrative analysis of mouse and human datasets. This core signature was subsequently used to screen for novel potential compounds that antagonistically affect the expression of signature genes. With this approach we were able to identify compounds that are 1) already used to treat DMD, 2) currently under investigation for treatment, and 3) so far unknown but promising candidates. Our study highlights the potential of meta-analyses through the combination of datasets to unravel previously unrecognized associations and reveal new relationships. © IEEE.

  17. Abundance and diversity of bacterial nitrifiers and denitrifiers and their functional genes in tannery wastewater treatment plants revealed by high-throughput sequencing.

    Directory of Open Access Journals (Sweden)

    Zhu Wang

    Full Text Available Biological nitrification/denitrification is frequently used to remove nitrogen from tannery wastewater containing high concentrations of ammonia. However, information is limited about the bacterial nitrifiers and denitrifiers and their functional genes in tannery wastewater treatment plants (WWTPs due to the low-throughput of the previously used methods. In this study, 454 pyrosequencing and Illumina high-throughput sequencing, combined with molecular methods, were used to comprehensively characterize structures and functions of nitrification and denitrification bacterial communities in aerobic and anaerobic sludge of two full-scale tannery WWTPs. Pyrosequencing of 16S rRNA genes showed that Proteobacteria and Synergistetes dominated in the aerobic and anaerobic sludge, respectively. Ammonia-oxidizing bacteria (AOB amoA gene cloning revealed that Nitrosomonas europaea dominated the ammonia-oxidizing community in the WWTPs. Metagenomic analysis showed that the denitrifiers mainly included the genera of Thauera, Paracoccus, Hyphomicrobium, Comamonas and Azoarcus, which may greatly contribute to the nitrogen removal in the two WWTPs. It is interesting that AOB and ammonia-oxidizing archaea had low abundance although both WWTPs demonstrated high ammonium removal efficiency. Good correlation between the qPCR and metagenomic analysis is observed for the quantification of functional genes amoA, nirK, nirS and nosZ, indicating that the metagenomic approach may be a promising method used to comprehensively investigate the abundance of functional genes of nitrifiers and denitrifiers in the environment.

  18. Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF

    Science.gov (United States)

    Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

    2015-01-01

    Background: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3–5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Results: Motoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Conclusions: Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS. PMID:25653590

  19. Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF.

    Directory of Open Access Journals (Sweden)

    Alexandre eHenriques

    2015-01-01

    Full Text Available ABSTRACTBackgroundAmyotrophic lateral sclerosis (ALS is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. ResultsMotoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age, when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age. Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12.ConclusionsOur data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

  20. Gene expression changes in spinal motoneurons of the SOD1(G93A) transgenic model for ALS after treatment with G-CSF.

    Science.gov (United States)

    Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1(G93A) mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Motoneurons from SOD1(G93A) mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1(G93A) motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1(G93A) motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

  1. Interleukin 28B gene variation at rs12979860 determines early viral kinetics during treatment in patients carrying genotypes 2 or 3 of hepatitis C virus

    DEFF Research Database (Denmark)

    Lindh, Magnus; Lagging, Martin; Färkkilä, Martti

    2011-01-01

    Single-nucleotide polymorphisms upstream of the interleukin 28B (interferon λ3) gene (IL28B) strongly influence treatment efficacy in patients carrying hepatitis C virus (HCV) of genotype 1. In patients receiving 12 or 24 weeks of interferon-ribavirin therapy for infection with genotype 2 or 3 (n...... = 341), we found that rs12979860 strikingly determined the first phase of viral elimination (P

  2. Treatment Adherence as a New Choice Factor for Optimization of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation and Hemostatic Gene Polymorphisms

    Directory of Open Access Journals (Sweden)

    Yu. P. Skirdenko

    2016-01-01

    Full Text Available Aim. To evaluate treatment adherence and prevalence of CYP2C9 and VKORC1 gene mutations in patients with atrial fibrillation (AF and provide rationale of choice for oral anticoagulation therapy.Material and methods. Treatment adherence was evaluated in 137 AF patients (aged 35-85 years with quantitative estimation of drug therapy adherence along with compliance to medical support and lifestyle modifications. Among them 82 patients underwent polymerase chain reaction (PCR analysis of CYP2C9 and VKORC1 gene polymorphisms.Results. Patients receiving anticoagulation therapy are characterized by lower level of adherence compared to patients without anticoagulants (65.2±19.3% vs 68.5±19.1%; Wald-Wolfowitz; p<0.05. Considering all studied parameters men are less adherent than women (54.7±18.6% vs 60.6±16.7%; Kolmogorov-Smirnov; p<0.05. Patients receiving new oral anticoagulants (NOAC have better compliance compared with patients of warfarin group. Mutations in CYP2C9 gene were detected in 32.9%, VKORC1 – in 68.3%, and their combination – in 21.9% of study participants. Warfarin therapy may be potentially dangerous in such patients due to low adherence.Conclusion. Considering high prevalence of CYP2C9 and VKORC1 gene mutations treatment adherence should be estimated to optimize choice of anticoagulation therapy. NOAC treatment should be considered in patients with low adherence for prevention of thromboembolic complications.

  3. Reduced RAR-β gene expression in Benzo(a)Pyrene induced lung cancer mice is upregulated by DOTAP lipo-ATRA treatment.

    Science.gov (United States)

    Viswanathan, S; Berlin Grace, V M

    2018-05-16

    Molecular targeted therapy for specific genes is an emerging research. Retinoic Acid Receptor (RAR-β) is a key tumor suppressor which is found to be lost drastically during much cancer progression. We hence, analyzed the expression level of RAR-β gene during B(a)P induced lung cancer development in mice and studied the lung cancer targeted action of All Trans Retinoic Acid (ATRA) in DOTAP liposomal formulation. The effect of its treatment on lung cancer was determined by histopathological analysis. RAR-β gene expression was assessed by RT-PCR and qPCR. A distinct band for RAR-β gene (density - 0.5123 for lung and 0.5160 for liver) was observed in normal mice, whereas no visible band was observed in cancer induced group, indicating loss of RAR-β gene expression. Both ATRA and lipo-ATRA treated groups showed detectable RAR-β expression with relatively lesser density than the normal group. The expression was more intense in lipo-ATRA treatment (density-0.2973) compared with free ATRA treatment (density-0.1549) in lung tissues. The qPCR results also have highlighted a highly significant (p ≤ 0.01) variation RQ values between lipo-ATRA group (15.46 ± 1.54) and free ATRA group (7.58 ± 1.30) in lung tissue sample on 30th day. The mean RQ value for normal lung on 30th day was 20.86 ± 2.58 against the cancer control. The 120th day mice also showed the similar RAR-β expression pattern with further declined expression levels as there was no treatment given after 30 days. Interestingly, the lipo-ATRA treatment could show a highly significant (p ≤ 0.001) expression (12.00 ± 2.31) when compared with free ATRA treatment (3.31 ± 0.58) which implies that the lipo-ATRA formulation could result in sustained delivery of ATRA in target site. Histopathology of lung and liver on 120th day also revealed an effective therapeutic indication in lipo-ATRA treatment compared to free ATRA treatment due to lipo-ATRA's stealth property and it

  4. Prioritization of Contaminants of Emerging Concern in Wastewater Treatment Plant Discharges using Chemical:Gene Interactions in Caged Fish.

    Data.gov (United States)

    U.S. Environmental Protection Agency — We examined whether contaminants present in surface waters could be prioritized for further assessment by linking the presence of specific chemicals to gene...

  5. A Prospective Treatment Option for Lysosomal Storage Diseases: CRISPR/Cas9 Gene Editing Technology for Mutation Correction in Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Chloe L. Christensen

    2017-02-01

    Full Text Available Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9. The CRISPR/Cas9 system holds promise for the correction of deleterious mutations by taking advantage of the homology directed repair pathway and by supplying a correction template to the affected patient’s cells. Currently, this technique is being applied in vitro in human-induced pluripotent stem cells (iPSCs to correct a variety of severe genetic diseases, but has not as of yet been used in iPSCs derived from patients affected with a lysosomal storage disease (LSD. If adopted into clinical practice, corrected iPSCs derived from cells that originate from the patient themselves could be used for therapeutic amelioration of LSD symptoms without the risks associated with allogeneic stem cell transplantation. CRISPR/Cas9 editing in a patient’s cells would overcome the costly, lifelong process associated with currently available treatment methods, including enzyme replacement and substrate reduction therapies. In this review, the overall utility of the CRISPR/Cas9 gene editing technique for treatment of genetic diseases, the potential for the treatment of LSDs and methods currently employed to increase the efficiency of this re-engineered biological system will be discussed.

  6. A Prospective Treatment Option for Lysosomal Storage Diseases: CRISPR/Cas9 Gene Editing Technology for Mutation Correction in Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Christensen, Chloe L; Choy, Francis Y M

    2017-02-24

    Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The CRISPR/Cas9 system holds promise for the correction of deleterious mutations by taking advantage of the homology directed repair pathway and by supplying a correction template to the affected patient's cells. Currently, this technique is being applied in vitro in human-induced pluripotent stem cells (iPSCs) to correct a variety of severe genetic diseases, but has not as of yet been used in iPSCs derived from patients affected with a lysosomal storage disease (LSD). If adopted into clinical practice, corrected iPSCs derived from cells that originate from the patient themselves could be used for therapeutic amelioration of LSD symptoms without the risks associated with allogeneic stem cell transplantation. CRISPR/Cas9 editing in a patient's cells would overcome the costly, lifelong process associated with currently available treatment methods, including enzyme replacement and substrate reduction therapies. In this review, the overall utility of the CRISPR/Cas9 gene editing technique for treatment of genetic diseases, the potential for the treatment of LSDs and methods currently employed to increase the efficiency of this re-engineered biological system will be discussed.

  7. No effect of C1473G polymorphism in the tryptophan hydroxylase 2 gene on the response of the brain serotonin system to chronic fluoxetine treatment in mice.

    Science.gov (United States)

    Bazhenova, Ekaterina Y; Sinyakova, Nadezhda A; Kulikova, Elizabeth A; Kazarinova, Irina A; Bazovkina, Daria V; Gainetdinov, Raul R; Kulikov, Alexander V

    2017-07-13

    Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that block serotonin transporter (SERT) and increase serotonin (5-HT) level in the synaptic cleft. The interaction between SERT and the key enzyme of 5-HT synthesis in the brain, tryptophan hydroxylase 2 (TPH2), is essential to maintain the brain 5-HT level. The G allele of C1473G polymorphism in Tph2 gene decreases enzyme activity by half in mouse brain. Here we studied effect of C1473G polymorphism on the reaction of brain 5-HT system to chronic fluoxetine treatment (120mg/l in drinking water, for 3 weeks) in adult males of the congenic B6-1473C and B6-1473G mouse lines with high and low enzyme activity, respectively. The polymorphism did not affect the levels of 5-HT, its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and Tph2 gene mRNA in the brain. Fluoxetine significantly attenuated 5-HT levels in the cortex and striatum, 5-HIAA concentrations in the cortex, hippocampus, striatum and midbrain, and Tph2 gene expression in the midbrain. However, we did not observed any effect of the genotype x treatment interaction on these neurochemical characteristics. Therefore, C1473G polymorphism does not seem to play an essential role in the reaction of the brain 5-HT system to chronic fluoxetine treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Gene expression profiling upon 212Pb-TCMC-trastuzumab treatment in the LS-174T i.p. xenograft model

    International Nuclear Information System (INIS)

    Yong, Kwon J; Milenic, Diane E; Baidoo, Kwamena E; Kim, Young-Seung; Brechbiel, Martin W

    2013-01-01

    Recent studies have demonstrated that therapy with 212 Pb-TCMC-trastuzumab resulted in (1) induction of apoptosis, (2) G2/M arrest, and (3) blockage of double-strand DNA damage repair in LS-174T i.p. (intraperitoneal) xenografts. To further understand the molecular basis of the cell killing efficacy of 212 Pb-TCMC-trastuzumab, gene expression profiling was performed with LS-174T xenografts 24 h after exposure to 212 Pb-TCMC-trastuzumab. DNA damage response genes (84) were screened using a quantitative real-time polymerase chain reaction array (qRT-PCR array). Differentially regulated genes were identified following exposure to 212 Pb-TCMC-trastuzumab. These included genes involved in apoptosis (ABL, GADD45α, GADD45γ, PCBP4, and p73), cell cycle (ATM, DDIT3, GADD45α, GTSE1, MKK6, PCBP4, and SESN1), and damaged DNA binding (DDB) and repair (ATM and BTG2). The stressful growth arrest conditions provoked by 212 Pb-TCMC-trastuzumab were found to induce genes involved in apoptosis and cell cycle arrest in the G2/M phase. The expression of genes involved in DDB and single-strand DNA breaks was also enhanced by 212 Pb-TCMC-trastuzumab while no modulation of genes involved in double-strand break repair was apparent. Furthermore, the p73/GADD45 signaling pathway mediated by p38 kinase signaling may be involved in the cellular response, as evidenced by the enhanced expression of genes and proteins of this pathway. These results further support the previously described cell killing mechanism by 212 Pb-TCMC-trastuzumab in the same LS-174T i.p. xenograft. Insight into these mechanisms could lead to improved strategies for rational application of radioimmunotherapy using α-particle emitters. The apoptotic response and associated gene modulations have not been clearly defined following exposure of cells to α-particle radioimmunotherapy (RIT). Gene expression profiling was performed with LS-174T i.p. (intraperitoneal) xenografts after exposure to 212 Pb

  9. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  10. Reduction in WT1 gene expression during early treatment predicts the outcome in patients with acute myeloid leukemia.

    Science.gov (United States)

    Andersson, Charlotta; Li, Xingru; Lorenz, Fryderyk; Golovleva, Irina; Wahlin, Anders; Li, Aihong

    2012-12-01

    Wilms tumor gene 1 (WT1) expression has been suggested as an applicable minimal residual disease marker in acute myeloid leukemia (AML). We evaluated the use of this marker in 43 adult AML patients. Quantitative assessment of WT1 gene transcripts was performed using real-time quantitative-polymerase chain reaction assay. Samples from both the peripheral blood and the bone marrow were analyzed at diagnosis and during follow-up. A strong correlation was observed between WT1 normalized with 2 different control genes (β-actin and ABL1, P0.05). A≥1-log reduction in WT1 expression in bone marrow samples taken freedom from relapse (P=0.010) when β-actin was used as control gene. Furthermore, a reduction in WT1 expression by ≥2 logs in peripheral blood samples taken at a later time point significantly correlated with a better outcome for overall survival (P=0.004) and freedom from relapse (P=0.012). This result was achieved when normalizing against both β-actin and ABL1. These results therefore suggest that WT1 gene expression can provide useful information for minimal residual disease detection in adult AML patients and that combined use of control genes can give more informative results.

  11. Adenovirus-mediated interleukin-12 gene transfer combined with cytosine deaminase followed by 5-fluorocytosine treatment exerts potent antitumor activity in Renca tumor-bearing mice

    International Nuclear Information System (INIS)

    Hwang, Kyung-Sun; Cho, Won-Kyung; Yoo, Jinsang; Yun, Hwan-Jung; Kim, Samyong; Im, Dong-Soo

    2005-01-01

    Therapeutic gene transfer affords a clinically feasible and safe approach to cancer treatment but a more effective modality is needed to improve clinical outcomes. Combined transfer of therapeutic genes with different modes of actions may be a means to this end. Interleukin-12 (IL-12), a heterodimeric immunoregulatory cytokine composed of covalently linked p35 and p40 subunits, has antitumor activity in animal models. The enzyme/prodrug strategy using cytosine deaminase (CD) and 5-fluorocytosine (5-FC) has been used for cancer gene therapy. We have evaluated the antitumor effect of combining IL-12 with CD gene transfer in mice bearing renal cell carcinoma (Renca) tumors. Adenoviral vectors were constructed encoding one or both subunits of murine IL-12 (Ad.p35, Ad.p40 and Ad.IL-12) or cytosine deaminase (Ad.CD). The functionality of the IL-12 or CD gene products expressed from these vectors was validated by splenic interferon (IFN)-γ production or viability assays in cultured cells. Ad.p35 plus Ad.p40, or Ad.IL-12, with or without Ad.CD, were administered (single-dose) intratumorally to Renca tumor-bearing mice. The animals injected with Ad.CD also received 5-FC intraperitoneally. The antitumor effects were then evaluated by measuring tumor regression, mean animal survival time, splenic natural killer (NK) cell activity and IFN-γ production. The inhibition of tumor growth in mice treated with Ad.p35 plus Ad.p40 and Ad.CD, followed by injection of 5-FC, was significantly greater than that in mice treated with Ad.CD/5-FC, a mixture of Ad.p35 plus Ad.p40, or Ad.GFP (control). The combined gene transfer increased splenic NK cell activity and IFN-γ production by splenocytes. Ad.CD/5-FC treatment significantly increased the antitumor effect of Ad.IL-12 in terms of tumor growth inhibition and mean animal survival time. The results suggest that adenovirus-mediated IL-12 gene transfer combined with Ad.CD followed by 5-FC treatment may be useful for treating cancers

  12. Restoration of tumor suppressor gene function by gene replacement or small molecule strategies for the treatment of small cell lung cancer

    DEFF Research Database (Denmark)

    Zandi, Roza

    2011-01-01

    markedly. PRIMA-1 Met also induced significant tumor growth delay in human SCLC mouse models without any signs of toxicity. These results suggest that PRIMA-1 Met can reactivate mutant p53 in SCLC cells, leading to the induction of apoptosis and tumor growth delay. To study the growth inhibitory effect......-mediated gene transfer in SCLC cells expressing various levels of endogenous FHIT protein. FHIT overexpression led to growth inhibition in all of the SCLC cell lines studied; although more effectively in cell lines with high levels of endogenous FHIT protein and transduction efficiency. FHIT-induced inhibition...... as potential therapeutic strategies for SCLC. However, as mutant p53 proteins tend to accumulate in SCLC cells, reintroduction of wild-type p53 may not be effective due to dominant-negative effects of the mutant protein. Therefore, a more effective approach would be to reactivate the endogenous mutant p53...

  13. Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

    Directory of Open Access Journals (Sweden)

    Francesc Vidal

    Full Text Available This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients.The study groups were made of 99 patients (efficacy pharmacogenetic substudy and of 114 patients (safety pharmacogenetic substudy. Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively. Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses.As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons. Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004. In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01. With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04. Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively, neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively. In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01 and thrombocytopenia (OR

  14. Plant Enhancers: A Call for Discovery

    NARCIS (Netherlands)

    Weber, B.; Zicola, J.; Oka, R.; Stam, M.

    2016-01-01

    Higher eukaryotes typically contain many different cell types, displaying different cellular functions that are influenced by biotic and abiotic cues. The different functions are characterized by specific gene expression patterns mediated by regulatory sequences such as transcriptional enhancers.

