WorldWideScience

Sample records for gene products progress

  1. Gene therapy for obesity: progress and prospects.

    Science.gov (United States)

    Gao, Mingming; Liu, Dexi

    2014-06-01

    Advances in understanding the molecular basis of obesity and obesity-associated diseases have made gene therapy a vital approach in coping with this world-wide epidemic. Gene therapy for obesity aims to increase or decrease gene product in favor of lipolysis and energy expenditure, leading toward fat reduction and loss of body weight. It involves successful delivery and expression of therapeutic genes in appropriate cells. The ultimate goal of gene therapy is to restore and maintain energy homeostasis. Here we summarize progress made in recent years in identifying genes responsible for obesity and present examples where the gene therapy approach has been applied to treating or preventing obesity. Discussion on advantages and limitations of gene therapy strategies employed is provided. The intent of this review is to inspire further studies toward the development of new strategies for successful treatment of obesity and obesity-associated diseases.

  2. Current progress of polymeric gene vectors

    Institute of Scientific and Technical Information of China (English)

    ZENG Xuan; SUN YunXia; ZHUO RenXi; ZHANG XianZheng

    2011-01-01

    After over 40 years ot progress,gene therapy provides great opportunities for treating diseases from various genetic disorders,infections and cancers.The success of gene therapy largely depends on the availability of suitable gene vectors.As an attractive alternative to virus-based gene therapy,non-viral gene delivery system has been developed and investigated due to their merits including low immunogenecity,convenient operability,and large-scale manufacturability [1].Because polycations can condense with DNA as a result of electrostatic interactions,form nanosize polyplexes,and protect DNA from degradation by DNase,cationic polymer becomes a major type of non-viral gene delivery vectors (Figure 1) [2].A wide range of polymeric vectors have been developed and investigated in the past decade,such as polyethylenimine (PEI)-based vectors,poly(L-lysine) (PLL)-based vectors,dendrimer-based vectors,polypeptide-based vectors,and chitosan-based vectors [3].However,unlike viral vectors that have the ability to infect host cells and overcome cellular barriers through the course of evolution,nonviral gene vectors exhibit Significantly reduced transfection efficiency as they are obstructed by various extra- and intracellular barriers,including serum proteins in blood stream,cell membrane,endosomal compartment and nuclear membrane [4].

  3. Recent progress in gene therapy for hemophilia.

    Science.gov (United States)

    Chuah, Marinee K; Nair, Nisha; VandenDriessche, Thierry

    2012-06-01

    Hemophilia A and B are X-linked monogenic disorders caused by deficiencies in coagulation factor VIII (FVIII) and factor IX (FIX), respectively. Current treatment for hemophilia involves intravenous infusion of clotting factor concentrates. However, this does not constitute a cure, and the development of gene-based therapies for hemophilia to achieve prolonged high level expression of clotting factors to correct the bleeding diathesis are warranted. Different types of viral and nonviral gene delivery systems and a wide range of different target cells, including hepatocytes, skeletal muscle cells, hematopoietic stem cells (HSCs), and endothelial cells, have been explored for hemophilia gene therapy. Adeno-associated virus (AAV)-based and lentiviral vectors are among the most promising vectors for hemophilia gene therapy. Stable correction of the bleeding phenotypes in hemophilia A and B was achieved in murine and canine models, and these promising preclinical studies prompted clinical trials in patients suffering from severe hemophilia. These studies recently resulted in the first demonstration that long-term expression of therapeutic FIX levels could be achieved in patients undergoing gene therapy. Despite this progress, there are still a number of hurdles that need to be overcome. In particular, the FIX levels obtained were insufficient to prevent bleeding induced by trauma or injury. Moreover, the gene-modified cells in these patients can become potential targets for immune destruction by effector T cells, specific for the AAV vector antigens. Consequently, more efficacious approaches are needed to achieve full hemostatic correction and to ultimately establish a cure for hemophilia A and B.

  4. Gene therapy for hemoglobinopathies: progress and challenges.

    Science.gov (United States)

    Dong, Alisa; Rivella, Stefano; Breda, Laura

    2013-04-01

    Hemoglobinopathies are genetic inherited conditions that originate from the lack or malfunction of the hemoglobin (Hb) protein. Sickle cell disease (SCD) and thalassemia are the most common forms of these conditions. The severe anemia combined with complications that arise in the most affected patients raises the necessity for a cure to restore hemoglobin function. The current routine therapies for these conditions, namely transfusion and iron chelation, have significantly improved the quality of life in patients over the years, but still fail to address the underlying cause of the diseases. A curative option, allogeneic bone marrow transplantation is available, but limited by the availability of suitable donors and graft-vs-host disease. Gene therapy offers an alternative approach to cure patients with hemoglobinopathies and aims at the direct recovery of the hemoglobin function via globin gene transfer. In the last 2 decades, gene transfer tools based on lentiviral vector development have been significantly improved and proven curative in several animal models for SCD and thalassemia. As a result, clinical trials are in progress and 1 patient has been successfully treated with this approach. However, there are still frontiers to explore that might improve this approach: the stoichiometry between the transgenic hemoglobin and endogenous hemoglobin with respect to the different globin genetic mutations; donor cell sourcing, such as the use of induced pluripotent stem cells (iPSCs); and the use of safer gene insertion methods to prevent oncogenesis. With this review we will provide insights about (1) the different lentiviral gene therapy approaches in mouse models and human cells; (2) current and planned clinical trials; (3) hurdles to overcome for clinical trials, such as myeloablation toxicity, insertional oncogenesis, and high vector expression; and (4) future perspectives for gene therapy, including safe harbors and iPSCs technology.

  5. Mutation avoidance and DNA repair proficiency in Ustilago maydis are differentially lost with progressive truncation of the REC1 gene product

    Energy Technology Data Exchange (ETDEWEB)

    Onel, K.; Thelen, M.P.; Ferguson, D.O.; Bennett, R.L.; Holloman, W.K. [Cornell Univ. Medical College, NY, NY (United States)

    1995-10-01

    The REC1 gene of Ustilago maydis has an uninterrupted open reading frame, predicted from the genomic sequence to encode a protein of 522 amino acid residues. Nevertheless, an intron is present, and functional activity of the gene in mitotic cells requires an RNA processing event to remove the intron. This results in a change in reading frame and production of a protein of 463 amino acid residues. The 3{prime}{r_arrow}5{prime} exonuclease activity of proteins derived form the REC1 genomic open reading frame, the intronless open reading frame, and several mutants was investigated. The mutants included a series of deletions constructed by removing restriction fragments at the 3{prime} end of the cloned REC1 gene and a set of mutant alleles previously isolated in screens for radiation sensitivity. The results indicated that elimination of the C-terminal third of the protein did not result in a serious reduction in 3{prime}{r_arrow}5{prime} exonuclease activity, but deletion into the midsection caused a severe loss of activity. The biological activity of the rec1-1 allele, which encodes a truncated polypeptide with full 3{prime}{r_arrow}5{prime} exonuclease activity, and the rec1-5 allele, which encodes a more severely truncated polypeptide with no exonuclease activity, was investigated. The two mutants were equally sensitive to the lethal effect of UV light, but the spontaneous mutation rate was elevated 10-fold over the wild-type rate in the rec1-1 mutant and 100-fold in the rec1-5 mutant. The elevated spontaneous mutation rate correlated with the ablation of exonuclease activity, but the radiation sensitivity did not. These results indicate that the C-terminal portion of the Rec1 protein is not essential for exonuclease activity but is crucial in the role of REC1 in DNA damage repair. 49 refs., 3 figs., 1 tab.

  6. Recent progresses in gene delivery-based bone tissue engineering.

    Science.gov (United States)

    Lu, Chia-Hsin; Chang, Yu-Han; Lin, Shih-Yeh; Li, Kuei-Chang; Hu, Yu-Chen

    2013-12-01

    Gene therapy has converged with bone engineering over the past decade, by which a variety of therapeutic genes have been delivered to stimulate bone repair. These genes can be administered via in vivo or ex vivo approach using either viral or nonviral vectors. This article reviews the fundamental aspects and recent progresses in the gene therapy-based bone engineering, with emphasis on the new genes, viral vectors and gene delivery approaches.

  7. Progress of gene targeting in mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Gene targeting is a powerful approach of study- ing the genefunction in vivo. Specific genetic modifications, including simple gene disruption, point mutations, large chromosomal deletions and rearrangements, targeted incor- poration of foreign genes, could be introduced into the mouse genome by gene targeting. Recent studies make it possible to do the gene targeting with temporal and spatial control.

  8. Recent progress in polymer-based gene delivery vectors

    Institute of Scientific and Technical Information of China (English)

    HUANG Shiwen; ZHUO Renxi

    2003-01-01

    The gene delivery system is one of the three components of a gene medicine, which is the bottle neck of current gene therapy. Nonviral vectors offer advantages over the viral system of safety, ease of manufacturing, etc. As important nonviral vectors, polymer gene delivery systems have gained increasing attention and have begun to show increasing promising. In this review, the fundamental and recent progress of polymer-based gene delivery vectors is reviewed.

  9. Recent progress in radioisotope production in Vietnam

    Energy Technology Data Exchange (ETDEWEB)

    Le Van So [Radioisotope Dept., Nuclear Research Institute, Dalat (Viet Nam)

    1998-10-01

    This is a report on the recent progress in radioisotope production in Vietnam. Using a nuclear research reactor of 500 KW with continuous operation cycles of 100 hours a month, the production of some important radioisotopes used in nuclear medicine and research was routinely carried out. More than 80 per cent of irradiation capacity of reactor for radioisotope production were exploited. The radioactivity of more than 150 Ci of {sup 131}I, {sup 99}Mo-{sup 99m}Tc, {sup 32}P, {sup 51}Cr, {sup 153}Sm, {sup 46}Sc, {sup 192}Ir was produced annually. Radiopharmaceuticals such as {sup 131}I-Hippuran and in-vivo Kits for {sup 99m}Tc labelling were also prepared routinely and regularly. More than 10 in-vivo Kits including modern radiopharmaceuticals such as HmPAO kit were supplied to hospitals in Vietnam. The research on the improvement of dry distillation technology for production of {sup 131}I was carried out. As a result obtained a new distillation apparatus made from glass was successfully put to routine use in place of expensive quartz distillation furnace. We have also continued the research programme on the development of {sup 99m}Tc generators using low power research reactors. Gel technology using Zr- and Ti- molybdate gel columns for {sup 99m}Tc generator production was developed and improved continually. Portable {sup 99m}Tc generator using Zr-({sup 99}Mo) molybdate gel column and ZISORB adsorbent column for {sup 99m}Tc concentration were developed. The ZISORB adsorbent of high adsorption capacity for {sup 99}Mo and other parent radionuclides was also studied for the development purpose of alternative technology of {sup 99m}Tc and other different radionuclide generator systems. The studies on the preparation of therapeutic radiopharmaceuticals labelling with {sup 153}Sm and {sup 131}I such as {sup 153}Sm-EDTMP, {sup 131}I-MIBG were carried out. (author)

  10. Inflammatory Bowel Disease: Progress Towards a Gene

    Directory of Open Access Journals (Sweden)

    David A van Heel

    2000-01-01

    Full Text Available The pathogenesis of ulcerative colitis (UC and Crohn’s disease (CD is still unknown, but the importance of genetic susceptibility has been clearly shown by epidemiological data from family and twin studies. Linkage studies have identified two susceptibility loci for inflammatory bowel disease (IBD on chromosomes 12 and 16. Importantly, these linkages have been replicated by independent investigators, and studies of positional candidates within these regions continue, together with fine mapping strategies. Regions of ’suggestive’ linkage on chromosomes 1, 3, 4, 6, 7, 10, 22 and X have also been reported in individual studies. Other important candidate genes investigated include the interleukin-1 receptor antagonist, MUC3 and genes of the human leukocyte antigen (HLA system. The apparently conflicting data in different studies from around the world may be explained by ethnic differences, case mix and genetic heterogeneity. Replicated class II HLA associations include HLA DRB1*0103 and DR2 (DRB1*1502, involved in UC susceptibility, and HLA DRB1*03 and DR4 as resistance alleles for CD and UC respectively. Animal studies have provided insights from targeted mutations and quantitative trait locus analysis. The goals of continuing research include narrowing the regions of linkages and analysis of candidate genes, and possibly the application of newly developed methods using single nucleotide polymorphisms. Advances in IBD genetics hold the potential to provide knowledge about the disease pathogenesis at the molecular level, with ensuing benefits for clinical practice.

  11. [Progress in gene therapy study of Leber congenital amaurosis].

    Science.gov (United States)

    Pan, Shan-Shan; Zheng, Qin-Xiang; Li, Wen-Sheng; Pang, Ji-Jing

    2011-01-01

    Leber congenital amaurosis (LCA) is an early onset retinal dystrophy that causes severe visual impairment. With the development of molecular genetics and the therapeutic gene replacement technology, the adeno-associated viral (AAV) vector-mediated gene therapy for LCA achieved encouraging progress in the past decade. The success of the Phase I clinical trials of human RPE65 gene therapy for LCA II patients makes it a pioneer in the field of retinal gene therapy and brings light to the cure of other hereditary retinopathy. This article briefly reviews the recent developments in the preclinical animal experiments and Phase I clinical trials for LCA.

  12. Progress in gene transfer by germ cells in mammals

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Use of germ cells as vectors for transgenesis in mammals has been well developed and offers exciting prospects for experimental and applied biology, agricultural and medical sciences.Such approach is referred to as either male germ cell mediated gene transfer (MGCMGT)or female germ cell mediated gene transfer(FGCMGT)technique.Sperm-mediated gene transfer (SMGT),including its alternative method,testis-mediated gene transfer(TMGT),becomes an established and reliable method for transgenesis.They have been extensively used for producing transgenic animals.The newly developed approach of FGCMGT,ovary-mediated gene transfer(OMGT) is also a novel and useful tool for efficient transgenesis.This review highlights an overview of the recent progress in germ cell mediated gene transfer techniques,methods developed and mechanisms of nucleic acid uptake by germ cells.

  13. Recent progress in development of radioisotope production

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Byung Mok [HANARO Center, Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1998-10-01

    The Korea multipurpose research reactor, HANARO(Hi-flux Advanced Neutron Application Reactor) is designed and constructed to obtain high density neutron flux (max. 5x10{sup 14} n/cm{sup 2}{center_dot}sec) with relatively low thermal output (30 MW) in order to utilize for various studies such as fuel and material test, radioisotope production, neutron activation analysis, neutron beam experiment, neutron transmutation doping, etc. HANARO has 32 vertical channels (3 in-core, 4 out-core, 25 reflector) and 7 horizontal channels. KAERI has constructed 4 concrete hot cells for production of Co-60, Ir-192, etc. and 6 lead hot cells for production of medical RIs(I-131, Mo-99, etc.). Other 11 lead hot cells will be completed by Feb. 1998 for production of Sm-153, Dy-165, Ho-166, etc. Clean room facilities were installed for production of radiopharmaceuticals. (author)

  14. Progress in Chimeric Vector and Chimeric Gene Based Cardiovascular Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    HU Chun-Song; YOON Young-sup; ISNER Jeffrey M.; LOSORDO Douglas W.

    2003-01-01

    Gene therapy for cardiovascular diseases has developed from preliminary animal experiments to clinical trials. However, vectors and target genes used currently in gene therapy are mainly focused on viral, nonviral vector and single target gene or monogene. Each vector system has a series of advantages and limitations. Chimeric vectors which combine the advantages of viral and nonviral vector,chimeric target genes which combine two or more target genes and novel gene delivery modes are being developed. In this article, we summarized the progress in chimeric vectors and chimeric genes based cardiovascular gene therapy, which including proliferative or occlusive vascular diseases such as atheroslerosis and restenosis, hypertonic vascular disease such as hypertension and cardiac diseases such as myocardium ischemia, dilated cardiomyopathy and heart failure, even heart transplantation. The development of chimeric vector, chimeric gene and their cardiovascular gene therapy is promising.

  15. [Research progress in relative crystallin genes of congenital cataract].

    Science.gov (United States)

    Wang, D D; Yang, H J; Yi, J L

    2016-02-01

    Congenital cataract is the common cause of visual disability in children. Nearly one third of congenital cataract cases may have a related genetic mutation. With the development of molecular genetics, especially gentechnik, more and more genes, such as crystallin genes, membrane protein genes, eytoskeletal protein genes and regulatory protein genes have been confirmed to participate in the process of congenital cataract. Furthermore, crystallin genes account for most of these genes and the crystallin has the highest amount of the whole protein in lens.It has been found that nearly one hundred mutations in crystallin genes are associated with the onset of congenital cataract. Researchers are exploring how these mutations further affect the function of cellular biology and eventually lead to cataract. Although more and more research results gradually reveal the pathogenesis of congenital cataract from the level of gene and protein, the specific pathogenesis is still unclear. The recent progression about inherited congenital cataract related with crysallin genes is summarized in this review.

  16. [Progress on X-linked mental retardation related gene JARID1C].

    Science.gov (United States)

    Lei, Xu; Gao, Xiao-Cai; Zhang, Fu-Chang

    2010-03-01

    JARID1C is one of the genes related to X-linked mental retardation. Its express product influences transcription and expression of the related genes in brain nervous system, and may be associated with human cognitive ability. Study on the functions of JARID1C not only helps to understand its molecular role in mental retardation and human cognitive ability, but also provides references for clinical diagnosis and prevention of mental retardation. This article reviews the progresses on JARID1C in location, isolation, physiological functions, and cognitive functions of its encoding product. The future re-search work of JARID1C is also discussed.

  17. Progress and Challenges in Microalgal Biodiesel Production

    Science.gov (United States)

    Mallick, Nirupama; Bagchi, Sourav K.; Koley, Shankha; Singh, Akhilesh K.

    2016-01-01

    The last decade has witnessed a tremendous impetus on biofuel research due to the irreversible diminution of fossil fuel reserves for enormous demands of transportation vis-a-vis escalating emissions of green house gasses (GHGs) into the atmosphere. With an imperative need of CO2 reduction and considering the declining status of crude oil, governments in various countries have not only diverted substantial funds for biofuel projects but also have introduced incentives to vendors that produce biofuels. Currently, biodiesel production from microalgal biomass has drawn an immense importance with the potential to exclude high-quality agricultural land use and food safe-keeping issues. Moreover, microalgae can grow in seawater or wastewater and microalgal oil can exceed 50–60% (dry cell weight) as compared with some best agricultural oil crops of only 5–10% oil content. Globally, microalgae are the highest biomass producers and neutral lipid accumulators contending any other terrestrial oil crops. However, there remain many hurdles in each and every step, starting from strain selection and lipid accumulation/yield, algae mass cultivation followed by the downstream processes such as harvesting, drying, oil extraction, and biodiesel conversion (transesterification), and overall, the cost of production. Isolation and screening of oleaginous microalgae is one pivotal important upstream factor which should be addressed according to the need of freshwater or marine algae with a consideration that wild-type indigenous isolate can be the best suited for the laboratory to large scale exploitation. Nowadays, a large number of literature on microalgal biodiesel production are available, but none of those illustrate a detailed step-wise description with the pros and cons of the upstream and downstream processes of biodiesel production from microalgae. Specifically, harvesting and drying constitute more than 50% of the total production costs; however, there are quite a less

  18. Progress and Challenges in Microalgal Biodiesel Production.

    Science.gov (United States)

    Mallick, Nirupama; Bagchi, Sourav K; Koley, Shankha; Singh, Akhilesh K

    2016-01-01

    The last decade has witnessed a tremendous impetus on biofuel research due to the irreversible diminution of fossil fuel reserves for enormous demands of transportation vis-a-vis escalating emissions of green house gasses (GHGs) into the atmosphere. With an imperative need of CO2 reduction and considering the declining status of crude oil, governments in various countries have not only diverted substantial funds for biofuel projects but also have introduced incentives to vendors that produce biofuels. Currently, biodiesel production from microalgal biomass has drawn an immense importance with the potential to exclude high-quality agricultural land use and food safe-keeping issues. Moreover, microalgae can grow in seawater or wastewater and microalgal oil can exceed 50-60% (dry cell weight) as compared with some best agricultural oil crops of only 5-10% oil content. Globally, microalgae are the highest biomass producers and neutral lipid accumulators contending any other terrestrial oil crops. However, there remain many hurdles in each and every step, starting from strain selection and lipid accumulation/yield, algae mass cultivation followed by the downstream processes such as harvesting, drying, oil extraction, and biodiesel conversion (transesterification), and overall, the cost of production. Isolation and screening of oleaginous microalgae is one pivotal important upstream factor which should be addressed according to the need of freshwater or marine algae with a consideration that wild-type indigenous isolate can be the best suited for the laboratory to large scale exploitation. Nowadays, a large number of literature on microalgal biodiesel production are available, but none of those illustrate a detailed step-wise description with the pros and cons of the upstream and downstream processes of biodiesel production from microalgae. Specifically, harvesting and drying constitute more than 50% of the total production costs; however, there are quite a less number

  19. Current Progress in Therapeutic Gene Editing for Monogenic Diseases.

    Science.gov (United States)

    Prakash, Versha; Moore, Marc; Yáñez-Muñoz, Rafael J

    2016-03-01

    Programmable nucleases allow defined alterations in the genome with ease-of-use, efficiency, and specificity. Their availability has led to accurate and widespread genome engineering, with multiple applications in basic research, biotechnology, and therapy. With regard to human gene therapy, nuclease-based gene editing has facilitated development of a broad range of therapeutic strategies based on both nonhomologous end joining and homology-dependent repair. This review discusses current progress in nuclease-based therapeutic applications for a subset of inherited monogenic diseases including cystic fibrosis, Duchenne muscular dystrophy, diseases of the bone marrow, and hemophilia and highlights associated challenges and future prospects.

  20. Research Progress on Pseudorabies Gene-deleted Vaccine

    Institute of Scientific and Technical Information of China (English)

    JIN Sheng-zao; CHEN Huang-chun; XIONG Fu

    2002-01-01

    Pseudorabies is caused by pseudorabies virus (PrV), which is a member of family Herpesviridae, subfamily Alphaherpesvirinae and is the agent of acute infectious disease in many domestic and wild animals. Swine was the natural host and reservior of PRV, which inflicts major economic loss in pig industries world wide. Immunization with safe, effective vaccine is main measurements to prevent the disease.In this assay, research progress on PRV gene-deleted vaccine used extensively today was discussed.

  1. Progress of Validation of GOSAT Standard Products

    Science.gov (United States)

    Uchino, Osamu

    2010-05-01

    Isamu Morino, Tomoaki Tanaka, Yuki Miyamoto, Yukio Yoshida, Tatsuya Yokota, Toshinobu Machida National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan Debra Wunch, Paul Wennberg Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, California, USA Geoffrey Toon Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California, USA Thorsten Warneke, Justus Notholt Institute of Environmental Physics, University of Bremen, Bremen, Germany David Griffith, Nicholas Deutscher Department of Chemistry, University of Wollongong, Wollongong New South Wales, Australia Vanessa Sherlock National Institute of Water and Atmospheric Research, Lauder, Central Otago, New Zealand Hidekazu Matsueda, Yousuke Sawa Meteorological Research Institute, 1-1 Nagamine, Tsukuba, Ibaraki 305-0052, Japan Colm Sweeney, Pieter Tans Earth System Research Laboratory, NOAA, Boulder, USA The Greenhouse gases Observing SATellite (GOSAT), launched on 23 January 2009, is the world's first satellite dedicated to measuring the concentrations of the two major greenhouse gases, carbon dioxide (CO2) and methane (CH4), from space. The data measured with the Thermal And Near-infrared Sensor for carbon Observation Fourier Transform Spectrometer (TANSO-FTS) and the Cloud and Aerosol Imager (TANSO-CAI) are processed into several types of data products. Column abundances of CO2 and CH4 (TANSO-FTS SWIR L2 data product) are retrieved from the FTS L1B spectral data. Validation of the FTS Level 2 data product is critical since the data is used for generating the FTS Level 3 (global distributions of column-averaged mixing ratio data of XCO2 and XCH4) and the FTS Level 4 (regional CO2 fluxes and three dimensional distribution of CO2 calculated from the estimated fluxes) products. The reference data to be used for validating abundances are required to have uncertainties of less than 1.0 % (0.3 % or 1 ppm is desirable) for CO2 and 2.0 % for CH4. Ground

  2. Identification of genes and gene products necessary for bacterial bioluminescence.

    OpenAIRE

    Engebrecht, J; Silverman, M.

    1984-01-01

    Expression of luminescence in Escherichia coli was recently achieved by cloning genes from the marine bacterium Vibrio fischeri. One DNA fragment on a hybrid plasmid encoded regulatory functions and enzymatic activities necessary for light production. We report the results of a genetic analysis to identify the luminescence genes (lux) that reside on this recombinant plasmid. lux gene mutations were generated by hydroxylamine treatment, and these mutations were ordered on a linear map by compl...

  3. Gene therapy for PIDs: progress, pitfalls and prospects.

    Science.gov (United States)

    Mukherjee, Sayandip; Thrasher, Adrian J

    2013-08-10

    Substantial progress has been made in the past decade in treating several primary immunodeficiency disorders (PIDs) with gene therapy. Current approaches are based on ex-vivo transfer of therapeutic transgene via viral vectors to patient-derived autologous hematopoietic stem cells (HSCs) followed by transplantation back to the patient with or without conditioning. The overall outcome from all the clinical trials targeting different PIDs has been extremely encouraging but not without caveats. Malignant outcomes from insertional mutagenesis have featured prominently in the adverse events associated with these trials and have warranted intense pre-clinical investigation into defining the tendencies of different viral vectors for genomic integration. Coupled with issues pertaining to transgene expression, the therapeutic landscape has undergone a paradigm shift in determining safety, stability and efficacy of gene therapy approaches. In this review, we aim to summarize the progress made in the gene therapy trials targeting ADA-SCID, SCID-X1, CGD and WAS, review the pitfalls, and outline the recent advancements which are expected to further enhance favourable risk benefit ratios for gene therapeutic approaches in the future.

  4. The role of S100 genes in breast cancer progression.

    LENUS (Irish Health Repository)

    McKiernan, Eadaoin

    2011-06-01

    The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman\\'s correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.

  5. The role of S100 genes in breast cancer progression.

    LENUS (Irish Health Repository)

    McKiernan, Eadaoin

    2012-02-01

    The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman\\'s correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.

  6. [The recent research progress of chemistry of marine natural products].

    Science.gov (United States)

    Shi, Qing-wen; Li, Li-geng; Wang, Yu-fang; Huo, Chang-hong; Zhang, Man-li

    2010-10-01

    Ocean is a unique and excellent resource that provides a diverse array of intriguing natural products. Marine natural products have demonstrated significant and extremely potent biological activities and have captured the attention of natural products chemists in the past few decades. It is increasingly recognized that a wealth of fascinating natural products and novel chemical entities will play a dominant role in the discovery of useful leads for the development of pharmaceutical agents and provide useful probes to lead to breakthroughs in a variety of life-science fields. This article focused on the research progress of chemistry of marine natural products in recent five years.

  7. Correlation between Gene Expression and Osteoarthritis Progression in Human

    Directory of Open Access Journals (Sweden)

    Leilei Zhong

    2016-07-01

    Full Text Available Osteoarthritis (OA is a multifactorial disease characterized by gradual degradation of joint cartilage. This study aimed to quantify major pathogenetic factors during OA progression in human cartilage. Cartilage specimens were isolated from OA patients and scored 0–5 according to the Osteoarthritis Research Society International (OARSI guidelines. Protein and gene expressions were measured by immunohistochemistry and qPCR, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assays were used to detect apoptotic cells. Cartilage degeneration in OA is a gradual progress accompanied with gradual loss of collagen type II and a gradual decrease in mRNA expression of SOX9, ACAN and COL2A1. Expression of WNT antagonists DKK1 and FRZB was lost, while hypertrophic markers (RUNX2, COL10A1 and IHH increased during OA progression. Moreover, DKK1 and FRZB negatively correlated with OA grading, while RUNX2 and IHH showed a significantly positive correlation with OA grading. The number of apoptotic cells was increased with the severity of OA. Taken together, our results suggested that genetic profiling of the gene expression could be used as markers for staging OA at the molecular level. This helps to understand the molecular pathology of OA and may lead to the development of therapies based on OA stage.

  8. Progression in vowel production: comparing deaf and hearing children

    NARCIS (Netherlands)

    van der Stelt, J.; Pols, L.C.W.; Wempe, T.G.

    2003-01-01

    An interesting but so far neglected topic in the development of infant sound production is the hypothesized progression toward adult vowel quality. Likely, this process is quite different for normally hearing babies and for deaf babies. A band filtering analysis method is used to measure the

  9. Natural products chemistry research 2010's progress in China.

    Science.gov (United States)

    Ye, Yang; Li, Xi-Qiang; Tang, Chun-Ping; Yao, Sheng

    2012-01-01

    This article reviews the progresses made by Chinese scientists in the field of natural products chemistry in 2010. Selected compounds with unique structural features and/or promising bioactivities were described herein on the basis of structural types. Copyright © 2012 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  10. Global gene expression profile progression in Gaucher disease mouse models

    Directory of Open Access Journals (Sweden)

    Zhang Wujuan

    2011-01-01

    Full Text Available Abstract Background Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells in visceral organs and their abnormal functions are obscure. Results To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct Gba1 point-mutated mice (V394L/V394L and D409 V/null. About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change, representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk of INFγ-regulated pro-inflammatory (13 and IL-4-regulated anti-inflammatory (11 cytokine/mediator networks showed tissue differential profiles in the lung and liver of the Gba1 mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the Gba1 mutation. Conclusions Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.

  11. Research Progress in Large-scale Production of Plasmid DNA for Gene Therapy%基因治疗用质粒DNA生产面临的问题及研究进展

    Institute of Scientific and Technical Information of China (English)

    胡春生; 张庆林; 张通

    2011-01-01

    Plasmid DNA encoding treatment gene for pharmaceutical applications was approved into the clinical trials.A pre-requisite to the success of plasmid-based therapies is the development of effective production of plasmid DNA.However, at present, there are several problems and bottlenecks in large-scale production of pharmaceutical plasmid DNA.Such as vector construction, cell lysis, bacteria chromosome DNA removing,bacteria endotoxin removing and quality-control in production process.The downstream for the large-scale production of plasmid DNA, limitations and the strategies used to obtain a final product that meets specifications was reviewed.%基因治疗已成为21世纪一些重大疾病的有效治疗策略,目前携带治疗基因的重组质粒已作为基因药物进入临床研究.对用于基因治疗的生物制品的生产与质量控制都有相当严格的要求.虽然已建立大规模符合药学规格的质粒DNA生产工艺,能满足临床需求,但在这些生产工艺中还存在一些难以克服的瓶颈,如:载体构建、细胞裂解、细菌染色体DNA去除、细菌内毒素去除、生产过程中质量控制等.就近年来大规模生产临床用质粒DNA遇到的相关问题及解决方案作一综述.

  12. On the bursting of gene products

    CERN Document Server

    Yvinec, Romain

    2011-01-01

    In this article we demonstrate that the so-called bursting production of molecular species during gene expression may be an artifact caused by low time resolution in experimental data collection and not an actual burst in production. We reach this conclusion through an analysis of a two-stage and binary model for gene expression, and demonstrate that in the limit when mRNA degradation is much faster than protein degradation they are equivalent. The negative binomial distribution is shown to be a limiting case of the binary model for fast "on to off" state transitions and high values of the ratio between protein synthesis and degradation rates. The gene products population increases by unity but multiple times in a time interval orders of magnitude smaller than protein half-life or the precision of the experimental apparatus employed in its detection. This rare-and-fast one-by-one protein synthesis has been interpreted as bursting.

  13. Progress and Prospects of Anti-HBV Gene Therapy Development

    Directory of Open Access Journals (Sweden)

    Mohube B. Maepa

    2015-07-01

    Full Text Available Despite the availability of an effective vaccine against hepatitis B virus (HBV, chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA. For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti-HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV.

  14. Research progress on isolation and cloning of functional genes in tea plants

    Institute of Scientific and Technical Information of China (English)

    MA Chunlei; CHEN Liang

    2007-01-01

    Tea,which has many sanitarian functions,is one of the most popular non-alcoholic soft and healthy beverages in the world.In many countries,as well as in China,tea (Camellia sinensis) is an important cash crop.It has great value as a source of secondary metabolic products.Molecular biology of tea plants has been one of the most active and kinetic research fields of tea science for the last decade.Isolation and cloning of important functional genes of tea plants have a critical significance on elucidating the molecular mechanism of high quality,yield and resistance,as well as genetic manipulating via biotechnological approaches for tea plants.In this paper,we introduced the research progress on the isolation and cloning of functional genes in tea plants.In addition,the brief prospect on the research of functional genes of tea plants in the near future is also given out.

  15. [Immune response genes products in human physiology].

    Science.gov (United States)

    Khaitov, R M; Alekseev, L P

    2012-09-01

    Current data on physiological role of human immune response genes' proteomic products (antigens) are discussed. The antigens are specified by a very high level of diversity that mediates a wide specter ofphysiological functions. They actually provide integrity and biological stability of human as species. These data reveal new ideas on many pathological processes as well as drafts new approaches for prophylaxis and treatment.