  15. Newer Gene Editing Technologies toward HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Premlata Shankar

    2013-11-01

    Full Text Available Despite the great success of highly active antiretroviral therapy (HAART in ameliorating the course of HIV infection, alternative therapeutic approaches are being pursued because of practical problems associated with life-long therapy. The eradication of HIV in the so-called “Berlin patient” who received a bone marrow transplant from a CCR5-negative donor has rekindled interest in genome engineering strategies to achieve the same effect. Precise gene editing within the cells is now a realistic possibility with recent advances in understanding the DNA repair mechanisms, DNA interaction with transcription factors and bacterial defense mechanisms. Within the past few years, four novel technologies have emerged that can be engineered for recognition of specific DNA target sequences to enable site-specific gene editing: Homing Endonuclease, ZFN, TALEN, and CRISPR/Cas9 system. The most recent CRISPR/Cas9 system uses a short stretch of complementary RNA bound to Cas9 nuclease to recognize and cleave target DNA, as opposed to the previous technologies that use DNA binding motifs of either zinc finger proteins or transcription activator-like effector molecules fused to an endonuclease to mediate sequence-specific DNA cleavage. Unlike RNA interference, which requires the continued presence of effector moieties to maintain gene silencing, the newer technologies allow permanent disruption of the targeted gene after a single treatment. Here, we review the applications, limitations and future prospects of novel gene-editing strategies for use as HIV therapy.

  16. Glasbury Bridge 1: The Jumper. Close Call.

    Science.gov (United States)

    Journal of Adventure Education and Outdoor Leadership, 1994

    1994-01-01

    Describes an incident in which a group of 10th-grade students in a 1-week outdoor residential program in the Wye Valley (Great Britain) defied program rules, drank alcohol, and had a close call with a near-drowning. Discusses five strategies for dealing with such groups coalesced around a rebellious leader. (SV)

  17. Implementing Distributed Algorithms using Remote Procedure Call

    NARCIS (Netherlands)

    Bal, H.E.; van Renesse, R.; Tanenbaum, A.S.

    1987-01-01

    Remote procedure call (RPC) is a simple yet powerful primitiv~ for communication and synchronization between distributed processes. A problem with RPC is that it tends to decrease the amount of parallelism in an application due to its synchronous nature. This paper shows how light-weight processes

  18. Calle San Martín

    Directory of Open Access Journals (Sweden)

    Gonzalo Cerda Brintrup

    1988-06-01

    Full Text Available En la década del 30 era un barrizal transitado por carretas, caballos y peatones, flanqueada por unas veredas algo más altas que la calle, limitadas por gruesos tablones que la Municipalidad reparaba de año en año.

  19. Inhibitors of calling behavior of Plodia interpunctella.

    Science.gov (United States)

    Hirashima, Akinori; Shigeta, Yoko; Eiraku, Tomohiko; Kuwano, Eiichi

    2003-01-01

    Some octopamine agonists were found to suppress the calling behavior of the stored product Indian meal moth, Plodia interpunctella. Compounds were screened using a calling behavior bioassay using female P. interpunctella. Four active derivatives, with inhibitory activity at the nanomolar range, were identified in order of decreasing activity: 2-(1-phenylethylamino)-2-oxazoline > 2-(2-ethyl,6-methylanilino)oxazolidine > 2-(2-methyl benzylamino)-2-thiazoline > 2-(2,6-diethylanilino)thiazolidine. Three-dimensional pharmacophore hypotheses were built from a set of 15 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a hydrogen-bond acceptor lipid, a hydrophobic aromatic and two hydrophobic aliphatic features was considered to be essential for inhibitory activity in the calling behavior. Active compounds mapped well onto all the hydrogen-bond acceptor lipid, hydrophobic aromatic and hydrophobic aliphatic features of the hypothesis. On the other hand, less active compounds were shown not to achieve the energetically favorable conformation that is found in the active molecules in order to fit the 3D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behavior is via an octopamine receptor.

  20. Inhibitors of calling behavior of Plodia interpunctella

    Directory of Open Access Journals (Sweden)

    Akinori Hirashima

    2003-01-01

    Full Text Available Some octopamine agonists were found to suppress the calling behavior of the stored product Indian meal moth, Plodia interpunctella. Compounds were screened using a calling behavior bioassay using female P. interpunctella. Four active derivatives, with inhibitory activity at the nanomolar range, were identified in order of decreasing activity: 2-(1-phenylethylamino-2-oxazoline > 2-(2-ethyl,6-methylanilinooxazolidine > 2-(2-methyl benzylamino-2-thiazoline > 2-(2,6-diethylanilinothiazolidine. Three-dimensional pharmacophore hypotheses were built from a set of 15 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a hydrogen-bond acceptor lipid, a hydrophobic aromatic and two hydrophobic aliphatic features was considered to be essential for inhibitory activity in the calling behavior. Active compounds mapped well onto all the hydrogen-bond acceptor lipid, hydrophobic aromatic and hydrophobic aliphatic features of the hypothesis. On the other hand, less active compounds were shown not to achieve the energetically favorable conformation that is found in the active molecules in order to fit the 3D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behavior is via an octopamine receptor.

  1. Computer Assisted Language Learning (CALL) Software: Evaluation ...

    African Journals Online (AJOL)

    Evaluating the nature and extent of the influence of Computer Assisted Language Learning (CALL) on the quality of language learning is highly problematic. This is owing to the number and complexity of interacting variables involved in setting the items for teaching and learning languages. This paper identified and ...

  2. What is this thing called growth?

    Science.gov (United States)

    Adrian M. Gilbert

    1954-01-01

    What is this thing called "growth"? We foresters are constantly thinking in terms of growth. We use growth data to evaluate a forest property. We use them to determine how much we can cut. We use them to weigh the results of a type of cutting.

  3. CIFSRF Concept Notes Call 2013 Instructions

    International Development Research Centre (IDRC) Digital Library (Canada)

    IDRC CRDI

    Cc: (the other principal investigators and third-party organisations). Subject: CultiAF 2013 Call for Concept Notes Submitted by (names of all principal ..... clerical, accounting, or secretarial help, general office expenses, office rental and utility ... Please provide the details of financial contributions that will be made to the ...

  4. 76 FR 36130 - Call for Candidates

    Science.gov (United States)

    2011-06-21

    ... financial information in decision-making. The Board meets in Washington, DC, for two days every other month... FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Call for Candidates AGENCY: Federal Accounting... candidates. Any applicant who provided the Federal Accounting Standards Advisory Board (FASAB or the Board...

  5. 78 FR 76257 - Rural Call Completion

    Science.gov (United States)

    2013-12-17

    ... must be held together with rubber bands or fasteners. Any envelopes must be disposed of before entering... Completion/Call Termination Handbook outlining standards and practices of the industry relevant to ensuring... telecommunications networks. Transmission facilities may be based on a single technology or a combination of...

  6. 17 CFR 31.18 - Margin calls.

    Science.gov (United States)

    2010-04-01

    ... transaction merchant is unable to effect personal contact with a leverage customer, a telegram sent to the....18 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION LEVERAGE TRANSACTIONS § 31.18 Margin calls. (a) No leverage transaction merchant shall liquidate a leverage contract because of...

  7. Make a 21st century phone call

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    Want to avoid roaming charges? Click to call anyone at CERN? How about merging your CERN landline with your existing smartphone? That's all easily done with Lync, CERN's new opt-in service that can take your calls to the next level.   The Lync application on Windows (left) and iPhone (right). Lync unites CERN's traditional telephone service with the digital sphere. "Lync gives you the gift of mobility, by letting you access your CERN landline on the go," explains Pawel Grzywaczewski, service manager of the Lync system. "Once you've registered your CERN telephone with the service, you can run the Lync application and make calls from a range of supported devices. No matter where you are in the world - be it simply out to lunch or off at an international conference - you can make a CERN call as though you were in the office. All you need is an Internet connection!" Following a recent upgrade, CERN's Lync service now has...

  8. When to call a linear system nonnegative

    NARCIS (Netherlands)

    Nieuwenhuis, J.W.

    1998-01-01

    In this paper we will consider discrete time invariant linear systems that allow for an input-state-output representation with a finite dimensional state space, and that have a finite number of inputs and outputs. The basic issue in this paper is when to call these systems nonnegative. An important

  9. Don't Call It School

    Science.gov (United States)

    Robb, Daniel

    2006-01-01

    "Homeschooling," "deschooling," and "unschooling" are commonly used terms in the alternative-education world, but each lacks specificity. In this article, the author describes what he discovered during several visits to North Star. Known officially as North Star: Self-Directed Learning for Teens, it is not as structured as a so-called "free"…

  10. Optimization of Overflow Policies in Call Centers

    DEFF Research Database (Denmark)

    Koole, G.M.; Nielsen, B.F.; Nielsen, T.B.

    2015-01-01

    . A Markov decision chain is used to determine the optimal policy. This policy outperforms considerably the ones used most often in practice, which use a fixed threshold. The present method can be used also for other call-center models and other situations where performance is based on actual waiting times...

  11. Japanese electric utilities call for IPP capacity

    Energy Technology Data Exchange (ETDEWEB)

    Jeffs, E.

    1997-03-01

    Japan`s ten power utilities have finally grasped the nettle, and called in IPPs to supply at least 3 GW of new capacity in each of the next ten years. The first twenty schemes awarded last year are all based on existing industrial energy producers, and consist mainly of coal- or oil-fired plants of 150 MW or less. 1 tab.

  12. Impact of mobility on call block, call drops and optimal cell size in small cell networks

    OpenAIRE

    Ramanath , Sreenath; Voleti , Veeraruna Kavitha; Altman , Eitan

    2011-01-01

    We consider small cell networks and study the impact of user mobility. Assuming Poisson call arrivals at random positions with random velocities, we discuss the characterization of handovers at the boundaries. We derive explicit expressions for call block and call drop probabilities using tools from spatial queuing theory. We also derive expressions for the average virtual server held up time. These expressions are used to derive optimal cell sizes for various profile of velocities in small c...

  13. Epigenetic silencing of apoptosis-inducing gene expression can be efficiently overcome by combined SAHA and TRAIL treatment in uterine sarcoma cells.

    Directory of Open Access Journals (Sweden)

    Leopold F Fröhlich

    Full Text Available The lack of knowledge about molecular pathology of uterine sarcomas with a representation of 3-7% of all malignant uterine tumors prevents the establishment of effective therapy protocols. Here, we explored advanced therapeutic options to the previously discovered antitumorigenic effects of the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA by combined treatment with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo-2L. In addition, we investigated the uterine sarcoma cell lines, MES-SA and ESS-1, regarding the underlying molecular mechanisms of SAHA and TRAIL-induced apoptosis and their resistance towards TRAIL. Compared to single SAHA or TRAIL treatment, the combination of SAHA with TRAIL led to complete cell death of both tumor cell lines after 24 to 48 hours. In contrast to single SAHA treatment, apoptosis occured faster and was more pronounced in ESS-1 cells than in MES-SA cells. Induction of SAHA- and TRAIL-induced apoptosis was accompanied by upregulation of the intrinsic apoptotic pathway via reduction of mitochondrial membrane potential, caspase-3, -6, and -7 activation, and PARP cleavage, but was also found to be partially caspase-independent. Apoptosis resistance was caused by reduced expression of caspase-8 and DR 4/TRAIL-R1 in ESS-1 and MES-SA cells, respectively, due to epigenetic silencing by DNA hypermethylation of gene promoter sequences. Treatment with the demethylating agent 5-Aza-2'-deoxycytidine or gene transfer therefore restored gene expression and increased the sensitivity of both cell lines against TRAIL-induced apoptosis. Our data provide evidence that deregulation of epigenetic silencing by histone acetylation and DNA hypermethylation might play a fundamental role in the origin of uterine sarcomas. Therefore, tumor growth might be efficiently overcome by a cytotoxic combinatorial treatment of HDAC inhibitors with TRAIL.

  14. Catechol-O-methyltransferase gene variants may associate with negative symptom response and plasma concentrations of prolactin in schizophrenia after amisulpride treatment.

    Science.gov (United States)

    Chen, Chun-Yen; Yeh, Yi-Wei; Kuo, Shin-Chang; Ho, Pei-Shen; Liang, Chih-Sung; Yen, Che-Hung; Lu, Ru-Band; Huang, San-Yuan

    2016-03-01

    Catechol-O-methyltransferase (COMT) enzyme is involved in the pathogenesis of psychotic symptoms and may be associated with a therapeutic response to antipsychotic drugs. The aim of this study was to examine the relationship between COMT variants, plasma prolactin level, and the therapeutic effectiveness of amisulpride treatment in patients with schizophrenia. A 12-week naturalistic study of amisulpride treatment was carried out in 185 Han Chinese patients with schizophrenia. The patients were screened for 14 single-nucleotide polymorphisms of the COMT gene. The Positive and Negative Syndrome Scale (PANSS) was used to assess the improvement of psychopathological symptoms from the baseline to the end point in each subject. For better presentation of time-course changes in response status, a mixed model for repeated-measures (MMRM) analysis of symptom improvement during the 12-week treatment period was conducted. The change in plasma prolactin level after amisulpride treatment was also examined (n=51). No significant differences in the genotype frequencies of the COMT variants investigated were observed between responders and non-responders. Moreover, an MMRM analysis of psychopathological symptom improvement during the 12-week treatment course showed that it depended significantly on COMT variants (rs4680, rs4633, and rs6267), particularly regarding changes in negative symptoms. The increase in plasma prolactin levels observed was influenced by the COMT rs4680 variant and was positively correlated with a reduction in PANSS negative scores. Our results suggest that variation of the COMT gene is associated with treatment response regarding negative symptoms and prolactin changes after amisulpride treatment in patients with schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Religious coalition opposes gene patents.

    Science.gov (United States)

    James, J S

    1995-05-19

    The biotechnology industry is concerned about a coalition of mainstream religious leaders, working with Jeremy Rifkin of the Foundation of Economic Trends, who oppose the patenting of human and animal life forms, body parts, and genes. The coalition called a press conference on May 18 to ask the government to prohibit the current patenting practices for genetic engineering. The biotechnology industry argues that patents indicate that a company's research tool has significant value, and encourages capitalists to invest their dollars in the development of new treatments for diseases. They also argue that the 29 biotech drugs that are on the market have been developed as a result of patents on genes. Although most business leaders are united in opposing restrictions, many scientists are divided, citing both religious and scientific reasons.

  16. Improvement of soybean transformation via Agrobacterium tumefaciens methods involving α-aminooxyacetic acid and sonication treatments enlightened by gene expression profile analysis.

    Science.gov (United States)

    Zhang, Yan-Min; Liu, Zi-Hui; Yang, Rui-Juan; Li, Guo-Liang; Guo, Xiu-Lin; Zhang, Hua-Ning; Zhang, Hong-Mei; Di, Rui; Zhao, Qing-Song; Zhang, Meng-Chen

    2016-06-01

    Antagonists and sonication treatment relieved the structural barriers of Agrobacterium entering into cells; hindered signal perception and transmission; alleviated defense responses and increased cell susceptibility to Agrobacterium infection. Soybean gene expression analysis was performed to elucidate the general response of soybean plant to Agrobacterium at an early stage of infection. Agrobacterium infection stimulated the PAMPs-triggered immunity (BRI1, BAK1, BZR1, FLS2 and EFR) and effector-triggered immunity (RPM1, RPS2, RPS5, RIN4, and PBS1); up-regulated the transcript factors (WRKY25, WRKY29, MEKK1P, MKK4/5P and MYC2) in MAPK pathway; strengthened the biosynthesis of flavonoid and isoflavonoid in the second metabolism; finally led to a fierce defense response of soybean to Agrobacterium infection and thereby lower transformation efficiency. To overcome it, antagonist α-aminooxyacetic acid (AOA) and sonication treatment along with Agrobacterium infection were applied. This novel method dramatically decreased the expression of genes coding for F3'H, HCT, β-glucosidase and IF7GT, etc., which are important for isoflavone biosynthesis or the interconversion of aglycones and glycon; genes coding for peroxidase, FLS2, PBS1 and transcription factor MYC2, etc., which are important components in plant-pathogen interaction; and genes coding for GPAT and α-L-fucosidase, which are important in polyesters formation in cell membrane and the degradation of fucose-containing glycoproteins and glycolipids on the external surface of cell membrane, respectively. This analysis implied that AOA and sonication treatment not only relieved the structural membrane barriers of Agrobacterium entering into cells, but also hindered the perception of 'invasion' signal on cell membrane and intercellular signal transmission, thus effectively alleviated the defense responses and increased the cell susceptibility to Agrobacterium infection. All these factors benefit the transformation

  17. Treatment with albumin-hydroxyoleic acid complex restores sensorimotor function in rats with spinal cord injury: Efficacy and gene expression regulation.

    Directory of Open Access Journals (Sweden)

    Gerardo Avila-Martin

    Full Text Available Sensorimotor dysfunction following incomplete spinal cord injury (SCI is often characterized by paralysis, spasticity and pain. Previously, we showed that intrathecal (i.t. administration of the albumin-oleic acid (A-OA complex in rats with SCI produced partial improvement of these symptoms and that oral 2-hydroxyoleic acid (HOA, a non-hydrolyzable OA analogue, was efficacious in the modulation and treatment of nociception and pain-related anxiety, respectively. Here we observed that intrathecal treatment with the complex albumin-HOA (A-HOA every 3 days following T9 spinal contusion injury improved locomotor function assessed with the Rotarod and inhibited TA noxious reflex activity in Wistar rats. To investigate the mechanism of action of A-HOA, microarray analysis was carried out in the spinal cord lesion area. Representative genes involved in pain and neuroregeneration were selected to validate the changes observed in the microarray analysis by quantitative real-time RT-PCR. Comparison of the expression between healthy rats, SCI rats, and SCI treated with A-HOA rats revealed relevant changes in the expression of genes associated with neuronal morphogenesis and growth, neuronal survival, pain and inflammation. Thus, treatment with A-HOA not only induced a significant overexpression of growth and differentiation factor 10 (GDF10, tenascin C (TNC, aspirin (ASPN and sushi-repeat-containing X-linked 2 (SRPX2, but also a significant reduction in the expression of prostaglandin E synthase (PTGES and phospholipases A1 and A2 (PLA1/2. Currently, SCI has very important unmet clinical needs. A-HOA downregulated genes involved with inflammation and upregulated genes involved in neuronal growth, and may serve to promote recovery of function after experimental SCI.

  18. Adiponectin gene polymorphism rs2241766 T/G is associated with response to pioglitazone treatment in type 2 diabetic patients from southern China.

    Directory of Open Access Journals (Sweden)

    Hong Yang

    Full Text Available INTRODUCTION: Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients. METHODS: Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR, and glycated hemoglobin (HbA1c% were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3 were amplified and sequenced to determine genotype. RESULTS: Serum adiponectin levels were significantly increased (p<0.001 whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001. Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001 was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001. CONCLUSIONS: The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.