  16. GENE EXPRESSION PROFILING OF GANGLIOGLIOMA MALIGNANT PROGRESSION BY cDNA ARRAY

    Institute of Scientific and Technical Information of China (English)

    ZHANG Quan-bin; HUANG Qiang; DONG Jun; WANG Ai-dong; SUN Ji-yong; LAN Qing; HU Geng-xi

    2005-01-01

    Objective: To establish gene expression profiles associated with malignant progression of ganglioglioma. Methods: The primary and two recurrent glioma specimens were collected intraoperatively from the same patient who experienced tumor transformation into anaplastic astrocytoma and glioblastoma multiform for the first and second recurrence respectively. Gene expression was assayed through cDNA array and bioinformatics analysis. Results: A total of 197 differentially expressed genes with differential ratio value more than 3 compared with normal brain tissue were obtained. Among 109 functionally denned genes, those associated with development ranked the first by frequency, followed by genes associated with metabolism, differentiation, signal transduction and so on. As a result of cluster analysis among 368 genes, eleven genes were up regulated with malignant progression, while six genes were down regulated. Conclusion: Gene expression profiles associated with malignant progression of glioma were successfully established, which provides a powerful tool for research on molecular mechanisms of malignant progression of gliomas.

  17. [Ribozyme riboswitch based gene expression regulation systems for gene therapy applications: progress and challenges].

    Science.gov (United States)

    Feng, Jing-Xian; Wang, Jia-wen; Lin, Jun-sheng; Diao, Yong

    2014-11-01

    Robust and efficient control of therapeutic gene expression is needed for timing and dosing of gene therapy drugs in clinical applications. Ribozyme riboswitch provides a promising building block for ligand-controlled gene-regulatory system, based on its property that exhibits tunable gene regulation, design modularity, and target specificity. Ribozyme riboswitch can be used in various gene delivery vectors. In recent years, there have been breakthroughs in extending ribozyme riboswitch's application from gene-expression control to cellular function and fate control. High throughput screening platforms were established, that allow not only rapid optimization of ribozyme riboswitch in a microbial host, but also straightforward transfer of selected devices exhibiting desired activities to mammalian cell lines in a predictable manner. Mathematical models were employed successfully to explore the performance of ribozyme riboswitch quantitively and its rational design predictably. However, to progress toward gene therapy relevant applications, both precision rational design of regulatory circuits and the biocompatibility of regulatory ligand are still of crucial importance.

  18. Connected speech production in three variants of primary progressive aphasia.

    Science.gov (United States)

    Wilson, Stephen M; Henry, Maya L; Besbris, Max; Ogar, Jennifer M; Dronkers, Nina F; Jarrold, William; Miller, Bruce L; Gorno-Tempini, Maria Luisa

    2010-07-01

    Primary progressive aphasia is a clinical syndrome defined by progressive deficits isolated to speech and/or language, and can be classified into non-fluent, semantic and logopenic variants based on motor speech, linguistic and cognitive features. The connected speech of patients with primary progressive aphasia has often been dichotomized simply as 'fluent' or 'non-fluent', however fluency is a multidimensional construct that encompasses features such as speech rate, phrase length, articulatory agility and syntactic structure, which are not always impacted in parallel. In this study, our first objective was to improve the characterization of connected speech production in each variant of primary progressive aphasia, by quantifying speech output along a number of motor speech and linguistic dimensions simultaneously. Secondly, we aimed to determine the neuroanatomical correlates of changes along these different dimensions. We recorded, transcribed and analysed speech samples for 50 patients with primary progressive aphasia, along with neurodegenerative and normal control groups. Patients were scanned with magnetic resonance imaging, and voxel-based morphometry was used to identify regions where atrophy correlated significantly with motor speech and linguistic features. Speech samples in patients with the non-fluent variant were characterized by slow rate, distortions, syntactic errors and reduced complexity. In contrast, patients with the semantic variant exhibited normal rate and very few speech or syntactic errors, but showed increased proportions of closed class words, pronouns and verbs, and higher frequency nouns, reflecting lexical retrieval deficits. In patients with the logopenic variant, speech rate (a common proxy for fluency) was intermediate between the other two variants, but distortions and syntactic errors were less common than in the non-fluent variant, while lexical access was less impaired than in the semantic variant. Reduced speech rate was

  19. Effects of iodonium-class flavin dehydrogenase inhibitors on growth, reactive oxygen production, cell cycle progression, NADPH oxidase 1 levels, and gene expression in human colon cancer cells and xenografts.

    Science.gov (United States)

    Doroshow, James H; Gaur, Shikha; Markel, Susan; Lu, Jiamo; van Balgooy, Josephus; Synold, Timothy W; Xi, Bixin; Wu, Xiwei; Juhasz, Agnes

    2013-04-01

    Iodonium-class flavoprotein dehydrogenase inhibitors have been demonstrated to possess antiproliferative potential and to inhibit reactive oxygen production in human tumor cells, although the mechanism(s) that explains the relationship between altered cell growth and the generation of reactive oxygen species (ROS) remains an area of active investigation. Because of the ability of these compounds to inhibit the activity of flavoprotein-containing epithelial NADPH oxidases, we chose to examine the effects of several iodonium-class flavoprotein inhibitors on human colon cancer cell lines that express high, functional levels of a single such oxidase (NADPH oxidase 1, or Nox1). We found that diphenyleneiodonium (DPI), di-2-thienyliodonium (DTI), and iodonium diphenyl inhibited the growth of Caco2, HT-29, and LS-174T colon cancer cells at concentrations (10-250nM for DPI, 0.5-2.5μM for DTI, and 155nM to 10μM for iodonium diphenyl) substantially lower than needed for DU145 human prostate cancer cells, which do not possess functional NADPH oxidase activity. Drug treatment was associated with decreased H2O2 production and diminished intracellular ROS levels, lasting up to 24h, after short-term (1-h) exposure to the iodonium analogs. Decreased tumor cell proliferation was caused, in part, by a profound block in cell cycle progression at the G1/S interface in both LS-174T and HT-29 cells exposed to either DPI or DTI; and the G1 block was produced, for LS-174T cells, by upregulation of p27 and a drug concentration-related decrease in the expression of cyclins D1, A, and E that was partially prevented by exogenous H2O2. Not only did DPI and DTI decrease intracellular ROS, they both also significantly decreased the mRNA expression levels of Nox1, potentially contributing to the prolonged reduction in tumor cell reactive oxygen levels. We also found that DPI and DTI significantly decreased the growth of both HT-29 and LS-174T human tumor xenografts, at dose levels that produced

  20. [Progress on biodiesel production with enzymatic catalysis in China].

    Science.gov (United States)

    Tan, Tianwei; Lu, Jike; Nie, Kaili; Zhang, Haixia; Deng, Li; Wang, Fang

    2010-07-01

    This paper reports the progress of biodiesel production with enzymatic catalysis in Beijing University of Chemical Technology, one of the leaders in biodiesel R & D in China, which includes screening of high-yield lipase production strains, optimization and scale-up of the lipase fermentation process, lipase immobilization, bioreactor development and scale-up, biodiesel separation and purification and the by-product glycerol utilization. Firstly, lipase fermentation was carried out at industrial scale with the 5 m3 stirred tank bioreactor, and the enzyme activity as high as 8 000 IU/mL was achieved by the species Candida sp. 99-125. Then, the lipase was purified and immobilized on textile membranes. Furthermore, biodiesel production was performed in the 5 m3 stirred tank bioreactor with an enzyme dosage as low as 0.42%, and biodiesel that met the German biodiesel standard was produced. And in the meantime, the byproduct glycerol was used for the production of 1,3-propanediol to partly offset the production cost of biodiesel, and 76.1 g/L 1,3-propanediol was obtained in 30 L fermentor with the species Klebsiella pneumoniae.

  1. Productivity growth and technological progress in the Brazilian agricultural sector

    Directory of Open Access Journals (Sweden)

    Marcelo Farid Pereira

    2002-12-01

    Full Text Available Starting in the 1970's, the Brazilian agricultural sector has experienced an important process of modernization, whose principal effects include advances in technological progress and gains in productivity. The primary objective of this paper is to analyze technological progress and total productivity growth in the Brazilian agricultural sector during the period from 1970 to 1996. The methodology used here is based on the Malmquist productivity index and techniques in mathematical programming called Data Envelopment Analysis. The results show that significant progress was made in this sector of the economy but concentrated in only some regions of the country.O setor agropecuário brasileiro passou por um processo de modernização a partir dos anos 70, conseqüentemente, espera-se que exista uma contrapartida de progresso tecnológico e de ganhos de produtividade para o setor. Diante de tal fato tem-se como objetivo, neste estudo, avaliar o progresso tecnológico e o crescimento da produtividade total dos fatores (PTF do setor agropecuário brasileiro ao longo do período de 1970 a 1996. A metodologia utilizada foi baseada no índice Malmquist de produtividade e nas técnicas de programação matemática denominadas de Análise de Envoltória de Dados (DEA. Os resultados alcançados foram condizentes com estudos prévios e apontam para progresso técnico e ganhos de produtividade para o setor, porém concentrados em algumas regiões.

  2. Progress in non-viral gene delivery systems fabricated via supramolecular assembly

    Institute of Scientific and Technical Information of China (English)

    WANG Youxiang; SHEN Jiacong

    2005-01-01

    Gene delivery systems are one of key issues that limit the development of gene therapy. The novel non-viral gene delivery systems fabricated via supramolecular assembly have begun to show increasing promising and applications in gene therapy due to its suitable nanometric size, controllable structure and excellent biocompatibility. In this review, the fundamental and recent progress of non-viral gene supramolecular assembly is reviewed. Artificial viruses--the future direction of non-viral gene delivery systems are also described.

  3. [Progress in research and application of gene engineering on medicinal plants].

    Science.gov (United States)

    Wang, Min; Huang, Lu-qi; Li, Meng-meng

    2008-06-01

    China is the country possessing the largest amount of trade and consumption of medicinal plants in the world. Research and application of gene engineering on medicinal plants are the one of the most promising ways to increase the productivity and quality of medicinal plants, reduce the resource stress, and enhance the competitive power and sustainable development ability of the medicinal plants industry. In spite of the great progress in research and application of plant gene engineering worldwide, the research of gene transformation has mostly been conducted on some model plants, and the application of transgenic plant has been limited to a few staple and important crop species. For medicinal plants, recently the researches of gene transformation has emerged, however, compared with other crop and economic plants, it is still a very limited amount. On the basis of a general introduction of application of transgenic plants, this paper focuses on the present situation of the research and application of gene engineering on medicinal plants, to put forward the problems in this field, and give a prospect for its development.

  4. Development and recent progresses of gene therapy for β-thalassemia

    Directory of Open Access Journals (Sweden)

    Santina Acuto

    2014-09-01

    Full Text Available β-thalassemias are among the most common inherited monogenic disorders worldwide due to mutations in the β-globin gene that reduce or abolish the production of the β-globin chain resulting in transfusion-dependent chronic anemia. Currently, the only curative treatment is allogeneic hematopoietic stem cells (HSCs transplantation, but this option is limited by the a vailability of HLA-matched donor. Gene therapy, based on autologous transplantation of genetically corrected HSCs, holds the promise to treat patients lacking a compati ble bone marrow donor. I nit ial attempts of gene transfer have been unsuccessful due to limitations of available vectors to stably transfer a globin gene in HSCs and reach high and regulated expression in the erythroid progeny. With the advent of lentiviral vectors (LVs, based on human immunodeficiency virus, many of the initial limitations have been overcome. Since 2000 when Sadelain and co-workers first demonstrated successful globin gene transfer in murine thalassemia models with improvement of the phenotype using a recombinant β globin/LV, several other groups have developed different vectors encoding either β, γ or mutated globin genes and confirmed these results in both murine models and erythroid progeny derived from patient’s HSCs. In light of these encouraging results, research has recently moved into clinical trials that are ongoing or soon to begin. One participant in an ongoing gene transfer trial for β-thalassemia has achieved clinical benefit with elimination of his transfusi on re quirement. Here , dev elopmen t and recent progress of gene therapy for β-thalassemia is reviewed.

  5. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  6. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  7. Overview of gene therapy clinical progress including cancer treatment with gene-modified T cells.

    Science.gov (United States)

    Brenner, Malcolm K; Okur, Fatma V

    2009-01-01

    It is now twenty years since the first legal gene transfer studies were approved, and there has been considerable disappointment in the slow rate of progress that followed the initial studies. Gradually, however, as the limitations of available vectors are acknowledged and overcome, and with advances in our understanding of the molecular and cell biology of genetic diseases and of cancer, unequivocal successes are now being reported. In this paper we describe the remaining major roadblocks to successful gene therapy and outline approaches to overcome them. We also illustrate how genetically modified immune system cells are already being used for the effective treatment of hematological and other malignancies, and how these approaches are being modified so that they can be effective in treating a broader range of malignancies.

  8. Comparative genomics of Bordetella pertussis reveals progressive gene loss in Finnish strains.

    Directory of Open Access Journals (Sweden)

    Eriikka Heikkinen

    Full Text Available BACKGROUND: Bordetella pertussis is a gram-negative bacterium that infects the human respiratory tract and causes pertussis or whooping cough. The disease has resurged in many countries including Finland where the whole-cell pertussis vaccine has been used for more than 50 years. Antigenic divergence has been observed between vaccine strains and clinical isolates in Finland. To better understand genome evolution in B. pertussis circulating in the immunized population, we developed an oligonucleotide-based microarray for comparative genomic analysis of Finnish strains isolated during the period of 50 years. METHODOLOGY/PRINCIPAL FINDINGS: The microarray consisted of 3,582 oligonucleotides (70-mer and covered 94% of 3,816 ORFs of Tohama I, the strain of which the genome has been sequenced. Twenty isolates from 1953 to 2004 were studied together with two Finnish vaccine strains and two international reference strains. The isolates were selected according to their characteristics, e.g. the year and place of isolation and pulsed-field gel electrophoresis profiles. Genomic DNA of the tested strains, along with reference DNA of Tohama I strain, was labelled and hybridized. The absence of genes as established with microarrays, was confirmed by PCR. Compared with the Tohama I strain, Finnish isolates lost 7 (8.6 kb to 49 (55.3 kb genes, clustered in one to four distinct loci. The number of lost genes increased with time, and one third of lost genes had functions related to inorganic ion transport and metabolism, or energy production and conversion. All four loci of lost genes were flanked by the insertion sequence element IS481. CONCLUSION/SIGNIFICANCE: Our results showed that the progressive gene loss occurred in Finnish B. pertussis strains isolated during a period of 50 years and confirmed that B. pertussis is dynamic and is continuously evolving, suggesting that the bacterium may use gene loss as one strategy to adapt to highly immunized populations.

  9. Progress in Antiproton Production at the Fermilab Tevatron Collider

    Energy Technology Data Exchange (ETDEWEB)

    Pasquinelli, Ralph J.; Drendel, Brian; Gollwitzer, Keith; Johnson, Stan; Lebedev, Valeri; Leveling, Anthony; Morgan, James; Nagaslaev, Vladimir; Peterson, Dave; Sondgeroth, Alan; Werkema, Steve; /Fermilab

    2009-04-01

    Fermilab Collider Run II has been ongoing since 2001. During this time peak luminosities in the Tevatron have increased from approximately 10 x 10{sup 30} cm{sup -2}sec{sup -1} to 300 x 10{sup 30} cm{sup 02}sec{sup -1}. A major contributing factor in this remarkable performance is a greatly improved antiproton production capability. Since the beginning of Run II, the average antiproton accumulation rate has increased from 2 x 10{sup 10}{anti p}/hr to about 24 x 10{sup 10}{anti p}/hr. Peak antiproton stacking rates presently exceed 28 x 10{sup 10}{anti p}/hr. The antiproton stacking rate has nearly doubled since 2005. It is this recent progress that is the focus of this paper. The process of transferring antiprotons to the Recycler Ring for subsequent transfer to the collider has been significantly restructured and streamlined, yielding additional cycle time for antiproton production. Improvements to the target station have greatly increased the antiproton yield from the production target. The performance of the Antiproton Source stochastic cooling systems has been enhanced by upgrades to the cooling electronics, accelerator lattice optimization, and improved operating procedures. In this paper, we will briefly report on each of these modifications.

  10. A stochastic model for identifying differential gene pair co-expression patterns in prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Mao Yu

    2009-07-01

    Full Text Available Abstract Background The identification of gene differential co-expression patterns between cancer stages is a newly developing method to reveal the underlying molecular mechanisms of carcinogenesis. Most researches of this subject lack an algorithm useful for performing a statistical significance assessment involving cancer progression. Lacking this specific algorithm is apparently absent in identifying precise gene pairs correlating to cancer progression. Results In this investigation we studied gene pair co-expression change by using a stochastic process model for approximating the underlying dynamic procedure of the co-expression change during cancer progression. Also, we presented a novel analytical method named 'Stochastic process model for Identifying differentially co-expressed Gene pair' (SIG method. This method has been applied to two well known prostate cancer data sets: hormone sensitive versus hormone resistant, and healthy versus cancerous. From these data sets, 428,582 gene pairs and 303,992 gene pairs were identified respectively. Afterwards, we used two different current statistical methods to the same data sets, which were developed to identify gene pair differential co-expression and did not consider cancer progression in algorithm. We then compared these results from three different perspectives: progression analysis, gene pair identification effectiveness analysis, and pathway enrichment analysis. Statistical methods were used to quantify the quality and performance of these different perspectives. They included: Re-identification Scale (RS and Progression Score (PS in progression analysis, True Positive Rate (TPR in gene pair analysis, and Pathway Enrichment Score (PES in pathway analysis. Our results show small values of RS and large values of PS, TPR, and PES; thus, suggesting that gene pairs identified by the SIG method are highly correlated with cancer progression, and highly enriched in disease-specific pathways. From

  11. Gene Delivery into Plant Cells for Recombinant Protein Production

    Directory of Open Access Journals (Sweden)

    Qiang Chen

    2015-01-01

    Full Text Available Recombinant proteins are primarily produced from cultures of mammalian, insect, and bacteria cells. In recent years, the development of deconstructed virus-based vectors has allowed plants to become a viable platform for recombinant protein production, with advantages in versatility, speed, cost, scalability, and safety over the current production paradigms. In this paper, we review the recent progress in the methodology of agroinfiltration, a solution to overcome the challenge of transgene delivery into plant cells for large-scale manufacturing of recombinant proteins. General gene delivery methodologies in plants are first summarized, followed by extensive discussion on the application and scalability of each agroinfiltration method. New development of a spray-based agroinfiltration and its application on field-grown plants is highlighted. The discussion of agroinfiltration vectors focuses on their applications for producing complex and heteromultimeric proteins and is updated with the development of bridge vectors. Progress on agroinfiltration in Nicotiana and non-Nicotiana plant hosts is subsequently showcased in context of their applications for producing high-value human biologics and low-cost and high-volume industrial enzymes. These new advancements in agroinfiltration greatly enhance the robustness and scalability of transgene delivery in plants, facilitating the adoption of plant transient expression systems for manufacturing recombinant proteins with a broad range of applications.

  12. Signal transduction pathways that regulate CAB gene expression. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Chory, J.

    1993-12-31

    We have completed the initial genetic and phenotypic characterization of several classes of new mutants that affect CAB gene expression. The doc mutants (for dark overexpression of cab) are characterized by elevated levels of CAB gene expression in the dark; however, unlike the previously isolated de-etiolated mutants (also isolated in my lab), the doc mutants still appear etiolated. The doc alleles define 3 loci, each of which maps to a separate chromosome. The details of the mutant isolation scheme and the genetic and phenotypic description of these new mutants are described. The second class of mutants, the gun mutants (for genomes uncoupled) show accumulation of CAB mRNA in the absence of chloroplast gene expression and development. Thus, the normally tightly coordinated expression between the chloroplast and nuclear genes that encode chloroplast-destined proteins has been uncoupled. We have shown that the Arabidopsis HY3 locus encodes the type B phytochrome apoprotein gene and have characterized the phenotypes of null hy3 alleles to ascertain a role for this phytochrome in Arabidopsis development. We have also isolated and characterized a number of alleles of the phytochrome A gene.

  13. Identifying genes for neurobehavioural traits in rodents: progress and pitfalls

    Directory of Open Access Journals (Sweden)

    Amelie Baud

    2017-04-01

    Full Text Available Identifying genes and pathways that contribute to differences in neurobehavioural traits is a key goal in psychiatric research. Despite considerable success in identifying quantitative trait loci (QTLs associated with behaviour in laboratory rodents, pinpointing the causal variants and genes is more challenging. For a long time, the main obstacle was the size of QTLs, which could encompass tens if not hundreds of genes. However, recent studies have exploited mouse and rat resources that allow mapping of phenotypes to narrow intervals, encompassing only a few genes. Here, we review these studies, showcase the rodent resources they have used and highlight the insights into neurobehavioural traits provided to date. We discuss what we see as the biggest challenge in the field – translating QTLs into biological knowledge by experimentally validating and functionally characterizing candidate genes – and propose that the CRISPR/Cas genome-editing system holds the key to overcoming this obstacle. Finally, we challenge traditional views on inbred versus outbred resources in the light of recent resource and technology developments.

  14. Identifying genes for neurobehavioural traits in rodents: progress and pitfalls.

    Science.gov (United States)

    Baud, Amelie; Flint, Jonathan

    2017-04-01

    Identifying genes and pathways that contribute to differences in neurobehavioural traits is a key goal in psychiatric research. Despite considerable success in identifying quantitative trait loci (QTLs) associated with behaviour in laboratory rodents, pinpointing the causal variants and genes is more challenging. For a long time, the main obstacle was the size of QTLs, which could encompass tens if not hundreds of genes. However, recent studies have exploited mouse and rat resources that allow mapping of phenotypes to narrow intervals, encompassing only a few genes. Here, we review these studies, showcase the rodent resources they have used and highlight the insights into neurobehavioural traits provided to date. We discuss what we see as the biggest challenge in the field - translating QTLs into biological knowledge by experimentally validating and functionally characterizing candidate genes - and propose that the CRISPR/Cas genome-editing system holds the key to overcoming this obstacle. Finally, we challenge traditional views on inbred versus outbred resources in the light of recent resource and technology developments. © 2017. Published by The Company of Biologists Ltd.

  15. Nonviral gene delivery: principle, limitations, and recent progress.

    Science.gov (United States)

    Al-Dosari, Mohammed S; Gao, Xiang

    2009-12-01

    Gene therapy is becoming a promising therapeutic modality for the treatment of genetic and acquired disorders. Nonviral approaches as alternative gene transfer vehicles to the popular viral vectors have received significant attention because of their favorable properties, including lack of immunogenicity, low toxicity, and potential for tissue specificity. Such approaches have been tested in preclinical studies and human clinical trials over the last decade. Although therapeutic benefit has been demonstrated in animal models, gene delivery efficiency of the nonviral approaches remains to be a key obstacle for clinical applications. This review focuses on existing and emerging concepts of chemical and physical methods for delivery of therapeutic nucleic acid molecules in vivo. The emphasis is placed on discussion about problems associated with current nonviral methods and recent efforts toward refinement of nonviral approaches.

  16. STUDY OF DELETION OF P16 GENE IN THE PROGRESSION OF BRAIN ASTROCYTOMAS

    Institute of Scientific and Technical Information of China (English)

    Zhai Guang; Yuan Xianhou

    1998-01-01

    Objective:To study the relationship between deletion of P16 gene and occurrence and progression of astrocytomas. Methods: The techniques of polymerase chain reaction (PCR) and immunohistochemistry were used to detect the deletion of exon2 of P16 gene and expression of P16 gene in 52 cases of Brain astrocytoma.Results: The deletion rate of exon2 of P16 gene in the tumors analyzed was 34.6%. Most of them with deletion of exon2 of p16 gene were high grade astrocytomas (grade Ⅲ 42%, grade Ⅳ 50%). 61.5% of the tumors were absent from expression of p16 and the deletion rate of p16 protein increased with the grade of astrocytoma (X2=10.83, P<0.005). Conclusion: Deletion of p16 gene and protein may correlate with the malignant progression of astrocytoma.

  17. Hierarchy in gene expression is predictive of risk, progression, and outcome in adult acute myeloid leukemia

    Science.gov (United States)

    Tripathi, Shubham; Deem, Michael W.

    2015-02-01

    Cancer progresses with a change in the structure of the gene network in normal cells. We define a measure of organizational hierarchy in gene networks of affected cells in adult acute myeloid leukemia (AML) patients. With a retrospective cohort analysis based on the gene expression profiles of 116 AML patients, we find that the likelihood of future cancer relapse and the level of clinical risk are directly correlated with the level of organization in the cancer related gene network. We also explore the variation of the level of organization in the gene network with cancer progression. We find that this variation is non-monotonic, which implies the fitness landscape in the evolution of AML cancer cells is non-trivial. We further find that the hierarchy in gene expression at the time of diagnosis may be a useful biomarker in AML prognosis.

  18. Progress in studies of gene therapy for Huntington's disease

    Directory of Open Access Journals (Sweden)

    JIN Fan-ying

    2012-06-01

    Full Text Available Huntington's disease (HD is a kind of inherited neurodegenerative disorder characterized by movement problems, cognitive decline and psychiatry disturbance. HD is caused by mutation in gene IT -15 involving the expansion of a trinucleotide (CAG repeat encoding glutamine, which leads to abnormal conformation of huntingtin (Htt protein and finally emerge cytotoxic functions. Currently, HD remains a fatal untreatable disease. Gene therapy for HD discussed in this review is under preclinical studies. Silencing of mutant IT-15 via RNA interference (RNAi or antisense oligonucleotide (ASO has shown some effectiveness in mouse model studies. Increasing the clearance of mutant Htt protein could be achieved by viral-mediated delivery of anti-Htt intrabodies (iAbs or induction of autophagy, and beneficial results have been observed. Ectopic expression of neurotrophic factors, such as nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF, mediated either by viral vectors or transplantation of genetically modified cells, has also been proved to be effective. Other gene-modifying methods aiming at correction of transcriptional dysregulation by histone modification, activation of endogenous neural stem cells, and normalization of calcium signaling and mitochondrial function, are also under intensive research. Gene therapy for Huntington's disease is promising, yet a long way remains from preclinical studies to clinical trials.

  19. Discovery of Novel Gene Elements Associated with Prostate Cancer Progression

    Science.gov (United States)

    2012-10-01

    transcripts more closely, we performed 5’ and 3’ rapid amplification of cDNA ends (RACE) for PCAT-1 and PCAT-14. Interestingly, the PCAT-14 locus...Sequencing Core. RNA-ligase-mediated rapid amplification of cDNA ends (RACE) 5’ and 3’ RACE was performed using the GeneRacer RLM-RACE kit (Invitrogen

  20. Progress of Production Technology of Clean Steel in Baosteel

    Institute of Scientific and Technical Information of China (English)

    CuiJian

    2005-01-01

    The progress in control technology of carbon, nitrogen, total oxygen, phosphorus, and stdphur as well as inclusions in steel is discussed at Baosteel. The purity obtained in IF steel and pipeline steel is introduced.

  1. Hollow Rotor Progressing Cavity Pump Technique for Oil Production

    Institute of Scientific and Technical Information of China (English)

    Cao Gang

    2002-01-01

    @@ Features of Hollow RotorProgressing Cavity Pump(HRPCP) (1) Keep the path forPCP well-flushing.Clean over the producing wells quickly without shutting off the wells. Heat loss is low while the efficiency is high.

  2. Gene Expression Profile Related to the Progression of Preneoplastic Nodules toward Hepatocellular Carcinoma in Rats

    Directory of Open Access Journals (Sweden)

    Julio Isael Pérez-Carréon

    2006-05-01

    Full Text Available In this study, we investigated the time course gene expression profile of preneoplastic nodules and hepatocellular carcinomas (HCC to define the genes implicated in cancer progression in a resistant hepatocyte model. Tissues that included early nodules (1 month, ENT-1, persistent nodules (5 months, ENT-5, dissected HCC (12 months, and normal livers (NIL from adult rats were analyzed by cDNA arrays including 1185 rat genes. Differential genes were derived in each type of sample (n = 3 by statistical analysis. The relationship between samples was described in a Venn diagram for 290 genes. From these, 72 genes were shared between tissues with nodules and HCC. In addition, 35 genes with statistical significance only in HCC and with extreme ratios were identified. Differential expression of 11 genes was confirmed by comparative reverse transcription-polymerase chain reaction, whereas that of 2 genes was confirmed by immunohistochemistry. Members involved in cytochrome P450 and second-phase metabolism were downregulated, whereas genes involved in glutathione metabolism were upregulated, implicating a possible role of glutathione and oxidative regulation. We provide a gene expression profile related to the progression of nodules into HCC, which contributes to the understanding of liver cancer development and offers the prospect for chemoprevention strategies or early treatment of HCC.

  3. Research progress of the correlation between gene polymorphism and stroke

    Directory of Open Access Journals (Sweden)

    Gao-yu CAI

    2015-03-01

    Full Text Available Stroke is a common disease which has serious impact on human health in modern society. It has complex pathogenesis and wide-ranging influencing factors. Accompanied with the development of molecular genetics, a number of single nucleotide polymorphisms (SNPs have been found to be closely related to the incidence of stroke in case-control studies on the correlation between genes and stroke by using molecular biology technologies. In order to have a better understanding on the correlation between gene polymorphism and stroke, this summary presents a review of literatures reported at home and abroad over the past year on the genetics of stroke. DOI: 10.3969/j.issn.1672-6731.2015.02.002

  4. The role of ACE gene polymorphism in rapidity of progression of focal segmental glomerulosclerosis.

    Directory of Open Access Journals (Sweden)

    Dixit M

    2002-10-01

    Full Text Available BACKGROUND: The insertion/deletion (I/D polymorphism of angiotensin converting enzyme (ACE gene has been associated with progression of renal diseases. AIMS: We investigated its role in the rate of progression of focal segmental glomerulosclerosis (FSGS. METHODS: Forty-seven patients with end-stage renal disease (ESRD due to FSGS were evaluated. RESULTS: The distribution of ACE genotype was II-25.5%, ID-55.5%, and DD-19%, as compared to 40 controls with genotype of 7.5%, 60%, and 32.5%, respectively (p= NS. In African Americans (AA the gene frequencies among patients and controls were I-43%, D-57% vs I-36%, D-64%, respectively. This was different than the gene frequencies in White/Hispanic (W/H patients I-61.5%, D-38.5% vs I-38.6%, D-61.4%, in controls (P < 0.05. In 22 patients with rapid progression (RP of FSGS to ESRD the genotype distribution was II-18%, ID -64%, and DD-18%. In 25 patients with FSGS who progressed slowly (SP the genotype was similar (II-32%, ID-48% and DD-20%, P >0.05. With respect to rate of progression, D allele frequency was similar in AA patients (RP 64% vs SP 50% and W/H patients (RP 36% vs SP 40%. CONCLUSION: Our study reveals no association between the I/D polymorphism of the ACE gene and the presence of and rapidity progression of FSGS.

  5. Combining Hierarchical and Associative Gene Ontology Relations with Textual Evidence in Estimating Gene and Gene Product Similarity

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; Posse, Christian; Gopalan, Banu; Riensche, Roderick M.; Beagley, Nathaniel; Baddeley, Bob L.; Tratz, Stephen C.; Gregory, Michelle L.

    2007-03-01

    Gene and gene product similarity is a fundamental diagnostic measure in analyzing biological data and constructing predictive models for functional genomics. With the rising influence of the Gene Ontology, two complementary approaches have emerged where the similarity between two genes or gene products is obtained by comparing Gene Ontology (GO) annotations associated with the genes or gene products. One approach captures GO-based similarity in terms of hierarchical relations within each gene subontology. The other approach identifies GO-based similarity in terms of associative relations across the three gene subontologies. We propose a novel methodology where the two approaches can be merged with ensuing benefits in coverage and accuracy, and demonstrate that further improvements can be obtained by integrating textual evidence extracted from relevant biomedical literature.

  6. The WSB1 gene is involved in pancreatic cancer progression.

    Directory of Open Access Journals (Sweden)

    Cendrine Archange

    Full Text Available BACKGROUND: Pancreatic cancer cells generate metastases because they can survive the stress imposed by the new environment of the host tissue. To mimic this process, pancreatic cancer cells which are not stressed in standard culture conditions are injected into nude mice. Because they develop xenografts, they should have developed adequate stress response. Characterizing that response might provide new strategies to interfere with pancreatic cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: In the human pancreatic cancer cell lines Panc-1, Mia-PaCa2, Capan-1, Capan-2 and BxPC3, we used Affymetrix DNA microarrays to compare the expressions of 22.000 genes in vitro and in the corresponding xenografts. We identified 228 genes overexpressed in xenografts and characterized the implication of one of them, WSB1, in the control of apoptosis and cell proliferation. WSB1 generates 3 alternatively spliced transcripts encoding distinct protein isoforms. In xenografts and in human pancreatic tumors, global expression of WSB1 mRNA is modestly increased whereas isoform 3 is strongly overexpressed and isoforms 1 and 2 are down-regulated. Treating Mia-PaCa2 cells with stress-inducing agents induced similar changes. Whereas retrovirus-forced expression of WSB1 isoforms 1 and 2 promoted cell growth and sensitized the cells to gemcitabine- and doxorubicin-induced apoptosis, WSB1 isoform 3 expression reduced cell proliferation and enhanced resistance to apoptosis, showing that stress-induced modulation of WSB1 alternative splicing increases resistance to apoptosis of pancreatic cancer cells. CONCLUSIONS/SIGNIFICANCE: Data on WSB1 regulation support the hypothesis that activation of stress-response mechanisms helps cancer cells establishing metastases and suggest relevance to cancer development of other genes overexpressed in xenografts.

  7. Research progress of gene target therapy for refractory epilepsy

    Directory of Open Access Journals (Sweden)

    Xing-hua TANG

    2014-12-01

    Full Text Available Nowadays, the strategies of gene therapy for the treatment of refractory epilepsy (RE mainly include modulating neurotransmitter systems, neuropeptide Y (NPY and neurotrophic factors. Among them, the hot target spots include γ-aminobutyric acid (GABA and its receptor, N-methyl-D-aspartate (NMDA and its receptor, galanin, NPY and neurotrophic factors. This paper reviews the chief research results, and advantages and disadvantages of studies, and provides evidence for the treatment of refractory epilepsy. doi: 10.3969/j.issn.1672-6731.2014.12.004

  8. Candidate genes for the progression of malignant gliomas identified by microarray analysis.

    Science.gov (United States)

    Bozinov, Oliver; Köhler, Sylvia; Samans, Birgit; Benes, Ludwig; Miller, Dorothea; Ritter, Markus; Sure, Ulrich; Bertalanffy, Helmut

    2008-01-01

    Malignant astrocytomas of World Health Organization (WHO) grade III or IV have a reduced median survival time, and possible pathways have been described for the progression of anaplastic astrocytomas and glioblastomas, but the molecular basis of malignant astrocytoma progression is still poorly understood. Microarray analysis provides the chance to accelerate studies by comparison of the expression of thousands of genes in these tumours and consequently identify targeting genes. We compared the transcriptional profile of 4,608 genes in tumours of 15 patients including 6 anaplastic astrocytomas (WHO grade III) and 9 glioblastomas (WHO grade IV) using microarray analysis. The microarray data were corroborated by real-time reverse transcription-polymerase chain reaction analysis of two selected genes. We identified 166 gene alterations with a fold change of 2 and higher whose mRNA levels differed (absolute value of the t statistic of 1.96) between the two malignant glioma groups. Further analyses confirmed same transcription directions for Olig2 and IL-13Ralpha2 in anaplastic astrocytomas as compared to glioblastomas. Microarray analyses with a close binary question reveal numerous interesting candidate genes, which need further histochemical testing after selection for confirmation. IL-13Ralpha2 and Olig2 have been identified and confirmed to be interesting candidate genes whose differential expression likely plays a role in malignant progression of astrocytomas.

  9. Maternal Environment Interacts with Modifier Genes to Influence Progression of Nephrotic Syndrome

    Science.gov (United States)

    Ratelade, Julien; Lavin, Tiphaine Aguirre; Muda, Andrea Onetti; Morisset, Ludivine; Mollet, Géraldine; Boyer, Olivia; Chen, Deborah S.; Henger, Anna; Kretzler, Matthias; Hubner, Norbert; Théry, Clotilde; Gubler, Marie-Claire; Montagutelli, Xavier; Antignac, Corinne; Esquivel, Ernie L.

    2008-01-01

    Mutations in the NPHS2 gene, which encodes podocin, are responsible for some cases of sporadic and familial autosomal recessive steroid-resistant nephrotic syndrome. Inter- and intrafamilial variability in the progression of renal disease among patients bearing NPHS2 mutations suggests a potential role for modifier genes. Using a mouse model in which the podocin gene is constitutively inactivated, we sought to identify genetic determinants of the development and progression of renal disease as a result of the nephrotic syndrome. We report that the evolution of renal disease as a result of nephrotic syndrome in Nphs2-null mice depends on genetic background. Furthermore, the maternal environment significantly interacts with genetic determinants to modify survival and progression of renal disease. Quantitative trait locus mapping suggested that these genetic determinants may be encoded for by genes on the distal end of chromosome 3, which are linked to proteinuria, and on the distal end of chromosome 7, which are linked to a composite trait of urea, creatinine, and potassium. These loci demonstrate epistatic interactions with other chromosomal regions, highlighting the complex genetics of renal disease progression. In summary, constitutive inactivation of podocin models the complex interactions between maternal and genetically determined factors on the progression of renal disease as a result of nephrotic syndrome in mice. PMID:18385421

  10. How changes in extracellular matrix mechanics and gene expression variability might combine to drive cancer progression.

    Directory of Open Access Journals (Sweden)

    Justin Werfel

    Full Text Available Changes in extracellular matrix (ECM structure or mechanics can actively drive cancer progression; however, the underlying mechanism remains unknown. Here we explore whether this process could be mediated by changes in cell shape that lead to increases in genetic noise, given that both factors have been independently shown to alter gene expression and induce cell fate switching. We do this using a computer simulation model that explores the impact of physical changes in the tissue microenvironment under conditions in which physical deformation of cells increases gene expression variability among genetically identical cells. The model reveals that cancerous tissue growth can be driven by physical changes in the microenvironment: when increases in cell shape variability due to growth-dependent increases in cell packing density enhance gene expression variation, heterogeneous autonomous growth and further structural disorganization can result, thereby driving cancer progression via positive feedback. The model parameters that led to this prediction are consistent with experimental measurements of mammary tissues that spontaneously undergo cancer progression in transgenic C3(1-SV40Tag female mice, which exhibit enhanced stiffness of mammary ducts, as well as progressive increases in variability of cell-cell relations and associated cell shape changes. These results demonstrate the potential for physical changes in the tissue microenvironment (e.g., altered ECM mechanics to induce a cancerous phenotype or accelerate cancer progression in a clonal population through local changes in cell geometry and increased phenotypic variability, even in the absence of gene mutation.

  11. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  12. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  13. Correlating Information Contents of Gene Ontology Terms to Infer Semantic Similarity of Gene Products

    Directory of Open Access Journals (Sweden)

    Mingxin Gan

    2014-01-01

    Full Text Available Successful applications of the gene ontology to the inference of functional relationships between gene products in recent years have raised the need for computational methods to automatically calculate semantic similarity between gene products based on semantic similarity of gene ontology terms. Nevertheless, existing methods, though having been widely used in a variety of applications, may significantly overestimate semantic similarity between genes that are actually not functionally related, thereby yielding misleading results in applications. To overcome this limitation, we propose to represent a gene product as a vector that is composed of information contents of gene ontology terms annotated for the gene product, and we suggest calculating similarity between two gene products as the relatedness of their corresponding vectors using three measures: Pearson’s correlation coefficient, cosine similarity, and the Jaccard index. We focus on the biological process domain of the gene ontology and annotations of yeast proteins to study the effectiveness of the proposed measures. Results show that semantic similarity scores calculated using the proposed measures are more consistent with known biological knowledge than those derived using a list of existing methods, suggesting the effectiveness of our method in characterizing functional relationships between gene products.

  14. Correlating information contents of gene ontology terms to infer semantic similarity of gene products.

    Science.gov (United States)

    Gan, Mingxin

    2014-01-01

    Successful applications of the gene ontology to the inference of functional relationships between gene products in recent years have raised the need for computational methods to automatically calculate semantic similarity between gene products based on semantic similarity of gene ontology terms. Nevertheless, existing methods, though having been widely used in a variety of applications, may significantly overestimate semantic similarity between genes that are actually not functionally related, thereby yielding misleading results in applications. To overcome this limitation, we propose to represent a gene product as a vector that is composed of information contents of gene ontology terms annotated for the gene product, and we suggest calculating similarity between two gene products as the relatedness of their corresponding vectors using three measures: Pearson's correlation coefficient, cosine similarity, and the Jaccard index. We focus on the biological process domain of the gene ontology and annotations of yeast proteins to study the effectiveness of the proposed measures. Results show that semantic similarity scores calculated using the proposed measures are more consistent with known biological knowledge than those derived using a list of existing methods, suggesting the effectiveness of our method in characterizing functional relationships between gene products.

  15. Integrating Ontological Knowledge and Textual Evidence in Estimating Gene and Gene Product Similarity

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; Posse, Christian; Gopalan, Banu; Tratz, Stephen C.; Gregory, Michelle L.

    2006-06-08

    With the rising influence of the Gene On-tology, new approaches have emerged where the similarity between genes or gene products is obtained by comparing Gene Ontology code annotations associ-ated with them. So far, these approaches have solely relied on the knowledge en-coded in the Gene Ontology and the gene annotations associated with the Gene On-tology database. The goal of this paper is to demonstrate that improvements to these approaches can be obtained by integrating textual evidence extracted from relevant biomedical literature.

  16. Association of mannan-binding lectin gene polymorphisms with progression of severe lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    常欣蓓

    2014-01-01

    Objective To investigate the association of single nucleotide polymorphisms(SNPs)of the mannan-binding lectin(MBL)gene with serum levels,development,progression and prognosis of severe lupus nephritis(LN).Methods A total of 107 severe lupus nephritis patients were enrolled in the study from January 2003 to October2013.Integrated capillary electrophoresis was used to detect MBL gene polymorphism in peripheral blood

  17. Association of NR1I2 gene polymorphisms and time of progression to AIDS

    Science.gov (United States)

    de Medeiros, Rúbia Marília; Menti, Carolina Fialho; Benelli, Jéssica Louise; Matte, Maria Cristina Cotta; de Melo, Marineide Gonçalves; Almeida, Sabrina Esteves de Matos; Fiegenbaum, Marilu

    2017-01-01

    BACKGROUND The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS. OBJECTIVE To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients. METHODS Blood samples were obtained from 96 HIV-1 positive individuals following informed consent. DNA was isolated and genotyped through real time polymerase chain reaction (PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic features and behaviors were answered and time of progression to AIDS was estimated based on medical chart analysis. FINDINGS Patients with the GG genotype for rs7643645 were shown to be related with a more rapid disease progression when compared to GA and AA genotypes. This result was maintained by the Multivariate Cox Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and CCR5del32 polymorphisms. MAIN CONCLUSIONS Recent studies reported the expression of the nuclear receptors in T-Lymphocytes, suggesting their possible role in the immune response. In addition, nuclear receptors have been shown to inhibit the HIV replication, although no such mechanism has been thoroughly elucidated to date. This is the first time an association between NR1I2 polymorphism and time of progression to AIDS is reported and supports an apparent relationship between the gene in the immune response and identifies another genetic factor influencing AIDS progression. PMID:28327790

  18. Gene-environment interaction in progression of AMD: the CFH gene, smoking and exposure to chronic infection.

    Science.gov (United States)

    Baird, Paul N; Robman, Luba D; Richardson, Andrea J; Dimitrov, Peter N; Tikellis, Gabriella; McCarty, Catherine A; Guymer, Robyn H

    2008-05-01

    A number of risk factors including the complement factor H (CFH) gene, smoking and Chlamydia pneumoniae have been associated with age-related macular degeneration (AMD). However, the mechanisms underlying how these risk factors might be involved in disease progression and disease aetiology is poorly understood. A cohort series of 233 individuals followed for AMD progression over a mean period of 7 years underwent a full eye examination, blood was taken for DNA and antibody titre and individuals completed a standard medical and general questionnaire. Y402H variants of the CFH gene were assessed with disease progression as well as examination of interaction between Y402H variants and smoking and Y402H variants and the pathogen C. pneumoniae. The CC risk genotype of Y402H was significantly associated with increased AMD progression [odds ratio (OR) 2.43, 95% confidence interval (95% CI) 1.07-5.49] as was smoking (OR 2.28, 95% CI 1.26-4.12). However, the risk of progression was greatly increased to almost 12-fold (OR 11.8, 95% CI 2.1-65.8) when, in addition to having the C risk allele, subjects also presented with the upper tertile of antibodies to the bacterial pathogen C. pneumoniae compared with those with the T allele of Y402H and the lowest antibody tertile. This demonstrates for the first time the existence of a gene environment-interaction between pathogenic load of C. pneumoniae and the CFH gene in the aetiology of AMD.

  19. Progress in human exposure assessment for biocidal products

    NARCIS (Netherlands)

    Hemmen, J.J. van

    2004-01-01

    An important shortcoming in our present knowledge required for risk assessment of biocidal products is the assessment of human exposure. This knowledge gap has been filled in a preliminary fashion with the TNsG on human exposure to biocidal products (available from the ECB website). Explicit User gu

  20. Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles.

    Directory of Open Access Journals (Sweden)

    Raquel Pinho

    Full Text Available The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson's disease (PD progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression

  1. Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

    DEFF Research Database (Denmark)

    Almstrup, K; Hoei-Hansen, C E; Nielsen, J E

    2005-01-01

    into CIS occurs early during foetal life. Progression into an overt tumour, however, typically first happens after puberty, where CIS cells transform into either a seminoma (SEM) or a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of CIS cells to that of testicular SEM...

  2. Comprehensive analysis of the achromatopsia genes CNGA3 and CNGB3 in progressive cone dystrophy

    NARCIS (Netherlands)

    Thiadens, A.A.H.J.; Roosing, S.; Collin, R.W.J.; Moll-Ramirez, N. van; Lith-Verhoeven, J.J. van; Schooneveld, M.J. van; Hollander, A.I. den; Born, L.I. van den; Hoyng, C.B.; Cremers, F.P.M.; Klaver, C.C.

    2010-01-01

    OBJECTIVE: To investigate whether the major achromatopsia genes (CNGA3 and CNGB3) play a role in the cause of progressive cone dystrophy (CD). DESIGN: Prospective multicenter study. PARTICIPANTS: Probands (N = 60) with autosomal recessive (ar) CD from various ophthalmogenetic clinics in The Netherla

  3. Progress in biodiesel and bioethanol production in Ukraine

    Energy Technology Data Exchange (ETDEWEB)

    Zhelyezna, T.; Geletukha, G. (Institute of Engineering Thermophysics NASU, SEC ' Biomass' , Kiev (Ukraine))

    2007-07-01

    Ukraine is highly dependent on imported energy carriers. Prices of fossil fuels and motor fuels have permanent trend to rise. On the other hand, Ukraine has practically all the necessary preconditions to start wide production of motor fuels from biomass for internal usage and export abroad. Ukrainian specialists have developed effective technology for the production of high octane oxygen containing admixture to petrol, which is the local analogue of bio ethanol. There are small scale plants for bio diesel production in about twelve oblasts of Ukraine, but the process is not commercial yet. Ukrainian government and Ministry of Agrarian Policy realise the importance of alternative liquid fuels and encourage the process of their production. At the moment main efforts are focused on the development of raw material base (orig.)

  4. Deduced products of C4-dicarboxylate transport regulatory genes of Rhizobium leguminosarum are homologous to nitrogen regulatory gene products.

    OpenAIRE

    Ronson, C W; Astwood, P M; Nixon, B T; Ausubel, F M

    1987-01-01

    We have sequenced two genes dctB and dctD required for the activation of the C4-dicarboxylate transport structural gene dctA in free-living Rhizobium leguminosarum. The hydropathic profile of the dctB gene product (DctB) suggested that its N-terminal region may be located in the periplasm and its C-terminal region in the cytoplasm. The C-terminal region of DctB was strongly conserved with similar regions of the products of several regulatory genes that may act as environmental sensors, includ...

  5. Deduced products of C4-dicarboxylate transport regulatory genes of Rhizobium leguminosarum are homologous to nitrogen regulatory gene products.

    OpenAIRE

    Ronson, C W; Astwood, P M; Nixon, B T; Ausubel, F M

    1987-01-01

    We have sequenced two genes dctB and dctD required for the activation of the C4-dicarboxylate transport structural gene dctA in free-living Rhizobium leguminosarum. The hydropathic profile of the dctB gene product (DctB) suggested that its N-terminal region may be located in the periplasm and its C-terminal region in the cytoplasm. The C-terminal region of DctB was strongly conserved with similar regions of the products of several regulatory genes that may act as environmental sensors, includ...

  6. Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product

    DEFF Research Database (Denmark)

    Sabroe, T.P.; Sabers, A.

    2008-01-01

    This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6......This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...

  7. SPIDER Progress Towards High Resolution Correlated Fission Product Data

    Science.gov (United States)

    Shields, Dan; Meierbachtol, Krista; Tovesson, Fredrik; Arnold, Charles; Blackeley, Rick; Bredeweg, Todd; Devlin, Matt; Hecht, Adam; Jandel, Marian; Jorgenson, Justin; Nelson, Ron; White, Morgan; Spider Team

    2014-09-01

    The SPIDER detector (SPectrometer for Ion DEtermination in fission Research) is under development with the goal of obtaining high-resolution, high-efficiency, correlated fission product data needed for many applications including the modeling of next generation nuclear reactors, stockpile stewardship, and the fundamental understanding of the fission process. SPIDER simultaneously measures velocity and energy of both fission products to calculate fission product yields (FPYs), neutron multiplicity (ν), and total kinetic energy (TKE). A detailed description of the prototype SPIDER detector components will be presented. Characterization measurements with alpha and spontaneous fission sources will also be discussed. LA-UR-14-24875. The SPIDER detector (SPectrometer for Ion DEtermination in fission Research) is under development with the goal of obtaining high-resolution, high-efficiency, correlated fission product data needed for many applications including the modeling of next generation nuclear reactors, stockpile stewardship, and the fundamental understanding of the fission process. SPIDER simultaneously measures velocity and energy of both fission products to calculate fission product yields (FPYs), neutron multiplicity (ν), and total kinetic energy (TKE). A detailed description of the prototype SPIDER detector components will be presented. Characterization measurements with alpha and spontaneous fission sources will also be discussed. LA-UR-14-24875. This work is in part supported by LANL Laboratory Directed Research and Development Projects 20110037DR and 20120077DR.

  8. Enhanced citrate production through gene insertion in Aspergillus niger

    DEFF Research Database (Denmark)

    Jongh, Wian de; Nielsen, Jens

    2007-01-01

    The effect of inserting genes involved in the reductive branch of the tricarboxylic acid (TCA) cycle on citrate production by Aspergillus niger was evaluated. Several different genes were inserted individually and in combination, i.e. malate dehydrogenase (mdh2) from Saccharomyces cerevisiae, two...

  9. Research progress of photoperiod regulated genes on flowering time in rice.

    Science.gov (United States)

    Deyan, Kong; Shoujun, Chen; Liguo, Zhou; Huan, Gao; Lijun, Luo; Zaochang, Liu

    2016-06-20

    Rice flowering regulation is an extremely complex process, which is controlled by genetic factors and external environment. Photoperiodic regulatory pathway is pivotal to control flowering in rice, in which florigen genes Hd3a and RTF1 are at the core and they are regulated by upstream Hd1-dependent, Ehd1-dependent, as well as both Hd1- and Ehd1-independent pathways. The three pathways bring a variety of light signal information together to Hd3a and RTF1 for further integration, and then transmit the signals in the form of florigen to the downstream flowering related genes. In this review, we summarize the research progress of photoperiod regulated genes on flowering time in rice, including the photoreceptors and circadian rhythm genes, the florigens, its upstream, downstream and interacting genes. We hope to provide a reference for in-depth study of rice flowering regulation.

  10. Butyrate induces reactive oxygen species production and affects cell cycle progression in human gingival fibroblasts.

    Science.gov (United States)

    Chang, M-C; Tsai, Y-L; Chen, Y-W; Chan, C-P; Huang, C-F; Lan, W-C; Lin, C-C; Lan, W-H; Jeng, J-H

    2013-02-01

    Short-chain fatty acids, such as butyric acid and propionic acid, are metabolic by-products generated by periodontal microflora such as Porphyromonas gingivalis, and contribute to the pathogenesis of periodontitis. However, the effects of butyrate on the biological activities of gingival fibroblasts (GFs) are not well elucidated. Human GFs were exposed to various concentrations of butyrate (0.5-16 mm) for 24 h. Viable cells that excluded trypan blue were counted. Cell cycle distribution of GFs was analyzed by propidium iodide-staining flow cytometry. Cellular reactive oxygen species (ROS) production was measured by flow cytometry using 2',7'-dichlorofluorescein (DCF). Total RNA and protein lysates were isolated and subjected to RT-PCR using specific primers or to western blotting using specific antibodies, respectively. Butyrate inhibited the growth of GFs, as indicated by a decrease in the number of viable cells. This event was associated with an induction of G0/G1 and G2/M cell cycle arrest by butyrate (4-16 mm) in GFs. However, no marked apoptosis of GFs was noted in this experimental condition. Butyrate (> 2 mm) inhibited the expression of cdc2, cdc25C and cyclinB1 mRNAs and reduced the levels of Cdc2, Cdc25C and cyclinB1 proteins in GFs, as determined using RT-PCR and western blotting, respectively. This toxic effect of butyrate was associated with the production of ROS. These results suggest that butyrate generated by periodontal pathogens may be involved in the pathogenesis of periodontal diseases via the induction of ROS production and the impairment of cell growth, cell cycle progression and expression of cell cycle-related genes in GFs. These events are important in the initiation and prolongation of inflammatory processes in periodontal diseases. © 2012 John Wiley & Sons A/S.

  11. Inflectional morphology in primary progressive aphasia: an elicited production study.

    Science.gov (United States)

    Wilson, Stephen M; Brandt, Temre H; Henry, Maya L; Babiak, Miranda; Ogar, Jennifer M; Salli, Chelsey; Wilson, Lisa; Peralta, Karen; Miller, Bruce L; Gorno-Tempini, Maria Luisa

    2014-09-01

    Inflectional morphology lies at the intersection of phonology, syntax and the lexicon, three language domains that are differentially impacted in the three main variants of primary progressive aphasia (PPA). To characterize spared and impaired aspects of inflectional morphology in PPA, we elicited inflectional morphemes in 48 individuals with PPA and 13 healthy age-matched controls. We varied the factors of regularity, frequency, word class, and lexicality, and used voxel-based morphometry to identify brain regions where atrophy was predictive of deficits on particular conditions. All three PPA variants showed deficits in inflectional morphology, with the specific nature of the deficits dependent on the anatomical and linguistic features of each variant. Deficits in inflecting low-frequency irregular words were associated with semantic PPA, with lexical/semantic deficits, and with left temporal atrophy. Deficits in inflecting pseudowords were associated with non-fluent/agrammatic and logopenic variants, with phonological deficits, and with left frontal and parietal atrophy.

  12. Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Yoshiyuki Takahara; Mitsuo Takahashi; Hiroki Wagatsuma; Fumihiko Yokoya; Qing-Wei Zhang; Mutsuyo Yamaguchi; Hiroyuki Aburatani; Norifumi Kawada

    2006-01-01

    AIM: To determine the gene expression profile data for the whole liver during development of dimethylnitrosamine (DMN)-induced hepatic fibrosis.METHODS: Marker genes were identified for different types of hepatic cells, including hepatic stellate cells (HSCs), Kupffer cells (including other inflammatory cells),and hepatocytes, using independent temporal DNA microarray data obtained from isolated hepatic cells.RESULTS: The cell-type analysis of gene expression gave several key results and led to formation of three hypotheses: (1) changes in the expression of HSCspecific marker genes during fibrosis were similar to gene expression data in in vitro cultured HSCs, suggesting a major role of the self-activating characteristics of HSCs in formation of fibrosis; (2) expression of mast cell-specific marker genes reached a peak during liver fibrosis,suggesting a possible role of mast cells in formation of fibrosis; and (3) abnormal expression of hepatocytespecific marker genes was found across several metabolic pathways during fibrosis, including sulfur-containing amino acid metabolism, fatty acid metabolism, and drug metabolism, suggesting a mechanistic relationship between these abnormalities and symptoms of liver fibrosis.CONCLUSION: Analysis of marker genes for specific hepatic cell types can identify the key aspects of fibrogenesis. Sequential activation of inflammatory cells and the self-supporting properties of HSCs play an important role in development of fibrosis.

  13. Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression

    Directory of Open Access Journals (Sweden)

    Mansukhani Mahesh

    2006-05-01

    Full Text Available Abstract Background Cervical Cancer (CC exhibits highly complex genomic alterations. These include hemizygous deletions at 4p15.3, 10q24, 5q35, 3p12.3, and 11q24, the chromosomal sites of Slit-Robo pathway genes. However, no candidate tumor suppressor genes at these regions have been identified so far. Slit family of secreted proteins modulates chemokine-induced cell migration of distinct somatic cell types. Slit genes mediate their effect by binding to its receptor Roundabout (Robo. These genes have shown to be inactivated by promoter hypermethylation in a number of human cancers. Results To test whether Slit-Robo pathway genes are targets of inactivation at these sites of deletion, we examined promoter hypermethylation of SLIT1, SLIT2, SLIT3, ROBO1, and ROBO3 genes in invasive CC and its precursor lesions. We identified a high frequency of promoter hypermethylation in all the Slit-Robo genes resulting in down regulated gene expression in invasive CC, but the inhibitors of DNA methylation and histone deacetylases (HDACs in CC cell lines failed to effectively reactivate the down-regulated expression. These results suggest a complex mechanism of inactivation in the Slit-Robo pathway in CC. By analysis of cervical precancerous lesions, we further show that promoter hypermethylation of Slit-Robo pathway occurs early in tumor progression. Conclusion Taken together, these findings suggest that epigenetic alterations of Slit-Robo pathway genes (i play a role in CC development, (ii further delineation of molecular basis of promoter methylation-mediated gene regulation provides a potential basis for epigenetic-based therapy in advanced stage CC, and (iii form epigenetic signatures to identify precancerous lesions at risk to progression.

  14. Neoplastic and stromal cells contribute to an extracellular matrix gene expression profile defining a breast cancer subtype likely to progress.

    Directory of Open Access Journals (Sweden)

    Tiziana Triulzi

    Full Text Available We recently showed that differential expression of extracellular matrix (ECM genes delineates four subgroups of breast carcinomas (ECM1, -2, -3- and -4 with different clinical outcome. To further investigate the characteristics of ECM signature and its impact on tumor progression, we conducted unsupervised clustering analyses in 6 additional independent datasets of invasive breast tumors from different platforms for a total of 643 samples. Use of four different clustering algorithms identified ECM3 tumors as an independent group in all datasets tested. ECM3 showed a homogeneous gene pattern, consisting of 58 genes encoding 43 structural ECM proteins. From 26 to 41% of the cases were ECM3-enriched, and analysis of datasets relevant to gene expression in neoplastic or corresponding stromal cells showed that both stromal and breast carcinoma cells can coordinately express ECM3 genes. In in vitro experiments, β-estradiol induced ECM3 gene production in ER-positive breast carcinoma cell lines, whereas TGFβ induced upregulation of the genes leading to ECM3 gene classification, especially in ER-negative breast carcinoma cells and in fibroblasts. Multivariate analysis of distant metastasis-free survival in untreated breast tumor patients revealed a significant interaction between ECM3 and histological grade (p = 0.001. Cox models, estimated separately in grade I-II and grade III tumors, indicated a highly significant association between ECM3 and worse survival probability only in grade III tumors (HR = 3.0, 95% CI = 1.3-7.0, p = 0.0098. Gene Set Enrichment analysis of ECM3 compared to non-ECM3 tumors revealed significant enrichment of epithelial-mesenchymal transition (EMT genes in both grade I-II and grade III subsets of ECM3 tumors. Thus, ECM3 is a robust cluster that identifies breast carcinomas with EMT features but with accelerated metastatic potential only in the undifferentiated (grade III phenotype. These findings support the

  15. Progress on optimizing miscanthus biomass production for the european bioeconomy

    NARCIS (Netherlands)

    Lewandowski, Iris; Clifton-Brown, John; Trindade, Luisa M.; Linden, van der Gerard C.; Schwarz, Kai Uwe; Müller-Sämann, Karl; Anisimov, Alexander; Chen, C.L.; Dolstra, Oene; Donnison, Iain S.; Farrar, Kerrie; Fonteyne, Simon; Harding, Graham; Hastings, Astley; Huxley, Laurie M.; Iqbal, Yasir; Khokhlov, Nikolay; Kiesel, Andreas; Lootens, Peter; Meyer, Heike; Mos, Michal; Muylle, Hilde; Nunn, Chris; Özgüven, Mensure; Roldán-Ruiz, Isabel; Schüle, Heinrich; Tarakanov, Ivan; Weijde, van der Tim; Wagner, Moritz; Xi, Qingguo; Kalinina, Olena

    2016-01-01

    This paper describes the complete findings of the EU-funded research project OPTIMISC, which investigated methods to optimize the production and use of miscanthus biomass. Miscanthus bioenergy and bioproduct chains were investigated by trialing 15 diverse germplasm types in a range of climatic and s

  16. Progress and prospects of gene therapy clinical trials for the muscular dystrophies.

    Science.gov (United States)

    Bengtsson, Niclas E; Seto, Jane T; Hall, John K; Chamberlain, Jeffrey S; Odom, Guy L

    2016-04-15

    Clinical trials represent a critical avenue for new treatment development, where early phases (I, I/II) are designed to test safety and effectiveness of new therapeutics or diagnostic indicators. A number of recent advances have spurred renewed optimism toward initiating clinical trials and developing refined therapies for the muscular dystrophies (MD's) and other myogenic disorders. MD's encompass a heterogeneous group of degenerative disorders often characterized by progressive muscle weakness and fragility. Many of these diseases result from mutations in genes encoding proteins of the dystrophin-glycoprotein complex (DGC). The most common and severe form among children is Duchenne muscular dystrophy, caused by mutations in the dystrophin gene, with an average life expectancy around 25 years of age. Another group of MD's referred to as the limb-girdle muscular dystrophies (LGMDs) can affect boys or girls, with different types caused by mutations in different genes. Mutation of the α-sarcoglycan gene, also a DGC component, causes LGMD2D and represents the most common form of LGMD. Early preclinical and clinical trial findings support the feasibility of gene therapy via recombinant adeno-associated viral vectors as a viable treatment approach for many MDs. In this mini-review, we present an overview of recent progress in clinical gene therapy trials of the MD's and touch upon promising preclinical advances.

  17. The plant mitochondrial mat-r gene/nad1 gene complex. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Wolstenholme, D.R.

    1994-06-01

    The authors have completed sequencing the segments (totalling 19 kb, both complementary strands) of the maize mtDNA molecule that encode the entire NADH dehydrogenase subunit (nadl) gene. They have identified nucleotides in mature transcripts of the nadl gene that are edited and have generated clones of cDNAs of entire mature (fully spliced) nadl transcripts. They have examined the relative rates of splicing in transcripts of the four nadl gene group II introns and begun examining nadl intron cDNAs to determine the extent and distribution of RNA edits in introns, in order to evaluate the possibility that intron excision and exon splicing might be editing independent.

  18. Heart failure-inducible gene therapy targeting protein phosphatase 1 prevents progressive left ventricular remodeling.

    Directory of Open Access Journals (Sweden)

    Yosuke Miyazaki

    Full Text Available BACKGROUND: The targeting of Ca(2+ cycling has emerged as a potential therapy for the treatment of severe heart failure. These approaches include gene therapy directed at overexpressing sarcoplasmic reticulum (SR Ca(2+ ATPase, or ablation of phospholamban (PLN and associated protein phosphatase 1 (PP1 protein complexes. We previously reported that PP1β, one of the PP1 catalytic subunits, predominantly suppresses Ca(2+ uptake in the SR among the three PP1 isoforms, thereby contributing to Ca(2+ downregulation in failing hearts. In the present study, we investigated whether heart-failure-inducible PP1β-inhibition by adeno-associated viral-9 (AAV9 vector mediated gene therapy is beneficial for preventing disease progression in genetic cardiomyopathic mice. METHODS: We created an adeno-associated virus 9 (AAV9 vector encoding PP1β short-hairpin RNA (shRNA or negative control (NC shRNA. A heart failure inducible gene expression system was employed using the B-type natriuretic protein (BNP promoter conjugated to emerald-green fluorescence protein (EmGFP and the shRNA sequence. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA were injected into the tail vein (2×10(11 GC/mouse of muscle LIM protein deficient mice (MLPKO, followed by serial analysis of echocardiography, hemodynamic measurement, biochemical and histological analysis at 3 months. RESULTS: In the MLPKO mice, BNP promoter activity was shown to be increased by detecting both EmGFP expression and the induced reduction of PP1β by 25% in the myocardium. Inducible PP1βshRNA delivery preferentially ameliorated left ventricular diastolic function and mitigated adverse ventricular remodeling. PLN phosphorylation was significantly augmented in the AAV9-BNP-EmGFP-PP1βshRNA injected hearts compared with the AAV9-BNP-EmGFP-NCshRNA group. Furthermore, BNP production was reduced, and cardiac interstitial fibrosis was abrogated at 3 months. CONCLUSION: Heart failure

  19. RERTR progress in Mo-99 production from LEU

    Energy Technology Data Exchange (ETDEWEB)

    Vandegrift, G.F.; Conner, C.; Aase, S.; Bakel, A.; Bowers, D.; Freiberg, E.; Gelis, A.; Quigley, K.J.; Snelgrove, J.L. [Argonne National Laboratory 9700 S. Cass Avenue, Argonne, IL (United States)

    2002-07-01

    The ANL RERTR program is performing R and D supporting conversion of {sup 99}Mo production from HEU to LEU targets. Irradiation and processing of LEU targets were demonstrated at the Argentine Ezeiza Atomic Center. Target irradiation and disassembly were flawless, but the processing is not fully developed. In addition to preparing for, assisting in, and analyzing results of the demonstration, we performed other R and D related to LEU conversion: (1) designing a prototype production dissolver for digesting irradiated LEU foils in alkaline solutions and developing means to simplify digestion, (2) modifying ion-exchange columns used in the CNEA recovery and purification of {sup 99}Mo to deal with the lower volumes generated from LEU-foil digestion, (3) measuring the performance of new inorganic sorbents that outperform alumina for recovering Mo(VI) from nitric acid solutions containing high concentrations of uranium nitrate, and (4) developing means to facilitate the concentration and calcination of waste nitric-acid/LEU-nitrate solutions from {sup 99} Mo production. (author)

  20. Long noncoding RNA BCAR4 promotes osteosarcoma progression through activating GLI2-dependent gene transcription.

    Science.gov (United States)

    Chen, Fenyong; Mo, Jiadong; Zhang, Li

    2016-10-01

    Despite great advances have been made in the understanding of biology of osteosarcoma, the molecular mechanisms involved in osteosarcoma tumorigenesis and progression are still largely unknown. Long noncoding RNA (lncRNA) is a new type of RNA molecule, which plays pivotal roles in many tumors. lncRNA BCAR4 has been identified as an oncogenetic lncRNA involved in the progression of breast cancer. However, the functions and clinical significances of BCAR4 in osteosarcoma are unknown now. In this study, we found that BCAR4 was significantly upregulated in osteosarcoma tissues. Increased expression of BCAR4 was significantly correlated with large tumor size, advanced Enneking stage, lung metastasis, and poor prognosis. Functional experiments demonstrated that knockdown of BCAR4 inhibits the proliferation and migration of osteosarcoma cell in vitro. Consistently, knockdown of BCAR4 inhibits osteosarcoma tumorigenesis and lung metastasis in vivo. Chromatin isolation by RNA purification assay showed that BCAR4 physically associates with the promoters of GLI2 target genes. The depletion of BCAR4 inhibits the expression of GLI2 target genes and GLI2 reporter luciferase activity in a dose-dependent manner. The expression of BCAR4 and GLI2 target genes is significantly correlated in osteosarcoma tissues. Depletion of DLI2 abolished the effects of BCAR4 on osteosarcoma. Taken together, these findings demonstrated that BCAR4 promotes osteosarcoma progression via activating GLI2-dependent gene transcription and serves as a potential prognostic biomarker and a therapeutic target of osteosarcoma.