  19. Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data

    DEFF Research Database (Denmark)

    Wan, Peng; Li, Qiyuan; Larsen, Jens Erik Pontoppidan

    2012-01-01

    The NCI60 database is the largest available collection of compounds with measured anti-cancer activity. The strengths and limitations for using the NCI60 database as a source of new anti-cancer agents are explored and discussed in relation to previous studies. We selected a sub-set of 2333...... and in a data set of expression profiles of 1901 genes for the corresponding tumor cell lines. Five clusters were identified based on the gene expression data using self-organizing maps (SOM), comprising leukemia, melanoma, ovarian and prostate, basal breast, and luminal breast cancer cells, respectively....... The strong difference in gene expression between basal and luminal breast cancer cells was reflected clearly in the chemosensitivity data. Although most compounds in the data set were of low potency, high efficacy compounds that showed specificity with respect to tissue of origin could be found. Furthermore...

  20. Test of critical steps towards a combined cell and gene therapy approach for the treatment of Duchenne muscular dystrophy

    DEFF Research Database (Denmark)

    Kajhøj, Tine Qvistgaard; Duch, Mogens R.; Pedersen, Finn Skou

    2015-01-01

    Background: Therapies for muscular dystrophies remain a major challenge in spite of advanced strategies using either cell or gene therapy. We here propose a combined approach of cell and gene therapy. As gene delivery vehicles with specific homing potential we have chosen mesoangioblasts which...... for myogenic properties in coculture. Survival and in situ myogenic differentiation were studied upon injection into degenerating M. gastrocnemius of athymic mice. In situ participation in muscle regeneration was confirmed on cryo-sections using EGFP fluorescence as marker. The ability of mesoangioblasts...... to serve as retroviral packaging cells was tested using the murine cell line NIH 3T3 fibroblasts as recipients in vitro and evaluation of transduction by fluorescence microscopy. Results: EGFP-MA retained the ability to differentiate into skeletal muscle myotubes upon co-culture with C2C12 cells. In vivo...

  1. Restoring rape survivors: justice, advocacy, and a call to action.

    Science.gov (United States)

    Koss, Mary P

    2006-11-01

    Rape results in mental and physical health, social, and legal consequences. For the latter, restorative justice-based programs might augment community response, but they generate controversy among advocates and policy makers. This article identifies survivors' needs and existing community responses to them. Survivors feel their legal needs are most poorly met due to justice system problems that can be summarized as attrition, retraumatization, and disparate treatment across gender, class, and ethnic lines. Empirical data support each problem and the conclusion that present justice options are inadequate. The article concludes by identifying common ground in advocacy and restorative justice goals and calls for a holistic approach to the needs of rape survivors that includes advocating for expanded justice alternatives. A call to action is issued to implement restorative alternatives to expand survivor choice and offender accountability. Conventional and restorative justice are often viewed as mutually exclusive whereas the author argues they are complementary.

  2. Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer--A preliminary report

    International Nuclear Information System (INIS)

    Teh, Bin S.; Aguilar-Cordova, Estuardo; Kernen, Kenneth; Chou, C.-C.; Shalev, Moshe; Vlachaki, Maria T.; Miles, Brian; Kadmon, Dov; Mai, W.-Y.; Caillouet, James; Davis, Maria; Ayala, Gustavo; Wheeler, Thomas; Brady, Jett; Carpenter, L. Steve; Lu, Hsin H.; Chiu, J. Kam; Woo, Shiao Y.; Thompson, Timothy; Butler, E. Brian

    2001-01-01

    Purpose: To report the preliminary results of a Phase I/II study combining radiotherapy and in situ gene therapy (adenovirus/herpes simplex virus thymidine kinase gene/valacyclovir) with or without hormonal therapy in the treatment of prostate cancer. Methods and Materials: Arm A: low-risk patients (T1-T2a, Gleason score <7, pretreatment PSA <10) were treated with combined radio-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated radiotherapy. Arm B: high-risk patients (T2b-T3, Gleason score ≥7, pretreatment PSA ≥10) were treated with combined radio-gene therapy and hormonal therapy. Hormonal therapy was comprised of a 4-month leuprolide injection and 2-week use of flutamide. Arm C: Stage D1 (positive pelvic lymph node) patients received the same regimen as Arm B, with the additional 45 Gy to the pelvic lymphatics. Treatment-related toxicity was assessed using Cancer Therapy Evaluation Program common toxicity score and Radiation Therapy Oncology Group (RTOG) toxicity score. Results: Thirty patients (13 in Arm A, 14 in Arm B, and 3 in Arm C) completed the trial. Median follow-up was 5.5 months. Eleven patients (37%) developed flu-like symptoms (Cancer Therapy Evaluation Program Grade 1) of fatigue and chills/rigors after gene therapy injection but recovered within 24 h. Four patients (13%) and 2 patients (7%) developed Grade 1 and 2 fever, respectively. There was no patient with weight loss. One patient in Arm B developed Grade 3 elevation in liver enzyme, whereas 11 and 2 patients developed Grade 1 and 2 abnormal liver function tests. There was no Grade 2 or above hematologic toxicity. Three patients had transient rise in creatinine. There was no RTOG Grade 3 or above lower gastrointestinal toxicity. Toxicity levels were as follows: 4 patients (13%), Grade 2; 6 patients (20%), Grade 1; and 20 patients (67%), no toxicity. There was 1 patient with RTOG Grade 3 genitourinary toxicity, 12 patients (40%) with Grade 2, 8 patients

  3. Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

    Directory of Open Access Journals (Sweden)

    Zanatta Daniela B

    2010-06-01

    Full Text Available Abstract Background Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. Methods B16 (mouse melanoma and C6 (rat glioma cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Results Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet

  4. Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

    International Nuclear Information System (INIS)

    Merkel, Christian A; Silva Soares, Rafael B da; Carvalho, Anna Carolina V de; Zanatta, Daniela B; Bajgelman, Marcio C; Fratini, Paula; Costanzi-Strauss, Eugenia; Strauss, Bryan E

    2010-01-01

    Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated by the combination of p19

  5. Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients.

    Science.gov (United States)

    Rosen, Michael J; Karns, Rebekah; Vallance, Jefferson E; Bezold, Ramona; Waddell, Amanda; Collins, Margaret H; Haberman, Yael; Minar, Phillip; Baldassano, Robert N; Hyams, Jeffrey S; Baker, Susan S; Kellermayer, Richard; Noe, Joshua D; Griffiths, Anne M; Rosh, Joel R; Crandall, Wallace V; Heyman, Melvin B; Mack, David R; Kappelman, Michael D; Markowitz, James; Moulton, Dedrick E; Leleiko, Neal S; Walters, Thomas D; Kugathasan, Subra; Wilson, Keith T; Hogan, Simon P; Denson, Lee A

    2017-05-01

    There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)-few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes. We used a real-time reverse-transcription quantitative polymerase chain reaction array to analyze messenger RNA (mRNA) expression patterns in rectal mucosal samples from 138 treatment-naive pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 to 2012. Results were validated in real-time reverse-transcription quantitative polymerase chain reaction analyses of rectal RNA from an independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children's Hospital Medical Center. We measured significant increases in mRNAs associated with a type 2 immune response (interleukin [IL]5 gene, IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared with patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P = .001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (odds ratio [OR], 6.469; 95% confidence interval [CI], 1.553-26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330-28.22), and remission after 12 months (OR, 5

  6. US calls for CO2 cut

    International Nuclear Information System (INIS)

    Roberts, M.

    1996-01-01

    The US Government has outraged energy-intensive industries by calling for an international agreement to reduce global emissions of carbon dioxide (CO 2 ) and other greenhouse gases. In a clear policy shift, the US--the world's largest emitter of greenhouse gases and not previously an advocate of curbing them--says it now intends to lead moves to prevent global warming. At last week's Second Conference of the Parties (COP-2) to the United Nations Framework Convention on Climate Change (FCCC), US Undersecretary for Global Affairs Timothy Wirth called for open-quotes an agreement that sets a realistic, verifiable, and binding medium-term emissions target.close quotes Individual countries should be free to choose how to meet targets, and the US favors market-based mechanisms, he says. open-quotes Climate change is a serious problem and will require sustained long-term investment to be addressed successfully,close quotes Wirth says

  7. Eight Leadership Emergency Codes Worth Calling.

    Science.gov (United States)

    Freed, David H

    Hospitals have a contemporary opportunity to change themselves before attempting to transform the larger US health care system. However, actually implementing change is much more easily described than accomplished in practice. This article calls out 8 dysfunctional behaviors that compromise professional standards at the ground level of the hospital. The construct of calling a code when one witnesses such behaviors is intended to make it safe for leaders to "See something, say something" and confront them in real time. The coordinated continuum of services that health care reform seeks to attain will not emerge until individual hospital organizations prepare themselves to operate better in their own spaces and the ones that immediately surround them.

  8. Comparison of six different sewage treatment processes-Reduction of estrogenic substances and effects on gene expression in exposed male fish

    International Nuclear Information System (INIS)

    Gunnarsson, L.; Adolfsson-Erici, M.; Bjoerlenius, B.; Rutgersson, C.; Foerlin, L.; Larsson, D.G.J.

    2009-01-01

    Treated sewage effluents often contain a mixture of estrogenic compounds in low concentrations. The total combined activity of these, however, may be sufficiently high to affect the reproduction of aquatic vertebrates. The introduction of advanced treatment technologies has been suggested as a way to remove micro-contaminants, including estrogenic substances. In this study, one municipal influent was treated with six different processes in parallel on a semi-large scale in order to assess their potential to reduce substances that could contribute to estrogenic effects in male fish. The effluent from a conventional, activated sludge treatment line was compared to a similarly treated effluent with a final sand-filtering step. The addition of ozonation (15 g O 3 /m 3 ), a moving bed biofilm reactor (MBBR) or both in combination was also evaluated. There was also a separate treatment line that was based on a membrane bioreactor. A small battery of hepatic estrogen-responsive genes was measured in the exposed fish using quantitative PCR. Concentrations of steroid estrogens and estrogenic phenols in the effluents were measured by GC-ECNI-MS. The ozonated effluents were the only tested effluents for which all measured biological effects in exposed fish were removed. Chemical data suggested that the MBBR technology was equally effective in removing the analyzed estrogens; however, elevated expression of estrogen-responsive genes suggested that some estrogenic substances were still present in the effluent. The membrane bioreactor removed most of the measured estrogens and it reduced the induction of the estrogen-responsive genes. However, fish exposed to this effluent had significantly enlarged livers. Given that the same influent was treated in parallel with a broad set of technologies and that the chemical analyses were combined with an in vivo assessment of estrogenic responses, this study provides valuable input into the assessment of advanced treatment processes for

  9. Comparison of Methods to Identify Pathogens and Associated Virulence Functional Genes in Biosolids from Two Different Wastewater Treatment Facilities in Canada.

    Directory of Open Access Journals (Sweden)

    Etienne Yergeau

    Full Text Available The use of treated municipal wastewater residues (biosolids as fertilizers is an attractive, inexpensive option for growers and farmers. Various regulatory bodies typically employ indicator organisms (fecal coliforms, E. coli and Salmonella to assess the adequacy and efficiency of the wastewater treatment process in reducing pathogen loads in the final product. Molecular detection approaches can offer some advantages over culture-based methods as they can simultaneously detect a wider microbial species range, including non-cultivable microorganisms. However, they cannot directly assess the viability of the pathogens. Here, we used bacterial enumeration methods together with molecular methods including qPCR, 16S rRNA and cpn60 gene amplicon sequencing and shotgun metagenomic sequencing to compare pre- and post-treatment biosolids from two Canadian wastewater treatment plants (WWTPs. Our results show that an anaerobic digestion WWTP was unsuccessful at reducing the live indicator organism load (coliforms, generic E. coli and Salmonella below acceptable regulatory criteria, while biosolids from a dewatering/pelletization WWTP met these criteria. DNA from other pathogens was detected by the molecular methods, but these species were considered less abundant. Clostridium DNA increased significantly following anaerobic digestion treatments. In addition to pathogen DNA, genes related to virulence and antibiotic resistance were identified in treated biosolids. Shotgun metagenomics revealed the widest range of pathogen DNA and, among the approaches used here, was the only approach that could access functional gene information in treated biosolids. Overall, our results highlight the potential usefulness of amplicon sequencing and shotgun metagenomics as complementary screening methods that could be used in parallel with culture-based methods, although more detailed comparisons across a wider range of sites would be needed.

  10. BUSINESS MODELS FOR EXTENDING OF 112 EMERGENCY CALL CENTER CAPABILITIES WITH E-CALL FUNCTION INSERTION

    Directory of Open Access Journals (Sweden)

    Pop Dragos Paul

    2010-12-01

    Full Text Available The present article concerns present status of implementation in Romania and Europe of eCall service and the proposed business models regarding eCall function implementation in Romania. eCall system is used for reliable transmission in case of crush between In Vehicle System and Public Service Answering Point, via the voice channel of cellular and Public Switched Telephone Network (PSTN. eCall service could be initiated automatically or manual the driver. All data presented in this article are part of researches made by authors in the Sectorial Contract Implementation study regarding eCall system, having as partners ITS Romania and Electronic Solution, with the Romanian Ministry of Communication and Information Technology as beneficiary.

  11. Circus: A Replicated Procedure Call Facility

    Science.gov (United States)

    1984-08-01

    298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 client client stubs ...... ...... ..... ..... runtime libary stub compiler binding agent...runtime libary Figure 1: Structure of the Circus system replicated procedure call paired message protocol unreliable datagrams Figure 2: Circus...114-121. [11) Digit &! Equipment Corporation, Intel Corporation, a.nd Xerox Corporation. The Ethernet: A Local Area Networlc. September 1080. [12

  12. Beware of the Spirits that You Call!

    DEFF Research Database (Denmark)

    Vasquez, Consuelo; Schoeneborn, Dennis; Sergi, Viviane

    This article proposes to study the constitution of organization by acknowledging the fundamentally intertwined nature of order and disorder. Adopting a dialectical lens, we explore the (dis)ordering properties of communication by focusing on both the symbolic and the material dimensions of language...... plays a key role in the development of projects (and more broadly organizations), keeping them in motion by calling forth continuous processes of meaning negotiation....

  13. [Work-family conflict in call center].

    Science.gov (United States)

    Ghislieri, Chiara; Ricotta, Simona; Colombo, Lara

    2012-01-01

    The working environment of call centers, which have seen a significant growth in recent years, has been the subject of several studies aiming at understanding its specific dynamics, with particular attention to the possible causes of stress and discomfort. Despite the fact that the work-family conflict is considered a source of stress responsible for undermining workers' well-being, and as such has been explored in many work environments, there is still very little research specific to call centers. This study had the following aims: to explore work-family conflict perceived by call-center operators taking account of any differences related to respondents'professional and personal characteristics; to understand which demands and resources can have an impact on work-family conflict in this context. The study was carried out on a sample of 898 call center operators in a telecommunications company through the administration of a self-reporting questionnaire. Data analysis included: t-test, one-way analysis of variance, linear correlations and multiple regressions. A higher perception of work-family conflict among workers having a full-time contract was observed compared to those having part-time contracts. Multiple regression analysis identified as sources of influence on work-family conflict: emotional dissonance, uneasiness due customer dissatisfaction, workload, avoidance coping and working hours. Work-family conflict in the context studied is not particularly critical: it is in part influenced by professional and personal characteristics of respondents and primarily caused by work demands. Managerial implications are discussed, especially referred to training activities.

  14. “Computer Assisted Language Learning” (CALL

    Directory of Open Access Journals (Sweden)

    Nazlı Gündüz

    2005-10-01

    Full Text Available This article will provide an overview of computers; an overview of the history of CALL, itspros and cons, the internet, World Wide Web, Multimedia, and research related to the uses of computers in the language classroom. Also, it also aims to provide some background for the beginnerson using the Internet in language classes today. It discusses some of the common types of Internetactivities that are being used today, what the minimum requirements are for using the Internet forlanguage learning, and some easy activities you can adapt for your classes. Some special terminology related to computers will also be used in this paper. For example, computer assisted language learning(CALL refers to the sets of instructions which need to be loaded into the computer for it to be able to work in the language classroom. It should be borne in mind that CALL does not refer to the use of acomputer by a teacher to type out a worksheet or a class list or preparing his/her own teaching alone.Hardware refers to any computer equipment used, including the computer itself, the keyboard, screen (or the monitor, the disc-drive, and the printer. Software (computer programs refers to the sets of instructions which need to be loaded into the computer for it to be able to work.

  15. Prioritization of contaminants of emerging concern in wastewater treatment plant discharges using chemical: Gene interactions in caged fish

    Science.gov (United States)

    We examined whether contaminants present in surface waters could be prioritized for further assessment by linking the presence of specific chemicals to gene expression changes in exposed fish. Fathead minnows were deployed in cages for 2, 4, or 8 days at three locations near two ...

  16. [Experimental study of interleukin-12 gene vaccines in the treatment of low-load malignant lymphoma (EL4)].

    Science.gov (United States)

    Jiang, Q; Da, W; Ou, Y

    2001-11-01

    Two kinds of murine interleukin-12 (mIL-12) fusion gene vaccines were used to treat the murine low-load malignant T cell lymphoma EL4 as minimal residual disease (MRD) model. C57BL/6 synergistical mice were subcutaneously inoculated with 1 x 10(6) wild-type (wt) EL4 tumor cells as low-load lymphoma model treated with two mIL-12 gene vaccines. Package cell line PA317/12 producing mIL-12 retrovirus (RV) was used as in vivo vaccine and EL4 tumor cells transferred with mIL-12 gene as ex vivo vaccine. In both mIL-12 gene vaccine-treated groups, there was no tumor growth in 50% mice 60 days after inoculation. Nine of these no tumor growth mice were re-challenged with 5 x 10(5) wt EL4 cells, and 5 of them survived without tumors in another 60 days. All control mice died with tumors within one month after inoculation. Among those developed tumors in both vaccine-treated groups, the development of tumors was delayed, the survival period prolonged (P EL4 MRD in C57BL/6 mice.