  1. Cancer classification through filtering progressive transductive support vector machine based on gene expression data

    Science.gov (United States)

    Lu, Xinguo; Chen, Dan

    2017-08-01

    Traditional supervised classifiers neglect a large amount of data which not have sufficient follow-up information, only work with labeled data. Consequently, the small sample size limits the advancement of design appropriate classifier. In this paper, a transductive learning method which combined with the filtering strategy in transductive framework and progressive labeling strategy is addressed. The progressive labeling strategy does not need to consider the distribution of labeled samples to evaluate the distribution of unlabeled samples, can effective solve the problem of evaluate the proportion of positive and negative samples in work set. Our experiment result demonstrate that the proposed technique have great potential in cancer prediction based on gene expression.

  2. PRODUCT GENE REPRESENTATION AND ACQUISITION METHOD BASED ON POPULATION OF PRODUCT CASES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The representation and acquisition of a product gene is a crucial problem in product evolutionary design. A new methodology of product gene representation and acquisition from a population of product cases is proposed, and the methodology for product evolutionary design based on a population of product cases is realized. By properly classifying product cases according to its product species, the populations of product cases are divided and a model is established. Knowledge of the scheme design is extracted and formulated as the function base, principle base, and structure base, which are then combined to form a product gene. Subsequently, the product gene tree is created and represented by object-oriented method. Then combining this method with the evolutionary reasoning technology, an intelligent and automatic evolutionary scheme design of product based on the population of product cases is realized. This design method will be helpful in the processing of knowledge formulation, accumulation, and reuse, and in addressing the difficulty of acquiring design knowledge in traditional design. In addition, the disadvantages of manual case adaptation and update in case-based reasoning can be eliminated. Moreover, by optimizing the design scheme in multiple levels and aspects of product function, principle, and structure etc., the level of creativity in the scheme design can be improved.

  3. Responsiveness of muscle tone characteristics to progressive force production.

    Science.gov (United States)

    Mustalampi, Sirpa; Häkkinen, Arja; Kautiainen, Hannu; Weir, Adam; Ylinen, Jari

    2013-01-01

    It is possible to measure muscle tone reliably, quickly and objectively using tonometers although they are not yet widely used. In clinical practice, it may be helpful if clinicians could assess the degree of contraction in different parts of a muscle without having to perform time-consuming electromyography measurements. The purpose of this study was to evaluate the responsiveness of different muscle tone characteristics to progressively increased contraction force of quadriceps muscle. Twenty healthy subjects (mean age 39.9 years, 50% women) volunteered. Using 2 different tonometers various muscle viscoelastic properties were measured. The frequency (hertz), logarithmic decrement, and stiffness (newtons per meter) of damped mechanical oscillation of the muscle tissue and tissue compliance (millijoules) were registered from rectus femoris muscle at rest and 20, 40, 60, 80% of maximal voluntary contraction determined using dynamometry. All the values changed linearly with increasing force level. Compliance, oscillation stiffness, and frequency parameters showed large effect sizes (ESs ≥ 0.8). The standardized respoknse mean for compliance was 5.3 (4.8-5.7) mJ, for oscillation stiffness 1.8 (1.3-2.2) N·m(-1), frequency 1.1 (0.6-1.5) Hz, and decrement -0.6 (-1.0 to -0.2). The results indicate that the compliance and oscillation stiffness parameters showed the highest responsiveness and can thus best detect changes in muscle contraction state. The additional value of using tonometers to measure these properties in clinical practice should be investigated further.

  4. Gene Delivery into Plant Cells for Recombinant Protein Production

    OpenAIRE

    Qiang Chen; Huafang Lai

    2015-01-01

    Recombinant proteins are primarily produced from cultures of mammalian, insect, and bacteria cells. In recent years, the development of deconstructed virus-based vectors has allowed plants to become a viable platform for recombinant protein production, with advantages in versatility, speed, cost, scalability, and safety over the current production paradigms. In this paper, we review the recent progress in the methodology of agroinfiltration, a solution to overcome the challenge of transgene d...

  5. Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

    Science.gov (United States)

    Rangel, Roberto; Lee, Song-Choon; Hon-Kim Ban, Kenneth; Guzman-Rojas, Liliana; Mann, Michael B.; Newberg, Justin Y.; McNoe, Leslie A.; Selvanesan, Luxmanan; Ward, Jerrold M.; Rust, Alistair G.; Chin, Kuan-Yew; Black, Michael A.; Jenkins, Nancy A.; Copeland, Neal G.

    2016-01-01

    Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1. Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC. PMID:27849608

  6. Oxidative stress: Lipid peroxidation products as predictors in disease progression

    Directory of Open Access Journals (Sweden)

    Suranjana Ray Halder

    2014-09-01

    Full Text Available Oxidative stress is implicated in the pathogenesis of numerous disease processes, including diabetes mellitus, atherosclerosis, ischemia reperfusion injury, rheumatoid arthritis, neurodegenerative diseases as well as in the aging process. Chemical modification of amino acids in protein during lipid peroxidation (LPO results in the formation of lipoxidation products, which may serve as indicators of oxidative stress in vivo. The various types of aldehydes such as 4-hydroxynonenal, malondialdehyde, acrolein and others produced during LPO may serve as potent oxidative stress biomarkers. Their activation in different signaling cascades lead to apoptosis, differentiation, proliferation, etc., Increased amount of these aldehydes in aging or with metabolic complications or in other diseases indicate their pathophysiological significance. Thus, LPO products or other oxidative stress biomarkers may open the way for the development of early detection, prevention, and therapeutic strategies for stress associated human diseases. Now-a-days, antioxidant supplementation has become an increasingly popular practice to restore the redox homeostatic condition of the cell. Disease specific, target directed, bioavailable antioxidants may be beneficial for sustenance of the quality-of-life in future days. [J Exp Integr Med 2014; 4(3.000: 151-164

  7. Products of rectangular random matrices: singular values and progressive scattering.

    Science.gov (United States)

    Akemann, Gernot; Ipsen, Jesper R; Kieburg, Mario

    2013-11-01

    We discuss the product of M rectangular random matrices with independent Gaussian entries, which have several applications, including wireless telecommunication and econophysics. For complex matrices an explicit expression for the joint probability density function is obtained using the Harish-Chandra-Itzykson-Zuber integration formula. Explicit expressions for all correlation functions and moments for finite matrix sizes are obtained using a two-matrix model and the method of biorthogonal polynomials. This generalizes the classical result for the so-called Wishart-Laguerre Gaussian unitary ensemble (or chiral unitary ensemble) at M=1, and previous results for the product of square matrices. The correlation functions are given by a determinantal point process, where the kernel can be expressed in terms of Meijer G-functions. We compare the results with numerical simulations and known results for the macroscopic level density in the limit of large matrices. The location of the end points of support for the latter are analyzed in detail for general M. Finally, we consider the so-called ergodic mutual information, which gives an upper bound for the spectral efficiency of a MIMO communication channel with multifold scattering.

  8. Co-expression of mitosis-regulating genes contributes to malignant progression and prognosis in oligodendrogliomas.

    Science.gov (United States)

    Liu, Yanwei; Hu, Huimin; Zhang, Chuanbao; Wang, Haoyuan; Zhang, Wenlong; Wang, Zheng; Li, Mingyang; Zhang, Wei; Zhou, Dabiao; Jiang, Tao

    2015-11-10

    The clinical prognosis of patients with glioma is determined by tumor grades, but tumors of different subtypes with equal malignancy grade usually have different prognosis that is largely determined by genetic abnormalities. Oligodendrogliomas (ODs) are the second most common type of gliomas. In this study, integrative analyses found that distribution of TCGA transcriptomic subtypes was associated with grade progression in ODs. To identify critical gene(s) associated with tumor grades and TCGA subtypes, we analyzed 34 normal brain tissue (NBT), 146 WHO grade II and 130 grade III ODs by microarray and RNA sequencing, and identified a co-expression network of six genes (AURKA, NDC80, CENPK, KIAA0101, TIMELESS and MELK) that was associated with tumor grades and TCGA subtypes as well as Ki-67 expression. Validation of the six genes was performed by qPCR in additional 28 ODs. Importantly, these genes also were validated in four high-grade recurrent gliomas and the initial lower-grade gliomas resected from the same patients. Finally, the RNA data on two genes with the highest discrimination potential (AURKA and NDC80) and Ki-67 were validated on an independent cohort (5 NBTs and 86 ODs) by immunohistochemistry. Knockdown of AURKA and NDC80 by siRNAs suppressed Ki-67 expression and proliferation of gliomas cells. Survival analysis showed that high expression of the six genes corporately indicated a poor survival outcome. Correlation and protein interaction analysis provided further evidence for this co-expression network. These data suggest that the co-expression of the six mitosis-regulating genes was associated with malignant progression and prognosis in ODs.

  9. Meta-analysis of gene expression signatures defining the epithelial to mesenchymal transition during cancer progression.

    Directory of Open Access Journals (Sweden)

    Christian J Gröger

    Full Text Available The epithelial to mesenchymal transition (EMT represents a crucial event during cancer progression and dissemination. EMT is the conversion of carcinoma cells from an epithelial to a mesenchymal phenotype that associates with a higher cell motility as well as enhanced chemoresistance and cancer stemness. Notably, EMT has been increasingly recognized as an early event of metastasis. Numerous gene expression studies (GES have been conducted to obtain transcriptome signatures and marker genes to understand the regulatory mechanisms underlying EMT. Yet, no meta-analysis considering the multitude of GES of EMT has been performed to comprehensively elaborate the core genes in this process. Here we report the meta-analysis of 18 independent and published GES of EMT which focused on different cell types and treatment modalities. Computational analysis revealed clustering of GES according to the type of treatment rather than to cell type. GES of EMT induced via transforming growth factor-β and tumor necrosis factor-α treatment yielded uniformly defined clusters while GES of models with alternative EMT induction clustered in a more complex fashion. In addition, we identified those up- and downregulated genes which were shared between the multitude of GES. This core gene list includes well known EMT markers as well as novel genes so far not described in this process. Furthermore, several genes of the EMT-core gene list significantly correlated with impaired pathological complete response in breast cancer patients. In conclusion, this meta-analysis provides a comprehensive survey of available EMT expression signatures and shows fundamental insights into the mechanisms that are governing carcinoma progression.

  10. Hepatic gene expression profiles associated with fibrosis progression and hepatocarcinogenesis in hepatitis C patients

    Institute of Scientific and Technical Information of China (English)

    Run-Xuan Shao; Takao Kawabe; Masao Omata; Yujin Hoshida; Motoyuki Otsuka; Naoya Kato; Ryosuke Tateishi; Takuma Teratani; Shuichiro Shiina; Hiroyoshi Taniguchi; Masaru Moriyama

    2005-01-01

    AIM: To determine fibrosis progression and hepatocellular carcinoma (HCC), using simultaneous gene expression analysis.METHODS: Total RNA samples were extracted from liver biopsies from 19 patients with hepatitis C virus (HCV)infection and 3 patients without HCV infection. Among the 19 HCV-infected patients, 7 and 12 patients had grade F1-2 and F3-4 fibrosis, respectively. Of the 12 patients with F3-4 fibrosis, 8 had HCC. Gene expression in the liver samples was determined using an oligonucleotide microarray. The following comparisons were performed:normal livers vs HCV-infected livers; F1-2 vs F3-4; and F3-4 with HCC vs F3-4 without HCC. Genes that were differentially expressed between these groups were identified based on signal-to-noise ratios.RESULTS: In the HCV-infected livers, genes involved in immune responses were highly expressed. Expression levels of genes for plasma proteins and drug-metabolizing enzymes were decreased and those of genes involved in the cell cycle and oncogenesis were increased in the F3-4 cases as compared to the F1-2 cases. Among the F3-4 cases, genes involved in carbohydrate metabolism tended to be more highly expressed in patients with HCC than in patients without HCC.CONCLUSION: We identified genes that are associated with fibrosis progression and hepatocarcinogenesis. This information may be used to detect increased carcinogenic potential in the livers of patients with HCV infection.

  11. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.

    Directory of Open Access Journals (Sweden)

    Howard Y Chang

    2004-02-01

    Full Text Available Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are unclear. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. The genes comprising this fibroblast common serum response are coordinately regulated in many human tumors, allowing us to identify tumors with gene expression signatures suggestive of active wounds. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. The molecular features that define this wound-like phenotype are evident at an early clinical stage, persist during treatment, and predict increased risk of metastasis and death in breast, lung, and gastric carcinomas. Thus, the transcriptional signature of the response of fibroblasts to serum provides a possible link between cancer progression and wound healing, as well as a powerful predictor of the clinical course in several common carcinomas.

  12. Research Progress on Production of Podophyllotoxin from Sinopodophyllum hexandrum

    Institute of Scientific and Technical Information of China (English)

    Liu Haijun; Xu Yan; Su Guoqing; Li Chunyan; Wang Li; Liu Yujun

    2004-01-01

    Podophyllotoxin is isolated mainly from the rhizomes of Podophyllum plants, and serves as the main precursor for synthesis of anticancer drugs, such as VP-16 and VM-26. VP-16 and VM-26 are used for curing lung cancer, testicular cancer, neuroblastoma, hepatoma and other tumors. However, these plants are all near-extinction species due to over-collection and their own biological characteristics. The chemical synthesis of podophyllotoxin is so complicated that its price is unbelievably high. This paper discusses the current status of the biosynthetic pathway of podophyllotoxin and that of the podophyllotoxin production using several biotechnological approaches such as plant organ cultures, plant cell cultures with both flasks and bioreactors, hairy root cultures, bioconversions and metabolic regulations.

  13. Molecular characterization of a maize regulatory gene. Progress report, July 1989--March 1990

    Energy Technology Data Exchange (ETDEWEB)

    Wessler, S.

    1990-12-31

    This progress report contains information concerning the characterization of the Maize regulatory gene. The findings of this research program have immediate significance. Firstly, it provides support for the notion that R proteins, produced by the regulatory gene, are functionally equivalent. Secondly, the success of these experiments provides a simple transient assay for either natural or constructed R protein mutations. The relative ease of this assay coupled with overnight results are important prerequisites to the proposed experiments involving a structure-function analysis of the R protein.

  14. A new gene ontology-based measure for the functional similarity of gene products

    Institute of Scientific and Technical Information of China (English)

    QI Guo-long; QIAN Shi-yu; FANG Ji-qian

    2013-01-01

    Background Although biomedical ontologies have standardized the representation of gene products across species and databases,a method for determining the functional similarities of gene products has not yet been developed.Methods We proposed a new semantic similarity measure based on Gene Ontology that considers the semantic influences from all of the ancestor terms in a graph.Our measure was compared with Resnik's measure in two applications,which were based on the association of the measure used with the gene co-expression and the proteinprotein interactions.Results The results showed a considerable association between the semantic similarity and the expression correlation and between the semantic similarity and the protein-protein interactions,and our measure performed the best overall.Conclusion These results revealed the potential value of our newly proposed semantic similarity measure in studying the functional relevance of gene products.

  15. Gene analogue finder: a GRID solution for finding functionally analogous gene products

    Directory of Open Access Journals (Sweden)

    Licciulli Flavio

    2007-09-01

    Full Text Available Abstract Background To date more than 2,1 million gene products from more than 100000 different species have been described specifying their function, the processes they are involved in and their cellular localization using a very well defined and structured vocabulary, the gene ontology (GO. Such vast, well defined knowledge opens the possibility of compare gene products at the level of functionality, finding gene products which have a similar function or are involved in similar biological processes without relying on the conventional sequence similarity approach. Comparisons within such a large space of knowledge are highly data and computing intensive. For this reason this project was based upon the use of the computational GRID, a technology offering large computing and storage resources. Results We have developed a tool, GENe AnaloGue FINdEr (ENGINE that parallelizes the search process and distributes the calculation and data over the computational GRID, splitting the process into many sub-processes and joining the calculation and the data on the same machine and therefore completing the whole search in about 3 days instead of occupying one single machine for more than 5 CPU years. The results of the functional comparison contain potential functional analogues for more than 79000 gene products from the most important species. 46% of the analyzed gene products are well enough described for such an analysis to individuate functional analogues, such as well-known members of the same gene family, or gene products with similar functions which would never have been associated by standard methods. Conclusion ENGINE has produced a list of potential functionally analogous relations between gene products within and between species using, in place of the sequence, the gene description of the GO, thus demonstrating the potential of the GO. However, the current limiting factor is the quality of the associations of many gene products from non

  16. Recent progress and future challenges in algal biofuel production [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Jonathan B. Shurin

    2016-10-01

    Full Text Available Modern society is fueled by fossil energy produced millions of years ago by photosynthetic organisms. Cultivating contemporary photosynthetic producers to generate energy and capture carbon from the atmosphere is one potential approach to sustaining society without disrupting the climate. Algae, photosynthetic aquatic microorganisms, are the fastest growing primary producers in the world and can therefore produce more energy with less land, water, and nutrients than terrestrial plant crops. We review recent progress and challenges in developing bioenergy technology based on algae. A variety of high-value products in addition to biofuels can be harvested from algal biomass, and these may be key to developing algal biotechnology and realizing the commercial potential of these organisms. Aspects of algal biology that differentiate them from plants demand an integrative approach based on genetics, cell biology, ecology, and evolution. We call for a systems approach to research on algal biotechnology rooted in understanding their biology, from the level of genes to ecosystems, and integrating perspectives from physical, chemical, and social sciences to solve one of the most critical outstanding technological problems.

  17. Exploration of new perspectives and limitations in Agrobacterium mediated gene transfer technology. Progress report, [June 1, 1992-- May 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Marton, L.

    1994-12-31

    This report describes progress aimed at constructing gene-transfer technology for Nicotiana plumbaginifolia. Most actual effort as described herein has so far been directed at exploring new perspectives and limitations in Agrobacterium mediated gene transfer. Accomplishments are described using a core homologous gene targeting vector.

  18. Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen.

    Science.gov (United States)

    Kok, Marleen; Linn, Sabine C; Van Laar, Ryan K; Jansen, Maurice P H M; van den Berg, Teun M; Delahaye, Leonie J M J; Glas, Annuska M; Peterse, Johannes L; Hauptmann, Michael; Foekens, John A; Klijn, Jan G M; Wessels, Lodewyk F A; Van't Veer, Laura J; Berns, Els M J J

    2009-01-01

    Molecular signatures that predict outcome in tamoxifen treated breast cancer patients have been identified. For the first time, we compared these response profiles in an independent cohort of (neo)adjuvant systemic treatment naïve breast cancer patients treated with first-line tamoxifen for metastatic disease. From a consecutive series of 246 estrogen receptor (ER) positive primary tumors, gene expression profiling was performed on available frozen tumors using 44K oligoarrays (n = 69). A 78-gene tamoxifen response profile (formerly consisting of 81 cDNA-clones), a 21-gene set (microarray-based Recurrence Score), as well as the HOXB13-IL17BR ratio (Two-Gene-Index, RT-PCR) were analyzed. Performance of signatures in relation to time to progression (TTP) was compared with standard immunohistochemical (IHC) markers: ER, progesterone receptor (PgR) and HER2. In univariate analyses, the 78-gene tamoxifen response profile, 21-gene set and HOXB13-IL17BR ratio were all significantly associated with TTP with hazard ratios of 2.2 (95% CI 1.3-3.7, P = 0.005), 2.3 (95% CI 1.3-4.0, P = 0.003) and 4.2 (95% CI 1.4-12.3, P = 0.009), respectively. The concordance among the three classifiers was relatively low, they classified only 45-61% of patients in the same category. In multivariate analyses, the association remained significant for the 78-gene profile and the 21-gene set after adjusting for ER and PgR. The 78-gene tamoxifen response profile, the 21-gene set and the HOXB13-IL17BR ratio were all significantly associated with TTP in an independent patient series treated with tamoxifen. The addition of multigene assays to ER (IHC) improves the prediction of outcome in tamoxifen treated patients and deserves incorporation in future clinical studies.

  19. Progressive retinal atrophy in Schapendoes dogs: mutation of the newly identified CCDC66 gene.

    Science.gov (United States)

    Dekomien, Gabriele; Vollrath, Conni; Petrasch-Parwez, Elisabeth; Boevé, Michael H; Akkad, Denis A; Gerding, Wanda M; Epplen, Jörg T

    2010-05-01

    Canine generalized progressive retinal atrophy (gPRA) is characterized by continuous degeneration of photoreceptor cells leading to night blindness and progressive vision loss. Until now, mutations in 11 genes have been described that account for gPRA in dogs, mostly following an autosomal recessive inheritance mode. Here, we describe a gPRA locus comprising the newly identified gene coiled-coil domain containing 66 (CCDC66) on canine chromosome 20, as identified via linkage analysis in the Schapendoes breed. Mutation screening of the CCDC66 gene revealed a 1-bp insertion in exon 6 leading to a stop codon as the underlying cause of disease. The insertion is present in all affected dogs in the homozygous state as well as in all obligatory mutation carriers in the heterozygous state. The CCDC66 gene is evolutionarily conserved in different vertebrate species and exhibits a complex pattern of differential RNA splicing resulting in various isoforms in the retina. Immunohistochemically, CCDC66 protein is detected mainly in the inner segments of photoreceptors in mouse, dog, and man. The affected Schapendoes retina lacks CCDC66 protein. Thus this natural canine model for gPRA yields superior potential to understand functional implications of this newly identified protein including its physiology, and it opens new perspectives for analyzing different aspects of the general pathophysiology of gPRA.

  20. Latest progress of BIGH3 gene in corneal diseases and diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Fan-Qian Song

    2017-03-01

    Full Text Available BIGH3 gene plays an important role in ocular diseases. On the one hand, it is closely related to the occurrence of corneal diseases. BIGH3 gene can inhibit corneal neovascularization, lead to corneal dystrophy, participate in keratoconus formation. On the other hand, it can lead to the formation of neovascularization in diabetic retinopathy. The latest experiments show that TGF beta secreted by macrophages can promote the expression of BIGH3 mRNA and BIGH3 protein, and promote apoptosis of retinal endothelial cells and pericytes, which leads to the formation of neovascularization in diabetic retinopathy. This article will describe the new progress of BIGH3 gene in ocular diseases from several aspects as mentioned above.

  1. A two-cassette reporter system for assessing target gene translation and target gene product inclusion body formation

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention relates to a dual cassette reporter system capable of assessing target gene translation and target gene product folding. The present invention further relates to vectors and host cells comprising the dual cassette reporter system. In addition the invention relates to the use...... of the dual cassette reporter system for assessing target gene translation and target gene product folding....

  2. The impact of osteopontin gene variations on multiple sclerosis development and progression.

    Science.gov (United States)

    Comi, Cristoforo; Cappellano, Giuseppe; Chiocchetti, Annalisa; Orilieri, Elisabetta; Buttini, Sara; Ghezzi, Laura; Galimberti, Daniela; Guerini, Franca; Barizzone, Nadia; Perla, Franco; Leone, Maurizio; D'Alfonso, Sandra; Caputo, Domenico; Scarpini, Elio; Cantello, Roberto; Dianzani, Umberto

    2012-01-01

    Osteopontin is a proinflammatory molecule, modulating TH1 and TH17 responses. Several reports suggest its involvement in multiple sclerosis (MS) pathogenesis. We previously reported that OPN gene variations at the 3' end are a predisposing factor for MS development and evolution. In this paper, we extended our analysis to a gene variation at the 5' end on the -156G > GG single nucleotide polymorphism (SNP) and replicated our previous findings at the 3' end on the +1239A > C SNP. We found that only +1239A > C SNP displayed a statistically significant association with MS development, but both +1239A > C and -156G > GG had an influence on MS progression, since patients homozygous for both +1239A and -156GG alleles displayed slower progression of disability and slower switch to secondary progression than those carrying +1239C and/or -156G and those homozygous for +1239A only. Moreover, patients homozygous for +1239A also displayed a significantly lower relapse rate than those carrying +1239C, which is in line with the established role of OPN in MS relapses.

  3. Fibroblast gene expression profile reflects the stage of tumour progression in oral squamous cell carcinoma.

    Science.gov (United States)

    Lim, Kue Peng; Cirillo, Nicola; Hassona, Yazan; Wei, Wenbin; Thurlow, Johanna K; Cheong, Sok Ching; Pitiyage, Gayani; Parkinson, E Ken; Prime, Stephen S

    2011-03-01

    Oral cancer is a highly aggressive malignancy with poor prognosis. This study examined the behaviour of fibroblast strains from normal oral mucosa, dysplastic epithelial tissue, and genetically stable (minimal copy number alterations-CNA; minimal loss of heterozygosity-LOH; wild-type p53; wild-type p16INK4A) and unstable (extensive CNA and LOH; inactivation of p53 and p16INK4A) oral squamous cell carcinoma (OSCC). Fibroblasts from genetically unstable OSCC relative to the other fibroblast subtypes grew more slowly and stimulated the invasion of a non-tumourigenic keratinocyte cell line into fibroblast-rich collagen gels. To understand these findings, genome-wide transcriptional profiles were generated using the GeneChip(®) cDNA whole transcript microarray platform. Principal component analysis showed that the fibroblasts could be distinguished according to the stage of tumour development. Tumour progression was associated with down-regulation of cell cycle- and cytokinesis-related genes and up-regulation of genes encoding transmembrane proteins including cell adhesion molecules. Gene expression was validated in independent fibroblast strains using qRT-PCR. Gene connectivity and interactome-transcriptome associations were determined using a systems biology approach to interrogate the gene expression data. Clusters of gene signatures were identified that characterized genetically unstable and stable OSCCs relative to each other and to fibroblasts from normal oral mucosa. The expression of highly connected genes associated with unstable OSCCs, including those that encode α-SMA and the integrin α6, correlated with poor patient prognosis in an independent dataset of head and neck cancer. The results of this study demonstrate that fibroblasts from unstable OSCCs represent a phenotypically distinguishable subset that plays a major role in oral cancer biology. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  4. Disease progression and phasic changes in gene expression in a mouse model of osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Richard F Loeser

    Full Text Available Osteoarthritis (OA is the most common form of arthritis and has multiple risk factors including joint injury. The purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model and to identify genes regulated during different stages of the disease, using RNA isolated from the joint "organ" and analyzed using microarrays. Histologic changes seen in OA, including articular cartilage lesions and osteophytes, were present in the medial tibial plateaus of the DMM knees beginning at the earliest (2 week time point and became progressively more severe by 16 weeks. 427 probe sets (371 genes from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin. Immunostaining revealed the presence of these three proteins in cartilage and soft tissues including ligaments as well as in the fibrocartilage covering osteophytes. The results support a phasic development of OA with early matrix remodeling and transcriptional activity followed by a more quiescent period that is not maintained. This implies that the response to an OA intervention will depend on the timing of the intervention. The quiescent period at 8 weeks may be due to the maturation of the osteophytes which are thought to temporarily stabilize the joint.

  5. Perinatal Gene-Gene and Gene-Environment Interactions on IgE Production and Asthma Development

    Directory of Open Access Journals (Sweden)

    Jen-Chieh Chang

    2012-01-01

    Full Text Available Atopic asthma is a complex disease associated with IgE-mediated immune reactions. Numerous genome-wide studies identified more than 100 genes in 22 chromosomes associated with atopic asthma, and different genetic backgrounds in different environments could modulate susceptibility to atopic asthma. Current knowledge emphasizes the effect of tobacco smoke on the development of childhood asthma. This suggests that asthma, although heritable, is significantly affected by gene-gene and gene-environment interactions. Evidence has recently shown that molecular mechanism of a complex disease may be limited to not only DNA sequence differences, but also gene-environmental interactions for epigenetic difference. This paper reviews and summarizes how gene-gene and gene-environment interactions affect IgE production and the development of atopic asthma in prenatal and childhood stages. Based on the mechanisms responsible for perinatal gene-environment interactions on IgE production and development of asthma, we formulate several potential strategies to prevent the development of asthma in the perinatal stage.

  6. Search for major genes with progeny test data to accelerate the development of genetically superior loblolly pine. Technical progress report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-02-15

    This report details the progress of the three tasks of this project. The tasks are: (1) develop genetic models and analytical methods; (2) molecular confirmation of major gene segregation; and (3) develop strategies for marker-assisted breeding.

  7. Appraisement on Contributive Ratio of Scientific and Technical Progresses in Milk Productive Enterprises by Model C2GS2

    Institute of Scientific and Technical Information of China (English)

    SUN Futian; SUN Liqun; YANG Guanglin

    2008-01-01

    Scientific and technical progress has been the driving forces of enterprises development. Milk productive enterprises are developing faster and growing better. It is very important to measure the contributive ratio of scientific and technical progress in milk productive enterprises. And the appraisement could help to develop milk productive enterprises. The model C2GS2 was established to appraise the contributive ratio of scientific and technical progress in milk productive enterprises in the research. And the appraisement on the contributive ratio of scientific and technical progress in milk productive enterprises was made by the model. In the results of appraisement, science and technology play a main role in milk productive enterprises. It is shown that our milk productive enterprises are developed by scientific and technical progress while not by input of productive factors.

  8. Cancer progression mediated by horizontal gene transfer in an in vivo model.

    Directory of Open Access Journals (Sweden)

    Catalina Trejo-Becerril

    Full Text Available It is known that cancer progresses by vertical gene transfer, but this paradigm ignores that DNA circulates in higher organisms and that it is biologically active upon its uptake by recipient cells. Here we confirm previous observations on the ability of cell-free DNA to induce in vitro cell transformation and tumorigenesis by treating NIH3T3 recipient murine cells with serum of colon cancer patients and supernatant of SW480 human cancer cells. Cell transformation and tumorigenesis of recipient cells did not occur if serum and supernatants were depleted of DNA. It is also demonstrated that horizontal cancer progression mediated by circulating DNA occurs via its uptake by recipient cells in an in vivo model where immunocompetent rats subjected to colon carcinogenesis with 1,2-dimethylhydrazine had increased rate of colonic tumors when injected in the dorsum with human SW480 colon carcinoma cells as a source of circulating oncogenic DNA, which could be offset by treating these animals with DNAse I and proteases. Though the contribution of biologically active molecules other than DNA for this phenomenon to occur cannot be ruled out, our results support the fact that cancer cells emit into the circulation biologically active DNA to foster tumor progression. Further exploration of the horizontal tumor progression phenomenon mediated by circulating DNA is clearly needed to determine whether its manipulation could have a role in cancer therapy.

  9. Cancer Progression Mediated by Horizontal Gene Transfer in an In Vivo Model

    Science.gov (United States)

    Trejo-Becerril, Catalina; Pérez-Cárdenas, Enrique; Taja-Chayeb, Lucía; Anker, Philippe; Herrera-Goepfert, Roberto; Medina-Velázquez, Luis A.; Hidalgo-Miranda, Alfredo; Pérez-Montiel, Delia; Chávez-Blanco, Alma; Cruz-Velázquez, Judith; Díaz-Chávez, José; Gaxiola, Miguel; Dueñas-González, Alfonso

    2012-01-01

    It is known that cancer progresses by vertical gene transfer, but this paradigm ignores that DNA circulates in higher organisms and that it is biologically active upon its uptake by recipient cells. Here we confirm previous observations on the ability of cell-free DNA to induce in vitro cell transformation and tumorigenesis by treating NIH3T3 recipient murine cells with serum of colon cancer patients and supernatant of SW480 human cancer cells. Cell transformation and tumorigenesis of recipient cells did not occur if serum and supernatants were depleted of DNA. It is also demonstrated that horizontal cancer progression mediated by circulating DNA occurs via its uptake by recipient cells in an in vivo model where immunocompetent rats subjected to colon carcinogenesis with 1,2-dimethylhydrazine had increased rate of colonic tumors when injected in the dorsum with human SW480 colon carcinoma cells as a source of circulating oncogenic DNA, which could be offset by treating these animals with DNAse I and proteases. Though the contribution of biologically active molecules other than DNA for this phenomenon to occur cannot be ruled out, our results support the fact that cancer cells emit into the circulation biologically active DNA to foster tumor progression. Further exploration of the horizontal tumor progression phenomenon mediated by circulating DNA is clearly needed to determine whether its manipulation could have a role in cancer therapy. PMID:23285175

  10. Indirect exclusion of four candidate genes for generalized progressive retinal atrophy in several breeds of dogs

    Directory of Open Access Journals (Sweden)

    Kraczyk Britta

    2006-11-01

    Full Text Available Abstract Background Generalized progressive retinal atrophy (gPRA is a hereditary ocular disorder with progressive photoreceptor degeneration in dogs. Four retina-specific genes, ATP binding cassette transporter retina (ABCA4, connexin 36 (CX36, c-mer tyrosin kinase receptor (MERTK and photoreceptor cell retinol dehydrogenase (RDH12 were investigated in order to identify mutations leading to autosomal recessive (ar gPRA in 29 breeds of dogs. Results Mutation screening was performed initially by PCR and single strand conformation polymorphism (SSCP analysis, representing a simple method with comparatively high reliability for identification of sequence variations in many samples. Conspicuous banding patterns were analyzed via sequence analyses in order to detect the underlying nucleotide variations. No pathogenetically relevant mutations were detected in the genes ABCA4, CX36, MERTK and RDH12 in 71 affected dogs of 29 breeds. Yet 30 new sequence variations were identified, both, in the coding regions and intronic sequences. Many of the sequence variations were in heterozygous state in affected dogs. Conclusion Based on the ar transmittance of gPRA in the breeds investigated, informative sequence variations provide evidence allowing indirect exclusion of pathogenetic mutations in the genes ABCA4 (for 9 breeds, CX36 (for 12 breeds, MERTK (for all 29 breeds and RDH12 (for 9 breeds.

  11. Gene polymorphisms of renin-angiotensin-aldosterone system components and the progression of chronic kidney diseases

    Directory of Open Access Journals (Sweden)

    Agata Kujawa-Szewieczek

    2010-08-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS plays an important role in the pathogenesis of hypertension as well as cardiovascular diseases and chronic kidney diseases. Among the most frequently studied RAAS gene polymorphisms are the angiotensin-converting enzyme insertion/deletion (I/D, angiotensinogen M235T and angiotensin II receptor type 1 A1166C polymorphisms.A significant correlation was found between the I/D polymorphism and cardiovascular morbidity and mortality rates. However, there was no significant correlation between I/D, M235T, A1166C polymorphism and arterial hypertension. The role of I/D polymorphism in the development and progression of chronic kidney disease is also non-conclusive. However, DD genotype has been identified as relevant for loss of renal function both in patients with IgA nephropathy and in patients of Asian origin with diabetic nephropathy.The relationship between RAAS gene polymorphism and transplanted kidney function has not been confirmed in large prospective and retrospective studies. Conclusion: there is no clear opinion concerning the influence of RAAS genotypes on the prevalence of post-transplant hypertension or erythrocytosis.Although a role of RAAS gene polymorphism in kidney function deterioration could not be ruled out, it is more likely that a variety of genetic and environmental factors influence the progression of chronic kidney diseases.

  12. Four genes predict high risk of progression from smoldering to symptomatic multiple myeloma (SWOG S0120).

    Science.gov (United States)

    Khan, Rashid; Dhodapkar, Madhav; Rosenthal, Adam; Heuck, Christoph; Papanikolaou, Xenofon; Qu, Pingping; van Rhee, Frits; Zangari, Maurizio; Jethava, Yogesh; Epstein, Joshua; Yaccoby, Shmuel; Hoering, Antje; Crowley, John; Petty, Nathan; Bailey, Clyde; Morgan, Gareth; Barlogie, Bart

    2015-09-01

    Multiple myeloma is preceded by an asymptomatic phase, comprising monoclonal gammopathy of uncertain significance and smoldering myeloma. Compared to the former, smoldering myeloma has a higher and non-uniform rate of progression to clinical myeloma, reflecting a subset of patients with higher risk. We evaluated the gene expression profile of smoldering myeloma plasma cells among 105 patients enrolled in a prospective observational trial at our institution, with a view to identifying a high-risk signature. Baseline clinical, bone marrow, cytogenetic and radiologic data were evaluated for their potential to predict time to therapy for symptomatic myeloma. A gene signature derived from four genes, at an optimal binary cut-point of 9.28, identified 14 patients (13%) with a 2-year therapy risk of 85.7%. Conversely, a low four-gene score (probe sets showed concordance with indices of chromosome instability. These data demonstrate high discriminatory power of a gene-based assay and suggest a role for dysregulation of mitotic checkpoints in the context of genomic instability as a hallmark of high-risk smoldering myeloma.

  13. New intronic splicing mutation in the LMNA gene causing progressive cardiac conduction defects and variable myopathy.

    Science.gov (United States)

    Rogozhina, Y; Mironovich, S; Shestak, A; Adyan, T; Polyakov, A; Podolyak, D; Bakulina, A; Dzemeshkevich, S; Zaklyazminskaya, E

    2016-12-31

    Most of mutations in the LMNA gene are unique and have been found in only a few unrelated families. The clinical interpretation of new genetic variants, especially beyond the coding area and canonical splice sites, is proving to be difficult and requires advanced investigation. This study included patients with progressive cardiac conduction defects with neuromuscular involvement. The clinical evaluation included medical history and 24-h Holter monitoring. The genetic evaluation included mutation screening in the LMNA gene by the Sanger sequence. Sanger sequencing was followed by RT-PCR of the target fragment of cDNA. In silico modeling was performed with CCBulder and Modeller software. The diagnosis of limb-girdle muscular dystrophy type 1B (LGMD1B) was established. The new intronic variant c.513+45T>G was found in the LMNA gene in the proband and affected daughter. The insertion of 45bp was confirmed in the proband's cDNA. The structural and possible functional effects of the aberrant protein were predicted. Variant c.513+45T>G in the LMNA gene likely translates into the longer lamin A/C proteins with additional 15 amino acids. This variant is thought to be pathogenic. Intronic variants in the LMNA gene located beside canonic splice sites may be responsible for some genotype-negative cases with clinical phenotype of laminopathies. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Urinary collagen degradation products as early markers of progressive renal fibrosis

    DEFF Research Database (Denmark)

    Hijmans, Ryanne S.; Rasmussen, Daniel Guldager Kring; Yazdani, Saleh

    2017-01-01

    Background: Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrot...

  15. Natural Products Version 2.0: Connecting Genes to Molecules

    Science.gov (United States)

    Walsh, Christopher T.; Fischbach, Michael A.

    2009-01-01

    Natural products have played a prominent role in the history of organic chemistry, and they continue to be important as drugs, biological probes, and targets of study for synthetic and analytical chemists. In this perspective, we explore how connecting Nature’s small molecules to the genes that encode them has sparked a renaissance in natural product research, focusing primarily on the biosynthesis of polyketides and nonribosomal peptides. We survey monomer biogenesis, coupling chemistries from templated and non-templated pathways, and the broad set of tailoring reactions and hybrid pathways that give rise to the diverse scaffolds and functionalization patterns of natural products. We conclude by considering two questions: What would it take to find all natural product scaffolds? What kind of scientists will be studying natural products in the future? PMID:20121095

  16. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance.

    Science.gov (United States)

    Pfeffer, Gerald; Gorman, Gráinne S; Griffin, Helen; Kurzawa-Akanbi, Marzena; Blakely, Emma L; Wilson, Ian; Sitarz, Kamil; Moore, David; Murphy, Julie L; Alston, Charlotte L; Pyle, Angela; Coxhead, Jon; Payne, Brendan; Gorrie, George H; Longman, Cheryl; Hadjivassiliou, Marios; McConville, John; Dick, David; Imam, Ibrahim; Hilton, David; Norwood, Fiona; Baker, Mark R; Jaiser, Stephan R; Yu-Wai-Man, Patrick; Farrell, Michael; McCarthy, Allan; Lynch, Timothy; McFarland, Robert; Schaefer, Andrew M; Turnbull, Douglass M; Horvath, Rita; Taylor, Robert W; Chinnery, Patrick F

    2014-05-01

    Despite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive external ophthalmoplegia remains unknown in a large proportion of patients. Here we show that mutations in SPG7 are a novel cause of progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. After excluding known causes, whole exome sequencing, targeted Sanger sequencing and multiplex ligation-dependent probe amplification analysis were used to study 68 adult patients with progressive external ophthalmoplegia either with or without multiple mitochondrial DNA deletions in skeletal muscle. Nine patients (eight probands) were found to carry compound heterozygous SPG7 mutations, including three novel mutations: two missense mutations c.2221G>A; p.(Glu741Lys), c.2224G>A; p.(Asp742Asn), a truncating mutation c.861dupT; p.Asn288*, and seven previously reported mutations. We identified a further six patients with single heterozygous mutations in SPG7, including two further novel mutations: c.184-3C>T (predicted to remove a splice site before exon 2) and c.1067C>T; p.(Thr356Met). The clinical phenotype typically developed in mid-adult life with either progressive external ophthalmoplegia/ptosis and spastic ataxia, or a progressive ataxic disorder. Dysphagia and proximal myopathy were common, but urinary symptoms were rare, despite the spasticity. Functional studies included transcript analysis, proteomics, mitochondrial network analysis, single fibre mitochondrial DNA analysis and deep re-sequencing of mitochondrial DNA. SPG7 mutations caused increased mitochondrial biogenesis in patient muscle, and mitochondrial fusion in patient fibroblasts associated with the clonal expansion of mitochondrial DNA mutations. In conclusion, the SPG7 gene should be screened in patients in whom a disorder of mitochondrial DNA maintenance is suspected when spastic ataxia is prominent. The complex neurological phenotype is likely a result of the clonal

  17. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  18. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2017-03-21

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  19. Use of Galerina marginata genes and proteins for peptide production

    Science.gov (United States)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  20. 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.

  1. The Setting of Progressive Energy Efficiency Performance Standards for Products through the Ecodesign Directive

    Directory of Open Access Journals (Sweden)

    Dalhammar, Carl

    2016-06-01

    Full Text Available The European Union (EU sets mandatory energy efficiency standards for appliances and other energy-relevant products through the Ecodesign Directive. The standards set so far have improved energy efficiency in a very cost-effective way. The main aim of the Directive is to remove the worst performing products from the market. There is a discussion on the potential to set more progressive legal standards in order to more rapidly improve the energy efficiency of products, or even induce ‘technology forcing’, which can be defined as standards requiring technology that goes beyond what is currently available on the market. This contribution examines different legal design options to set progressive energy standards and discusses the advantages and drawbacks with applying stricter standard-setting. The European ecodesign standards for vacuum cleaners are analyzed as they provide a recent example of standards with elements of technology forcing.

  2. [Mechanisms of inhibition of viral replication in plants]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1992-09-01

    Progress is described concerning genetic mapping CMV movement genes for CMV coat protein in squash and ToMV gene in tomato. These gene products appear to be involved in resistance to squash and tomato mosaic viruses respectively.

  3. Progress and problems with the use of suicide genes for targeted cancer therapy.

    Science.gov (United States)

    Karjoo, Zahra; Chen, Xuguang; Hatefi, Arash

    2016-04-01

    Among various gene therapy methods for cancer, suicide gene therapy attracts a special attention because it allows selective conversion of non-toxic compounds into cytotoxic drugs inside cancer cells. As a result, therapeutic index can be increased significantly by introducing high concentrations of cytotoxic molecules to the tumor environment while minimizing impact on normal tissues. Despite significant success at the preclinical level, no cancer suicide gene therapy protocol has delivered the desirable clinical significance yet. This review gives a critical look at the six main enzyme/prodrug systems that are used in suicide gene therapy of cancer and familiarizes readers with the state-of-the-art research and practices in this field. For each enzyme/prodrug system, the mechanisms of action, protein engineering strategies to enhance enzyme stability/affinity and chemical modification techniques to increase prodrug kinetics and potency are discussed. In each category, major clinical trials that have been performed in the past decade with each enzyme/prodrug system are discussed to highlight the progress to date. Finally, shortcomings are underlined and areas that need improvement in order to produce clinical significance are delineated.

  4. Identification of Drosophila Gene Products Required for Phagocytosis of Candidaalbicans.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available Phagocytosis is a highly conserved aspect of innate immunity. We used Drosophila melanogaster S2 cells as a model system to study the phagocytosis of Candida albicans, the major fungal pathogen of humans, by screening an RNAi library representing 7,216 fly genes conserved among metazoans. After rescreening the initial genes identified and eliminating certain classes of housekeeping genes, we identified 184 genes required for efficient phagocytosis of C. albicans. Diverse biological processes are represented, with actin cytoskeleton regulation, vesicle transport, signaling, and transcriptional regulation being prominent. Secondary screens using Escherichia coli and latex beads revealed several genes specific for C. albicans phagocytosis. Characterization of one of those gene products, Macroglobulin complement related (Mcr, shows that it is secreted, that it binds specifically to the surface of C. albicans, and that it promotes its subsequent phagocytosis. Mcr is closely related to the four Drosophila thioester proteins (Teps, and we show that TepII is required for efficient phagocytosis of E. coli (but not C. albicans or Staphylococcus aureus and that TepIII is required for the efficient phagocytosis of S. aureus (but not C. albicans or E. coli. Thus, this family of fly proteins distinguishes different pathogens for subsequent phagocytosis.

  5. Loss of circadian clock gene expression is associated with tumor progression in breast cancer.

    Science.gov (United States)

    Cadenas, Cristina; van de Sandt, Leonie; Edlund, Karolina; Lohr, Miriam; Hellwig, Birte; Marchan, Rosemarie; Schmidt, Marcus; Rahnenführer, Jörg; Oster, Henrik; Hengstler, Jan G

    2014-01-01

    Several studies suggest a link between circadian rhythm disturbances and tumorigenesis. However, the association between circadian clock genes and prognosis in breast cancer has not been systematically studied. Therefore, we examined the expression of 17 clock components in tumors from 766 node-negative breast cancer patients that were untreated in both neoadjuvant and adjuvant settings. In addition, their association with metastasis-free survival (MFS) and correlation to clinicopathological parameters were investigated. Aiming to estimate functionality of the clockwork, we studied clock gene expression relationships by correlation analysis. Higher expression of several clock genes (e.g., CLOCK, PER1, PER2, PER3, CRY2, NPAS2 and RORC) was found to be associated with longer MFS in univariate Cox regression analyses (HR<1 and FDR-adjusted P < 0.05). Stratification according to molecular subtype revealed prognostic relevance for PER1, PER3, CRY2 and NFIL3 in the ER+/HER2- subgroup, CLOCK and NPAS2 in the ER-/HER2- subtype, and ARNTL2 in HER2+ breast cancer. In the multivariate Cox model, only PER3 (HR = 0.66; P = 0.016) and RORC (HR = 0.42; P = 0.003) were found to be associated with survival outcome independent of established clinicopathological parameters. Pairwise correlations between functionally-related clock genes (e.g., PER2-PER3 and CRY2-PER3) were stronger in ER+, HER2- and low-grade carcinomas; whereas, weaker correlation coefficients were observed in ER- and HER2+ tumors, high-grade tumors and tumors that progressed to metastatic disease. In conclusion, loss of clock genes is associated with worse prognosis in breast cancer. Coordinated co-expression of clock genes, indicative of a functional circadian clock, is maintained in ER+, HER2-, low grade and non-metastasizing tumors but is compromised in more aggressive carcinomas.

  6. Antibacterial Discovery and Development: From Gene to Product and Back

    Directory of Open Access Journals (Sweden)

    Victor Fedorenko

    2015-01-01

    Full Text Available Concern over the reports of antibiotic-resistant bacterial infections in hospitals and in the community has been publicized in the media, accompanied by comments on the risk that we may soon run out of antibiotics as a way to control infectious disease. Infections caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and other Enterobacteriaceae species represent a major public health burden. Despite the pharmaceutical sector’s lack of interest in the topic in the last decade, microbial natural products continue to represent one of the most interesting sources for discovering and developing novel antibacterials. Research in microbial natural product screening and development is currently benefiting from progress that has been made in other related fields (microbial ecology, analytical chemistry, genomics, molecular biology, and synthetic biology. In this paper, we review how novel and classical approaches can be integrated in the current processes for microbial product screening, fermentation, and strain improvement.

  7. Antibacterial Discovery and Development: From Gene to Product and Back

    Science.gov (United States)

    Fedorenko, Victor; Genilloud, Olga; Horbal, Liliya; Marcone, Giorgia Letizia; Marinelli, Flavia; Paitan, Yossi; Ron, Eliora Z.

    2015-01-01

    Concern over the reports of antibiotic-resistant bacterial infections in hospitals and in the community has been publicized in the media, accompanied by comments on the risk that we may soon run out of antibiotics as a way to control infectious disease. Infections caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and other Enterobacteriaceae species represent a major public health burden. Despite the pharmaceutical sector's lack of interest in the topic in the last decade, microbial natural products continue to represent one of the most interesting sources for discovering and developing novel antibacterials. Research in microbial natural product screening and development is currently benefiting from progress that has been made in other related fields (microbial ecology, analytical chemistry, genomics, molecular biology, and synthetic biology). In this paper, we review how novel and classical approaches can be integrated in the current processes for microbial product screening, fermentation, and strain improvement. PMID:26339625

  8. LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives

    Science.gov (United States)

    2010-01-01

    reviews the progress made in the 18 years since the first clinical trial for gene therapy of FH, with emphasis on the development, design, performance and limitations of viral based gene transfer vectors used in studies to ameliorate the effects of LDLR deficiency. PMID:21144047

  9. Current status of gene therapy for breast cancer: progress and challenges

    Directory of Open Access Journals (Sweden)

    McCrudden CM

    2014-11-01

    Full Text Available Cian M McCrudden, Helen O McCarthySchool of Pharmacy, Queen’s University Belfast, Belfast, UKAbstract: Breast cancer is characterized by a series of genetic mutations and is therefore ideally placed for gene therapy intervention. The aim of gene therapy is to deliver a nucleic acid-based drug to either correct or destroy the cells harboring the genetic aberration. More recently, cancer gene therapy has evolved to also encompass delivery of RNA interference technologies, as well as cancer DNA vaccines. However, the bottleneck in creating such nucleic acid pharmaceuticals lies in the delivery. Deliverability of DNA is limited as it is prone to circulating nucleases; therefore, numerous strategies have been employed to aid with biological transport. This review will discuss some of the viral and nonviral approaches to breast cancer gene therapy, and present the findings of clinical trials of these therapies in breast cancer patients. Also detailed are some of the most recent developments in nonviral approaches to targeting in breast cancer gene therapy, including transcriptional control, and the development of recombinant, multifunctional bio-inspired systems. Lastly, DNA vaccines for breast cancer are documented, with comment on requirements for successful pharmaceutical product development.Keywords: breast cancer, gene therapy, nonviral, clinical trial

  10. RETRACTED: Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression.

    Science.gov (United States)

    Yang, Chun-Hua; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei

  11. Plasmid genes required for microcin B17 production.

    Science.gov (United States)

    San Millán, J L; Kolter, R; Moreno, F

    1985-09-01

    The production of the antibiotic substance microcin B17 (Mcc) is determined by a 3.5-kilobase DNA fragment from plasmid pMccB17. Several Mcc- mutations on plasmid pMccB17 were obtained by both transposon insertion and nitrosoguanidine mutagenesis. Plasmids carrying these mutations were tested for their ability to complement Mcc- insertion or deletion mutations on pMM102 (pMM102 is a pBR322 derivative carrying the region encoding microcin B17). Results from these experiments indicate that at least four plasmid genes are required for microcin production.

  12. Natural product proteomining, a quantitative proteomics platform, allows rapid discovery of biosynthetic gene clusters for different classes of natural products.

    Science.gov (United States)

    Gubbens, Jacob; Zhu, Hua; Girard, Geneviève; Song, Lijiang; Florea, Bogdan I; Aston, Philip; Ichinose, Koji; Filippov, Dmitri V; Choi, Young H; Overkleeft, Herman S; Challis, Gregory L; van Wezel, Gilles P

    2014-06-19

    Information on gene clusters for natural product biosynthesis is accumulating rapidly because of the current boom of available genome sequencing data. However, linking a natural product to a specific gene cluster remains challenging. Here, we present a widely applicable strategy for the identification of gene clusters for specific natural products, which we name natural product proteomining. The method is based on using fluctuating growth conditions that ensure differential biosynthesis of the bioactivity of interest. Subsequent combination of metabolomics and quantitative proteomics establishes correlations between abundance of natural products and concomitant changes in the protein pool, which allows identification of the relevant biosynthetic gene cluster. We used this approach to elucidate gene clusters for different natural products in Bacillus and Streptomyces, including a novel juglomycin-type antibiotic. Natural product proteomining does not require prior knowledge of the gene cluster or secondary metabolite and therefore represents a general strategy for identification of all types of gene clusters.

  13. Progress in the Study of Acupuncture in Regulating Post-Cerebral Ischemia/Reperfusion Cell-Apoptosis Related Gene Expression

    Institute of Scientific and Technical Information of China (English)

    卜渊; 耿德勤; 曾因明

    2003-01-01

    @@ Cerebralvascular disease has already become one of the serious illnesses that threatens human health. Along with the development of medicine, although the therapeutic method harvested huge progress, currently ideal therapeutic methods are lacking. The conventional acupuncture has definite therapeutic effect on cerebropathy. Clinical practice and various animal experiments confirmed that acupuncture could alleviate the pathologic damage after cerebral ischemic injury and promote the nerve function recovery. Past studies showed that the role of acupuncture in treating cerebral ischemia is realized through alleviating post-ischemic neuron necrosis, while recent study discovered that acupuncture has inhibitory effect on post-ischemia induced neuronal necrosis(1), which brought the mechanism of acupuncture in treating cerebral ischemia from the biochemical and metabolical level to the molecular biologic level. The studies revealed that after cerebral ischemia, many genes were induced to express themselves, protein product they coded directly or indirectly participated in the regulation of post-cerebral ischemia apoptosis of neuron, some promoting the apoptosis, while others inhibiting apoptosis with some of the function still unclear. The anti-apoptotic effect of acupuncture is accomplished through regulating the relevant apoptotic gene expression(2), and now it is reviewed as follows:

  14. 利用花药相关基因及启动子创制雄性不育种质研究进展%Research Progress on Production of Male Sterile Germplasm by Genetic Engineering with Anther Developmental Genes or Specific Promoters

    Institute of Scientific and Technical Information of China (English)

    杨晓杰; 房卫平; 谢德意; 周小玲; 赵元明; 赵付安; 唐中杰; 李付广

    2011-01-01

    Heterosis is the effective way of increasing crop yield and improving quality,and diverse germplasm of crop male sterility and fertility restoration is one of the key factors in heterosis utilization. This paper reviews the recent research results of the cloning and fuctional verification of anther development genes,and the progress of creating crop male sterile and their corresponding fertility restorer germplasm by genetic transformation engeering with the key genes associated with anther development. It also discusses the technical strategy and reseach priorities of creating plant male sterile lines,and corresponding fertility restore and maintain lines by the plant trans-genic technology,as well as the current status and perspective of creating "three lines" in heterosis utilization in practice by plant genetic engineering.%杂种优势利用是大幅度提高作物产量、改良作物品质的有效途径,而作物雄性不育及优良的育性恢复种质是利用杂种优势的关键因素.为此,综述了近年来有关花药发育重要基因克隆和功能验证研究方面的重要成果,以及运用植物遗传转化工程创制植物雄性不育种质的进展.同时讨论了利用转基因技术创制作物雄性不育系、恢复系和保持系的技术策略,并对利用植物遗传转化技术创制植物杂种优势利用中“三系”种质的现状进行了分析和展望.

  15. Progress With Developing Use of Gene Editing To Cure Chronic Infection With Hepatitis B Virus.

    Science.gov (United States)

    Ely, Abdullah; Moyo, Buhle; Arbuthnot, Patrick

    2016-04-01

    Chronic infection with hepatitis B virus (HBV) occurs in approximately 6% of the world's population. Carriers of the virus are at risk for life-threatening complications, and developing curative treatment remains a priority. The main shortcoming of licensed therapies is that they do not affect viral covalently closed circular DNA (cccDNA), a stable intermediate of replication. Harnessing gene editing to mutate cccDNA provides the means to inactivate HBV gene expression permanently. Reports have described use of engineered zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated (Cas) nucleases. Although inhibition of viral replication has been demonstrated, reliably detecting mutations in cccDNA has been difficult. Also, the dearth of murine models that mimic cccDNA formation has hampered analysis in vivo. To reach a stage of clinical use, efficient delivery of the editors to HBV-infected hepatocytes and limiting unintended off-target effects will be important. Investigating therapeutic efficacy in combination with other treatment strategies, such as immunotherapies, may be useful to augment antiviral effects. Advancing gene editing as a mode of treating HBV infection is now at an interesting stage and significant progress is likely to be made in the immediate future.

  16. Disaggregated productivity growth and technological progress in the interpretation of Spanish economic growth, 1958-1975

    OpenAIRE

    Sanchís Llopis, M. Teresa

    2005-01-01

    Spanish economic records in terms of GDP growth and convergence to European levels in the sixties, provide an excellent opportunity to look at a central question underlying in the interpretation of any process of economic growth. The relevance of industrial specific technological progress is confronted to a general and multifaceted productivity change coming from a variety of sectors and causes. This paper exploits sectoral growth accounting methodology in two different ways in order to answe...

  17. CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Alan Lopez-Lopez

    Full Text Available The objective of this study was to investigate the association of functional variants of the human CX3CR1 gene (Fractalkine receptor with the risk of Amyotrophic Lateral Sclerosis (ALS, the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients (142 sporadic [sALS] and 45 familial and 378 controls were recruited. We investigated CX3CR1 V249I (rs3732379 and T280M (rs3732378 genotypes and their haplotypes as predictors of survival, the progression rate of the symptoms (as measured by ALSFRS-R and FVC decline and the risk of suffering ALS disease. The results indicated that sALS patients with CX3CR1 249I/I or 249V/I genotypes presented a shorter survival time (42.27 ± 4.90 than patients with 249V/V genotype (67.65 ± 7.42; diff -25.49 months 95%CI [-42.79,-8.18]; p = 0.004; adj-p = 0.018. The survival time was shorter in sALS patients with spinal topography and CX3CR1 249I alleles (diff =  -29.78 months; 95%CI [-49.42,-10.14]; p = 0.003. The same effects were also observed in the spinal sALS patients with 249I-280M haplotype (diff =  -27.02 months; 95%CI [-49.57, -4.48]; p = 0.019. In the sALS group, the CX3CR1 249I variant was associated with a faster progression of the disease symptoms (OR = 2.58; 95IC% [1.32, 5.07]; p = 0.006; adj-p = 0.027. There was no evidence for association of these two CX3CR1 variants with ALS disease risk. The association evidenced herein is clinically relevant and indicates that CX3CR1 could be a disease-modifying gene in sALS. The progression rate of the disease's symptoms and the survival time is affected in patients with one or two copies of the CX3CR1 249I allele. The CX3CR1 is the most potent ALS survival genetic factor reported to date. These results reinforce the role of the immune system in ALS pathogenesis.

  18. Metabolic engineering of Arabidopsis for butanetriol production using bacterial genes.

    Science.gov (United States)

    Abdel-Ghany, Salah E; Day, Irene; Heuberger, Adam L; Broeckling, Corey D; Reddy, Anireddy S N

    2013-11-01

    1,2,4-butanetriol (butanetriol) is a useful precursor for the synthesis of the energetic material butanetriol trinitrate and several pharmaceutical compounds. Bacterial synthesis of butanetriol from xylose or arabinose takes place in a pathway that requires four enzymes. To produce butanetriol in plants by expressing bacterial enzymes, we cloned native bacterial or codon optimized synthetic genes under different promoters into a binary vector and stably transformed Arabidopsis plants. Transgenic lines expressing introduced genes were analyzed for the production of butanetriol using gas chromatography coupled to mass spectrometry (GC-MS). Soil-grown transgenic plants expressing these genes produced up to 20 µg/g of butanetriol. To test if an exogenous supply of pentose sugar precursors would enhance the butanetriol level, transgenic plants were grown in a medium supplemented with either xylose or arabinose and the amount of butanetriol was quantified. Plants expressing synthetic genes in the arabinose pathway showed up to a forty-fold increase in butanetriol levels after arabinose was added to the medium. Transgenic plants expressing either bacterial or synthetic xylose pathways, or the arabinose pathway showed toxicity symptoms when xylose or arabinose was added to the medium, suggesting that a by-product in the pathway or butanetriol affected plant growth. Furthermore, the metabolite profile of plants expressing arabinose and xylose pathways was altered. Our results demonstrate that bacterial pathways that produce butanetriol can be engineered into plants to produce this chemical. This proof-of-concept study for phytoproduction of butanetriol paves the way to further manipulate metabolic pathways in plants to enhance the level of butanetriol production.

  19. [Mutation screening for the causative gene in a four-generation Chinese pedigree with progressive cardiac conduction defect].

    Science.gov (United States)

    Tan, X J; Huang, H; He, F; Zhu, L; Li, H; Jiang, Y S; Li, H; Huang, X H; Sun, Z S; Li, Z H

    2016-05-24

    To define the potential causative gene mutation in a Chinese pedigree with progressive cardiac conduction defect (PCCD). Sanger sequencing was performed to define potential causative gene mutation in a four-generation family with 68 members including seven PCCD patients (5 male) from 2010 to 2015.No causative gene was detected by screening known candidate genes related to PCCD including SCN5A, NKX2.5 and LMNA.High-throughput sequencing technology on exon-enriched DNA was then used to search the causative genes in 2 patients and one normal family member. Eight new non-synonymous single nucleotide variants including AQP7 gene (exon5: c.T343C: p.Y115H), CACNA1B gene (NM_001243812: exon19: c.A2986G: p.T996A), CATSPERB gene (exon27: c.C3254G: p.P1085R), CLCA2 gene (exon11: c.G1725T: p.W575C), CLCA3P gene (ncRNA_intronic), MYLK-AS1 gene (ncRNA_intronic), TTN gene (ncRNA_UTR3), LMNA gene (LMNA: NM_170708: exon5: c.C922T: p.Q308X) were identified by comparing and filtering the results with known public databases.Then, more detailed biological analysis on these 8 genes was conducted.Traditional Sanger sequencing validated the exome sequencing results, and found that the mutation c. 1725G﹥T in gene CLCA2 segregated with the phenotype of this PCCD pedigree.The mutation c. 1725G﹥T in gene CLCA2 was thus be considered as the causative PCCD gene in this pedigree from the perspective of genetics and genomics. The heterozygote mutation c. 1725G﹥T in gene CLCA2 might be causative gene in this PCCD pedigree.This finding adds new gene mutation variant responsible for PCCD.

  20. HTGR accident initiation and progression analysis status report. Volume V. AIPA fission product source terms

    Energy Technology Data Exchange (ETDEWEB)

    Alberstein, D.; Apperson, C.E. Jr.; Hanson, D.L.; Myers, B.F.; Pfeiffer, W.W.

    1976-02-01

    The primary objective of the Accident Initiation and Progression Analysis (AIPA) Program is to provide guidance for high-temperature gas-cooled reactor (HTGR) safety research and development. Among the parameters considered in estimating the uncertainties in site boundary doses are uncertainties in fission product source terms generated under normal operating conditions, i.e., fuel body inventories, circulating coolant activity, total plateout activity in the primary circuit, and plateout distributions. The volume presented documents the analyses of these source term uncertainties. The results are used for the detailed consequence evaluations, and they provide the basis for evaluation of fission products important for HTGR maintenance and shielding.

  1. Recent progress concerning the production of controlled highly oriented electrospun nanofibrous arrays

    Science.gov (United States)

    Manea, L. R.; Hristian, L.; Leon, A. L.; Popa, A.