  17. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

    LENUS (Irish Health Repository)

    Bull, S J

    2009-12-01

    Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King\\'s College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The \\'low IL-6\\' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The \\'high transcription\\' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the \\'protective\\' effect of the 5-HTTLPR polymorphism was evident only in the presence of the \\'low IL-6\\' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the \\'high IL-6\\' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role

  18. Oral Tolerance: A New Tool for the Treatment of Gastrointestinal Inflammatory Disorders and Liver-Directed Gene Therapy

    Directory of Open Access Journals (Sweden)

    Yaron Ilan

    1999-01-01

    Full Text Available Oral tolerance is a method of downregulating an immune response by feeding antigens. The use of oral tolerance toward adenoviruses and colitis-extracted proteins for long term gene therapy and alleviation of experimental colitis, and the mechanisms of tolerance induction are presented. Adenoviruses are efficient vectors in liver-directed gene therapy; however, the antiviral immune response precludes the ability to achieve long term gene expression and prohibits the ability to reinject the recombinant virus. Oral tolerance induction via feeding of viral-extracted proteins prevented the antiadenoviral humoral and cellular immune responses, thus enabling long term gene therapy using these viruses. Moreover, pre-existing immune response to the virus was overcome by tolerance induction, enabling prolonged gene expression in a presensitized host. Inflammatory bowel diseases are immune-mediated disorders where an imbalance between proinflammatory (T helper cell type 1 and anti-inflammatory (T helper cell type 2 cytokines are thought to play a role in the pathogenesis. In the experimental colitis model, the feeding of colitis-extracted proteins downregulated the anticolon immune response. Tolerance induction toward colitis-extracted proteins ameliorated colonic inflammation as shown by decreased diarrhea and reduction of colonic ulcerations, intestinal and peritoneal adhesions, wall thickness and edema. Histological parameters for colitis were markedly improved in tolerized animals. In both models, tolerized animals developed an increase in transforming growth factor-beta, interleukin-4 and interleukin-10, and a decrease in the mRNA of interferon-gamma lymphocytes and serum levels. Adoptive transfer of tolerized lymphocytes enabled the transfer of tolerance toward adenoviruses and colon-extracted proteins. Thus, oral tolerance induces suppressor lymphocytes that mediate immune response downregulation by induction of a shift from a proinflammatory T

  19. A Rice CaMBP Gene is Induced in Organ-Specific Manner by Both Chilling and Heat-Shock Treatments

    Directory of Open Access Journals (Sweden)

    Jia WAN

    2008-09-01

    Full Text Available A rice CaMBP gene, OsCaMBP (AB363406, was isolated from a chilling treated rice using the fluorescent differential display (FDD screening method. Its cDNA sequence (2094 bp contains an opening reading frame (ORF encoding a 569 amino acids protein (63.2 kD. OsCaMBP has the typical structural features of the CaMBP family, including the conserved IQ calmodulin-binding motif at the N-terminus. Homology analysis revealed 38.25%–47.28% identities of OsCaMBP with other CaMBPs in plants. RT-PCR analysis showed that the expression of OsCaMBP was remarkably inducible under the chilling (8°C and heat-shock (42°C treatments. OsCaMBP was undetectable under the normal conditions, and induced under the chilling treatment for 1 h, as well as the heat-shock treatment for 15 min, suggesting that the gene plays important roles in the signaling pathway in rice under both chilling and heat-shock stresses.

  20. Reference gene selection for qRT-PCR assays in Stellera chamaejasme subjected to abiotic stresses and hormone treatments based on transcriptome datasets.

    Science.gov (United States)

    Liu, Xin; Guan, Huirui; Song, Min; Fu, Yanping; Han, Xiaomin; Lei, Meng; Ren, Jingyu; Guo, Bin; He, Wei; Wei, Yahui

    2018-01-01

    Stellera chamaejasme Linn, an important poisonous plant of the China grassland, is toxic to humans and livestock. The rapid expansion of S. chamaejasme has greatly damaged the grassland ecology and, consequently, seriously endangered the development of animal husbandry. To draft efficient prevention and control measures, it has become more urgent to carry out research on its adaptive and expansion mechanisms in different unfavorable habitats at the genetic level. Quantitative real-time polymerase chain reaction (qRT-PCR) is a widely used technique for studying gene expression at the transcript level; however, qRT-PCR requires reference genes (RGs) as endogenous controls for data normalization and only through appropriate RG selection and qRT-PCR can we guarantee the reliability and robustness of expression studies and RNA-seq data analysis. Unfortunately, little research on the selection of RGs for gene expression data normalization in S. chamaejasme has been reported. In this study, 10 candidate RGs namely, 18S , 60S , CYP , GAPCP1 , GAPDH2 , EF1B , MDH , SAND , TUA1 , and TUA6 , were singled out from the transcriptome database of S. chamaejasme , and their expression stability under three abiotic stresses (drought, cold, and salt) and three hormone treatments (abscisic acid, ABA; gibberellin, GA; ethephon, ETH) were estimated with the programs geNorm, NormFinder, and BestKeeper. Our results showed that GAPCP1 and EF1B were the best combination for the three abiotic stresses, whereas TUA6 and SAND , TUA1 and CYP , GAPDH2 and 60S were the best choices for ABA, GA, and ETH treatment, respectively. Moreover, GAPCP1 and 60S were assessed to be the best combination for all samples, and 18S was the least stable RG for use as an internal control in all of the experimental subsets. The expression patterns of two target genes ( P5CS2 and GI ) further verified that the RGs that we selected were suitable for gene expression normalization. This work is the first attempt to

  1. Reference gene selection for qRT-PCR assays in Stellera chamaejasme subjected to abiotic stresses and hormone treatments based on transcriptome datasets

    Directory of Open Access Journals (Sweden)

    Xin Liu

    2018-04-01

    Full Text Available Background Stellera chamaejasme Linn, an important poisonous plant of the China grassland, is toxic to humans and livestock. The rapid expansion of S. chamaejasme has greatly damaged the grassland ecology and, consequently, seriously endangered the development of animal husbandry. To draft efficient prevention and control measures, it has become more urgent to carry out research on its adaptive and expansion mechanisms in different unfavorable habitats at the genetic level. Quantitative real-time polymerase chain reaction (qRT-PCR is a widely used technique for studying gene expression at the transcript level; however, qRT-PCR requires reference genes (RGs as endogenous controls for data normalization and only through appropriate RG selection and qRT-PCR can we guarantee the reliability and robustness of expression studies and RNA-seq data analysis. Unfortunately, little research on the selection of RGs for gene expression data normalization in S. chamaejasme has been reported. Method In this study, 10 candidate RGs namely, 18S, 60S, CYP, GAPCP1, GAPDH2, EF1B, MDH, SAND, TUA1, and TUA6, were singled out from the transcriptome database of S. chamaejasme, and their expression stability under three abiotic stresses (drought, cold, and salt and three hormone treatments (abscisic acid, ABA; gibberellin, GA; ethephon, ETH were estimated with the programs geNorm, NormFinder, and BestKeeper. Result Our results showed that GAPCP1 and EF1B were the best combination for the three abiotic stresses, whereas TUA6 and SAND, TUA1 and CYP, GAPDH2 and 60S were the best choices for ABA, GA, and ETH treatment, respectively. Moreover, GAPCP1 and 60S were assessed to be the best combination for all samples, and 18S was the least stable RG for use as an internal control in all of the experimental subsets. The expression patterns of two target genes (P5CS2 and GI further verified that the RGs that we selected were suitable for gene expression normalization. Discussion

  2. The relationships between IFNL4 genotype, intrahepatic interferon-stimulated gene expression and interferon treatment response differs in HCV-1 compared with HCV-3.

    Science.gov (United States)

    Holmes, J A; Congiu, M; Bonanzinga, S; Sandhu, M K; Kia, Y H; Bell, S J; Nguyen, T; Iser, D M; Visvanathan, K; Sievert, W; Bowden, D S; Desmond, P V; Thompson, A J

    2015-08-01

    The biological mechanism underlying the association between IFNL4/IFNL3 polymorphism and peginterferon/ribavirin (PR) response in HCV-1 is thought to involve differential intrahepatic interferon-stimulated gene expression. HCV-3 is more sensitive to PR, but there are no studies of the association between IFNL4 polymorphism, PR treatment response and liver interferon-stimulated gene expression in HCV-3. We evaluated the association between IFNL4/IFNL3 genotypes, PR treatment outcomes and intrahepatic interferon-stimulated gene expression, according to HCV genotype. HCV-1 and HCV-3 patients who received PR therapy were identified. IFNL3 (rs12979860) and IFNL4 genotype (rs368234815) were determined. A second cohort with stored liver specimens was identified. Expression of ISGs was measured by rt-PCR. Two hundred and fifty-nine patients were identified: 55% HCV-1, 45% HCV-3. IFNL4 genotype frequency was TT/TT 44%, TT/ΔG 42% andΔG/ΔG 14%. Linkage disequilibrium with IFNL3 genotype was high (r(2) = 0.98). The association between IFNL4 genotype and PR response was attenuated in HCV-3 vs. HCV-1 (HCV-3: SVR 89% vs. 76% vs. 72% for TT/TT vs. TT/ΔG vs. ΔG/ΔG, P = 0.09; HCV-1: SVR: 82% vs. 29% vs. 24%, P < 0.001). Intrahepatic ISG expression was evaluated in 92 patients; 61% HCV-1. The association between IFNL4 genotype and liver ISG expression was significantly different for HCV-3 vs. HCV-1 (P-value for interaction = 0.046), with levels of interferon-stimulated gene expression being highest in HCV-1 patients who carried a poor-response IFNL4 genotype. The relationship between IFNL4 genotype and PR treatment response as well as intrahepatic interferon-stimulated gene expression differs between HCV-1 and HCV-3. These data suggest fundamental differences in host-virus interactions according to HCV genotype. © 2015 John Wiley & Sons Ltd.

  3. Treatment

    Directory of Open Access Journals (Sweden)

    Safaa M. Raghab

    2013-08-01

    The main goal of this study is to utilize a natural low cost material “as an accelerator additive to enhance the chemical treatment process using Alum coagulant and the accelerator substances were Perlite and Bentonite. The performance of the chemical treatment was enhanced using the accelerator substances with 90 mg/l Alum as a constant dose. Perlite gave better performance than the Bentonite effluent. The removal ratio for conductivity, turbidity, BOD and COD for Perlite was 86.7%, 87.4%, 89.9% and 92.8% respectively, and for Bentonite was 83.5%, 85.0%, 86.5% and 85.0% respectively at the same concentration of 40 mg/l for each.

  4. Polymorphism of the vitamin D3 receptor gene and bone mineral density in girls with functional hypothalamic amenorrhea subjected to oestroprogestagen treatment.

    Science.gov (United States)

    Sowińska-Przepiera, Elżbieta; Andrysiak-Mamos, Elżbieta; Syrenicz, Justyna; Jarząbek-Bielecka, Grażyna; Friebe, Zbigniew; Syrenicz, Anhelli

    2011-01-01

    We investigated whether the vitamin D3 receptor gene (VDR) polymorphism can modulate therapeutic response of functional hypothalamic amenorrhea (FHA) patients to the oestroprogestagen (EP) treatment. The study included 84 FHA girls and 50 controls. FHA patients underwent a four-year sequential EP therapy with 17-β oestradiol (2 mg from the 2(nd) to 25(th) day of the menstrual cycle) and didrogesterone (10 mg from the 16(th) to the 25(th) day). Their hormonal parameters were monitored along with bone turnover marker levels and bone mineral density (BMD). Additionally, the VDR gene BsmI polymorphism was determined. Hormonal therapy was reflected by a substantial improvement of BMD. However, the values of BMD observed after four years of treatment in FHA patients were still significantly lower than baseline bone mineral density determined in the control group (1.007 ± 0.100 vs. 1.141 ± 0.093 g/cm(2), respectively; p < 0.001). No significant effects of the VDR genotype were observed on the dynamics of BMD during consecutive years of hormonal treatment and mean bone mineral density determined after completing the therapy (1.006 ± 0.101 vs. 1.013 ± 0.114 vs. 1.006 ± 0.094 g/cm(2) for BB, bb and Bb genotypes, respectively; p = 0.973). This study did not confirm that VDR polymorphism can modulate therapeutic outcome of FHA girls subjected to the hormonal treatment. Nonetheless, this study confirmed the effectiveness of EP therapy in the simultaneous treatment of menstrual disorders and the normalisation of bone mineral density in FHA patients.

  5. Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort.

    Science.gov (United States)

    Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C H; Chang, Yao-Sheng; Liu, Yu-Li

    2013-10-01

    Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.

  6. High Levels of Antibiotic Resistance Genes and Their Correlations with Bacterial Community and Mobile Genetic Elements in Pharmaceutical Wastewater Treatment Bioreactors.

    Directory of Open Access Journals (Sweden)

    Wenda Tao

    Full Text Available To understand the diversity and abundance of antibiotic resistance genes (ARGs in pharmaceutical wastewater treatment bioreactors, the ARGs in sludge from two full-scale pharmaceutical wastewater treatment plants (PWWTPs were investigated and compared with sludge samples from three sewage treatment plants (STPs using metagenomic approach. The results showed that the ARG abundances in PWWTP sludge ranged from 54.7 to 585.0 ppm, which were higher than those in STP sludge (27.2 to 86.4 ppm. Moreover, the diversity of ARGs in PWWTP aerobic sludge (153 subtypes was higher than that in STP aerobic sludge (118 subtypes. In addition, it was found that the profiles of ARGs in PWWTP aerobic sludge were similar to those in STP aerobic sludge but different from those in PWWTP anaerobic sludge, suggesting that dissolve oxygen (DO could be one of the important factors affecting the profiles of ARGs. In PWWTP aerobic sludge, aminoglycoside, sulfonamide and multidrug resistance genes were frequently detected. While, tetracycline, macrolide-lincosamide-streptogramin and polypeptide resistance genes were abundantly present in PWWTP anaerobic sludge. Furthermore, we investigated the microbial community and the correlation between microbial community and ARGs in PWWTP sludge. And, significant correlations between ARG types and seven bacterial genera were found. In addition, the mobile genetic elements (MGEs were also examined and correlations between the ARGs and MGEs in PWWTP sludge were observed. Collectively, our results suggested that the microbial community and MGEs, which could be affected by DO, might be the main factors shaping the profiles of ARGs in PWWTP sludge.

  7. Calling patterns in human communication dynamics.

    Science.gov (United States)

    Jiang, Zhi-Qiang; Xie, Wen-Jie; Li, Ming-Xia; Podobnik, Boris; Zhou, Wei-Xing; Stanley, H Eugene

    2013-01-29

    Modern technologies not only provide a variety of communication modes (e.g., texting, cell phone conversation, and online instant messaging), but also detailed electronic traces of these communications between individuals. These electronic traces indicate that the interactions occur in temporal bursts. Here, we study intercall duration of communications of the 100,000 most active cell phone users of a Chinese mobile phone operator. We confirm that the intercall durations follow a power-law distribution with an exponential cutoff at the population level but find differences when focusing on individual users. We apply statistical tests at the individual level and find that the intercall durations follow a power-law distribution for only 3,460 individuals (3.46%). The intercall durations for the majority (73.34%) follow a Weibull distribution. We quantify individual users using three measures: out-degree, percentage of outgoing calls, and communication diversity. We find that the cell phone users with a power-law duration distribution fall into three anomalous clusters: robot-based callers, telecom fraud, and telephone sales. This information is of interest to both academics and practitioners, mobile telecom operators in particular. In contrast, the individual users with a Weibull duration distribution form the fourth cluster of ordinary cell phone users. We also discover more information about the calling patterns of these four clusters (e.g., the probability that a user will call the c(r)-th most contact and the probability distribution of burst sizes). Our findings may enable a more detailed analysis of the huge body of data contained in the logs of massive users.

  8. [MVK gene abnormality and new approach to treatment of hyper IgD syndrome and periodic fever syndrome].

    Science.gov (United States)

    Naruto, Takuya

    2007-04-01

    Hyper IgD and periodic fever syndrome (HIDS; OMIM 260920) is one of the hereditary autoinflammatory syndromes characterized by recurrent episodes of fever and inflammation.. HIDS is an autosomal recessive disorder characterized by recurrent fever attacks in early childhood. HIDS caused by mevalonate kinase (MK) mutations, also that is the gene of mevalonic aciduria (OMIM 251170). During febrile episodes, urinary mevalonate concentrations were found to be significantly elevated in patients. Diagnosis of HIDS was retrieving gene or measurement of the enzyme activity in peripheral blood lymphocyte in general. This of HIDS is an activity decline of MK, and a complete deficiency of MK becomes a mevalonic aciduria with a nervous symptom. The relation between the fever and inflammation of mevalonate or isoprenoid products are uncertain. The therapy attempt with statins, which is inhibited the next enzyme after HMG-CoA reductase, or inhibit the proinflammatory cytokines.

  9. Call for another special issue / book

    Science.gov (United States)

    Bostenaru Dan, M.

    2009-04-01

    We would like to continue the series of special issue or maybe edit a book on this topic. To complete the formerly edited special issues we would like to link natural hazards research to cultural heritage research. We see a way of doing this connected to "integrated conservation", which sees the involvment of urban planning in conservation, as well as the (urban) sociology, the integration of the user, the participatism. We further call for investigation of GIS applications for the investigation of natural hazards' impact in this field. We are open for further ideas and wait for you at the Splinter meeting.

  10. Call center. Centrados en el cliente

    OpenAIRE

    Leal-Alonso-de-Castañeda, José Enrique

    2003-01-01

    La empresa actual ha de estar preparada para responder al Cliente tal y como éste espera, porque no se busca un cliente puntual, sino un cliente fiel. La globalización de la economía y del acceso a los mercados exige que la empresa sea capaz de atraer al cliente no sólo con un servicio de calidad, sino además con una atención de calidad. La implantación de un Call Center (Centro de Atención al Cliente, Centro de Atención de Llamadas) constituye por todo ello una estrategia de negocio qu...

  11. JPEG XS call for proposals subjective evaluations

    Science.gov (United States)

    McNally, David; Bruylants, Tim; Willème, Alexandre; Ebrahimi, Touradj; Schelkens, Peter; Macq, Benoit

    2017-09-01

    In March 2016 the Joint Photographic Experts Group (JPEG), formally known as ISO/IEC SC29 WG1, issued a call for proposals soliciting compression technologies for a low-latency, lightweight and visually transparent video compression scheme. Within the JPEG family of standards, this scheme was denominated JPEG XS. The subjective evaluation of visually lossless compressed video sequences at high resolutions and bit depths poses particular challenges. This paper describes the adopted procedures, the subjective evaluation setup, the evaluation process and summarizes the obtained results which were achieved in the context of the JPEG XS standardization process.

  12. First Class Call Stacks: Exploring Head Reduction

    Directory of Open Access Journals (Sweden)

    Philip Johnson-Freyd

    2016-06-01

    Full Text Available Weak-head normalization is inconsistent with functional extensionality in the call-by-name λ-calculus. We explore this problem from a new angle via the conflict between extensionality and effects. Leveraging ideas from work on the λ-calculus with control, we derive and justify alternative operational semantics and a sequence of abstract machines for performing head reduction. Head reduction avoids the problems with weak-head reduction and extensionality, while our operational semantics and associated abstract machines show us how to retain weak-head reduction's ease of implementation.

  13. What Is This Thing Called Learner's Lexicography?

    DEFF Research Database (Denmark)

    Nielsen, Sandro

    2010-01-01

    Learner lexicography as a research area has attracted increased attention during the past decades, but what is actually the true nature of learner lexicography? This question calls for a complex answer. Learner lexicography has as its objective to develop principles that help practitioners......, namely its functions, data and structures, as this strengthens the basis of learner lexicography because it leads to a proper study and understanding of the competences and needs of learners. Finally, the modern theory of dictionary functions encourages theoretical and practical lexicographers to adopt...

  14. Social learning: medical student perceptions of geriatric house calls.

    Science.gov (United States)

    Abbey, Linda; Willett, Rita; Selby-Penczak, Rachel; McKnight, Roberta

    2010-01-01

    Bandura's social learning theory provides a useful conceptual framework to understand medical students' perceptions of a house calls experience at Virginia Commonwealth University School of Medicine. Social learning and role modeling reflect Liaison Committee on Medical Education guidelines for "Medical schools (to) ensure that the learning environment for medical students promotes the development of explicit and appropriate professional attributes (attitudes, behaviors, and identity) in their medical students." This qualitative study reports findings from open-ended survey questions from 123 medical students who observed a preceptor during house calls to elderly homebound patients. Their comments included reflections on the medical treatment as well as interactions with family and professional care providers. Student insights about the social learning process they experienced during house calls to geriatric patients characterized physician role models as dedicated, compassionate, and communicative. They also described patient care in the home environment as comprehensive, personalized, more relaxed, and comfortable. Student perceptions reflect an appreciation of the richness and complexity of details learned from home visits and social interaction with patients, families, and caregivers.