    2016-08-01

    Among the foreground domains of all the research-development programs at national and international level, a special place is occupied by that concerning the nanosciences, nanotechnologies, new materials and technologies. Electrospinning found a well-deserved place in this space, offering the preparation of nanomaterials with distinctive properties and applications in medicine, environment, photonic sensors, filters, etc. These multiple applications are generated by the fact that the electrospinning technology makes available the production of nanofibers with controllable characteristics (length, porosity, density, and mechanical characteristics), complexity and architecture. The apparition of 3D printing technology favors the production of complex nanofibrous structures, controlled assembly, self-assembly of electrospun nanofibers for the production of scaffolds used in various medical applications. The architecture of fibrous deposits has a special influence on the subsequent development of the cells of the reconstructed organism. The present work proposes to study of recent progress concerning the production of controlled highly oriented electrospun nanofibrous arrays and progress in research on the production of complex 2D and 3D structures.

  2. Progress in the production of bioethanol on starch-based feedstocks

    Directory of Open Access Journals (Sweden)

    Dragiša Savić

    2009-10-01

    Full Text Available Bioethanol produced from renewable biomass, such as sugar, starch, or lignocellulosic materials, is one of the alternative energy resources, which is both renewable and environmentally friendly. Although, the priority in global future ethanol production is put on lignocellulosic processing, which is considered as one of the most promising second-generation biofuel technologies, the utilizetion of lignocellulosic material for fuel ethanol is still under improvement. Sugar- based (molasses, sugar cane, sugar beet and starch-based (corn, wheat, triticale, potato, rice, etc. feedstock are still currently predominant at the industrial level and they are, so far, economically favorable compared to lingocelluloses. Currently, approx. 80 % of total world ethanol production is obtained from the fermentation of simple sugars by yeast. In Serbia, one of the most suitable and available agricultural raw material for the industrial ethanol production are cereals such as corn, wheat and triticale. In addition, surpluses of this feedstock are being produced in our country constantly. In this paper, a brief review of the state of the art in bioethanol production and biomass availability is given, pointing out the progress possibilities on starch-based production. The progress possibilities are discussed in the domain of feedstock choice and pretreatment, optimization of fermentation, process integration and utilization of the process byproducts.

  3. Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

    Directory of Open Access Journals (Sweden)

    Atique M Ahmed

    2014-08-01

    Full Text Available Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all. Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94% and 134 (92% patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen

  4. Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

    Science.gov (United States)

    Ahmed, Atique M; Pinheiro, Miguel M; Divis, Paul C; Siner, Angela; Zainudin, Ramlah; Wong, Ing Tien; Lu, Chan Woon; Singh-Khaira, Sarina K; Millar, Scott B; Lynch, Sean; Willmann, Matthias; Singh, Balbir; Krishna, Sanjeev; Cox-Singh, Janet

    2014-08-01

    Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human

  5. Relevance of breast cancer antiestrogen resistance genes in human breast cancer progression and tamoxifen resistance.

    Science.gov (United States)

    van Agthoven, Ton; Sieuwerts, Anieta M; Meijer-van Gelder, Marion E; Look, Maxime P; Smid, Marcel; Veldscholte, Jos; Sleijfer, Stefan; Foekens, John A; Dorssers, Lambert C J

    2009-02-01

    We have previously identified a set of breast cancer antiestrogen resistance (BCAR) genes causing estrogen independence and tamoxifen resistance in vitro using a functional genetic screen. Here, we explored whether these BCAR genes provide predictive value for tamoxifen resistance and prognostic information for tumor aggressiveness in breast cancer patients. mRNA levels of 10 BCAR genes (AKT1, AKT2, BCAR1, BCAR3, EGFR, ERBB2, GRB7, SRC, TLE3, and TRERF1) were measured in estrogen receptor-positive breast tumors using quantitative reverse-transcriptase polymerase chain reaction. Normalized mRNA levels were evaluated for association with progression-free survival (PFS) in 242 patients receiving tamoxifen as first-line monotherapy for recurrent disease, and with distant metastasis-free survival (MFS) in 413 lymph node-negative (LNN) primary breast cancer patients who did not receive systemic adjuvant therapy. Concerning tamoxifen resistance, BCAR3, ERBB2, GRB7, and TLE3 mRNA levels were predictive for PFS, independent of traditional predictive factors. By combining GRB7 (or ERBB2) and TLE3 mRNA levels, patients could be classified in three subgroups with distinct PFS. For the evaluation of tumor aggressiveness, AKT2, EGFR, and TRERF1 mRNA levels were all significantly associated with MFS, independent of traditional prognostic factors. Using the combined AKT2 and EGFR mRNA status, four prognostic groups were identified with different MFS outcomes. The majority of BCAR genes, which were revealed to confer tamoxifen resistance and estrogen independence in vitro by functional screening, have clinical relevance, and associate with tamoxifen resistance and/or tumor aggressiveness in breast cancer patients.

  6. RNA sequencing identifies crucial genes in papillary thyroid carcinoma (PTC) progression.

    Science.gov (United States)

    Qiu, Jie; Zhang, Wenwei; Xia, Qingsheng; Liu, Fuxue; Li, Li; Zhao, Shuwei; Gao, Xian; Zang, Chuanshan; Ge, Ruifeng; Sun, Yan

    2016-02-01

    The study aims to uncover molecular mechanisms of PTC (papillary thyroid carcinoma) progression and provide therapeutic biomarkers. The paired tumor and control tissues were obtained from 5 PTC patients. RNA was extracted and cDNA libraries were constructed. RNA-sequencing (RNA-seq) was performed on the Illumina HiSeq2000 platform using paired-end method. After preprocessing of the RNA-seq data, gene expression value was calculated by RPKM. Then the differentially expressed genes (DEGs) were identified with edgeR. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted for the DEGs. Module analysis of the PPI network was also performed. Transcription factors (TFs) of DEGs were predicted. A cohort of 496 up-regulated DEGs mainly correlating with the ECM degradation pathways, and 440 down-regulated DEGs predominantly enriching in transmembrane transport process were identified. Hub nodes in the PPI network were RRM2 and a set of collagens (COL1A1, COL3A1 and COL5A1), which were also remarkable in module 3 and module 5, respectively. Genes in module 3 were associated with cell cycle pathways, while in module 5 were related to ECM degradation pathways. PLAU, PSG1 and EGR2 were the crucial TFs with higher transcriptional activity in PTC than in control. Several genes including COL1A1, COL3A1, RRM2, PLAU, and EGR2 might be used as biomarkers of PTC therapy. Among them, COL1A1 and COL3A1 might exert their functions via involving in ECM degradation pathway, while RRM2 through cell cycle pathway. PLAU might be an active TF, whereas EGR2 might be a tumor suppressor. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model

    Directory of Open Access Journals (Sweden)

    Gopalakrishnan Velliyur K

    2005-03-01

    Full Text Available Abstract Background The changes in gene expression profile as prostate cancer progresses from an androgen-dependent disease to an androgen-independent disease are still largely unknown. Methods We examined the gene expression profile in the LNCaP prostate cancer progression model during chronic treatment with Casodex using cDNA microarrays consisting of 2305 randomly chosen genes. Results Our studies revealed a representative collection of genes whose expression was differentially regulated in LNCaP cells upon treatment with Casodex. A set of 15 genes were shown to be highly expressed in Casodex-treated LNCaP cells compared to the reference sample. This set of highly expressed genes represents a signature collection unique to prostate cancer since their expression was significantly greater than that of the collective pool of ten cancer cell lines of the reference sample. The highly expressed signature collection included the hypoxia-related genes membrane metallo-endopeptidase (MME, cyclin G2, and Bcl2/adenovirus E1B 19 kDa (BNIP3. Given the roles of these genes in angiogenesis, cell cycle regulation, and apoptosis, we further analyzed their expression and concluded that these genes may be involved in the molecular changes that lead to androgen-independence in prostate cancer. Conclusion Our data indicate that one of the mechanisms of Casodex action in prostate cancer cells is induction of hypoxic gene expression.

  8. Progressively restricted expression of a new homeobox-containing gene during Xenopus laevis embryogenesis.

    Science.gov (United States)

    Su, M W; Suzuki, H R; Solursh, M; Ramirez, F

    1991-04-01

    We have isolated cDNAs encoding a novel Xenopus homeodomain-containing protein homologous to the mouse Hox-7.1 and the Drosophila muscle segment homebox (msh). Northern blot and RNAase protection experiments established that transcripts of the frog gene, termed Xhox-7.1, first appear at about the beginning of gastrulation. After a rapid increase, mRNA levels plateau between the neurula and middle-tailbud stages, and decrease steadily thereafter. In situ hybridization localized the Xhox-7.1 message to the dorsal mesodermal mantle of gastrula stage embryos. Comparison of the hybridization patterns of progressively more anterior cross-section of tailbud stage embryos localized the signal to the dorsal neural tube and neural crest, to specific regions of the lateral plate mesoderm, and to the cardiogenic region. By the tadpole stage, the Xhox-7.1 message appears only at specific sites in the central nervous system, such as in the dorsal hindbrain. Thus, during embryonic development levels of Xhox-7.1 expression decrease as the transcript becomes more progressively localized. Finally, evidence is presented of a distinct msh-like transcript (provisionally termed Xhox-7.1') which begins to accumulate at early-gastrula stage, as well.

  9. Progressive nonfluent aphasia associated with a new mutation V363I in tau gene.

    Science.gov (United States)

    Munoz, David G; Ros, Raquel; Fatas, Marta; Bermejo, Felix; de Yebenes, Justo García

    2007-01-01

    Reported here is a new missense mutation V363I in exon 12 of the microtubule-associated protein tau (MAPT) gene associated with progressive nonfluent aphasia, with onset at the age of 69 years in a woman. Although near mute, she maintained complex activities and had no discernible deficits outside of language until the age of 75 years, when progressive gait and swallowing disturbances appeared. There was a history of late-onset aphasia and apraxia in her father. All of her children were asymptomatic adults, but psycholinguistic abnormalities were detected in those bearing the mutation, consisting of difficulties in comprehension, both reading (symbol discrimination and comprehension of oral spelling) and oral (matching sentences to pictures and comprehension of locative relationships). A mutation-bearing sibling showed no abnormalities at 70 years old, consistent with the limited penetrance expected in late-onset disease. The mutation, corresponding to a highly conserved residue in the fourth tubulin-binding repeat, was not present in 194 normal individuals with the same genetic background.

  10. Involvement of distinct PKC gene products in T cell functions

    Directory of Open Access Journals (Sweden)

    Gottfried eBaier

    2012-08-01

    Full Text Available It is well established that members of the Protein kinase C(PKC family seem to have important roles in T cells. Focusing on the physiological and non-redundant PKC functions established in primary mouse T cells via germline gene-targeting approaches, our current knowledge defines two particularly critical PKC gene products, PKCθ and PKCα, as the flavor of PKC in T cells that appear to have a positive role in signaling pathways that are necessary for full antigen receptor-mediated T cell activation ex vivo and T cell-mediated immunity in vivo. Consistently, in spite of the current dogma that PKCθ inhibition might be sufficient to achieve complete immunosuppressive effects, more recent results have indicated that the pharmacological inhibition of PKCθ, and additionally, at least PKCα, appears to be needed to provide a successful approach for the prevention of allograft rejection and treatment of autoimmune diseases.

  11. Alphavirus vectors: applications for DNA vaccine production and gene expression.

    Science.gov (United States)

    Lundstrom, K

    2000-01-01

    Replication-deficient alphavirus vectors have been developed for efficient high-level transgene expression. The broad host range of alphaviruses has allowed infection of a wide variety of mammalian cell lines and primary cultures. Particularly, G protein-coupled receptors have been expressed at high levels and subjected to binding and functional studies. Expression in suspension cultures has greatly facilitated production of large quantities of recombinant proteins for structural studies. Injection of recombinant alphavirus vectors into rodent brain resulted in local reporter gene expression. Highly neuron-specific expression was obtained in hippocampal slice cultures in vivo. Additionally, preliminary studies in animal models suggest that alphavirus vectors can be attractive candidates for gene therapy applications. Traditionally alphavirus vectors, either attenuated strains or replication-deficient particles, have been used to elicit efficient immune responses in animals. Recently, the application of alphaviruses has been extended to naked nucleic acids. Injection of DNA as well as RNA vectors has demonstrated efficient antigen production. In many cases, protection against lethal challenges has been obtained after immunization with alphavirus particles or nucleic acid vectors. Alphavirus vectors can therefore be considered as potentially promising vectors for vaccine production.

  12. Single gene insertion drives bioalcohol production by a thermophilic archaeon

    Energy Technology Data Exchange (ETDEWEB)

    Basen, M; Schut, GJ; Nguyen, DM; Lipscomb, GL; Benn, RA; Prybol, CJ; Vaccaro, BJ; Poole, FL; Kelly, RM; Adams, MWW

    2014-12-09

    Bioethanol production is achieved by only two metabolic pathways and only at moderate temperatures. Herein a fundamentally different synthetic pathway for bioalcohol production at 70 degrees C was constructed by insertion of the gene for bacterial alcohol dehydrogenase (AdhA) into the archaeon Pyrococcus furiosus. The engineered strain converted glucose to ethanol via acetate and acetaldehyde, catalyzed by the host-encoded aldehyde ferredoxin oxidoreductase (AOR) and heterologously expressed AdhA, in an energy-conserving, redox-balanced pathway. Furthermore, the AOR/AdhA pathway also converted exogenously added aliphatic and aromatic carboxylic acids to the corresponding alcohol using glucose, pyruvate, and/or hydrogen as the source of reductant. By heterologous coexpression of a membrane-bound carbon monoxide dehydrogenase, CO was used as a reductant for converting carboxylic acids to alcohols. Redirecting the fermentative metabolism of P. furiosus through strategic insertion of foreign genes creates unprecedented opportunities for thermophilic bioalcohol production. Moreover, the AOR/AdhA pathway is a potentially game-changing strategy for syngas fermentation, especially in combination with carbon chain elongation pathways.

  13. Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

    Institute of Scientific and Technical Information of China (English)

    Yoshiyuki Takahara; Mitsuo Takahashi; Qing-Wei Zhang; Hirotaka Wagatsuma; Maiko Mori; Akihiro Tamori; Susumu Shiomi; Shuhei Nishiguchi

    2008-01-01

    AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients.METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis.RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/ Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients.CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis.

  14. 76 FR 9028 - Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products; Availability

    Science.gov (United States)

    2011-02-16

    ... Industry: Potency Tests for Cellular and Gene Therapy Products'' dated January 2011. The guidance document provides manufacturers of cellular and gene therapy (CGT) products with recommendations for developing... document entitled ``Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products''...

  15. The C. elegans hox gene lin-39 controls cell cycle progression during vulval development.

    Science.gov (United States)

    Roiz, Daniel; Escobar-Restrepo, Juan Miguel; Leu, Philipp; Hajnal, Alex

    2016-10-01

    Cell fate specification during organogenesis is usually followed by a phase of cell proliferation to produce the required number of differentiated cells. The Caenorhabditis elegans vulva is an excellent model to study how cell fate specification and cell proliferation are coordinated. The six vulval precursor cells (VPCs) are born at the first larval stage, but they arrest in the G1 phase of the cell cycle until the beginning of the third larval stage, when their fates are specified and the three proximal VPCs proliferate to generate 22 vulval cells. An epidermal growth factor (EGF) signal from the gonadal anchor cell combined with lateral DELTA/NOTCH signaling between the VPCs determine the primary (1°) and secondary (2°) fates, respectively. The hox gene lin-39 plays a key role in integrating these spatial patterning signals and in maintaining the VPCs as polarized epithelial cells. Using a fusion-defective eff-1(lf) mutation to keep the VPCs polarized, we find that VPCs lacking lin-39 can neither activate lateral NOTCH signaling nor proliferate. LIN-39 promotes cell cycle progression through two distinct mechanisms. First, LIN-39 maintains the VPCs competent to proliferate by inducing cdk-4 cdk and cye-1 cyclinE expression via a non-canonical HOX binding motif. Second, LIN-39 activates in the adjacent VPCs the NOTCH signaling pathway, which promotes VPC proliferation independently of LIN-39. The hox gene lin-39 is therefore a central node in a regulatory network coordinating VPC differentiation and proliferation.

  16. Rhodococcus fascians infection accelerates progression of tobacco BY-2 cells into mitosis through rapid changes in plant gene expression.

    Science.gov (United States)

    Vandeputte, Olivier; Vereecke, Danny; Mol, Adeline; Lenjou, Marc; Van Bockstaele, Dirk; El Jaziri, Mondher; Baucher, Marie

    2007-01-01

    * To characterize plant cell cycle activation following Rhodococcus fascians infection, bacterial impact on cell cycle progression of tobacco BY-2 cells was investigated. * S-phase-synchronized BY-2 cells were cocultivated with R. fascians and cell cycle progression was monitored by measuring mitotic index, cell cycle gene expression and flow cytometry parameters. Cell cycle alteration was further investigated by cDNA-AFLP (amplified fragment length polymorphism). * It was shown that cell cycle progression of BY-2 cells was accelerated only upon infection with bacteria whose virulence gene expression was induced by a leafy gall extract. Thirty-eight BY-2 genes showed a differential expression within 6 h post-infection. Among these, seven were previously associated with specific plant cell cycle phases (in particular S and G2/M phases). Several genes also showed a differential expression during leafy gall formation. * R. fascians-infected BY-2 cells provide a simple model to identify plant genes related to leafy gall development. R. fascians can also be regarded as a useful biotic agent to alter cell cycle progression and, thereby, gain a better understanding of cell cycle regulation in plants.

  17. Microarray Expression Data Identify DCC as a Candidate Gene for Early Meningioma Progression.

    Science.gov (United States)

    Schulten, Hans-Juergen; Hussein, Deema; Al-Adwani, Fatima; Karim, Sajjad; Al-Maghrabi, Jaudah; Al-Sharif, Mona; Jamal, Awatif; Al-Ghamdi, Fahad; Baeesa, Saleh S; Bangash, Mohammed; Chaudhary, Adeel; Al-Qahtani, Mohammed

    2016-01-01

    Meningiomas are the most common primary brain tumors bearing in a minority of cases an aggressive phenotype. Although meningiomas are stratified according to their histology and clinical behavior, the underlying molecular genetics predicting aggressiveness are not thoroughly understood. We performed whole transcript expression profiling in 10 grade I and four grade II meningiomas, three of which invaded the brain. Microarray expression analysis identified deleted in colorectal cancer (DCC) as a differentially expressed gene (DEG) enabling us to cluster meningiomas into DCC low expression (3 grade I and 3 grade II tumors), DCC medium expression (2 grade I and 1 grade II tumors), and DCC high expression (5 grade I tumors) groups. Comparison between the DCC low expression and DCC high expression groups resulted in 416 DEGs (p-value2). The most significantly downregulated genes in the DCC low expression group comprised DCC, phosphodiesterase 1C (PDE1C), calmodulin-dependent 70kDa olfactomedin 2 (OLFM2), glutathione S-transferase mu 5 (GSTM5), phosphotyrosine interaction domain containing 1 (PID1), sema domain, transmembrane domain (TM) and cytoplasmic domain, (semaphorin) 6D (SEMA6D), and indolethylamine N-methyltransferase (INMT). The most significantly upregulated genes comprised chromosome 5 open reading frame 63 (C5orf63), homeodomain interacting protein kinase 2 (HIPK2), and basic helix-loop-helix family, member e40 (BHLHE40). Biofunctional analysis identified as predicted top upstream regulators beta-estradiol, TGFB1, Tgf beta complex, LY294002, and dexamethasone and as predicted top regulator effectors NFkB, PIK3R1, and CREBBP. The microarray expression data served also for a comparison between meningiomas from female and male patients and for a comparison between brain invasive and non-invasive meningiomas resulting in a number of significant DEGs and related biofunctions. In conclusion, based on its expression levels, DCC may constitute a valid biomarker to

  18. Vitreoscilla hemoglobin gene ( vgb) improves lutein production in Chlorella vulgaris

    Science.gov (United States)

    Ma, Ruijuan; Lin, Xiangzhi

    2014-03-01

    Vitreoscilla hemoglobin is an oxygen-binding protein that promotes oxygen delivery and reduces oxygen consumption under low oxygen conditions to increase the efficiency of cell respiration and metabolism. In this study, we introduced a Vitreoscilla hemoglobin gene ( vgb) into Chlorella vulgaris by Agrobacterium tumefaciens -mediated transformation (ATMT). PCR analysis confirmed that the vgb gene was successfully integrated into the Chlorella vulgaris genome. Analysis of biomass obtained in shake flasks revealed transformant biomass concentrations as high as 3.28 g/L, which was 38.81% higher than that of the wild-type strain. Lutein content of transformants also increased slightly. Further experiments recovered a maximum lutein yield of 2.91 mg/L from the transformants, which was 36.77% higher than that of the wild-type strain. The above results suggest that integrated expression of the vgb gene may improve cell growth and lutein yield in Chlorella vulgaris, with applications to lutein production from Chlorella during fermentation.

  19. Current progress in high cell density yeast bioprocesses for bioethanol production.

    Science.gov (United States)

    Westman, Johan O; Franzén, Carl Johan

    2015-08-01

    High capital costs and low reaction rates are major challenges for establishment of fermentation-based production systems in the bioeconomy. Using high cell density cultures is an efficient way to increase the volumetric productivity of fermentation processes, thereby enabling faster and more robust processes and use of smaller reactors. In this review, we summarize recent progress in the application of high cell density yeast bioprocesses for first and second generation bioethanol production. High biomass concentrations obtained by retention of yeast cells in the reactor enables easier cell reuse, simplified product recovery and higher dilution rates in continuous processes. High local cell density cultures, in the form of encapsulated or strongly flocculating yeast, furthermore obtain increased tolerance to convertible fermentation inhibitors and utilize glucose and other sugars simultaneously, thereby overcoming two additional hurdles for second generation bioethanol production. These effects are caused by local concentration gradients due to diffusion limitations and conversion of inhibitors and sugars by the cells, which lead to low local concentrations of inhibitors and glucose. Quorum sensing may also contribute to the increased stress tolerance. Recent developments indicate that high cell density methodology, with emphasis on high local cell density, offers significant advantages for sustainable second generation bioethanol production.

  20. The GEOGLAM Rangelands and Pasture Productivity Activity: Recent Progress and Future Directions

    Science.gov (United States)

    Guerschman, J. P.; Held, A. A.; Donohue, R. J.; Renzullo, L. J.; Sims, N.; Kerblat, F.; Grundy, M.

    2015-12-01

    Rangelands and pastures cover about a third of the world's land area and support livestock production which represents ~40% of global agricultural gross domestic product. The global consumption of animal protein shows a clear increasing trend, driven by both total population and per capita income increases, putting a growing pressure on the sustainability of grazing lands worldwide. Despite their relevance, rangelands have received less attention than croplands regarding global monitoring of the resource productivity and condition. The Rangelands and Pasture Productivity (RaPP) activity is a component within the Global Agricultural Monitoring initiative established under the Group on Earth Observations (GEOGLAM) in 2013. GEOGLAM RaPP is aimed at providing the global community with the means to monitor the world's rangelands and pastures on a routine basis, and the capacity to produce animal protein in real-time, at global, regional and national levels. Since its launch two years ago GEOGLAM RAPP has made progress in the four implementation elements. These include: 1- the establishment of community of practice; 2- the development of a global monitoring system for rangeland condition; 3- the establishment of pilot sites in main rangeland systems for satellite data products validation and model testing; and 4- integration with livestock production models. Three international workshops have been held building the community of practice. A prototype monitoring system that provides global visualisations and querying capability of vegetation cover data and anomalies has been established. Pilot sites, mostly in areas with long records of field measurements of rangeland condition and productivity have been proposed for nine countries. The link to global livestock models, including physical and economic components, have been established. Future challenges for GEOGLAM RaPP have also been identified and include: better representation of the areas occupied by rangelands

  1. Progress of R and D and production of timing RPCs in Tsinghua University

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yi, E-mail: yiwang@mail.tsinghua.edu.cn [Department of Engineering Physics, Tsinghua University, Beijing 10084 (China); Key Laboratory of Particle and Radiation Imaging, Ministry of Education (China); Chen Huangshan; Ding Weicheng; Wang Jingbo; Li Yuanjing; Cheng Jianping [Department of Engineering Physics, Tsinghua University, Beijing 10084 (China); Key Laboratory of Particle and Radiation Imaging, Ministry of Education (China)

    2012-01-01

    Multi-gap resistive plate chamber (MRPC) is a new kind of gas detector. It has good time resolution and high efficiency and has been adopted to construct the full barrel time-of-flight (TOF) detector for the STAR experiment at RHIC. The high rate TOF of CBM is also proposed to be assembled with MRPCs. Tsinghua University is a collaboration member of the two experiments and has made substantial progress on the R and D and production of MRPC. In this paper, we describe the development of low-resistivity glass and high rate MRPC, and the development of 1 m long counter is also described.

  2. Low VOC drying of lumber and wood panel products. Progress report No. 5

    Energy Technology Data Exchange (ETDEWEB)

    Wild, P.; Yan, Hui; Banerjee, S. [and others

    1997-10-01

    This progress report summarizes three accomplishments in a study of low volatile organic compound (VOC) drying of lumber and wood panel products. A mathematical model for predicting moisture emissions from particle was constructed and is being extended to VOCs. VOCs emissions from drying boards show that VOCs appear to be evenly released from all surfaces. Preliminary results from monthly analyses of loblolly pines indicate that resin acids appear to decrease between March to August, and that no consistent trends are apparent for terpenes. 3 refs., 13 figs., 1 tab.

  3. Research Progress of Nanog Gene%Nanog基因研究进展

    Institute of Scientific and Technical Information of China (English)

    季文

    2011-01-01

    Nanog基因是2003年报道的在囊胚期的内细胞团、原始生殖细胞以及胚胎干细胞表达的新转录因子,它对维持胚胎干细胞自我增殖和亚全能性起关键性作用,对其的研究将对发育生物学基础研究、再生医学的发展以及新药的开发产生深远的影响.通过近年来对Nanog基因在胚胎干细胞、体细胞、肿瘤细胞的表达和作用机制的研究,推测Nanog基因的表达调控与癌症的发生、发展有关,对未来的肿瘤研究趋势予以展望.通过深入研究Nanog基因的表达及其调控机制有助于探索控制和治疗癌症的新方法.%Nanog gene is a new transcription factor reported in 2003 to be expressed in blastular inner cell mass, primitive germ cells and embryonic stem cells. Nanog plays a crucial role in the maintenance of self-renewal and pluripotency of embryonic stem cells. The research of Nanog is of great significance for developmental biology,regenerative medicine, and development of new drugs. Recently, Nanog gene has been extensively studied for its expression and mechanism of action in embryonic stem cells,somatic cells, and tumor cells. The regulation of Nanog gene is predicted to be associated with the occurrence and progress of cancer,as a promising target for prospective tumor treatment. The further investigation into the expression and regulation mechanism of Nanog gene helps to explore the novel preventive and therapeutic regimens of cancer.

  4. Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Gen Tamura

    2006-01-01

    The development and progression of gastric cancer involves a number of genetic and epigenetic alterations of tumor suppressor and tumor-related genes. The majority of differentiated carcinomas arise from intestinal metaplastic mucosa and exhibit structurally altered tumor suppressor genes, typified by p53,which is inactivated via the classic two-hit mechanism,i.e. loss of heterozygosity (LOH) and mutation of the remaining allele. LOH at certain chromosomal loci accumulates during tumor progression. Approximately 20% of differentiated carcinomas show evidence of mutator pathway tumorigenesis due to hMLH1inactivation via hypermethylation of promoter CpG islands, and exhibit high-frequency microsatellite instability. In contrast, undifferentiated carcinomas rarely exhibit structurally altered tumor suppressor genes. For instance, while methylation of E-cadherin is often observed in undifferentiated carcinomas,mutation of this gene is generally associated with the progression from differentiated to undifferentiated carcinomas. Hypermethylation of tumor suppressor and tumor-related genes, including APC, CHFR, DAP-kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN,RASSF1A, RUNX3, and TSLC1, can be detected in both differentiated and undifferentiated carcinomas at varying frequencies. However, the significance of the hypermethylation varies according to the analyzed genomic region, and hypermethylation of these genes can also be present in non-neoplastic gastric epithelia.Promoter demethylation of specific genes, such as MAGE and synuclein y, can occur during the progressive stages of both histological types, and is associated with patient prognosis. Thus, while the molecular pathways of gastric carcinogenesis are dependent on histological background, specific genetic alterations can still be used for risk assessment, diagnosis, and prognosis.

  5. Genes related to xylose fermentation and methods of using same for enhanced biofuel production

    Science.gov (United States)

    Wohlbach, Dana J.; Gasch, Audrey P.

    2014-08-05

    The present invention provides isolated gene sequences involved in xylose fermentation and related recombinant yeast which are useful in methods of enhanced biofuel production, particularly ethanol production. Methods of bioengineering recombinant yeast useful for biofuel production are also provided.

  6. Genes related to xylose fermentation and methods of using same for enhanced biofuel production

    Energy Technology Data Exchange (ETDEWEB)

    Wohlbach, Dana J.; Gasch, Audrey P.

    2016-11-29

    The present invention provides isolated gene sequences involved in xylose fermentation and related recombinant yeast which are useful in methods of enhanced biofuel production, particularly ethanol production. Methods of bioengineering recombinant yeast useful for biofuel production are also provided.

  7. EFFECTS OF MUTATION AND EXPRESSION OF PTEN GENE mRNA ON TUMORIGENESIS AND PROGRESSION OF EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    陈颖; 郑华川; 杨雪飞; 孙丽梅; 辛彦

    2004-01-01

    Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary (n = 5), ovarian cyst (n =5), ovarian borderline tumor (n=9), epithelial ovarian cancer (n=60), and ovarian cancer cell line (n= 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clinicopathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5 (7.1%) cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst (P < 0.05). The level of PTEN gene mRNA expression was negatively correlated with clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05). Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.

  8. Acetic acid production from marine algae. Progress report No. 3, January 1, 1978--March 31, 1978

    Energy Technology Data Exchange (ETDEWEB)

    Sanderson, J.E.; Wise, D.L.

    1978-06-01

    The program for acetic acid production from marine algae has made significant progress in the current quarter. Some of the significant developments during this period are: (1) conversion of the available reducing equivalents in Chondrus crispus to organic acids has been carried to better than 80% completion; (2) thermophilic fermentations produce higher ratios of acetic acid to total acid than is the case for mesophilic fermentations (80% vs. 50%); (3) a membrane extraction process for removing organic acid products has been developed which has potential for commercial use; (4) a large scale fermentation was shown to convert over 50% of the available carbon in five days; (5) a reducing equivalents balance on the large scale fermentation was closed to with 96% of theoretical.

  9. Intratesticular signals regulate germ cell progression and production of qualitatively mature spermatozoa in vertebrates

    Directory of Open Access Journals (Sweden)

    Rosaria eMeccariello

    2014-05-01

    Full Text Available Spermatogenesis, a highly conserved process in vertebrates, is mainly under the hypothalamic-pituitary control, being regulated by the secretion of pituitary gonadotropins, FSH and LH, in response to stimulation exerted by Gonadotropin Releasing Hormone (GnRH from hypothalamic neurons. At testicular level, gonadotropins bind specific receptors located on the somatic cells regulating the production of steroids and factors necessary to ensure a correct spermatogenesis. Indeed, besides the endocrine route, a complex network of cell-to-cell communications regulates germ cell progression, and a combination of endocrine and intragonadal signals sustains the production of high quality mature spermatozoa. In this review we focus on the recent advances in the area of the intragonadal signals supporting sperm development.

  10. Recent progress of in-flight separators and rare isotope beam production

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Toshiyuki, E-mail: kubo@ribf.riken.jp

    2016-06-01

    New-generation in-flight separators are being developed worldwide, including the Super-FRS separator at the GSI Facility for Antiproton and Ion Research (FAIR), the ARIS separator at the Michigan State University (MSU) Facility for Rare Isotopes Beams (FRIB), and the BigRIPS separator at the RIKEN RI Beam Factory (RIBF), each of which is aimed at expanding the frontiers of rare isotope (RI) production and advancing experimental studies on exotic nuclei far from stability. Here, the recent progress of in-flight separators is reviewed, focusing on the advanced features of these three representative separators. The RI beam production that we have conducted using the BigRIPS separator at RIKEN RIBF is also outlined.

  11. Genes, language, cognition, and culture: towards productive inquiry.

    Science.gov (United States)

    Fitch, W Tecumseh

    2011-04-01

    The Queen Mary conference on “Integrating Genetic and Cultural Evolutionary Approaches to Language,” and the papers in this special issue, clearly illustrate the excitement and potential of trans-disciplinary approaches to language as an evolved biological capacity (phylogeny) and an evolving cultural entity (glossogeny). Excepting the present author, the presenters/authors are mostly young rising stars in their respective fields, and include scientists with backgrounds in linguistics, animal communication, neuroscience, evolutionary biology, anthropology, and computer science. On display was a clear willingness to engage with different approaches and terminology and a commitment to shared standards of scientific rigor, empirically driven theory, and logical argument. Because the papers assembled here, together with the introduction, speak for themselves, I will focus in this “extro-duction” on some of the terminological and conceptual difficulties which threaten to block this exciting wave of scientific progress in understanding language evolution, in both senses of that term. In particular I will first argue against the regrettably widespread practice of opposing cultural and genetic explanations of human cognition as if they were dichotomous. Second, I will unpack the debate concerning “general-purpose” and “domain-specific” mechanisms, which masquerades as a debate about nativism but is nothing of the sort. I believe that framing discussions of language in these terms has generated more heat than light, and that a modern molecular understanding of genes, development, behavior, and evolution renders many of the assumptions underlying this debate invalid.