  15. Pharmacodynamic/Pharmacogenomic Modeling of Insulin Resistance Genes in Rat Muscle After Methylprednisolone Treatment: Exploring Regulatory Signaling Cascades

    Directory of Open Access Journals (Sweden)

    Zhenling Yao

    2008-01-01

    Full Text Available Corticosteroids (CS effects on insulin resistance related genes in rat skeletal muscle were studied. In our acute study, adrenalectomized (ADX rats were given single doses of 50 mg/kg methylprednisolone (MPL intravenously. In our chronic study, ADX rats were implanted with Alzet mini-pumps giving zero-order release rates of 0.3 mg/kg/h MPL and sacrificed at various times up to 7 days. Total RNA was extracted from gastrocnemius muscles and hybridized to Affymetrix GeneChips. Data mining and literature searches identified 6 insulin resistance related genes which exhibited complex regulatory pathways. Insulin receptor substrate-1 (IRS-1, uncoupling protein 3 (UCP3, pyruvate dehydrogenase kinase isoenzyme 4 (PDK4, fatty acid translocase (FAT and glycerol-3-phosphate acyltransferase (GPAT dynamic profiles were modeled with mutual effects by calculated nuclear drug-receptor complex (DR(N and transcription factors. The oscillatory feature of endothelin-1 (ET-1 expression was depicted by a negative feedback loop. These integrated models provide test- able quantitative hypotheses for these regulatory cascades.

  16. Gene-environment effects on hippocampal neurodevelopment

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    Mental disorders like schizophrenia and autism put a heavy load on today’s societies, creating a steady call for revealing underlying disease mechanisms and the development of effective treatments. The etiology of major psychiatric illnesses is complex involving gene by environment susceptibility...... factors. Hence, a deeper understanding is needed of how cortical neurodevelopmental deficiencies can arise from such gene-environment interactions. The convergence of genetic and environmental risk factors is a recent field of research. It is now clear that disease, infection and stress factors may...... and antipsychotics mediate their effects on hippocampal neurodevelopment through deregulation of the Zbtb20 gene. A short presentation of the status of this work will shown....

  17. The advertisement calls of Quasipaa shini (Ahl, 1930) (Anura: Dicroglossidae).

    Science.gov (United States)

    Kong, Shen Shen; Zheng, Rong Quan; Zhang, Qi Peng

    2016-12-04

    The genus Quasipaa (Family Dicroglossidae) is currently composed of 11 species distributed in China and Southeast Asia: Quasipaa acanthophora (Dubois & Ohler 2009), Q. boulengeri (Günther 1889), Q. courtoisi (Angel 1922), Q. delacouri (Angel 1928), Q. exilispinosa (Liu & Hu, 1975), Q. fasciculispina (Inger 1970), Q. jiulongensis (Huang & Liu, 1985), Q. shini (Ahl 1930), Q. spinosa (David 1875), Q. verrucospinosa (Bourret 1937), Q. yei (Chen, Qu & Jiang 2002) (Frost 2016). These species are morphologically similar, and their taxonomy is subject to controversy (Che et al. 2009). Analyses of nuclear and mitochondrial genes suggest the genus likely encompass additional cryptic species (Ye et al. 2013). Bioacoustics has contributed to studies on the taxonomy of the genus (Ye et al. 2013; Shen et al. 2015), however, to date, only the advertisement calls of Q. spinosa are known (Yu & Zheng 2009; Chen et al. 2012; Shen et al. 2015). Here, we describe the advertisement calls of Q. shini, which inhabits streams in the southern part of central China(Guizhou, Hunan, Guangxi and Jiangxi) and is characterized by the presence of keratinized skin spines on the lateral surfaces of the body.

  18. ToTem: a tool for variant calling pipeline optimization.

    Science.gov (United States)

    Tom, Nikola; Tom, Ondrej; Malcikova, Jitka; Pavlova, Sarka; Kubesova, Blanka; Rausch, Tobias; Kolarik, Miroslav; Benes, Vladimir; Bystry, Vojtech; Pospisilova, Sarka

    2018-06-26

    High-throughput bioinformatics analyses of next generation sequencing (NGS) data often require challenging pipeline optimization. The key problem is choosing appropriate tools and selecting the best parameters for optimal precision and recall. Here we introduce ToTem, a tool for automated pipeline optimization. ToTem is a stand-alone web application with a comprehensive graphical user interface (GUI). ToTem is written in Java and PHP with an underlying connection to a MySQL database. Its primary role is to automatically generate, execute and benchmark different variant calling pipeline settings. Our tool allows an analysis to be started from any level of the process and with the possibility of plugging almost any tool or code. To prevent an over-fitting of pipeline parameters, ToTem ensures the reproducibility of these by using cross validation techniques that penalize the final precision, recall and F-measure. The results are interpreted as interactive graphs and tables allowing an optimal pipeline to be selected, based on the user's priorities. Using ToTem, we were able to optimize somatic variant calling from ultra-deep targeted gene sequencing (TGS) data and germline variant detection in whole genome sequencing (WGS) data. ToTem is a tool for automated pipeline optimization which is freely available as a web application at  https://totem.software .

  19. CoVaCS: a consensus variant calling system.

    Science.gov (United States)

    Chiara, Matteo; Gioiosa, Silvia; Chillemi, Giovanni; D'Antonio, Mattia; Flati, Tiziano; Picardi, Ernesto; Zambelli, Federico; Horner, David Stephen; Pesole, Graziano; Castrignanò, Tiziana

    2018-02-05

    The advent and ongoing development of next generation sequencing technologies (NGS) has led to a rapid increase in the rate of human genome re-sequencing data, paving the way for personalized genomics and precision medicine. The body of genome resequencing data is progressively increasing underlining the need for accurate and time-effective bioinformatics systems for genotyping - a crucial prerequisite for identification of candidate causal mutations in diagnostic screens. Here we present CoVaCS, a fully automated, highly accurate system with a web based graphical interface for genotyping and variant annotation. Extensive tests on a gold standard benchmark data-set -the NA12878 Illumina platinum genome- confirm that call-sets based on our consensus strategy are completely in line with those attained by similar command line based approaches, and far more accurate than call-sets from any individual tool. Importantly our system exhibits better sensitivity and higher specificity than equivalent commercial software. CoVaCS offers optimized pipelines integrating state of the art tools for variant calling and annotation for whole genome sequencing (WGS), whole-exome sequencing (WES) and target-gene sequencing (TGS) data. The system is currently hosted at Cineca, and offers the speed of a HPC computing facility, a crucial consideration when large numbers of samples must be analysed. Importantly, all the analyses are performed automatically allowing high reproducibility of the results. As such, we believe that CoVaCS can be a valuable tool for the analysis of human genome resequencing studies. CoVaCS is available at: https://bioinformatics.cineca.it/covacs .

  20. Persistence of antibiotic resistance genes and bacterial community changes in drinking water treatment system: From drinking water source to tap water.

    Science.gov (United States)

    Su, Hao-Chang; Liu, You-Sheng; Pan, Chang-Gui; Chen, Jun; He, Liang-Ying; Ying, Guang-Guo

    2018-03-01

    As emerging contaminants, antibiotic resistance genes (ARGs) have become a public concern. This study aimed to investigate the occurrence and diversity of ARGs, and variation in the composition of bacterial communities in source water, drinking water treatment plants, and tap water in the Pearl River Delta region, South China. Various ARGs were present in the different types of water. Among the 27 target ARGs, floR and sul1 dominated in source water from three large rivers in the region. Pearson correlation analysis suggested that sul1, sul2, floR, and cmlA could be potential indicators for ARGs in water samples. The total abundance of the detected ARGs in tap water was much lower than that in source water. Sand filtration and sedimentation in drinking water treatment plants could effectively remove ARGs; in contrast, granular activated carbon filtration increased the abundance of ARGs. It was found that Pseudomonas may be involved in the proliferation and dissemination of ARGs in the studied drinking water treatment system. Bacteria and ARGs were still present in tap water after treatment, though they were significantly reduced. More research is needed to optimize the water treatment process for ARG removal. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Interactionability in Computer Game: Call of Duty

    Directory of Open Access Journals (Sweden)

    masoud Kowsari

    2009-11-01

    Full Text Available For a long time communication theorists have criticized public media for being unilateral. What they prescript is to transform pattern of communication into bilateral one; in other words, to make media interactional. Telephone is the first fully interactional, however, there was a long road to the contemporary communication and information media which are highly interactional. Nevertheless, not all the modern media are equally interactional. Therefore, it is necessary to evaluate levels of interactionability in modern media and strength them. As other concepts in communication, interaction has different definitions, implying various aspects of the audience-media relation. And this feature of multi-dimensionality is to be considered. Quistis (2002 suggests a model in which all the technical, social, and comprehensive aspects of interaction are inherent. In other words, not only the technical aspect of media, but also audience’s perception plays a key role in the model. Visual-computer games are good instance of interactionability in modern media. However, not all games are equally interactional. Analyzing a well-known computer game “Call of Duty”, this article attempts to study different levels of interactionability. The main question is: how can one offer a pragmatic definition of three dimensions of interactionability to study computer games; and how this features are in Call of Duty applied?

  2. Theology links Christian ministry with God's call.

    Science.gov (United States)

    O'Connell, L J

    1984-03-01

    Catholic health care ministry originates in and is shaped by the theme of call in the Old and New Testaments. To be specifically Catholic, health professionals and facilities must define their ministries according to the values expressed in this theological tradition. Sponsorship. The opportunity to provide health care enables religious communities to contribute to God's ongoing creation process and to reiterate Christ's call to minister to others. Although health care facility sponsorship thrusts religious communities into the arena of big business, the abandonment of the health care mission could be considered a betrayal of evangelical values. Quality of life. The implicit concern for human dignity that distinguishes Catholic health care facilities should be evident in personalized patient care, just working conditions, and a commitment to healing in the civic community. Stewardship in ethics. The development of business policies and procedures and institutional responses to social change should be carefully considered in light of the Catholic understanding of loving covenant and the Christian way of life. Shared ministry. Health care facilities have played a leading role in implementing the Second Vatican Council's vision of ministry. Sponsoring communities' continued willingness to share responsibilities with laity will be imperative in meeting the health care demands of the future.

  3. Influence of the glutation S-transferases T1 and M1 gene polymorphisms on androgenic status and semen quality after surgical treatment of varicocele

    Directory of Open Access Journals (Sweden)

    P. V. Glybochko

    2013-01-01

    Full Text Available Aim: to examine androgenic status in men after surgical treatment of varicocele; to investigate genotype GSTT1 and GSTM1 in patients with pathozoospermia. Thirty men after surgical treatment of varicocele were recruited to this study. All subjects were evaluated by history, physical examination, semen analysis, serum FSH, LH, E2, PL, inhibin B and total testosterone determination. GSTT1, CSTM1 gene polymorphisms were determined by polymerase chain reaction. Total testosterone and inhibin B levels were significantly lower in patients with pathozoospermia. Patients with the GSTM1(- genotype had lower sperm concentrations than those with the GSTM1(+ genotype.Our results suggest that the GSTM1(- genotype is risk factor for androgen deficiency and pathozoospermia.

  4. A comparison of the gene expression profiles and pathway network analyses after treatment of Prostate cancer cell lines with different Ganoderma lucidum based extracts.

    Directory of Open Access Journals (Sweden)

    Chi H.J. Kao

    2014-05-01

    Full Text Available Background: Ganoderma lucidum is a type of fungus commonly consumed in Asia for the promotion of health and longevity. The observed biological activity of G. lucidum includes anti-cancer and anti-inflammatory effects which may be useful in the treatment and prevention of cancer and other chronic diseases. G. lucidum grows under conditions which range from tropical to temperate and has a different physiology depending on the geographical region in which it is grown. For this reason, the health benefits may vary depending on the form of G. lucidum and the environmental conditions to which it was exposed. This led us to investigate the effect of wildly grown G. lucidum, from the Himalayan region versus other commercially available G. lucidum products, on two human cancer cell lines. Methods: Extraction of the bioactive components found in G. lucidum is essential, as the fungus is tough and indigestible. Four different Ganoderma extracts were prepared. Thereafter, the extracts were tested on two human prostate cancer cell lines, and the IC50s were determined. This was followed by the use of Affymetrix GeneChip® PrimeView™ Human Gene Expression Arrays to identify the changes in gene expression due to the treatment of prostate cancer cell lines (PC3 and DU145 with Ganoderma extracts. Several key genes identified with Affymetrix analysis were validated using RT-PCR. Results and Discussion: We found that all the Ganoderma extracts showed growth inhibition in the cancer cell lines tested. Using Affymetrix microarray analysis, we identified four main biologically active pathways: cell cycle control/apoptosis, cell-cell adhesion, DNA repair, and inflammatory /immune response, where activity was influenced by the Ganoderma extracts used. Using RT-PCR, we tested ten genes associated with all four pathways. The RT-PCR results supported our findings in the Affymetrix analysis, i.e. that G. lucidum extracts have an anti-inflammatory and cell cycle effect and

  5. Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs

    Science.gov (United States)

    Xu, Lingyan; Xia, Jie; Wang, Dongmei; Qian, Min

    2018-01-01

    Type 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weight loss. However, hepatic lipid accumulation could be observed in mice treated with ketogenic diet. On the other hand, exercise is a well-known approach for treating nonalcoholic fatty liver disease. We thus hypothesize that the combination of ketogenic diet and exercise could improve insulin sensitivity, while minimizing adverse effect of hepatic steatosis. In order to test this hypothesis, we established diabetic mice model with streptozotocin (STZ) and divided them into control group, ketogenic diet group, and ketogenic diet with aerobic exercise group. We found that after six weeks of intervention, mice treated with ketogenic diet and ketogenic diet combined with exercise both have lower body weights, HbAlc level, HOMA index, and improvements in insulin sensitivity, compared with diabetes group. In addition, mice in ketogenic diet intervention exhibited hepatic steatosis shown by serum and hepatic parameters, as well as histochemistry staining in the liver, which could be largely relieved by exercise. Furthermore, gene analysis revealed that ketogenic diet in combination with exercise reduced PPARγ and lipid synthetic genes, as well as enhancing PPARα and lipid β-oxidation gene program in the liver compared to those in ketogenic diet without exercise. Overall, the present study demonstrated that the combination of ketogenic diet and a moderate-intensity aerobic exercise intervention improved insulin sensitivity in diabetic mice, while avoiding hepatic steatosis, which provided a novel strategy in the combat of diabetes. PMID:29743883

  6. Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs.

    Science.gov (United States)

    Zhang, Qiang; Xu, Lingyan; Xia, Jie; Wang, Dongmei; Qian, Min; Ding, Shuzhe

    2018-01-01

    Type 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weight loss. However, hepatic lipid accumulation could be observed in mice treated with ketogenic diet. On the other hand, exercise is a well-known approach for treating nonalcoholic fatty liver disease. We thus hypothesize that the combination of ketogenic diet and exercise could improve insulin sensitivity, while minimizing adverse effect of hepatic steatosis. In order to test this hypothesis, we established diabetic mice model with streptozotocin (STZ) and divided them into control group, ketogenic diet group, and ketogenic diet with aerobic exercise group. We found that after six weeks of intervention, mice treated with ketogenic diet and ketogenic diet combined with exercise both have lower body weights, HbAlc level, HOMA index, and improvements in insulin sensitivity, compared with diabetes group. In addition, mice in ketogenic diet intervention exhibited hepatic steatosis shown by serum and hepatic parameters, as well as histochemistry staining in the liver, which could be largely relieved by exercise. Furthermore, gene analysis revealed that ketogenic diet in combination with exercise reduced PPAR γ and lipid synthetic genes, as well as enhancing PPAR α and lipid β -oxidation gene program in the liver compared to those in ketogenic diet without exercise. Overall, the present study demonstrated that the combination of ketogenic diet and a moderate-intensity aerobic exercise intervention improved insulin sensitivity in diabetic mice, while avoiding hepatic steatosis, which provided a novel strategy in the combat of diabetes.

  7. NUESTRA PORTADA. Jugar en la calle

    Directory of Open Access Journals (Sweden)

    Ramon Balius i Juli

    2008-06-01

    Full Text Available Esta vez Nuestra Portada tiene un carácter excepcional. La ocupan dos obras del que fue el “ninotaire” (dibujante de humor inteligente más importante de nuestro país: Francesc Vila i Rufas, conocido por todos como Cesc (1927–2006. Ambos dibujos destacan por sus inconfundibles características de sencillez y, a la vez, de grandeza argumental, que nos han movido a titular este comentario como “Jugar en la calle”. Comenzaré recordando mi precaria experiencia de infancia y primera juventud en esta actividad de índole “suburbana”. Son muchas las personas de mi edad que en algún momento de sus primeros años han jugado en la calle. Recuerdo que la primera vez que lo hice fue hacia 1938, en Sant Boi de Llobregat (denominado entonces Vilaboi, jugando al fútbol. Pasé unos meses en este pueblo huyendo de las bombas que caían sobre Barcelona. También por aquel tiempo, o quizá uno o dos años después, tuve el deseo, que no he podido satisfacer, de deslizarme sobre unos artefactos de madera con ruedas de cojinetes de bolas por la calle de Enric Granados, donde vivía (los construían los chicos del barrio, en formas rudimentarias, que hoy recordarían a los patinetes o los “skateboards”. Durante el bachillerato, al salir de la Escuela Pia de Balmes esquina con Travesera de Gracia, algunas veces había jugado también a fútbol en la calle Tuset, que por aquellos años no estaba bien urbanizada y tenía unas aceras amplísimas sin asfaltar. En los primeros cursos de la carrera de Medicina, participé en unos continuos e inacabables partidos de fútbol que, desde primera hora de la mañana y hasta el mediodía, se organizaban diariamente en el patio claustrado de la Facultad. Generalmente jugábamos entre clase y clase, aunque existía un núcleo de jugadores entusiastas que no entraban en las aulas en ningún momento. Esta competición se clausuró al cabo de bastantes años, cuando el Decano decidió adornar el patio con

  8. Physical and sexual violence, mental health indicators, and treatment seeking among street-based population groups in Tegucigalpa, Honduras Violencia física y sexual, indicadores de salud mental y búsqueda de tratamiento en grupos de población en situación de calle en Tegucigalpa, Honduras

    Directory of Open Access Journals (Sweden)

    Javier Rio Navarro

    2012-05-01

    Full Text Available OBJECTIVE: To establish the prevalence of exposure to physical and sexual violence, mental health symptoms, and medical treatment-seeking behavior among three street-based subpopulation groups in Tegucigalpa, Honduras, and to assess the association between sociodemographic group, mental health indicators, and exposure to violence. METHODS: An anonymous, cross-sectional survey among randomly selected street-based adolescents, adults, and commercial sex workers (CSWs was undertaken at the end of 2010 in Tegucigalpa. Médecins Sans Frontières (MSF mapped places where the study population gathers. Stratified probability samples were drawn for all groups, using two-stage random sampling. Trained MSF staff administered on-site standardized face-to-face questionnaires. RESULTS: Self-reported exposure to severe physical violence in the previous year was 20.9% among street-based adolescents, 28.8% among adults, and 30.6% among CSWs. For the physical violence event self-defined as most severe, 50.0% of the adolescents, 81.4% of the adults, and 70.6% of the CSWs sought medical treatment. Their exposure to severe sexual violence was 8.6%, 28.8%, and 59.2%, respectively. After exposure to the self-defined most severe sexual violence event, 14.3% of adolescents, 31.9% of adults, and 29.1% of CSWs sought treatment. Common mental health and substance abuse symptoms were highly prevalent and strongly associated with exposure to physical (odds ratio 4.5, P OBJETIVO: Establecer la prevalencia de la exposición a la violencia física y sexual, los síntomas relacionados con la salud mental, y las conductas de búsqueda de tratamiento médico en tres grupos de subpoblaciones en situación de calle en Tegucigalpa, Honduras, y evaluar la asociación entre el grupo sociodemográfico, los indicadores de salud mental y la exposición a la violencia. MÉTODOS: A fines del 2010 en Tegucigalpa se llevó a cabo una encuesta transversal, de carácter anónimo, en

  9. Transcriptome Analysis of Salicylic Acid Treatment in Rehmannia glutinosa Hairy Roots Using RNA-seq Technique for Identification of Genes Involved in Acteoside Biosynthesis

    Directory of Open Access Journals (Sweden)

    Fengqing Wang

    2017-05-01

    Full Text Available Rehmannia glutinosa is a common bulk medicinal material that has been widely used in China due to its active ingredients. Acteoside, one of the ingredients, has antioxidant, antinephritic, anti-inflammatory, hepatoprotective, immunomodulatory, and neuroprotective effects, is usually selected as a quality-control component for R. glutinosa herb in the Chinese Pharmacopeia. The acteoside biosynthesis pathway in R. glutinosa has not yet been clearly established. Herein, we describe the establishment of a genetic transformation system for R. glutinosa mediated by Agrobacterium rhizogenes. We screened the optimal elicitors that markedly increased acteoside accumulation in R. glutinosa hairy roots. We found that acteoside accumulation dramatically increased with the addition of salicylic acid (SA; the optimal SA dose was 25 μmol/L for hairy roots. RNA-seq was applied to analyze the transcriptomic changes in hairy roots treated with SA for 24 h in comparison with an untreated control. A total of 3,716, 4,018, and 2,715 differentially expressed transcripts (DETs were identified in 0 h-vs.-12 h, 0 h-vs.-24 h, and 12 h-vs.-24 h libraries, respectively. KEGG pathway-based analysis revealed that 127 DETs were enriched in “phenylpropanoid biosynthesis.” Of 219 putative unigenes involved in acteoside biosynthesis, 54 were found to be up-regulated at at least one of the time points after SA treatment. Selected candidate genes were analyzed by quantitative real-time PCR (qRT-PCR in hairy roots with SA, methyl jasmonate (MeJA, AgNO3 (Ag+, and putrescine (Put treatment. All genes investigated were up-regulated by SA treatment, and most candidate genes were weakly increased by MeJA to some degree. Furthermore, transcription abundance of eight candidate genes in tuberous roots of the high-acteoside-content (HA cultivar QH were higher than those of the low-acteoside-content (LA cultivar Wen 85-5. These results will pave the way for understanding the molecular

  10. Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance

    DEFF Research Database (Denmark)

    Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun

    2014-01-01

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conse......Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity...... is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved...... in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls...

  11. Comprometimento organizacional de trabalhadores de call center

    Directory of Open Access Journals (Sweden)

    Kely César Martins Paiva

    2015-09-01

    Full Text Available RESUMOO Neste artigo, analisa-se como se apresenta o comprometimento organizacional de trabalhadores de um call center, localizado em Belo (A Horizonte (Minas Gerais, Brasil. Após o delineamento conceitual UJ do tema central, são expostos os resultados de um estudo de caso descritivo, realizado com abordagens quantitativa e qualitativa. Os dados de 399 questionários e 22 entrevistas são, respectivamente, tratados estatisticamente e submetidos à análise de conteúdo. A base de comprometimento que predominou entre esses infoproletários foi "obrigação pelo desempenho" e, em menor grau, "afetiva". Foi observado que quanto maior é o seu tempo de experiência nesse tipo de organização, menores são os níveis de comprometimento de modo geral, fatos esclarecidos, parcialmente, por meio das entrevistas.

  12. Museo a todo pedal: Calle 26

    Directory of Open Access Journals (Sweden)

    Catalina Delgado

    2018-05-01

    Full Text Available Este texto reseña el proyecto urbano “MUSEO A TODO PEDAL: CALLE 26” realizado con la intención de promover el conocimiento y la apropiación crítica del patrimonio escultórico de la Avenida El Dorado en la ciudad de Bogotá, Colombia. La gestión dio inicio en octubre de 2014 con una serie de actividades, entre ellas, el lanzamiento oficial de la Guía de Monumentos y Sitios y la organización de una carrera ciclística de observación. Es del interés de RevistArquis, publicar este proyecto en diálogo con el ensayo de uno de los autores publicado en el Vol. 1 (2015 Número 07 “Usos Cotidianos y Populares de la Bicicleta en Bogotá”. This paper reviews the urban project “MUSEO A TODO PEDAL: CALLE 26” held to promote awareness and critical appropriation of the sculptural heritage of Avenida El Dorado in Bogota, Colombia. The urban project began in October 2014 with a series of activities including the official launch of the Guide on Monuments and Sites and the organization of a watching cycling road race. RevistArquis is honored to publish this project in dialogue with the essay by the same author published in Vol. 1 (2015 Number 07 “Usos Cotidianos y Populares de la Bicicleta en Bogotá”.

  13. Methylation pattern of the intergenic spacer of rRNA genes in excised cotyledons of Cucurbita pepo L. (Zucchini) after hormone treatment

    International Nuclear Information System (INIS)

    Ananiev, E.; Abdulova, G.; Grozdanov, P.; Karagyozov, L.

    2003-01-01

    High molecular mass genomic DNA was isolated from excised marrow cotyledons (Cucurbita pepo L. zucchini) treated with 6-benzyladenine (BA) of methyl ester of jasmonic acid (MeJA) for 24 h in darkness. DNA purified from contaminating polysaccharides with Celite column was completely digested with the restriction enzyme Eco RI and the changes in the methylation pattern of the intergenic spacer (IGS) of r RNA genes were studied after subsequent digestion with the couple of restriction enzymes-isoschizomers MSP I and Hpa II by the method of 'indirect end labelling'. As rDNA units probe a cloned 32 P-labelled Eco RI 2.1 kb fragment spanning in the most part of 18S r RNA gene from flax rDNA was used. Results showed heavy methylation of the rRNA genes. As judged from the almost total lack of digestion with HPA II, there were no methylation free regions in repeated rDNA units or little if any were observed. A hypo methylated Hps II site was detected near the promoter region in some of the repeats. Digestion with Msp I affected nearly 50% of the repeating units. The Msp digestion fragments of the 6.2 kb Eco RI fragment of r DNA were few in number and large in size (0.5 - 2.5 kb). This suggested that in addition with -CpG- sequences, methylation in -CpNpG- might not be random. Methylation pattern in IGS was not changed upon treatment of the cotyledons in vivo with BA and MeJA. Thus, previously observed hormone-mediated effects on the eactivity of rRNA gene expression were not accompanied by any significant changes of the methylation pattern in IGS. (authors)

  14. Molecular analysis of expansion, differentiation, and growth factor treatment of human chondrocytes identifies differentiation markers and growth-related genes.

    Science.gov (United States)

    Benz, Karin; Breit, Stephen; Lukoschek, Martin; Mau, Hans; Richter, Wiltrud

    2002-04-26

    This study is intended to optimise expansion and differentiation of cultured human chondrocytes by growth factor application and to identify molecular markers to monitor their differentiation state. We dissected the molecular consequences of matrix release, monolayer, and 3D-alginate culture, growth factor optimised expansion, and re-differentiation protocols by gene expression analysis. Among 19 common cartilage molecules assessed by cDNA array, six proved best to monitor differentiation. Instant down-regulation at release of cells from the matrix was strongest for COL 2A1, fibromodulin, and PRELP while LUM, CHI3L1, and CHI3L2 were expansion-related. Both gene sets reflected the physiologic effects of the most potent growth-inducing (PDGF-BB) and proteoglycan-inducing (BMP-4) factors. Only CRTAC1 expression correlated with 2D/3D switches while the molecular phenotype of native chondrocytes was not restored. The markers and optimised protocols we suggest can help to improve cell therapy of cartilage defects and chondrocyte differentiation from stem cell sources.

  15. From nestling calls to fledgling silence: adaptive timing of change in response to aerial alarm calls.

    Science.gov (United States)

    Magrath, Robert D; Platzen, Dirk; Kondo, Junko

    2006-09-22

    Young birds and mammals are extremely vulnerable to predators and so should benefit from responding to parental alarm calls warning of danger. However, young often respond differently from adults. This difference may reflect: (i) an imperfect stage in the gradual development of adult behaviour or (ii) an adaptation to different vulnerability. Altricial birds provide an excellent model to test for adaptive changes with age in response to alarm calls, because fledglings are vulnerable to a different range of predators than nestlings. For example, a flying hawk is irrelevant to a nestling in a enclosed nest, but is dangerous to that individual once it has left the nest, so we predict that young develop a response to aerial alarm calls to coincide with fledging. Supporting our prediction, recently fledged white-browed scrubwrens, Sericornis frontalis, fell silent immediately after playback of their parents' aerial alarm call, whereas nestlings continued to calling despite hearing the playback. Young scrubwrens are therefore exquisitely adapted to the changing risks faced during development.

  16. Sharing programming resources between Bio* projects through remote procedure call and native call stack strategies

    DEFF Research Database (Denmark)

    Prins, Pjotr; Goto, Naohisa; Yates, Andrew

    2012-01-01

    Open-source software (OSS) encourages computer programmers to reuse software components written by others. In evolutionary bioinformatics, OSS comes in a broad range of programming languages, including C/C++, Perl, Python, Ruby, Java, and R. To avoid writing the same functionality multiple times...... for different languages, it is possible to share components by bridging computer languages and Bio* projects, such as BioPerl, Biopython, BioRuby, BioJava, and R/Bioconductor. In this chapter, we compare the two principal approaches for sharing software between different programming languages: either by remote...... procedure call (RPC) or by sharing a local call stack. RPC provides a language-independent protocol over a network interface; examples are RSOAP and Rserve. The local call stack provides a between-language mapping not over the network interface, but directly in computer memory; examples are R bindings, RPy...

  17. Staffing to Maximize Profit for Call Centers with Impatient and Repeat-Calling Customers

    Directory of Open Access Journals (Sweden)

    Jun Gong

    2015-01-01

    Full Text Available Motivated by call center practice, we study the optimal staffing of many-server queues with impatient and repeat-calling customers. A call center is modeled as an M/M/s+M queue, which is developed to a behavioral queuing model in which customers come and go based on their satisfaction with waiting time. We explicitly take into account customer repeat behavior, which implies that satisfied customers might return and have an impact on the arrival rate. Optimality is defined as the number of agents that maximize revenues net of staffing costs, and we account for the characteristic that revenues are a direct function of staffing. Finally, we use numerical experiments to make certain comparisons with traditional models that do not consider customer repeat behavior. Furthermore, we indicate how managers might allocate staffing optimally with various customer behavior mechanisms.

  18. Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease

    NARCIS (Netherlands)

    Taravini, Irene R.; Larramendy, Celia; Gomez, Gimena; Saborido, Mariano D.; Spaans, Floor; Fresno, Cristobal; Gonzalez, German A.; Fernandez, Elmer; Murer, Mario G.; Gershanik, Oscar S.

    Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although

  19. Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid [human

    NARCIS (Netherlands)

    IJssennagger, Noortje; Janssen, Aafke; Mil, van Saskia; Kersten, Sander

    2016-01-01

    Background: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6α-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH)

  20. Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid [mouse

    NARCIS (Netherlands)

    IJssennagger, Noortje; Janssen, Aafke; Kersten, Sander; Mil, van S.W.C.

    2016-01-01

    Background: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6α-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH)

  1. Sharing programming resources between Bio* projects through remote procedure call and native call stack strategies.

    Science.gov (United States)

    Prins, Pjotr; Goto, Naohisa; Yates, Andrew; Gautier, Laurent; Willis, Scooter; Fields, Christopher; Katayama, Toshiaki

    2012-01-01

    Open-source software (OSS) encourages computer programmers to reuse software components written by others. In evolutionary bioinformatics, OSS comes in a broad range of programming languages, including C/C++, Perl, Python, Ruby, Java, and R. To avoid writing the same functionality multiple times for different languages, it is possible to share components by bridging computer languages and Bio* projects, such as BioPerl, Biopython, BioRuby, BioJava, and R/Bioconductor. In this chapter, we compare the two principal approaches for sharing software between different programming languages: either by remote procedure call (RPC) or by sharing a local call stack. RPC provides a language-independent protocol over a network interface; examples are RSOAP and Rserve. The local call stack provides a between-language mapping not over the network interface, but directly in computer memory; examples are R bindings, RPy, and languages sharing the Java Virtual Machine stack. This functionality provides strategies for sharing of software between Bio* projects, which can be exploited more often. Here, we present cross-language examples for sequence translation, and measure throughput of the different options. We compare calling into R through native R, RSOAP, Rserve, and RPy interfaces, with the performance of native BioPerl, Biopython, BioJava, and BioRuby implementations, and with call stack bindings to BioJava and the European Molecular Biology Open Software Suite. In general, call stack approaches outperform native Bio* implementations and these, in turn, outperform RPC-based approaches. To test and compare strategies, we provide a downloadable BioNode image with all examples, tools, and libraries included. The BioNode image can be run on VirtualBox-supported operating systems, including Windows, OSX, and Linux.

  2. Erlotinib treatment in patients with advanced lung adenocarcinoma with CISH-positive and CISH-negative EGFR gene alterations.

    Science.gov (United States)

    Hou, Ming-Mo; Huang, Shiu-Feng; Kuo, Han-Pin; Yang, Cheng-Ta; Tsai, Ying-Huang; Yu, Chih-Teng; Lin, Horng-Chyuan; Chen, Chih-Hung; Wang, Chih-Liang; Chung, Fu-Tsai; Hsieh, Jia-Juan; Hsu, Todd; Cheng, Hsin-Yi; Ou, Li-Ying; Wang, Hung-Ming; Lin, Yung-Chang; Chang, Nai-Jen; Chang, John Wen-Cheng

    2012-03-01

    Epidermal growth factor receptor (EGFR) positivity as assessed by chromogenic in situ hybridization (CISH) has been demonstrated to be associated with EGFR mutation status. This study was conducted to compare the responsiveness of CISH-positive and CISH-negative lung adenocarcinomas to erlotinib. Patients received erlotinib (150 mg/day) alone until disease progression or intolerable toxicity. EGFR gene status was examined by CISH. The response rate (RR), progression-free survival (PFS), overall survival (OS) and toxicity profiles were assessed. Thirty-one patients underwent response evaluations and CISH analyses, 12 of whom harboured CISH-positive adenocarcinomas. The overall RR (p=0.035), median PFS (p=0.091) and median OS (p=0.408) were higher in the CISH-positive group. No difference in toxicity profiles was observed between these two groups. EGFR status as assessed by CISH can predict the response to erlotinib in patients with advanced lung adenocarcinoma.

  3. Cloning of genes related to aliphatic glucosinolate metabolism and the mechanism of sulforaphane accumulation in broccoli sprouts under jasmonic acid treatment.

    Science.gov (United States)

    Guo, Liping; Yang, Runqiang; Gu, Zhenxin

    2016-10-01

    Cytochrome P450 79F1 (CYP79F1), cytochrome P450 83A1 (CYP83A1), UDP-glucosyltransferase 74B1 (UGT74B1), sulfotransferase 18 (ST5b) and flavin-containing monooxygenase GS-OX1 (FMOGS - OX1 ) are important enzymes in aliphatic glucosinolate biosynthesis. In this study, their full-length cDNA in broccoli was firstly cloned, then the mechanism of sulforaphane accumulation under jasmonic acid (JA) treatment was investigated. The full-length cDNA of CYP79F1, CYP83A1, UGT74B1, ST5b and FMOGS - OX1 comprised 1980, 1652, 1592, 1378 and 1623 bp respectively. The increase in aliphatic glucosinolate accumulation in broccoli sprouts treated with JA was associated with elevated expression of genes in the aliphatic glucosinolate biosynthetic pathway. Application of 100 µmol L(-1) JA increased myrosinase (MYR) activity but did not affect epithiospecifier protein (ESP) activity in broccoli sprouts, which was supported by the expression of MYR and ESP. Sulforaphane formation in 7-day-old sprouts treated with 100 µmol L(-1) JA was 3.36 and 1.30 times that in the control and 300 µmol L(-1) JA treatment respectively. JA enhanced the accumulation of aliphatic glucosinolates in broccoli sprouts via up-regulation of related gene expression. Broccoli sprouts treated with 100 µmol L(-1) JA showed higher sulforphane formation than those treated with 300 µmol L(-1) JA owing to the higher glucoraphanin content and myrosinase activity under 100 µmol L(-1) JA treatment. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  4. Hypothermia for Stroke: call to action 2010

    DEFF Research Database (Denmark)

    Macleod, Malcolm R; Petersson, Jesper; Norrving, Bo

    2010-01-01

    The European Hypothermia Stroke Research Workshop was held in January 2010, in response to the alarming prospects of a significant increase of stroke expected in the coming years globally. Considering that a minority of patients (around 10%) are currently eligible for thrombolytic treatment, ther...

  5. Doctor, Do You Make (School) House Calls?

    Science.gov (United States)

    Ekstrand, Richard E.