  12. Identifying the Interaction between Genes and Gene Products Based on Frequently Seen Verbs in Medline Abstracts.

    Science.gov (United States)

    Sekimizu; Park; Tsujii

    1998-01-01

    We have selected the most frequently seen verbs from raw texts made up of 1-million-words of Medline abstracts, and we were able to identify (or bracket) noun phrases contained in the corpus, with a precision rate of 90%. Then, based on the noun-phrase-bracketted corpus, we tried to find the subject and object terms for some frequently seen verbs in the domain. The precision rate of finding the right subject and object for each verb was about 73%. This task was only made possible because we were able to linguistically analyze (or parse) a large quantity of a raw corpus. Our approach will be useful for classifying genes and gene products and for identifying the interaction between them. It is the first step of our effort in building a genome-related thesaurus and hierarchies in a fully automatic way.

  13. Identification of the dnaA and dnaN gene products of Escherichia coli.

    Science.gov (United States)

    Yuasa, S; Sakakibara, Y

    1980-01-01

    A specialized transducing lambda phage carrying the dnaN genes of Escherichia coli specifies two proteins of about 41 and 48 kilodaltons (kd). The temperature-sensitive mutations, dnaN59 and dnaA167, were found to result in altered isoelectric points of the 41 and 48 kd proteins, respectively. Thus the dnaN gene product was identified as a weakly acidic 41 and 48 kd protein. The synthesis of the dnaN gene product is greatly reduced by insertion of a transposon Tn3 in the dnaA gene and by deletion in the gene at the distal end to the dnaN gene. Temperature-sensitive dnaA mutations, on the dnaN gene product. These results indicate that the synthesis of the dnaN gene product is dependent on the structural integrity of the dnaA gene.

  14. Polymorphism screening of four genes encoding advanced glycation end-product putative receptors. Association study with nephropathy in type 1 diabetic patients

    DEFF Research Database (Denmark)

    Poirier, Odette; Nicaud, Viviane; Vionnet, N

    2001-01-01

    Advanced glycation end-products (AGEs) may play an important role in the pathogenesis and progression of cardiovascular and renal complications of diabetes. Four putative AGE receptors (RAGEs), AGE-R1, AGE-R2, and AGE-R3 have been described. In this study, we scanned the sequence of the genes enc...

  15. Application of affymetrix array and massively parallel signature sequencing for identification of genes involved in prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Eichner Lillian J

    2005-07-01

    Full Text Available Abstract Background Affymetrix GeneChip Array and Massively Parallel Signature Sequencing (MPSS are two high throughput methodologies used to profile transcriptomes. Each method has certain strengths and weaknesses; however, no comparison has been made between the data derived from Affymetrix arrays and MPSS. In this study, two lineage-related prostate cancer cell lines, LNCaP and C4-2, were used for transcriptome analysis with the aim of identifying genes associated with prostate cancer progression. Methods Affymetrix GeneChip array and MPSS analyses were performed. Data was analyzed with GeneSpring 6.2 and in-house perl scripts. Expression array results were verified with RT-PCR. Results Comparison of the data revealed that both technologies detected genes the other did not. In LNCaP, 3,180 genes were only detected by Affymetrix and 1,169 genes were only detected by MPSS. Similarly, in C4-2, 4,121 genes were only detected by Affymetrix and 1,014 genes were only detected by MPSS. Analysis of the combined transcriptomes identified 66 genes unique to LNCaP cells and 33 genes unique to C4-2 cells. Expression analysis of these genes in prostate cancer specimens showed CA1 to be highly expressed in bone metastasis but not expressed in primary tumor and EPHA7 to be expressed in normal prostate and primary tumor but not bone metastasis. Conclusion Our data indicates that transcriptome profiling with a single methodology will not fully assess the expression of all genes in a cell line. A combination of transcription profiling technologies such as DNA array and MPSS provides a more robust means to assess the expression profile of an RNA sample. Finally, genes that were differentially expressed in cell lines were also differentially expressed in primary prostate cancer and its metastases.

  16. Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with progressive atherosclerosis and incident cardiovascular disease

    Science.gov (United States)

    Pechlaner, Raimund; Willeit, Peter; Summerer, Monika; Santer, Peter; Egger, Georg; Kronenberg, Florian; Demetz, Egon; Weiss, Günter; Tsimikas, Sotirios; Witztum, Joseph L.; Willeit, Karin; Iglseder, Bernhard; Paulweber, Bernhard; Kedenko, Lyudmyla; Haun, Margot; Meisinger, Christa; Gieger, Christian; Müller-Nurasyid, Martina; Peters, Annette; Willeit, Johann; Kiechl, Stefan

    2015-01-01

    Objective The enzyme heme oxygenase-1 (HO-1) exerts cytoprotective effects in response to various cellular stressors. A variable number tandem repeat (VNTR) polymorphism in the HO-1 gene promoter region has previously been linked to cardiovascular disease (CVD). We examined this association prospectively in the general population. Approach and Results Incidence of stroke, myocardial infarction, or vascular death was registered between 1995 and 2010 in 812 participants of the Bruneck Study aged 45 to 84 years (49.4% males). Carotid atherosclerosis progression was quantified by high-resolution ultrasound. HO-1 VNTR length was determined by polymerase chain reaction. Subjects with ≥32 tandem repeats on both HO-1 alleles compared to the rest of the population (recessive trait) featured substantially increased CVD risk (hazard ratio [95% confidence interval], 5.45 (2.39, 12.42); PSAPHIR, and KORA prospective studies (HR [95% CI], 3.26 [1.50, 7.33]; P=0.0043). Conclusions This study found a strong association between the HO-1 VNTR polymorphism and CVD risk confined to subjects with a high number of repeats on both HO-1 alleles, and provides evidence for accelerated atherogenesis and decreased anti-oxidant defence in this vascular high-risk group. PMID:25359861

  17. Polymorphism screening of four genes encoding advanced glycation end-product putative receptors. Association study with nephropathy in type 1 diabetic patients

    DEFF Research Database (Denmark)

    Poirier, Odette; Nicaud, Viviane; Vionnet, N

    2001-01-01

    Advanced glycation end-products (AGEs) may play an important role in the pathogenesis and progression of cardiovascular and renal complications of diabetes. Four putative AGE receptors (RAGEs), AGE-R1, AGE-R2, and AGE-R3 have been described. In this study, we scanned the sequence of the genes....... The minor allele of a polymorphism located in the promoter region of the RAGE gene (C-1152A) conferred a weak protective effect (P

  18. Expression regulation of design process gene in product design

    DEFF Research Database (Denmark)

    Fang, Lusheng; Li, Bo; Tong, Shurong

    2011-01-01

    is proposed and analyzed, as well as its three categories i.e., the operator gene, the structural gene and the regulator gene. Second, the trigger mechanism that design objectives and constraints trigger the operator gene is constructed. Third, the expression principle of structural gene is analyzed......To improve the design process efficiency, this paper proposes the principle and methodology that design process gene controls the characteristics of design process under the framework of design process reuse and optimization based on design process gene. First, the concept of design process gene...... with the example of design management gene. Last, the regulation mode that the regulator gene regulates the expression of the structural gene is established and it is illustrated by taking the design process management gene as an example. © (2011) Trans Tech Publications....

  19. Bioactive natural products in cancer prevention and therapy: Progress and promise.

    Science.gov (United States)

    Bishayee, Anupam; Sethi, Gautam

    2016-10-01

    Natural products represent a rich source for the discovery and development of cancer preventive and anticancer drugs. Nearly, 80% of all drugs approved by the United States Food and Drug Administration during the last three decades for cancer therapy are either natural products per se or are based thereon, or mimicked natural products in one form or another. With the advent and refinement of new technologies, such as genetic techniques for production of secondary plant metabolites, combinatorial synthesis and high-throughput screening, it is expected that novel compounds from natural sources, including medicinal plants, would be identified and developed as safe and effective chemopreventive and anticancer drugs. Numerous bioactive natural compounds have been shown to be useful in prevention and therapy of cancer by targeting various signaling molecules and pathways. Extensive literature underscores the anticancer and chemopreventive activity of a plethora of naturally occurring agents, including phytochemicals. Several of these molecules have been tested in clinical trials and some of them have shown promise in combination therapy when administered along with standard chemotherapeutic agents. Thus, accelerated chemopreventive and chemotherapeutic drug development from natural sources is of great importance. In this special theme issue, contributions from eminent scientists and scholars around the world presented critical analysis of the current progress and promise of natural bioactive constituents in cancer prevention and therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Progress on lipid extraction from wet algal biomass for biodiesel production.

    Science.gov (United States)

    Ghasemi Naghdi, Forough; González González, Lina M; Chan, William; Schenk, Peer M

    2016-11-01

    Lipid recovery and purification from microalgal cells continues to be a significant bottleneck in biodiesel production due to high costs involved and a high energy demand. Therefore, there is a considerable necessity to develop an extraction method which meets the essential requirements of being safe, cost-effective, robust, efficient, selective, environmentally friendly, feasible for large-scale production and free of product contamination. The use of wet concentrated algal biomass as a feedstock for oil extraction is especially desirable as it would avoid the requirement for further concentration and/or drying. This would save considerable costs and circumvent at least two lengthy processes during algae-based oil production. This article provides an overview on recent progress that has been made on the extraction of lipids from wet algal biomass. The biggest contributing factors appear to be the composition of algal cell walls, pre-treatments of biomass and the use of solvents (e.g. a solvent mixture or solvent-free lipid extraction). We compare recently developed wet extraction processes for oleaginous microalgae and make recommendations towards future research to improve lipid extraction from wet algal biomass.

  1. Study of gene expression and OTA production by Penicillium nordicum during a small-scale seasoning process of salami.

    Science.gov (United States)

    Ferrara, Massimo; Magistà, Donato; Epifani, Filomena; Cervellieri, Salvatore; Lippolis, Vincenzo; Gallo, Antonia; Perrone, Giancarlo; Susca, Antonia

    2016-06-16

    Penicillium nordicum, an important and consistent producer of ochratoxin A (OTA), is a widely distributed contaminant of protein rich food with elevated NaCl. It is usually found on dry-cured meat products and is considered the main species responsible for their contamination by OTA. The aim of this work was to study the gene expression of a polyketide synthase (otapksPN) involved in P. nordicum OTA biosynthesis, and OTA production during a small-scale seasoning process. Fresh pork sausages were surface inoculated with P. nordicum and seasoned for 30days. Gene expression and OTA production were monitored throughout the seasoning process after 4, 5, 6, 7, 10, 14, and 30days. The expression of otapksPN gene was already detected after 4days and increased significantly after 7days of seasoning, reaching the maximum expression level after 10days (1.69×10(4)copies/100mg). Consistently with gene expression monitoring, OTA was detected from the 4th day and its content increased significantly from the 7th day, reaching the maximum level after 10days. In the late stages of the seasoning process, OTA did not increase further and the number of gene copies was progressively reduced after 14 and 30days.

  2. Dynamics of Colonization and Expression of Pathogenicity Related Genes in Fusarium oxysporum f.sp. ciceri during Chickpea Vascular Wilt Disease Progression

    Science.gov (United States)

    Upasani, Medha L.; Gurjar, Gayatri S.; Gupta, Vidya S.

    2016-01-01

    Fusarium wilt caused by Fusarium oxysporum f.sp. ciceri (Foc) is a constant threat to chickpea productivity in several parts of the world. Understanding the molecular basis of chickpea-Foc interaction is necessary to improve chickpea resistance to Foc and thereby the productivity of chickpea. We transformed Foc race 2 using green fluorescent protein (GFP) gene and used it to characterize pathogen progression and colonization in wilt-susceptible (JG62) and wilt-resistant (Digvijay) chickpea cultivars using confocal microscopy. We also employed quantitative PCR (qPCR) to estimate the pathogen load and progression across various tissues of both the chickpea cultivars during the course of the disease. Additionally, the expression of several candidate pathogen virulence genes was analyzed using quantitative reverse transcriptase PCR (qRT-PCR), which showed their characteristic expression in wilt-susceptible and resistant chickpea cultivars. Our results suggest that the pathogen colonizes the susceptible cultivar defeating its defense; however, albeit its entry in the resistant plant, further proliferation is severely restricted providing an evidence of efficient defense mechanism in the resistant chickpea cultivar. PMID:27227745

  3. Specific changes in the expression of imprinted genes in prostate cancer-implications for cancer progression and epigenetic regulation

    Institute of Scientific and Technical Information of China (English)

    Teodora Ribarska; Klaus-Marius Bastian; Annemarie Koch; Wolfgang A Schulz

    2012-01-01

    Epigenetic dysregulation comprising DNA hypermethylation and hypomethylation,enhancer of zeste homologue 2 (EZH2)overexpression and altered patterns of histone modifications is associated with the progression of prostate cancer.DNA methylation,EZH2 and histone modifications also ensure the parental-specific monoallelic expression of at least 62 imprinted genes.Although it is therefore tempting to speculate that epigenetic dysregulation may extend to imprinted genes,expression changes in cancerous prostates are only well documented for insulin-like growth factor 2 (IGF2).A literature and database survey on imprinted genes in prostate cancer suggests that the expression of most imprinted genes remains unchanged despite global disturbances in epigenetic mechanisms.Instead,selective genetic and epigenetic changes appear to lead to the inactivation of a sub-network of imprinted genes,which might function in the prostate to limit cell growth induced viathe PI3K/Akt pathway,modulate androgen responses and regulate differentiation.Whereas dysregulation of IG F2 may constitute an early change in prostate carcinogenesis,inactivation of this imprinted gene network is rather associated with cancer progression.

  4. Cell fusion in tumor progression: the isolation of cell fusion products by physical methods

    Directory of Open Access Journals (Sweden)

    Vincitorio Massimo

    2011-09-01

    Full Text Available Abstract Background Cell fusion induced by polyethylene glycol (PEG is an efficient but poorly controlled procedure for obtaining somatic cell hybrids used in gene mapping, monoclonal antibody production, and tumour immunotherapy. Genetic selection techniques and fluorescent cell sorting are usually employed to isolate cell fusion products, but both procedures have several drawbacks. Results Here we describe a simple improvement in PEG-mediated cell fusion that was obtained by modifying the standard single-step procedure. We found that the use of two PEG undertreatments obtains a better yield of cell fusion products than the standard method, and most of these products are bi- or trinucleated polykaryocytes. Fusion rate was quantified using fluorescent cell staining microscopy. We used this improved cell fusion and cell isolation method to compare giant cells obtained in vitro and giant cells obtained in vivo from patients with Hodgkin's disease and erythroleukemia. Conclusions In the present study we show how to improve PEG-mediated cell fusion and that cell separation by velocity sedimentation offers a simple alternative for the efficient purification of cell fusion products and to investigate giant cell formation in tumor development.

  5. Association of cGH EcoRV Gene with Production in Tolaki Chicken

    Directory of Open Access Journals (Sweden)

    Muhammad Amrullah Pagala

    2017-02-01

    Full Text Available cGH (Chicken Growth Hormone gene plays a crucial role in production responses of chicken. The objective of the research was to investigate the association of cGH gene with production in Tolaki chicken. Tolaki chicken is native chickens from Southeast Sulawesi Province of Indonesian. cGH gene was genotyped in 58 Tolaki chicken with PCR-RFLP. PCR was used to amplify genomic DNA for GH gene (399 bp. The amplicon was cutted by EcoRV and produced three genotypes: AA, AG, and GG and two alleles: A and G allele. The study showed the association of GH gene polymorphism with Production traits. GG genotype have better production (daily weight gain and feed conversion than AG genotype in Tolaki chicken, providing evidence that GH gene might be an important candidate gene for production traits.

  6. Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

    Directory of Open Access Journals (Sweden)

    Southey Bruce R

    2011-06-01

    Full Text Available Abstract Background Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival. Methods A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers. Results A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively or with other cancers (10, 19, and 15 genes, respectively and the rest (16, 4, and 10 genes, respectively are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events. Most genes (from 90 to 96% were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations

  7. 异戊二烯的生产方法%PROGRESS OF PRODUCTION METHODS OF ISOPRENE

    Institute of Scientific and Technical Information of China (English)

    吴红飞

    2012-01-01

    异戊二烯是合成橡胶的重要单体,主要用于生成异戊橡胶、丁基橡胶和SIS热塑性弹性等,也广泛应用于医药、农药、黏结剂及香料等领域.介绍了国内外异戊二烯生产方法的研究进展,详述了C5馏分分离法、脱氢法以及化学合成法等工艺,并对主要方法进行了对比,分析了其优缺点,同时对异戊二烯生产技术的发展提出了建议.%Isoprene, an important monomer for producing synthetic rubber, is mainly used in the production of isoprene rubber, butyl rubber, thermoplastic SIS elastomer and so on. It is also widely used in medicine, pesticides, bonding agents, spices, etc. The reseach progress of production methods of isoprene at home and abroad was introduced in this paper. Methods of the separation of C5 fraction, dehydrogenation, and chemical synthesis were amplified. Moreover, their merits and demerits were analyzed and compared. In the end, suggestions on the development of isoprene production technologies were given.

  8. [Progress in engineering Escherichia coli for production of high-value added organic acids and alcohols].

    Science.gov (United States)

    Wang, Jiming; Liu, Wei; Xu, Xin; Zhang, Haibo; Xian, Mo

    2013-10-01

    Confronted with the gradual exhaustion of the earth's fossil energy resources and the grimmer environmental deterioration, the bio-based process to produce high-value added platform chemicals from renewable biomass is attracting growing interest. Escherichia coli has been chosen as a workhouse for the production of many valuable chemicals due to various advantages, such as clear genetic background, convenient to be genetically modified and good growth properties with low nutrient requirements. Rational strain development of E. coli achieved by metabolic engineering strategies has provided new processes for efficiently biotechnological production of various high-value chemical building blocks. This review focuses on recent progresses in metabolic engineering of E. coli that lead to efficient recombinant biocatalysts for production of high-value organic acids such as succinic acid, 3-hydroxypropanoic acid and glucaric acid as well as alcohols like glycerol and xylitol. Besides, this review also discusses several other platform chemicals, including 2,5-furan dicarboxylic acid, aspartic acid, glutamic acid, itaconic acid, levulinic acid, 3-hydroxy-gamma-butyrolactone and sorbitol, which have not been produced by E. coli until now.

  9. Progress and obstacles in the production and application of recombinant lignin-degrading peroxidases.

    Science.gov (United States)

    Lambertz, Camilla; Ece, Selin; Fischer, Rainer; Commandeur, Ulrich

    2016-04-01

    Lignin is 1 of the 3 major components of lignocellulose. Its polymeric structure includes aromatic subunits that can be converted into high-value-added products, but this potential cannot yet been fully exploited because lignin is highly recalcitrant to degradation. Different approaches for the depolymerization of lignin have been tested, including pyrolysis, chemical oxidation, and hydrolysis under supercritical conditions. An additional strategy is the use of lignin-degrading enzymes, which imitates the natural degradation process. A versatile set of enzymes for lignin degradation has been identified, and research has focused on the production of recombinant enzymes in sufficient amounts to characterize their structure and reaction mechanisms. Enzymes have been analyzed individually and in combinations using artificial substrates, lignin model compounds, lignin and lignocellulose. Here we consider progress in the production of recombinant lignin-degrading peroxidases, the advantages and disadvantages of different expression hosts, and obstacles that must be overcome before such enzymes can be characterized and used for the industrial processing of lignin.

  10. Hydrogen storage and production in utility systems. Second annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Salzano, F.J. (ed.)

    1975-08-01

    Progress in the following three areas is reported: engineering analysis and design; hydrogen production and auxiliaries; and hydrogen storage development. Process designs for the 26-MW electric storage facility were completed. Work to determine the allowed break-even capital cost of ''black box'' electric storage devices is completed. Studies of the performance and temperature dependence of power consumption versus current density were completed for the Solid Polymer Electrolyte and KOH small multi-cell modules. Test Bed A-1, for long-term attrition studies, was operated for 1200 hydride-dehydride cycles. About 60 percent of the starting FeTi alloy suffered a factor of ten size reduction, but the ability to absorb hydrogen showed no decrease. (LK)

  11. Research Progress on Pesticide Residue Analysis Techniques in Agro-products

    Directory of Open Access Journals (Sweden)

    HE Ze-ying

    2016-07-01

    Full Text Available There are constant occurrences of acute pesticide poisoning among consumers and pesticide residue violations in agro-products import/export trading. Pesticide residue analysis is the important way to protect the food safety and the interest of import/export enterprises. There has been a rapid development in pesticide residue analysis techniques in recent years. In this review, the research progress in the past five years were discussed in the respects of samples preparation and instrument determination. The application, modification and development of the QuEChERS method in samples preparation and the application of tandem mass spectrometry and high resolution mass spectrometry were reviewed. And the implications for the future of the field were discussed.

  12. Aberrant DNA methylation of WNT pathway genes in the development and progression of CIMP-negative colorectal cancer.

    Science.gov (United States)

    Galamb, Orsolya; Kalmár, Alexandra; Péterfia, Bálint; Csabai, István; Bodor, András; Ribli, Dezső; Krenács, Tibor; Patai, Árpád V; Wichmann, Barnabás; Barták, Barbara Kinga; Tóth, Kinga; Valcz, Gábor; Spisák, Sándor; Tulassay, Zsolt; Molnár, Béla

    2016-08-02

    The WNT signaling pathway has an essential role in colorectal carcinogenesis and progression, which involves a cascade of genetic and epigenetic changes. We aimed to analyze DNA methylation affecting the WNT pathway genes in colorectal carcinogenesis in promoter and gene body regions using whole methylome analysis in 9 colorectal cancer, 15 adenoma, and 6 normal tumor adjacent tissue (NAT) samples by methyl capture sequencing. Functional methylation was confirmed on 5-aza-2'-deoxycytidine-treated colorectal cancer cell line datasets. In parallel with the DNA methylation analysis, mutations of WNT pathway genes (APC, β-catenin/CTNNB1) were analyzed by 454 sequencing on GS Junior platform. Most differentially methylated CpG sites were localized in gene body regions (95% of WNT pathway genes). In the promoter regions, 33 of the 160 analyzed WNT pathway genes were differentially methylated in colorectal cancer vs. normal, including hypermethylated AXIN2, CHP1, PRICKLE1, SFRP1, SFRP2, SOX17, and hypomethylated CACYBP, CTNNB1, MYC; 44 genes in adenoma vs. NAT; and 41 genes in colorectal cancer vs. adenoma comparisons. Hypermethylation of AXIN2, DKK1, VANGL1, and WNT5A gene promoters was higher, while those of SOX17, PRICKLE1, DAAM2, and MYC was lower in colon carcinoma compared to adenoma. Inverse correlation between expression and methylation was confirmed in 23 genes, including APC, CHP1, PRICKLE1, PSEN1, and SFRP1. Differential methylation affected both canonical and noncanonical WNT pathway genes in colorectal normal-adenoma-carcinoma sequence. Aberrant DNA methylation appears already in adenomas as an early event of colorectal carcinogenesis.

  13. [The progress of TMPRSS2-ETS gene fusions and their mechanism in prostate cancer].

    Science.gov (United States)

    Guo, Xiao-Qiang; Gui, Yao-Ting; Cai, Zhi-Ming

    2011-02-01

    The gene fusions between transmembrane protease serine 2 (TMPRSS2) and E26 (ETS) transcription factors are present in over 50% of patients with prostate cancer. TMPRSS2-ERG is the most common gene fusion type. The ERG overexpression induced by TMPRSS2-ERG gene fusion contributes to the development of prostate cancer. Both androgen receptor binding and genotoxic stress induce chromosomal proximity and TMPRSS2-ETS gene fusions. TMPRSS2-ERG gene fusion functions as a biomarker for prostate cancer, which can be easily detected in urine. This review focuses on the characteristics, oncogenic and rearranged mechanism, and clinical application of TMPRSS2-ETS gene fusions.

  14. Association between Single Nucleotide Polymorphism of Vitamin D Receptor Gene FokI Polymorphism and Clinical Progress of Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Li Ruan

    2015-01-01

    Full Text Available Background. The aim of the study was to investigate the association between single nucleotide polymorphism (SNP of vitamin D receptor (VDR gene and clinical progress of benign prostatic hyperplasia (BPH in Chinese men. Methods. The DNA was extracted from blood of 200 BPH patients with operation (progression group and 200 patients without operation (control group, respectively. The genotypes of VDR gene FokI SNP represented by “F/f” were identified by PCR-restriction fragment length polymorphism. The odds ratio (OR of having progression of BPH for having the genotype were calculated. Results. Our date indicated that the f alleles of the VDR gene FokI SNP associated with the progression of BPH (P=0.009. Conclusion. For the first time, our study demonstrated that VDR gene FokI SNP may be associated with the risk of BPH progress.

  15. Extended gene expression by medium exchange and repeated transient transfection for recombinant protein production enhancement.

    Science.gov (United States)

    Cervera, Laura; Gutiérrez-Granados, Sonia; Berrow, Nicholas Simon; Segura, Maria Mercedes; Gòdia, Francesc

    2015-05-01

    Production of recombinant products in mammalian cell cultures can be achieved by stable gene expression (SGE) or transient gene expression (TGE). The former is based on the integration of a plasmid DNA into the host cell genome allowing continuous gene expression. The latter is based on episomal plasmid DNA expression. Conventional TGE is limited to a short production period of usually about 96 h, therefore limiting productivity. A novel gene expression approach termed extended gene expression (EGE) is explored in this study. The aim of EGE is to prolong the production period by the combination of medium exchange and repeated transfection of cell cultures with plasmid DNA to improve overall protein production. The benefit of this methodology was evaluated for the production of three model recombinant products: intracellular GFP, secreted GFP, and a Gag-GFP virus-like particles (VLPs). Productions were carried out in HEK 293 cell suspension cultures grown in animal-derived component free media using polyethylenimine (PEI) as transfection reagent. Transfections were repeated throughout the production process using different plasmid DNA concentrations, intervals of time, and culture feeding conditions in order to identify the best approach to achieve sustained high-level gene expression. Using this novel EGE strategy, the production period was prolonged between 192 and 240 h with a 4-12-fold increase in production levels, depending on the product type considered. © 2014 Wiley Periodicals, Inc.

  16. Patterns of expression of cell cycle/apoptosis genes along the spectrum of thyroid carcinoma progression

    NARCIS (Netherlands)

    B. Saltman; B. Singh; C.V. Hedvat; V.B. Wreesmann; R. Ghossein

    2006-01-01

    Background. Genetic screening studies suggest that genetic changes underlie progression from well differentiated, to anoplastic thyroid cancers. The aim of this study is to determine to what extent cell cycle/apoptosis regulators contribute to cancer progression. Methods. Tissue microarrarys (TMAs)

  17. [Collaborative study on regulatory science for facilitating clinical development of gene therapy products for genetic diseases].

    Science.gov (United States)

    Uchida, Eriko; Igarashi, Yuka; Sato, Yoji

    2014-01-01

    Gene therapy products are expected as innovative medicinal products for intractable diseases such as life-threatening genetic diseases and cancer. Recently, clinical developments by pharmaceutical companies are accelerated in Europe and the United States, and the first gene therapy product in advanced countries was approved for marketing authorization by the European Commission in 2012. On the other hand, more than 40 clinical studies for gene therapy have been completed or ongoing in Japan, most of them are conducted as clinical researches by academic institutes, and few clinical trials have been conducted for approval of gene therapy products. In order to promote the development of gene therapy products, revision of the current guideline and/or preparation of concept paper to address the evaluation of the quality and safety of gene therapy products are necessary and desired to clearly show what data should be submitted before First-in-Human clinical trials of novel gene therapy products. We started collaborative study with academia and regulatory agency to promote regulatory science toward clinical development of gene therapy products for genetic diseases based on lentivirus and adeno-associated virus vectors; National Center for Child Health and Development (NCCHD), Nippon Medical School and PMDA have been joined in the task force. At first, we are preparing pre-draft of the revision of the current gene therapy guidelines in this project.

  18. Application Progress of CRISPR/Cas9 System for Gene Editing in Tumor Research

    OpenAIRE

    Liu, Chao; Li, Zhiwei; Zhang, Yanqiao

    2015-01-01

    TCRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR-associated nuclease 9) gene editing system is a new type of gene editing technology developed based on the immune mechanism of archaea resisting the invasion of exogenous nucleic acid. Compared with traditional gene editing system, CRISPR/Cas9 system is more efficient, easier operating, and less cytotoxic. Currently, CRISPR/Cas9 gene editing technology has been applied to many aspects of cancer research, including r...

  19. Immediate-early gene product ICP22 inhibits the trans-transcription activating function of P53-mdm-2

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    As a product of HSVI immediate-early gene, ICP22 is capable of interacting with various cellular tran-scriptive and regulatory molecules during viral infection so as to impact the normal cellular molecular mechanism. ICP22 expressed in transfected cells can push the cells’ entering into S phase with binding to mdm-1 promoter region and impact its trans-transcription activating effect by P53. Consequently, the MDM-2 binds to P53, and the degradation effects by the ubiquitous pathway are decreased, improving indirectly the P53 levels in cells and making the cells progress into the S phase.

  20. Immediate-early gene product ICP22 inhibits the trans-transcription activating function of P53-mdm-2

    Institute of Scientific and Technical Information of China (English)

    GUO HongXiong; CUN Wei; LIU LongDing; WANG LiChun; ZHAO HongLing; DONG ChengHong; LI QiHan

    2007-01-01

    As a product of HSVI immediate-early gene, ICP22 is capable of interacting with various cellular transcriptive and regulatory molecules during viral infection so as to impact the normal cellular molecular mechanism. ICP22 expressed in transfected cells can push the cells' entering into S phase with binding to mdm-1 promoter region and impact its trans-transcription activating effect by P53. Consequently, the MDM-2 binds to P53, and the degradation effects by the ubiquitous pathway are decreased, improving indirectly the P53 levels in cells and making the cells progress into the S phase.

  1. Differentially expressed genes during human cutaneous melanocytic tumor progression : a focus on cancer/testis-associated genes

    NARCIS (Netherlands)

    Zendman, Albert Johan Willem

    2003-01-01

    Human cutaneous melanoma, the skin cancer originating from the pigment producing melanocyte, is one of the most aggressive types of tumors due to its early dissemination. The progression of melanoma surpasses several stages from common nevi to metastatic tumors. For diagnostic and clinical purposes

  2. Effect of MDR1 gene polymorphism on progression of end-stage renal disease

    Institute of Scientific and Technical Information of China (English)

    Wei-xia ZHANG; Bing CHEN; Wen ZHANG; Nan CHEN; Zi-cheng YU; Wei-min CAI

    2007-01-01

    Aim: P-glycoprotein is localized at the apical brush-border membrane of the proxi-mal renal tubule and functions as extruding toxins and xenobiotics out of cells.The difference of P-glycoprotein's function resulted from single nucleotide poly-morphisms in MDR1 (multidrug resistance gene encoding for P-gp) and may be the cause of interindividual differences in susceptibility to end-stage renal dis-ease (ESRD). The purpose of this study is to compare the genotype frequency of C3435T and G1199A polymorphisms in MDR1 between ESRD patients and healthy controls in the Chinese population to determine whether the alteration of the P-gp function is associated with ESRD. Methods: Two hundred and eighty-four healthy Chinese controls and 244 Chinese patients with ESRD were involved in this study.Allele specific PCR and polymerase chain reaction-restriction fragment length polymorphism assay were used to determine the genotype MDR1 G1199A and C3435T, respectively. Results: The genotype distribution of 3435CC, 3435CT,and 3435Tr were 0.35, 0.50, and 0.15, respectively, in the control group and 0.38,0.47, and 0.15 in the group with the ESRD patients. No variant allele 1199G>A was found in any of the patients. The value of serum creatinine for genotypes 3435CC,3435CT, and 3435Tr in the ESRD patients were 753.8±276.0 μmol/L, 849.6±342.2μmol/L, and 987.0±512.0 μmol/L, respectively. The difference between 3435TT and 3435CC reached statistical significance (P<0.05). Conclusion: The low expression of P-glycoprotein was not the etiological factor for the kidney disease,but it may contribute to the progression of ESRD and affect the severity. Chinese people do not carry the 1199G>A variant allele. More studies are needed to clarify the cause and interindividual differences in the susceptibility for the risk of ESRD.

  3. Differential Expression of Genes Associated with the Progression of Renal Disease in the Kidneys of Liver-Specific Glucokinase Gene Knockout Mice

    Directory of Open Access Journals (Sweden)

    Gang Niu

    2013-03-01

    Full Text Available Liver glucokinase (GCK deficient mice possess mild renal complications associated with diabetes. To investigate the progression of kidney disease and identify candidate genes involved in the pathogenesis of renal damage, we examined changes in tissue structure and gene expression in the kidneys of liver-specific GCK knockout (gckw/− mice and age-matched normal wild-type control (gckw/w mice as they aged. Suppression subtractive hybridization (SSH was used to identify candidate genes that showed a pattern of differential expression between kidneys of gckw/− and gckw/w mice at 60 weeks of age. Differential expression of the candidate genes was examined by real-time qPCR in liver-specific gckw/− and gckw/w mice at 16, 26, 40, 60, and 85 weeks of age. Among the candidate genes, only glutathione peroxidase-3 (GPX3 was confirmed to show differential expression by qPCR in the 60-week old mice, however two others genes, MALAT1 and KEG, showed significant changes at other ages. This study shows that liver-specific glucokinase deficient mice display changes in kidney morphology by 40 weeks of age, and that renal complication may be correlated with a reduction in GPX3 levels. Since decreased GPX3 mRNA expression was observed at 26 weeks, which is younger than the age when pathological changes can be seen in kidney biopsies, GPX3 may serve as an early marker for kidney damage.