    1982-01-01

    Raises several questions concerning the provision of emergency and routine medical treatment during school hours for health-impaired children whose conditions are chronic and severe. Examples of standards to be met when school personnel respond to impaired children's health needs are offered. (RH)

  6. Hypermethylated 14-3-3-σ and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis

    International Nuclear Information System (INIS)

    Zurita, Mercedes; Lara, Pedro C; Moral, Rosario del; Torres, Blanca; Linares-Fernández, José Luis; Arrabal, Sandra Ríos; Martínez-Galán, Joaquina; Oliver, Francisco Javier; Ruiz de Almodóvar, José Mariano

    2010-01-01

    Numerous hypermethylated genes have been reported in breast cancer, and the silencing of these genes plays an important role in carcinogenesis, tumor progression and diagnosis. These hypermethylated promoters are very rarely found in normal breast. It has been suggested that aberrant hypermethylation may be useful as a biomarker, with implications for breast cancer etiology, diagnosis, and management. The relationship between primary neoplasm and metastasis remains largely unknown. There has been no comprehensive comparative study on the clinical usefulness of tumor-associated methylated DNA biomarkers in primary breast carcinoma and metastatic breast carcinoma. The objective of the present study was to investigate the association between clinical extension of breast cancer and methylation status of Estrogen Receptor1 (ESR1) and Stratifin (14-3-3-σ) gene promoters in disease-free and metastatic breast cancer patients. We studied two cohorts of patients: 77 patients treated for breast cancer with no signs of disease, and 34 patients with metastatic breast cancer. DNA was obtained from serum samples, and promoter methylation status was determined by using DNA bisulfite modification and quantitative methylation-specific PCR. Serum levels of methylated gene promoter 14-3-3-σ significantly differed between Control and Metastatic Breast Cancer groups (P < 0.001), and between Disease-Free and Metastatic Breast Cancer groups (P < 0.001). The ratio of the 14-3-3-σ level before the first chemotherapy cycle to the level just before administration of the second chemotherapy cycle was defined as the Biomarker Response Ratio [BRR]. We calculated BRR values for the 'continuous decline' and 'rise-and-fall' groups. Subsequent ROC analysis showed a sensitivity of 75% (95% CI: 47.6 - 86.7) and a specificity of 66.7% (95% CI: 41.0 - 86.7) to discriminate between the groups for a cut-off level of BRR = 2.39. The area under the ROC curve (Z = 0.804 ± 0

  7. Pathological aspects of so called "hilar cholangiocarcinoma".

    Science.gov (United States)

    Castellano-Megías, Víctor M; Ibarrola-de Andrés, Carolina; Colina-Ruizdelgado, Francisco

    2013-07-15

    Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, "hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.

  8. From Systematic Review to Call for Action.

    Science.gov (United States)

    Sawin, Erika Metzler; Sobel, Linda L; Annan, Sandra L; Schminkey, Donna L

    2017-06-01

    Intimate partner violence (IPV) is a global public health and criminal justice concern with significant impacts; especially high rates are seen among rural Hispanic American (HA) communities, the fastest growing population in the United States. They experience additional barriers to care including extreme poverty, lesser education, gender norms, and language and immigration issues. A systematic literature review was conducted using Cooper's framework to identify evidence supporting associations between interventions and prevention, reduction, and elimination of IPV among rural HA women. Searches conducted on databases including CINAHL, PubMed, Medline, Women's Studies International, MedicLatina, and JSTOR used the MeSH terms Hispanic Americans (Latino/a and Hispanic), domestic violence, and intimate partner violence. Selected studies were published between January 1, 2000, and January 1, 2014. Of the 617 yielded articles, only 6 met the inclusion criteria. Of these, none closely examined rurality or provided valid and reliable measures of outcomes, instead reporting program descriptions and suggested interventions. We identify key findings to guide program, screening, and tool development. Our study identifies a gap in knowledge, research, and effective practices and issues a call for action to create evidence-based tools to prevent, reduce, and eliminate IPV in these underserved populations.

  9. A study of so-called hypochondriasis.

    Science.gov (United States)

    von Scheele, C; Nordgren, L; Kempi, V; Hetta, J; Hallborg, A

    1990-01-01

    Twenty-four patients with unexplained somatic complaints were subjected to a thorough somatic examination. Only when the examination proved negative was the patient entered into the study. The patients were clinically appraised according to criteria given in DSM-III. Generalized anxiety disorder (GAD) was diagnosed in 12, somatization disorder (SD) in 8, and hypochondriasis in 4 patients. Seventeen of the 24 patients agreed to participate in biochemical investigations including a TRH load, a dexamethasone test, and a determination of the monoamine metabolites 5-HIAA and HVA in cerebrospinal fluid (CSF). A normal TSH increase and a normal suppression of cortisol were registered. The HVA values correlated significantly with the 5-HIAA values as well as with the alexithymia scores. Concerning alexithymia and maturity level, no difference as to social class was found. The patients filled in a Zung depression chart. The Zung scale and the 5-HIAA values were both inconsistent with depressive illness. In so-called hypochondriasis a long-term relationship, including selected somatic and biochemical examinations and thorough information, was crucial in abating the patient's distrust and thus the need for health care.

  10. Individual and contextual variation in Thomas langur male loud calls

    NARCIS (Netherlands)

    Wich, S.A.; Koski, S.; Vries, Han de; Schaik, Carel P. van

    2003-01-01

    Individual and contextual differences in male loud calls of wild Thomas langurs (Presbytis thomasi) were studied in northern Sumatra, Indonesia. Loud calls were given in the following contexts: morning calls, vocal responses to other groups, between-group encounter calls and alarmcalls. Loud

  11. Linking Calling Orientations to Organizational Attachment via Organizational Instrumentality

    Science.gov (United States)

    Cardador, M. Teresa; Dane, Erik; Pratt, Michael G.

    2011-01-01

    Despite an emerging interest in callings, researchers know little about whether calling orientations matter in the workplace. We explore the under-examined relationship between a calling orientation and employees' attachment to their organizations. Although some theory suggests that callings may be negatively related to organizational attachment,…

  12. Development of antibiotic resistance genes in microbial communities during long-term operation of anaerobic reactors in the treatment of pharmaceutical wastewater.

    Science.gov (United States)

    Aydin, Sevcan; Ince, Bahar; Ince, Orhan

    2015-10-15

    Biological treatment processes offer the ideal conditions in which a high diversity of microorganisms can grow and develop. The wastewater produced during these processes is contaminated with antibiotics and, as such, they provide the ideal setting for the acquisition and proliferation of antibiotic resistance genes (ARGs). This research investigated the occurrence and variation in the ARGs found during the one-year operation of the anaerobic sequencing batch reactors (SBRs) used to treat pharmaceutical wastewater that contained combinations of sulfamethoxazole-tetracycline-erythromycin (STE) and sulfamethoxazole-tetracycline (ST). The existence of eighteen ARGs encoding resistance to sulfamethoxazole (sul1, sul2, sul3), erythromycin (ermA, ermF, ermB, msrA, ereA), tetracycline (tetA, tetB, tetC, tetD, tetE, tetM, tetS, tetQ, tetW, tetX) and class Ι integron gene (intΙ 1) in the STE and ST reactors was investigated by quantitative real-time PCR. Due to the limited availability of primers to detect ARGs, Illumina sequencing was also performed on the sludge and effluent of the STE and ST reactors. Although there was good reactor performance in the SBRs, which corresponds to min 80% COD removal efficiency, tetA, tetB, sul1, sul2 and ermB genes were among those ARGs detected in the effluent from STE and ST reactors. A comparison of the ARGs acquired from the STE and ST reactors revealed that the effluent from the STE reactor had a higher number of ARGs than that from the ST reactor; this could be due to the synergistic effects of erythromycin. According to the expression of genes results, microorganisms achieve tetracycline and erythromycin resistance through a combination of three mechanisms: efflux pumping protein, modification of the antibiotic target and modifying enzymes. There was also a significant association between the presence of the class 1 integron and sulfamethoxazole resistance genes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Treatment efficacy and immune stimulation by AdCD40L gene therapy of spontaneous canine malignant melanoma.

    Science.gov (United States)

    Westberg, Sara; Sadeghi, Arian; Svensson, Emma; Segall, Thomas; Dimopoulou, Maria; Korsgren, Olle; Hemminki, Akseli; Loskog, Angelica S I; Tötterman, Thomas H; von Euler, Henrik

    2013-01-01

    Malignant melanoma is a serious disease in both humans and dogs, and the high metastatic potential results in poor prognosis for many patients. Its similarities with human melanoma make spontaneous canine melanoma an excellent model for comparative studies of novel therapies and tumor biology. We report a pilot study of local adenovector CD40L (AdCD40L) immunogene treatment in 19 cases of canine melanoma (14 oral, 4 cutaneous, and 1 conjunctival). Three patients were World Health Organization stage I, 2 were stage II, 10 stage III, and 4 stage IV. One to 6 intratumoral injections of AdCD40L were given every 7 days, followed by cytoreductive surgery in 9 cases and only immunotherapy in 10 cases. Tumor tissue was infiltrated with T and B lymphocytes after treatment, suggesting immune stimulation. The best overall response included 5 complete responses, 8 partial responses, and 4 stable and 2 progressive disease statuses according to the World Health Organization response criteria. Median survival was 160 days (range, 20-1141 d), with 3 dogs still alive at submission. Our results suggest that local AdCD40L therapy is safe and could have beneficial effects in dogs, supporting further treatment development. Clinical translation to human patients is in progress.

  14. Calling under pressure: short-finned pilot whales make social calls during deep foraging dives.

    Science.gov (United States)

    Jensen, Frants H; Perez, Jacobo Marrero; Johnson, Mark; Soto, Natacha Aguilar; Madsen, Peter T

    2011-10-22

    Toothed whales rely on sound to echolocate prey and communicate with conspecifics, but little is known about how extreme pressure affects pneumatic sound production in deep-diving species with a limited air supply. The short-finned pilot whale (Globicephala macrorhynchus) is a highly social species among the deep-diving toothed whales, in which individuals socialize at the surface but leave their social group in pursuit of prey at depths of up to 1000 m. To investigate if these animals communicate acoustically at depth and test whether hydrostatic pressure affects communication signals, acoustic DTAGs logging sound, depth and orientation were attached to 12 pilot whales. Tagged whales produced tonal calls during deep foraging dives at depths of up to 800 m. Mean call output and duration decreased with depth despite the increased distance to conspecifics at the surface. This shows that the energy content of calls is lower at depths where lungs are collapsed and where the air volume available for sound generation is limited by ambient pressure. Frequency content was unaffected, providing a possible cue for group or species identification of diving whales. Social calls may be important to maintain social ties for foraging animals, but may be impacted adversely by vessel noise.

  15. Occurrence and transformation of veterinary antibiotics and antibiotic resistance genes in dairy manure treated by advanced anaerobic digestion and conventional treatment methods.

    Science.gov (United States)

    Wallace, Joshua S; Garner, Emily; Pruden, Amy; Aga, Diana S

    2018-05-01

    Manure treatment technologies are rapidly developing to minimize eutrophication of surrounding environments and potentially decrease the introduction of antibiotics and antibiotic resistant genes (ARGs) into the environment. While laboratory and pilot-scale manure treatment systems boast promising results, antibiotic and ARG removals in full-scale systems receiving continuous manure input have not been evaluated. The effect of treatment on ARGs is similarly lacking. This study examines the occurrence and transformation of sulfonamides, tetracyclines, tetracycline degradation products, and related ARGs throughout a full-scale advanced anaerobic digester (AAD) receiving continuous manure and antibiotic input. Manure samples were collected throughout the AAD system to evaluate baseline antibiotic and ARG input (raw manure), the effect of hygenization (post-pasteurized manure) and anaerobic digestion (post-digestion manure) on antibiotic and ARG levels. Antibiotics were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the ARGs tet(O), tet(W), sul1 and sul2 were analyzed by quantitative polymerase chain reaction (Q-PCR). Significant reductions in the concentrations of chlortetracycline, oxytetracycline, tetracycline and their degradation products were observed in manure liquids following treatment (p < 0.001), concomitant to significant increases in manure solids (p < 0.001). These results suggest sorption is the major removal route for tetracyclines during AAD. Significant decreases in the epimer-to-total residue ratios for chlortetracycline and tetracycline in manure solids further indicate degradation is desorption-limited. Moreover, sul1 and sul2 copies decreased significantly (p < 0.001) following AAD in the absence of sulfonamide antibiotics, while tetracyclines-resistant genes remained unchanged. A cross-sectional study of dairy farms utilizing natural aeration and liquid-solid separation treatments was additionally performed

  16. Pre-treatment with N-acetylcysteine upregulates superoxide dismutase 2 and catalase genes in cadmium-induced oxidative stress in the chick omphalocele model.

    Science.gov (United States)

    Doi, Takashi; Puri, Prem; Bannigan, John; Thompson, Jennifer

    2011-02-01

    In the chick embryo, administration of the heavy metal Cadmium (Cd) induces omphalocele phenotype. Cd is a potent inhibitor of antioxidant enzymes and causes accumulation of reactive oxygen species (ROSs) such as hydrogen peroxide. Previous work with the Cd chick model has demonstrated that increased levels of MDA, as a marker for oxidative stress, 24 h post Cd treatment (24H) are identical in chick embryos exposed to Cd. Furthermore, of the several antioxidants assessed, only N-acetylcysteine (NAC) has been shown to reduce MDA levels to control values in the Cd-treated chick embryo. However, the molecular mechanisms by which NAC acts to maintain oxidative stress in the Cd-induced ventral body wall defect chick model remains to be unclear. We designed this study to investigate the hypothesis that gene expression levels of antioxidant enzymes are downregulated in malformed embryos exposed to Cd compared to controls and to determine the effect of pre-treatment with NAC on the expression levels of genes encoding antioxidant enzymes. After 60 h incubation, chick embryos were pre-treated with NAC and exposed to either chick saline or Cd. Chicks were then harvested at 24H and divided into five groups: control, Cd group without malformation [Cd(-)], Cd group with malformation [Cd(+)], NAC + Cd(-) and NAC + Cd(+). Real-time PCR was performed to evaluate the relative mRNA expression levels of antioxidant enzymes, including superoxide dismutase (SOD)-1, SOD2, catalase (CAT) and glutathione peroxidase (GPX)-4. Differences between five groups were tested by Tukey-Kramer post-hoc test following one-way ANOVA. Statistical significance was accepted at p < 0.05. Immunohistochemistry was also performed to evaluate protein expression. The mRNA expression levels of SOD2 and CAT were significantly decreased in Cd(+) as compared to controls, whereas there was no significant difference between controls and Cd(-) (p < 0.05 vs. controls). In addition, gene expression levels of

  17. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  18. Neural Correlates of Threat Perception: Neural Equivalence of Conspecific and Heterospecific Mobbing Calls Is Learned

    Science.gov (United States)

    Avey, Marc T.; Hoeschele, Marisa; Moscicki, Michele K.; Bloomfield, Laurie L.; Sturdy, Christopher B.

    2011-01-01

    Songbird auditory areas (i.e., CMM and NCM) are preferentially activated to playback of conspecific vocalizations relative to heterospecific and arbitrary noise [1]–[2]. Here, we asked if the neural response to auditory stimulation is not simply preferential for conspecific vocalizations but also for the information conveyed by the vocalization. Black-capped chickadees use their chick-a-dee mobbing call to recruit conspecifics and other avian species to mob perched predators [3]. Mobbing calls produced in response to smaller, higher-threat predators contain more “D” notes compared to those produced in response to larger, lower-threat predators and thus convey the degree of threat of predators [4]. We specifically asked whether the neural response varies with the degree of threat conveyed by the mobbing calls of chickadees and whether the neural response is the same for actual predator calls that correspond to the degree of threat of the chickadee mobbing calls. Our results demonstrate that, as degree of threat increases in conspecific chickadee mobbing calls, there is a corresponding increase in immediate early gene (IEG) expression in telencephalic auditory areas. We also demonstrate that as the degree of threat increases for the heterospecific predator, there is a corresponding increase in IEG expression in the auditory areas. Furthermore, there was no significant difference in the amount IEG expression between conspecific mobbing calls or heterospecific predator calls that were the same degree of threat. In a second experiment, using hand-reared chickadees without predator experience, we found more IEG expression in response to mobbing calls than corresponding predator calls, indicating that degree of threat is learned. Our results demonstrate that degree of threat corresponds to neural activity in the auditory areas and that threat can be conveyed by different species signals and that these signals must be learned. PMID:21909363

  19. Neural correlates of threat perception: neural equivalence of conspecific and heterospecific mobbing calls is learned.

    Science.gov (United States)

    Avey, Marc T; Hoeschele, Marisa; Moscicki, Michele K; Bloomfield, Laurie L; Sturdy, Christopher B

    2011-01-01

    Songbird auditory areas (i.e., CMM and NCM) are preferentially activated to playback of conspecific vocalizations relative to heterospecific and arbitrary noise. Here, we asked if the neural response to auditory stimulation is not simply preferential for conspecific vocalizations but also for the information conveyed by the vocalization. Black-capped chickadees use their chick-a-dee mobbing call to recruit conspecifics and other avian species to mob perched predators. Mobbing calls produced in response to smaller, higher-threat predators contain more "D" notes compared to those produced in response to larger, lower-threat predators and thus convey the degree of threat of predators. We specifically asked whether the neural response varies with the degree of threat conveyed by the mobbing calls of chickadees and whether the neural response is the same for actual predator calls that correspond to the degree of threat of the chickadee mobbing calls. Our results demonstrate that, as degree of threat increases in conspecific chickadee mobbing calls, there is a corresponding increase in immediate early gene (IEG) expression in telencephalic auditory areas. We also demonstrate that as the degree of threat increases for the heterospecific predator, there is a corresponding increase in IEG expression in the auditory areas. Furthermore, there was no significant difference in the amount IEG expression between conspecific mobbing calls or heterospecific predator calls that were the same degree of threat. In a second experiment, using hand-reared chickadees without predator experience, we found more IEG expression in response to mobbing calls than corresponding predator calls, indicating that degree of threat is learned. Our results demonstrate that degree of threat corresponds to neural activity in the auditory areas and that threat can be conveyed by different species signals and that these signals must be learned.

  20. Neural correlates of threat perception: neural equivalence of conspecific and heterospecific mobbing calls is learned.

    Directory of Open Access Journals (Sweden)

    Marc T Avey

    Full Text Available Songbird auditory areas (i.e., CMM and NCM are preferentially activated to playback of conspecific vocalizations relative to heterospecific and arbitrary noise. Here, we asked if the neural response to auditory stimulation is not simply preferential for conspecific vocalizations but also for the information conveyed by the vocalization. Black-capped chickadees use their chick-a-dee mobbing call to recruit conspecifics and other avian species to mob perched predators. Mobbing calls produced in response to smaller, higher-threat predators contain more "D" notes compared to those produced in response to larger, lower-threat predators and thus convey the degree of threat of predators. We specifically asked whether the neural response varies with the degree of threat conveyed by the mobbing calls of chickadees and whether the neural response is the same for actual predator calls that correspond to the degree of threat of the chickadee mobbing calls. Our results demonstrate that, as degree of threat increases in conspecific chickadee mobbing calls, there is a corresponding increase in immediate early gene (IEG expression in telencephalic auditory areas. We also demonstrate that as the degree of threat increases for the heterospecific predator, there is a corresponding increase in IEG expression in the auditory areas. Furthermore, there was no significant difference in the amount IEG expression between conspecific mobbing calls or heterospecific predator calls that were the same degree of threat. In a second experiment, using hand-reared chickadees without predator experience, we found more IEG expression in response to mobbing calls than corresponding predator calls, indicating that degree of threat is learned. Our results demonstrate that degree of threat corresponds to neural activity in the auditory areas and that threat can be conveyed by different species signals and that these signals must be learned.

  1. Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

    Science.gov (United States)

    Ryk, Charlotta; Koskela, Lotta Renström; Thiel, Tomas; Wiklund, N Peter; Steineck, Gunnar; Schumacher, Martin C; de Verdier, Petra J

    2015-12-01

    Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. All NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests. BCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment. Our results suggest that the investigated polymorphisms influence patient response

  2. Successful treatment with risperidone increases 5-HT 3A receptor gene expression in patients with paranoid schizophrenia - data from a prospective study.

    Science.gov (United States)

    Chen, Hongying; Fan, Yong; Zhao, Lei; Hao, Yong; Zhou, Xiajun; Guan, Yangtai; Li, Zezhi

    2017-09-01

    The relationship between peripheral 5-HT3A receptor mRNA level and risperidone efficiency in paranoid schizophrenia patients is still unknown. A total 52 first-episode and drug-naive paranoid schizophrenia patients who were treated with risperidone and 53 matched healthy controls were enrolled. Patients were naturalistically followed up for 8 weeks. Positive and Negative Syndrome Scale (PANSS) was applied to assess symptom severity of the patients at baseline and at the end of 8th week. There was no difference in 5-HT3A receptor mRNA level between paranoid schizophrenia patients and healthy controls at baseline ( p  = .24). Among 47 patients who completed 8-week naturalistic follow-up, 37 were responders to risperidone treatment. 5-HT3A receptor mRNA level of paranoid schizophrenia patients did not change in overall patients after 8-week treatment with risperidone ( p  = .29). However, 5-HT3A receptor mRNA level in responders increased significantly ( p  = .04), but not in nonresponders ( p  = .81). Successful treatment with risperidone increases 5-HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that 5-HT3A receptor may be involved in the mechanism of risperidone effect.

  3. Optimal scheduling in call centers with a callback option

    OpenAIRE

    Legros , Benjamin; Jouini , Oualid; Koole , Ger

    2016-01-01

    International audience; We consider a call center model with a callback option, which allows to transform an inbound call into an outbound one. A delayed call, with a long anticipated waiting time, receives the option to be called back. We assume a probabilistic customer reaction to the callback offer (option). The objective of the system manager is to characterize the optimal call scheduling that minimizes the expected waiting and abandonment costs. For the single-server case, we prove that ...

  4. [A call for qualitative research in Orthodontics].

    Science.gov (United States)

    Yitschaky, O; Hofnung, T; Zini, A

    2015-01-01

    Qualitative research is an umbrella term for an array of attitudes and strategies for conducting inquiries that are aimed at discerning how human beings understand, experience, and interpret the social world. It is employed in many different academic disciplines most particularly in the social sciences and humanities, however recently more and more qualitative research is being conducted under the medical sciences including dentistry and orthodontics. This is due to its nature of in-depth investigation, which can provide answers to questions that cannot be satisfactorily answered using quantitative methods alone. The aims of this article are to discuss the characteristics of qualitative research, to review the orthodontic English literature, and to highlight the advantages of qualitative research in orthodontics. The literature review yielded several important conclusions regarding qualitative research in orthodontics: 1. most of the qualitative research done in orthodontics chose to use semi structured in-depth interviews for data collection; 2. qualitative research highlights aspects that are very important, and sometimes crucial to everyday practice and long term treatment; 3. there is a lack of qualitative studies in the field of orthodontics. Taking into account the nature of the orthodontic treatment, which is a prolonged one, demanding of a good orthodontist-patient rapport, and a wide perspective on behalf of the clinician, filling the gap in the discipline through conducting more qualitative studies aimed at understanding the point of view of the patient, as well as that of the clinician, may be beneficial for the improvement of the treatment.

  5. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    Directory of Open Access Journals (Sweden)

    Ming Lei

    2016-02-01

    Full Text Available The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata.

  6. Identification of Mycobacterial Genes Involved in Antibiotic Sensitivity: Implications for the Treatment of Tuberculosis with β-Lactam-Containing Regimens

    Science.gov (United States)

    Viswanathan, Gopinath; Yadav, Sangya

    2017-01-01

    ABSTRACT In a Mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaA, dprE2, rpsT, and parA displayed hypersusceptibility to antibiotics, including the β-lactams meropenem, ampicillin, amoxicillin, and cefotaxime. Sub-MIC levels of octoclothepin, a psychotic drug inhibiting ParA, phenocopied the parA insertion and enhanced the bactericidal activity of meropenem against Mycobacterium tuberculosis in combination with clavulanate. Our study identifies novel factors associated with antibiotic resistance, with implications in repurposing β-lactams for tuberculosis treatment. PMID:28438925

  7. Neuroprotective effect of non-viral gene therapy treatment based on tetanus toxin C-fragment in a severe mouse model of Spinal Muscular Atrophy.

    Directory of Open Access Journals (Sweden)

    Sara Olivan Garcia

    2016-08-01

    Full Text Available Spinal muscular atrophy (SMA is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC, which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons in vitro and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3 and p62 and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln, TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease.

  8. Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

    Science.gov (United States)

    Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

    2016-08-01

    Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.

  9. Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases

    Science.gov (United States)

    Manring, Heather; Abreu, Eduardo; Brotto, Leticia; Weisleder, Noah; Brotto, Marco

    2013-01-01

    Research over the last decade strengthened the understanding that skeletal muscles are not only the major tissue in the body from a volume point of view but also function as a master regulator contributing to optimal organismal health. These new contributions to the available body of knowledge triggered great interest in the roles of skeletal muscle beyond contraction. The World Health Organization, through its Global Burden of Disease (GBD) report, recently raised further awareness about the key importance of skeletal muscles as the GDB reported musculoskeletal (MSK) diseases have become the second greatest cause of disability, with more than 1.7 billion people in the globe affected by a diversity of MSK conditions. Besides their role in MSK disorders, skeletal muscles are also seen as principal metabolic organs with essential contributions to metabolic disorders, especially those linked to physical inactivity. In this review, we have focused on the unique function of new genes/proteins (i.e., MTMR14, MG29, sarcalumenin, KLF15) that during the last few years have helped provide novel insights about muscle function in health and disease, muscle fatigue, muscle metabolism, and muscle aging. Next, we provide an in depth discussion of how these genes/proteins converge into a common function of acting as regulators of intracellular calcium homeostasis. A clear link between dysfunctional calcium homeostasis is established and the special role of store-operated calcium entry is analyzed. The new knowledge that has been generated by the understanding of the roles of previously unknown modulatory genes of the skeletal muscle excitation-contraction coupling (ECC) process brings exciting new possibilities for treatment of MSK diseases, muscle regeneration, and skeletal muscle tissue engineering. The next decade of skeletal muscle and MSK research is bound to bring to fruition applied knowledge that will hopefully offset the current heavy and sad burden of MSK diseases on the

  10. Antigen uptake and expression of antigen presentation-related immune genes in flounder (Paralichthys olivaceus) after vaccination with an inactivated Edwardsiella tarda immersion vaccine, following hyperosmotic treatment.

    Science.gov (United States)

    Gao, Yingli; Tang, Xiaoqian; Sheng, Xiuzhen; Xing, Jing; Zhan, Wenbin

    2016-08-01

    Antigen uptake is a critical process for activation of the immune system, and therefore the ability to enhance antigen uptake is a primary consideration in the development of an immersion vaccination of fish. In the present work, flounders (Paralichthys olivaceus) were immersed in three hyperosmotic solutions with 40, 50 and 60‰ salinities, then transferred into seawater of normal salinity (i.e. 30‰) containing formalin-inactivated Edwardsiella tarda for 30 min. The antigen uptake in vaccinated flounder was determined using an absolute quantitative PCR (qPCR). The results showed significantly higher antigen uptake in the tissues of flounders immersed in solutions with 50‰ and 60‰ salinity compared to the control group directly immersed in vaccine (DI) (P immersed in the 50‰ salinity solution, whereas there was no significant difference in antigen uptake between the 40‰ salinity group and the DI group (P > 0.05). A rapid and significant increase in antigen uptake was detected in the mucosal-associated tissues including the gill, skin and intestine (P immersion, which was significantly higher than the levels of uptake measured in the other tissues (P immersion (hpi). The expression profiles of four antigen presentation-related immune genes (MHC Iα, MHC IIα, CD4-1 and CD8α) were investigated after immersion. These four genes showed a significantly stronger response in the immersed flounders exposed to 50‰ salinity compared with the DI group (P immersion, notably 50‰ salinity significantly enhanced antigen uptake and the expression of selected genes associated with antigen presentation, providing evidence for an enhanced immune activation of the fish's immune response by the hyperosmotic immersion treatment prior to vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury★

    Science.gov (United States)

    Wang, Dong; Fan, Yuhong; Zhang, Jianjun

    2013-01-01

    Inhibition of neurite growth, which is in large part mediated by the Nogo-66 receptor, affects neural regeneration following bone marrow mesenchymal stem cell transplantation. The tissue engineering scaffold poly(D,L-lactide-co-glycolic acid) has good histocompatibility and can promote the growth of regenerating nerve fibers. The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells, which were subsequently transplanted with poly(D,L-lactide-co-glycolic acid) into the spinal cord lesion regions in rats. Simultaneously, rats treated with scaffold only were taken as the control group. Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation, rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced cells plus the poly(D,L-lactide-co-glycolic acid) scaffold compared with rats treated with scaffold only, and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased. At 8 weeks after transplantation, horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers, as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury. These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly(D,L-lactide-co-glycolic acid) scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury. PMID:25206713

  12. Profile of Mutations in the Reverse Transcriptase and Overlapping Surface Genes of Hepatitis B Virus (HBV) in Treatment-Naïve Indonesian HBV Carriers.

    Science.gov (United States)

    Yamani, Laura Navika; Yano, Yoshihiko; Utsumi, Takako; Wasityastuti, Widya; Rinonce, Hanggoro Tri; Widasari, Dewiyani Indah; Juniastuti; Lusida, Maria Inge; Soetjipto; Hayashi, Yoshitake

    2017-11-22

    Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome are an important factor in low therapeutic effectiveness. Nonetheless, the prevalence of these mutations in HBV strains isolated previously in Indonesia has not been systematically examined. Therefore, in this study, we investigated the profile of mutations in the RT region and the associations of these mutations with amino acid changes in the surface protein in the virus of treatment-naïve Indonesian HBV carriers. Overall, 96 sequences of the full-length Indonesian HBV genomes (genotype B, n = 54; genotype C, n = 42) were retrieved from the National Center for Biotechnology Information. Naturally occurring primary and/or compensatory drug resistance mutations were found in 6/54 (11.1%) genotype B strains and in 1/42 (2.4%) genotype C strains. The potential mutations underlying resistance to a nucleos(t)ide analog and/or pretreatment mutations were more frequent in both genotypes but more frequent in genotype C strains than in genotype B strains. The A-B interdomain region in the RT gene was more frequently mutated in genotype C than in genotype B (3.51 ± 2.53 vs. 1.08 ± 1.52, P < 0.001). Knowledge about the mutational profiles of the RT gene and changes in the surface protein may help clinicians to select the most appropriate antiviral drug and vaccination or HBV immunoglobulin regimen for management of HBV infection in Indonesia.

  13. Topical stabilized retinol treatment induces the expression of HAS genes and HA production in human skin in vitro and in vivo.

    Science.gov (United States)

    Li, Wen-Hwa; Wong, Heng-Kuan; Serrano, José; Randhawa, Manpreet; Kaur, Simarna; Southall, Michael D; Parsa, Ramine

    2017-05-01

    Skin Aging manifests primarily with wrinkles, dyspigmentations, texture changes, and loss of elasticity. During the skin aging process, there is a loss of moisture and elasticity in skin resulting in loss of firmness finally leading to skin sagging. The key molecule involved in skin moisture is hyaluronic acid (HA), which has a significant water-binding capacity. HA levels in skin decline with age resulting in decrease in skin moisture, which may contribute to loss of firmness. Clinical trials have shown that topically applied ROL effectively reduces wrinkles and helps retain youthful appearance. In the current study, ROL was shown to induce HA production and stimulates the gene expression of all three forms of hyaluronic acid synthases (HAS) in normal human epidermal keratinocytes monolayer cultures. Moreover, in human skin equivalent tissues and in human skin explants, topical treatment of tissues with a stabilized-ROL formulation significantly induced the gene expression of HAS mRNA concomitant with an increased HA production. Finally, in a vehicle-controlled human clinical study, histochemical analysis confirmed increased HA accumulation in the epidermis in ROL-treated human skin as compared to vehicle. These results show that ROL increases skin expression of HA, a significant contributing factor responsible for wrinkle formation and skin moisture, which decrease during aging. Taken together with the activity to increase collagen, elastin, and cell proliferation, these studies establish that retinol provides multi-functional activity for photodamaged skin.

  14. Transcriptional activation of a geranylgeranyl diphosphate synthase gene, GGPPS2, isolated from Scoparia dulcis by treatment with methyl jasmonate and yeast extract.

    Science.gov (United States)

    Yamamura, Y; Mizuguchi, Y; Taura, F; Kurosaki, F

    2014-10-01

    A cDNA clone, designated SdGGPPS2, was isolated from young seedlings of Scoparia dulcis. The putative amino acid sequence of the translate of the gene showed high homology with geranylgeranyl diphosphate synthase (GGPPS) from various plant sources, and the N-terminal residues exhibited the characteristics of chloroplast targeting sequence. An appreciable increase in the transcriptional level of SdGGPPS2 was observed by exposure of the leaf tissues of S. dulcis to methyl jasmonate, yeast extract or Ca(2+) ionophore A23187. In contrast, SdGGPPS1, a homologous GGPPS gene of the plant, showed no or only negligible change in the expression level upon treatment with these stimuli. The truncated protein heterologously expressed in Escherichia coli in which the putative targeting domain was deleted catalyzed the condensation of farnesyl diphosphate and isopentenyl diphosphate to liberate geranylgeranyl diphosphate. These results suggested that SdGGPPS2 plays physiological roles in methyl jasmonate and yeast extract-induced metabolism in the chloroplast of S. dulcis cells.

  15. LOX Gene Transcript Accumulation in Olive (Olea europaea L. Fruits at Different Stages of Maturation: Relationship between Volatile Compounds, Environmental Factors, and Technological Treatments for Oil Extraction

    Directory of Open Access Journals (Sweden)

    Innocenzo Muzzalupo

    2012-01-01

    Full Text Available The quality of olive oil is influenced by genetic and environmental factors and by the maturation state of drupes, but it is equally affected by technological treatments of the process. This work investigates the possible correlation between olive LOX gene transcript accumulation, evaluated in fruits collected at different stages of maturation, and chemical biomarkers of its activity. During olive fruit ripening, the same genotype harvested from two different farms shows a positive linear trend between LOX relative transcript accumulation and the content of volatile compounds present in the olive oil aroma. Interestingly, a negative linear trend was observed between LOX relative transcript accumulation and the content of volatile compounds present in the olive pastes obtained from olive fruits with and without malaxation. The changes in the olive LOX transcript accumulation reveal its environmental regulation and suggest differential physiological functions for the LOXs.

  16. Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis

    DEFF Research Database (Denmark)

    Börnsen, Lars; Christensen, Jeppe Romme; Ratzer, Rikke

    2015-01-01

    Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for......-induced CD4+ T-cell autoreactivity in interferon-β-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.......Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used...... for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels...

  17. Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC of hepatitis C patients during the first 10 weeks of treatment

    Directory of Open Access Journals (Sweden)

    Edenberg Howard J

    2008-11-01

    Full Text Available Abstract Background and Aims This study determined the kinetics of gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntron™ and ribavirin (administered by weight in HCV patients and compared it with the recently completed Virahep C study 12 in which Peginterferon-alfa2a (Pegasys™ and ribavirin were administered. Methods RNA was isolated from peripheral blood monocytes (PBMC from twenty treatment-naïve patients just before treatment (day 1 and at days 3, 6, 10, 13, 27, 42 and 70 days after treatment. Gene expression at each time was measured using Affymetrix microarrays and compared to that of day 1. Results The expression of many genes differed significantly (p ≤ 0.001 and changed at least 1.5-fold at days 3 (290 probes and 10 (255 probes, but the number dropped at days 6 (165 and 13 (142. Most genes continued to be up regulated throughout the trial period. A second group of genes, including CXCL10, CMKLR1 (chemokine receptor 1, TRAIL, IL1Rα and genes associated with complement and lipid metabolism, was transiently induced early in treatment. CDKN1C (cyclin kinase inhibitor 1 was induced early but repressed at later times. Genes induced at later times were mostly related to blood chemistry and oxygen transport. By week 10, 11 of the patients demonstrated a positive response to therapy, and the final sustained viral response (SVR was 35%. The levels of gene induction or decrease was very similar to that previously reported with Pegasys/ribavirin treatment. Conclusion The response to Pegintron/ribavirin was similar to that reported for Pegasys/ribavirin despite some differences in the amount administered. We did not detect major differences at the genomic level between patients responding to treatment or non-responders, perhaps because of limited power. Gene induction occurred in a cyclic fashion, peaking right after administration of interferon and declining between administrations of the drug. Our

  18. Lack of Association of Multidrug Resistance Gene-1 Polymorphisms with Treatment Outcome in Chronic Myeloid Leukemia Patients Treated with Imatinib

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    Yaya Kassogue

    2015-10-01

    Full Text Available Background: Despite the impressive results obtained with imatinib, inadequate response or resistance are observed in certain patients. It is known that imatinib is a substrate of a multidrug resistance gene (MDR1. Thus, interindividual genetic differences linked to single nucleotide polymorphisms in MDR1 may influence the metabolism of imatinib. The present study has aimed to examine the impact of MDR1 polymorphisms on the hematologic and cytogenetic responses in 70 chronic myeloid leukemia patients who received imatinib. Methods: We used a polymerase chain reaction followed by restriction fragment length polymorphism to identify different profiles of 1236C>T, 2677G>T and 3435C>T in MDR1. Results: The distribution of the three SNPs in responders and poor responders did not show any particular trend (P>0.05. The T allele was slightly higher in responders, but not significantly regardless of the type of SNP (40.3% vs. 33.8% for 1236C>T; 25% vs. 14.7% for 2677G>T and 33.3% vs. 22% for 3435C>T. The dominant model showed a similar trend (P>0.05. Diplotypes composed by the T allele in different exons were frequent in responders. Haplotype analysis showed that 1236C-2677G-3435C was slightly higher in poor responders (60.02% compared to responders (50.42%. However, 1236T-2677T-3435T was frequent in responders (16.98% compared to poor responders (13.1%. Overall, none of the haplotypes were associated with IM response in our cohort (global haplotype association test, P=0.39. Conclusion: The identification of 1236C>T, 2677G>T and 3435C>T polymorphisms may not be advantageous to predict imatinib response for our chronic myeloid leukemia patients.

  19. Imbalanced Protein Expression Patterns of Anabolic, Catabolic, Anti-Catabolic and Inflammatory Cytokines in Degenerative Cervical Disc Cells: New Indications for Gene Therapeutic Treatments of Cervical Disc Diseases

    Science.g