  4. Screening Key Genes Associated with the Development and Progression of Non-small Cell Lung Cancer Based on Gene-enrichment Analysis and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Wenwu HE

    2012-07-01

    Full Text Available Background and objective Non-small cell lung cancer (NSCLC is one of the most common malignant tumors; however, its causes are still not completely understood. This study was designed to screen the key genes and pathways related to NSCLC occurrence and development and to establish the scientific foundation for the genetic mechanisms and targeted therapy of NSCLC. Methods Both gene set-enrichment analysis (GSEA and meta-analysis (meta were used to screen the critical pathways and genes that might be corretacted with the development and progression of lung cancer at the transcription level. Results Using the GSEA and meta methods, focal adhesion and regulation of actin cytoskeleton were determined to be the more prominent overlapping significant pathways. In the focal adhesion pathway, 31 genes were statistically significant (P<0.05, whereas in the regulation of actin cytoskeleton pathway, 32 genes were statistically significant (P<0.05. Conclusion The focal adhesion and the regulation of actin cytoskeleton pathways might play important roles in the occurrence and development of NSCLC. Further studies are needed to determine the biological function for the positiue genes.

  5. Frontal white matter tracts sustaining speech production in primary progressive aphasia.

    Science.gov (United States)

    Mandelli, Maria Luisa; Caverzasi, Eduardo; Binney, Richard J; Henry, Maya L; Lobach, Iryna; Block, Nikolas; Amirbekian, Bagrat; Dronkers, Nina; Miller, Bruce L; Henry, Roland G; Gorno-Tempini, Maria Luisa

    2014-07-16

    In primary progressive aphasia (PPA), speech and language difficulties are caused by neurodegeneration of specific brain networks. In the nonfluent/agrammatic variant (nfvPPA), motor speech and grammatical deficits are associated with atrophy in a left fronto-insular-striatal network previously implicated in speech production. In vivo dissection of the crossing white matter (WM) tracts within this "speech production network" is complex and has rarely been performed in health or in PPA. We hypothesized that damage to these tracts would be specific to nfvPPA and would correlate with differential aspects of the patients' fluency abilities. We prospectively studied 25 PPA and 21 healthy individuals who underwent extensive cognitive testing and 3 T MRI. Using residual bootstrap Q-ball probabilistic tractography on high angular resolution diffusion-weighted imaging (HARDI), we reconstructed pathways connecting posterior inferior frontal, inferior premotor, insula, supplementary motor area (SMA) complex, striatum, and standard ventral and dorsal language pathways. We extracted tract-specific diffusion tensor imaging (DTI) metrics to assess changes across PPA variants and perform brain-behavioral correlations. Significant WM changes in the left intrafrontal and frontostriatal pathways were found in nfvPPA, but not in the semantic or logopenic variants. Correlations between tract-specific DTI metrics with cognitive scores confirmed the specific involvement of this anterior-dorsal network in fluency and suggested a preferential role of a posterior premotor-SMA pathway in motor speech. This study shows that left WM pathways connecting the speech production network are selectively damaged in nfvPPA and suggests that different tracts within this system are involved in subcomponents of fluency. These findings emphasize the emerging role of diffusion imaging in the differential diagnosis of neurodegenerative diseases.

  6. A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13

    Energy Technology Data Exchange (ETDEWEB)

    Balciuniene, J.; Holmgren, G.; Forsman, K. [University Hospital, Umea (Sweden)] [and others

    1995-11-20

    Inherited retinal dystrophy is a common cause of visual impairment. Cone dystrophy affects the cone function and is manifested as progressive loss of the central vision, defective color vision, and photophobia. Linkage was demonstrated between progressive cone dystrophy (CORD5) and genetic markers on chromosome 17p12-p13 in a five-generation family. Multipoint analysis gave a maximum lod score of 7.72 at the marker D17S938. Recombinant haplotypes in the family suggest that the cone dystrophy locus is located in a 25-cM interval between the markers D17S926/D17S849 and D17S804/D17S945. Furthermore, one recombination was detected between the disease locus and a microsatellite marker in the candidate gene RCV1, encoding the retinal protein recoverin. Two additional candidate genes encoding retinal guanylate cyclase (GUC2D) and pigment epithelium-derived factor (PEDF) are located at 17p13.1. Moreover, loci for retinitis pigmentosa and Leber congenital amaurosis have been mapped to the same region. Identification of the cone dystrophy locus may be of importance not only for identifying functional genes in the cone system, but also for identifying genes for other retinal disorders. 34 refs., 3 figs., 2 tabs.

  7. Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer

    Science.gov (United States)

    Heger, Zbynek; Merlos Rodrigo, Miguel Angel; Michalek, Petr; Polanska, Hana; Masarik, Michal; Vit, Vitezslav; Plevova, Mariana; Pacik, Dalibor; Eckschlager, Tomas; Stiborova, Marie

    2016-01-01

    The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential. PMID:27824899

  8. Application Progress of CRISPR/Cas9 System for Gene Editing in Tumor Research

    Directory of Open Access Journals (Sweden)

    Chao LIU

    2015-09-01

    Full Text Available TCRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR-associated nuclease 9 gene editing system is a new type of gene editing technology developed based on the immune mechanism of archaea resisting the invasion of exogenous nucleic acid. Compared with traditional gene editing system, CRISPR/Cas9 system is more efficient, easier operating, and less cytotoxic. Currently, CRISPR/Cas9 gene editing technology has been applied to many aspects of cancer research, including research on cancer genes, constructing animal tumor models, screening tumor resistance-associated and phenotypic-related genes and cancer gene therapy. In this review, the application of the CRISPR/Cas9 system in tumor research were introduced.

  9. Enhancement of photoassimilate utilization by manipulation of the ADPglucose pyrophosphorylase gene. Progress report, [April 15, 1987--April 14, 1988

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.

    1988-12-31

    Many agronomically important crops are viewed as significant resources of renewable energy. Overall crop productivity could be increased if the efficiency of photoassimilate conversion into dry matter such as starch were improved in storage tissues. Starch production is controlled by the catalytic activity of ADPglucose pyrophosphorylase in the first step of starch biosynthesis. This research focuses on the genetic structure and molecular mechanisms by which it is controlled during plant development and how it is affected by environmental and hormonal conditions. The current goal is to isolate the genes for this enzyme present in both cereal endosperm and potato tuber tissues, and to elucidate its structure and the controlling sequences responsible for gene expression. The long term goal is the improvement of starch production in storage organs by manipulating this gene so that it encodes an enzyme refractive to inorganic phosphate inhibition.

  10. Cumulative Epigenetic Abnormalities in Host Genes with Viral and Microbial Infection during Initiation and Progression of Malignant Lymphoma/Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Oka, Takashi, E-mail: oka@md.okayama-u.ac.jp [Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Sato, Hiaki [Department of Medical Technology, Graduate School of Health Science, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Ouchida, Mamoru [Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Utsunomiya, Atae [Department of Hematology, Imamura Bun-in Hospital, 11-23 Kamoike Shinnmachi, Kagoshima, 890-0064 (Japan); Yoshino, Tadashi [Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan)

    2011-02-04

    Although cancers have been thought to be predominantly driven by acquired genetic changes, it is becoming clear that microenvironment-mediated epigenetic alterations play important roles. Aberrant promoter hypermethylation is a prevalent phenomenon in human cancers as well as malignant lymphoma/leukemia. Tumor suppressor genes become frequent targets of aberrant hypermethylation in the course of gene-silencing due to the increased and deregulated DNA methyltransferases (DNMTs). The purpose of this article is to review the current status of knowledge about the contribution of cumulative epigenetic abnormalities of the host genes after microbial and virus infection to the crisis and progression of malignant lymphoma/leukemia. In addition, the relevance of this knowledge to malignant lymphoma/leukemia assessment, prevention and early detection will be discussed.

  11. Progress on Transferring Elite Genes from Non-AA Genome Wild Rice into Oryza sativa through Interspecific Hybridization

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The progress of research on transferring elite genes from non-AA genome wild rice into Oryza sativa through interspecific hybridization are in three respects,that is,breeding monosomic alien addition lines (MAALs),constructing introgression lines (ILs) and analyzing the heredity of the characters and mapping the related genes.There are serious reproductive barriers,mainly incrossability and hybrid sterility,in the interspecific hybridization of O.sativa with non-AA genome wild rice.These are the 'bottleneck' for transferring elite genes from wild rice to O.sativa.Combining traditional crossing method with biotechnique is a reliable way to overcome the reproductive barriers and to improve the utilizing efficiency of non-AA genome wild rice.

  12. Requirements for Clinical Trials with Gene Therapy and Transplant Products in Switzerland.

    Science.gov (United States)

    Marti, Andreas

    2015-01-01

    This chapter aims to describe and summarize the regulation of gene and cell therapy products in Switzerland and its legal basis. Product types are briefly described, as are Swiss-specific terminologies such as the term "transplant product," which means products manufactured from cells, tissues, or even whole organs. Although some parts of this chapter may show a guideline character, they are not legally binding, but represent the current thinking of Swissmedic, the Swiss Agency for Therapeutic Products. As so far the experience with marketing approval of gene therapy and cell therapy products in Switzerland is limited, this chapter focuses on the regulation of clinical trials conducted with these products. Quality, nonclinical, and clinical aspects are summarized separately for gene therapy products and transplant products.

  13. Form gene clustering method about pan-ethnic-group products based on emotional semantic

    Science.gov (United States)

    Chen, Dengkai; Ding, Jingjing; Gao, Minzhuo; Ma, Danping; Liu, Donghui

    2016-09-01

    The use of pan-ethnic-group products form knowledge primarily depends on a designer's subjective experience without user participation. The majority of studies primarily focus on the detection of the perceptual demands of consumers from the target product category. A pan-ethnic-group products form gene clustering method based on emotional semantic is constructed. Consumers' perceptual images of the pan-ethnic-group products are obtained by means of product form gene extraction and coding and computer aided product form clustering technology. A case of form gene clustering about the typical pan-ethnic-group products is investigated which indicates that the method is feasible. This paper opens up a new direction for the future development of product form design which improves the agility of product design process in the era of Industry 4.0.

  14. Disease Progression, Response to ACEI/ATRA Therapy and Influence of ACE Gene in IgA Nephritis

    Institute of Scientific and Technical Information of China (English)

    Keng-Thye Woo; Yeow-Kok Lau; Yi Zhao; Fang-E Liu; Hwee-Boon Tan; Eng-Keng Tan; Fook-Chong Stephanie; Choong-Meng Chan; Kok-Seng Wong

    2007-01-01

    Various studies have shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (ID) polymorphism may play a role in the progression to end stage renal failure (ESRF) in patients with IgA nephritis (IgAN). In this randomized controlled trial, patients were followed up for 5 years to determine their long-term renal outcome to ACEI/ATRA therapy and to ascertain if their ACE gene profile could play a role in determining their response to therapy. Seventy-five patients with IgAN were enlisted. Thirty-seven were on ACEI/ATRA therapy for 62±5 months and thirty-eight were untreated and served as controls. All patients had their ACE gene ID polymorphism genotyped. Compared to controls, treated patients had lower serum creatinine (p<0.001), lower proteinuria (p<0.002) and fewer numbers progressing to ESRF (p<0.002). Among patients with genotype Ⅱ, there were less ESRF in the treatment group when compared to the untreated control group (p<0.02). The advantage of therapy was not seen in patients with ID or DD genotypes. ACEI/ATRA therapy was found to be effective in retarding disease progression in IgAN with years to ESRF significantly extended in patients at all levels of renal function, including patients whose outcome were ESRF. Genotyping showed better response to therapy only for those with genotype Ⅱ.The common mechanism is probably through lower levels of ACE, glomerular pressure and proteinuria resulting in reduced renal damage and retardation of progression to ESRF.

  15. Identification of alcA, a Bordetella bronchiseptica gene necessary for alcaligin production.

    Science.gov (United States)

    Giardina, P C; Foster, L A; Toth, S I; Roe, B A; Dyer, D W

    1995-12-29

    The alcA gene, essential for the production of the dihydroxamate siderophore, alcaligin, by Bordetella bronchiseptica, was cloned and sequenced. The alcA gene was identified on a 4.7-kb EcoRI genomic fragment adjacent to a Tn5lac transposon insertion that inactivated alcaligin production in strain MBORD846. Analysis of the alcA nucleotide sequence revealed a putative Fur-binding site, suggesting that expression of this gene is repressed by iron. The deduced amino-acid sequence of this open reading frame had significant homology with the Escherichia coli iucD gene product, an enzyme required for biosynthesis of the dihydroxamate siderophore aerobactin.

  16. Long-term follow-up of cancer patients treated with gene therapy medicinal products.

    Science.gov (United States)

    Galli, Maria Cristina

    2012-06-01

    European Union requirements are discussed for the long-term follow-up of advanced therapy medicinal products, as well as how they can be applied to cancer patients treated with gene therapy medicinal products in the context of clinical trials, as described in a specific guideline issued by Gene Therapy Working Party at the European Medicine Agency.

  17. Aflatoxin conducive and non-conducive growth conditions reveal new gene associations with aflatoxin production.

    Science.gov (United States)

    Price, Michael S; Conners, Shannon B; Tachdjian, Sabrina; Kelly, Robert M; Payne, Gary A

    2005-06-01

    Research on aflatoxin (AF) production has traditionally focused on defining the AF biosynthetic pathway with the goal of identifying potential targets for intervention. To understand the effect of nitrogen source, carbon source, temperature, and pH on the regulation of AF biosynthesis, a targeted cDNA microarray consisting of genes associated with AF production over time was employed. Expression profiles for genes involved in AF biosynthesis grouped into five clades. A putative regulon was identified consisting of 20 genes that were induced in the conducive nitrogen and pH treatments and the non-conducive carbon and temperature treatments, as well as four other putative regulons corresponding to each of the four variables studied. Seventeen genes exhibited consistent induction/repression profiles across all the experiments. One of these genes was consistently downregulated with AF production. Overexpression of this gene resulted in repression of AF biosynthesis. The cellular function of this gene is currently unresolved.

  18. FSim: A Novel Functional Similarity Search Algorithm and Tool for Discovering Functionally Related Gene Products

    Directory of Open Access Journals (Sweden)

    Qiang Hu

    2014-01-01

    Full Text Available Background. During the analysis of genomics data, it is often required to quantify the functional similarity of genes and their products based on the annotation information from gene ontology (GO with hierarchical structure. A flexible and user-friendly way to estimate the functional similarity of genes utilizing GO annotation is therefore highly desired. Results. We proposed a novel algorithm using a level coefficient-weighted model to measure the functional similarity of gene products based on multiple ontologies of hierarchical GO annotations. The performance of our algorithm was evaluated and found to be superior to the other tested methods. We implemented the proposed algorithm in a software package, FSim, based on R statistical and computing environment. It can be used to discover functionally related genes for a given gene, group of genes, or set of function terms. Conclusions. FSim is a flexible tool to analyze functional gene groups based on the GO annotation databases.

  19. Research Progress on Gene Related to Lycopene Biosynthesis and Gene Engineering%番茄红素生物合成相关基因及其基因工程研究进展

    Institute of Scientific and Technical Information of China (English)

    祝光涛; 国艳梅; 王孝宣; 高建昌; 胡鸿; 杜永臣

    2012-01-01

    Lycopene is one of the important natural pigments, which is mainly derived from plant fruits and microorganisms. The metabolic pathway of lycopene has been clarified and many related genes have been cloned. Therefore it is possible to improve the lycopene yield by genetic engineering technology. In this paper, the latest research progress related to genes in lycopene biosynthesis, their application in microorganism gene engineering and plant gene engineering were reviewed. The paper also discussed the research orientation for further improving lycopene production in the future.%番茄红素是一种重要的天然色素,它主要来源于植物果实和微生物中.随着番茄红素代谢途径的阐明和生物合成相关基因的克隆,使得运用基因工程技术提高番茄红素产量成为可能.本文对番茄红素生物合成相关基因的最新研究进展及其在微生物和植物基因工程中的应用情况进行了综述,并探讨了今后进一步提高番茄红素产量的研究方向.

  20. Reciprocal Regulation of Pyoluteorin Production with Membrane Transporter Gene Expression in Pseudomonas fluorescens Pf-5

    OpenAIRE

    2005-01-01

    Pyoluteorin is a chlorinated polyketide antibiotic secreted by the rhizosphere bacterium Pseudomonas fluorescens Pf-5. Genes encoding enzymes and transcriptional regulators involved in pyoluteorin production are clustered in the genome of Pf-5. Sequence analysis of genes adjacent to the known pyoluteorin biosynthetic gene cluster revealed the presence of an ABC transporter system. We disrupted two putative ABC transporter genes by inserting transcriptional fusions to an ice nucleation reporte...

  1. Identification of potentially hazardous human gene products in GMO risk assessment.

    Science.gov (United States)

    Bergmans, Hans; Logie, Colin; Van Maanen, Kees; Hermsen, Harm; Meredyth, Michelle; Van Der Vlugt, Cécile

    2008-01-01

    Genetically modified organisms (GMOs), e.g. viral vectors, could threaten the environment if by their release they spread hazardous gene products. Even in contained use, to prevent adverse consequences, viral vectors carrying genes from mammals or humans should be especially scrutinized as to whether gene products that they synthesize could be hazardous in their new context. Examples of such potentially hazardous gene products (PHGPs) are: protein toxins, products of dominant alleles that have a role in hereditary diseases, gene products and sequences involved in genome rearrangements, gene products involved in immunomodulation or with an endocrine function, gene products involved in apoptosis, activated proto-oncogenes. For contained use of a GMO that carries a construct encoding a PHGP, the precautionary principle dictates that safety measures should be applied on a "worst case" basis, until the risks of the specific case have been assessed. The potential hazard of cloned genes can be estimated before empirical data on the actual GMO become available. Preliminary data may be used to focus hazard identification and risk assessment. Both predictive and empirical data may also help to identify what further information is needed to assess the risk of the GMO. A two-step approach, whereby a PHGP is evaluated for its conceptual dangers, then checked by data bank searches, is delineated here.

  2. Utilization of agricultural wastes for production of ethanol. Progress report, October 1979-May 1980

    Energy Technology Data Exchange (ETDEWEB)

    Singh, B.

    1980-05-01

    The project proposes to develop methods to utilize agricultural wastes, especially cottonseed hulls and peanut shells to produce ethanol. Initial steps will involve development of methods to break down cellulose to a usable form of substrates for chemical or biological digestion. The process of ethanol production will consist of (a) preparatory step to separate fibrous (cellulose) and non-fibrous (non-cellulosic compounds). The non-cellulosic residues which may include grains, fats or other substrates for alcoholic fermentation. The fibrous residues will be first pre-treated to digest cellulose with acid, alkali, and sulfur dioxide gas or other solvents. (b) The altered cellulose will be digested by suitable micro-organisms and cellulose enzymes before alcoholic fermentation. The digester and fermentative unit will be specially designed to develop a prototype for pilot plant for a continuous process. The first phase of the project will be devoted toward screening of a suitable method for cellulose modification, separation of fibrous and non-fibrous residues, the micro-organism and enzyme preparations. Work is in progress on: the effects of various microorganisms on the degree of saccharification; the effects of higher concentrations of acids, alkali, and EDTA on efficiency of microbial degradation; and the effects of chemicals on enzymatic digestion.

  3. Multistate atmospheric power production pollution study - MAP3S. Progress report for FY 1977 and FY 1978

    Energy Technology Data Exchange (ETDEWEB)

    MacCracken, Michael C.; Ballantine, David S.

    1979-07-01

    Research progress on the transport, transformation, and fate of pollutants released by energy-related activities is summarized. Information is reported under the following section headings: power production emissions; non-power production emissions; measuring pollutants and their properties; regional pollutant distribution; transport; pollutant transformation; surface removal processes; wet removal processes; weather and climate modification; numerical modeling and analysis; special activities; and, MAP3S research directions. (JGB)

  4. Chromosome engineering for alien gene introgression in wheat: Progress and prospective

    Science.gov (United States)

    Chromosome engineering is a useful strategy for introgression of desirable genes from wild relatives into cultivated wheat. However, it has been a challenge to transfer a small amount of alien chromatin containing the gene of interest from one genome to another non-homologous genome through classic...

  5. Artificial microRNA mediated gene silencing in plants: progress and perspectives.

    Science.gov (United States)

    Tiwari, Manish; Sharma, Deepika; Trivedi, Prabodh Kumar

    2014-09-01

    Homology based gene silencing has emerged as a convenient approach for repressing expression of genes in order to study their functions. For this purpose, several antisense or small interfering RNA based gene silencing techniques have been frequently employed in plant research. Artificial microRNAs (amiRNAs) mediated gene silencing represents one of such techniques which can utilize as a potential tool in functional genomics. Similar to microRNAs, amiRNAs are single-stranded, approximately 21 nt long, and designed by replacing the mature miRNA sequences of duplex within pre-miRNAs. These amiRNAs are processed via small RNA biogenesis and silencing machinery and deregulate target expression. Holding to various refinements, amiRNA technology offers several advantages over other gene silencing methods. This is a powerful and robust tool, and could be applied to unravel new insight of metabolic pathways and gene functions across the various disciplines as well as in translating observations for improving favourable traits in plants. This review highlights general background of small RNAs, improvements made in RNAi based gene silencing, implications of amiRNA in gene silencing, and describes future themes for improving value of this technology in plant science.

  6. The -786T>C promoter polymorphism of the NOS3 gene is associated with prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Goulart Luiz R

    2008-09-01

    Full Text Available Abstract Background There is no biological or epidemiological data on the association between NOS3 promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of NOS3 gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage. Methods This study aimed evaluating the NOS3 promoter polymorphisms by PCR-SSCP and sequencing, associating genotypes and haplotypes with NOS3 expression levels through semi-quantitative RT-PCR, and with PCA3 mRNA detection, a specific tumor biomarker, in the peripheral blood of pre-surgical samples from 177 patients; 83 PCa and 94 BPH. Results Three novel SNPs were identified -764A>G, -714G>T and -649G>A in the NOS3 gene promoter region, which together with the -786T>C generated four haplotypes (N, T, C, A. NOS3 gene expression levels were affected by the -786T>C polymorphism, and there was a 2-fold increase in NOS3 levels favored by the incorporation of each C allele. NOS3 levels higher than 80% of the constitutive gene expression level (B2M presented a 4-fold increase in PCa occurrence. Conclusion The -786T>C polymorphism was the most important promoter alteration of the NOS3 gene that may affect the PCa progression, but not its occurrence, and the incorporation of the C allele is associated with increased levels of NOS3 transcripts. The NOS3 transcript levels presented a bimodal behavior in tumor development and may be used as a biomarker together with the PCA3 marker for molecular staging of the prostate cancer.

  7. The -786T>C promoter polymorphism of the NOS3 gene is associated with prostate cancer progression.

    Science.gov (United States)

    Marangoni, Karina; Araújo, Thaíse G; Neves, Adriana F; Goulart, Luiz R

    2008-09-29

    There is no biological or epidemiological data on the association between NOS3 promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of NOS3 gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage. This study aimed evaluating the NOS3 promoter polymorphisms by PCR-SSCP and sequencing, associating genotypes and haplotypes with NOS3 expression levels through semi-quantitative RT-PCR, and with PCA3 mRNA detection, a specific tumor biomarker, in the peripheral blood of pre-surgical samples from 177 patients; 83 PCa and 94 BPH. Three novel SNPs were identified -764A>G, -714G>T and -649G>A in the NOS3 gene promoter region, which together with the -786T>C generated four haplotypes (N, T, C, A). NOS3 gene expression levels were affected by the -786T>C polymorphism, and there was a 2-fold increase in NOS3 levels favored by the incorporation of each C allele. NOS3 levels higher than 80% of the constitutive gene expression level (B2M) presented a 4-fold increase in PCa occurrence. The -786T>C polymorphism was the most important promoter alteration of the NOS3 gene that may affect the PCa progression, but not its occurrence, and the incorporation of the C allele is associated with increased levels of NOS3 transcripts. The NOS3 transcript levels presented a bimodal behavior in tumor development and may be used as a biomarker together with the PCA3 marker for molecular staging of the prostate cancer.

  8. The effects of progressing and nonprogressing Mycobacterium avium ssp. paratuberculosis infection on milk production in dairy cows

    NARCIS (Netherlands)

    Smith, Rebecca L.; Gröhn, Y. T.; Pradhan, A. K.; Whitlock, R. H.; Van Kessel, J. S.; Smith, J. M.; Wolfgang, D. R.; Schukken, Y. H.

    2016-01-01

    Longitudinal data from 3 commercial dairy herds in the northeast United States, collected from 2004 to 2011, were analyzed to determine the effect of Mycobacterium avium ssp. paratuberculosis (MAP) infection status and progression path on milk production. Disease status, as indicated by MAP test res

  9. Mutation Analysis Identifies GUCY2D as the Major Gene Responsible for Autosomal Dominant Progressive Cone Degeneration

    Science.gov (United States)

    Kitiratschky, Veronique B. D.; Wilke, Robert; Renner, Agnes B.; Kellner, Ulrich; Vadalà, Maria; Birch, David G.; Wissinger, Bernd; Zrenner, Eberhart; Kohl, Susanne

    2017-01-01

    Purpose Heterozygous mutations in the GUCY2D gene, which encodes the membrane-bound retinal guanylyl cyclase-1 protein (RetGC-1), have been shown to cause autosomal dominant inherited cone degeneration and cone–rod degeneration (adCD, adCRD). The present study was a comprehensive screening of the GUCY2D gene in 27 adCD and adCRD unrelated families of these rare disorders. Methods Mutation analysis was performed by direct sequencing as well as PCR and subsequent restriction length polymorphism analysis (PCR/RFLP). Haplotype analysis was performed in selected patients by using microsatellite markers. Results GUCY2D gene mutations were identified in 11 (40%) of 27 patients, and all mutations clustered to codon 838, including two known and one novel missense mutation: p.R838C, p.R838H, and p.R838G. Haplotype analysis showed that among the studied patients only two of the six analyzed p.R838C mutation carriers shared a common haplotype and that none of the p.R838H mutation carriers did. Conclusions GUCY2D is a major gene responsible for progressive autosomal dominant cone degeneration. All identified mutations localize to codon 838. Haplotype analysis indicates that in most cases these mutations arise independently. Thus, codon 838 is likely to be a mutation hotspot in the GUCY2D gene. PMID:18487367

  10. 木炭生产技术研究进展%Research progress of charcoal production

    Institute of Scientific and Technical Information of China (English)

    黄博林; 陈小阁; 张义堃; 郑毅骏; 刘宝庆

    2015-01-01

    木炭作为一种重要的生产、生活原料,在工业生产和家庭生活中应用广泛。现有的木炭生产技术主要有内热式炭化、外热式炭化和循环气流加热式炭化技术,本文概述了3种炭化技术与设备的研发现状,并总结了炭化工艺改进的理论研究进展:长低温停留时间,然后快速升温到高温段保温的加热工艺有利于提高木炭产率和品质,同时节省炭化时间和能量;适当提高原料湿度和炭化压力将促进木材热解,增大压力还能提高木炭得率;减小原料尺寸可以提升炭化速率,但会使得炭得率降低。最后指出当前国内木炭生产主要存在工业化水平低、理论研究滞后和缺乏相关的生产使用标准等问题,未来的木炭生产将沿着工业化、高效化和标准化方向发展。%Charcoal is widely used in industrial production and households. Charcoal production methods can be divided into three types according to different heating modes,namely internal heating, external heating and heating with recycle gas. In this paper,the research progress of charcoal production and equipmpent and theoretical study of carbonization technology improvement are summarized. Long residence time at a low temperature and then rising rapidly to a high temperature and standing for a period of time helps to increase yield and quality of charcoal as well as save time and energy. High moisture content and operation pressure can promote carbonization. Besides, pyrolysis at an elevated pressure can increase charcoal yield. Carbonization time will decrease with increasing feedstock size,however,charcoal yield will decrease as well. Finally the main problems existing in China’s charcoal production industry are lower level of industrialization,lacking theoretical research and standards for charcoal production and usage. Industrialization,high efficiency and standardization shall be the development trend of charcoal

  11. A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia.

    Science.gov (United States)

    Corbett, Mark A; Schwake, Michael; Bahlo, Melanie; Dibbens, Leanne M; Lin, Meng; Gandolfo, Luke C; Vears, Danya F; O'Sullivan, John D; Robertson, Thomas; Bayly, Marta A; Gardner, Alison E; Vlaar, Annemarie M; Korenke, G Christoph; Bloem, Bastiaan R; de Coo, Irenaeus F; Verhagen, Judith M A; Lehesjoki, Anna-Elina; Gecz, Jozef; Berkovic, Samuel F

    2011-05-13

    The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome characterized by early-onset ataxia, action myoclonus by age 6, scoliosis, and mildly elevated serum creatine kinase. This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi.

  12. A Mutation in the Golgi Qb-SNARE Gene GOSR2 Causes Progressive Myoclonus Epilepsy with Early Ataxia

    Science.gov (United States)

    Corbett, Mark A.; Schwake, Michael; Bahlo, Melanie; Dibbens, Leanne M.; Lin, Meng; Gandolfo, Luke C.; Vears, Danya F.; O'Sullivan, John D.; Robertson, Thomas; Bayly, Marta A.; Gardner, Alison E.; Vlaar, Annemarie M.; Korenke, G. Christoph; Bloem, Bastiaan R.; de Coo, Irenaeus F.; Verhagen, Judith M.A.; Lehesjoki, Anna-Elina; Gecz, Jozef; Berkovic, Samuel F.

    2011-01-01

    The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome characterized by early-onset ataxia, action myoclonus by age 6, scoliosis, and mildly elevated serum creatine kinase. This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi. PMID:21549339

  13. Microarray analysis of differentially expressed genes regulating lipid metabolism during melanoma progression.

    Science.gov (United States)

    Sumantran, Venil N; Mishra, Pratik; Sudhakar, N

    2015-04-01

    A new hallmark of cancer involves acquisition of a lipogenic phenotype which promotes tumorigenesis. Little is known about lipid metabolism in melanomas. Therefore, we used BRB (Biometrics Research Branch) class comparison tool with multivariate analysis to identify differentially expressed genes in human cutaneous melanomas, compared with benign nevi and normal skin derived from the microarray dataset (GDS1375). The methods were validated by identifying known melanoma biomarkers (CITED1, FGFR2, PTPRF, LICAM, SPP1 and PHACTR1) in our results. Eighteen genes regulating metabolism of fatty acids, lipid second messengers and gangliosides were 2-9 fold upregulated in melanomas of GDS-1375. Out of the 18 genes, 13 were confirmed by KEGG pathway analysis and 10 were also significantly upregulated in human melanoma cell lines of NCI-60 Cell Miner database. Results showed that melanomas upregulated PPARGC1A transcription factor and its target genes regulating synthesis of fatty acids (SCD) and complex lipids (FABP3 and ACSL3). Melanoma also upregulated genes which prevented lipotoxicity (CPT2 and ACOT7) and regulated lipid second messengers, such as phosphatidic acid (AGPAT-4, PLD3) and inositol triphosphate (ITPKB, ITPR3). Genes for synthesis of pro-tumorigenic GM3 and GD3 gangliosides (UGCG, HEXA, ST3GAL5 and ST8SIA1) were also upregulated in melanoma. Overall, the microarray analysis of GDS-1375 dataset indicated that melanomas can become lipogenic by upregulating genes, leading to increase in fatty acid metabolism, metabolism of specific lipid second messengers, and ganglioside synthesis.

  14. Weaver gene 3'UTR novel mutations: Associations with production ...

    African Journals Online (AJOL)

    use

    2011-11-21

    Nov 21, 2011 ... Key words: Dairy goat, weaver gene, milk performance traits, single nucleotide polymorphism. INTRODUCTION ... Cattle weaver syndrome is related to cattle milk ..... Moreover, this study contributed to its evaluation as genetic ...

  15. Idaho Natural Production Monitoring and Evaluation : Annual Progress Report February 1, 2007 - January 31, 2008.

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Timothy; Johnson, June; Putnam, Scott

    2008-12-01

    River stocks of steelhead and spring/summer Chinook salmon still have significant natural reproduction and thus are the focal species for this project's investigations. The overall goal is to monitor the abundance, productivity, distribution, and stock-specific life history characteristics of naturally produced steelhead trout and Chinook salmon in Idaho (IDFG 2007). We have grouped project tasks into three objectives, as defined in our latest project proposal and most recent statement of work. The purpose of each objective involves enumerating or describing individuals within the various life stages of Snake River anadromous salmonids. By understanding the transitions between life stages and associated controlling factors, we hope to achieve a mechanistic understanding of stock-specific population dynamics. This understanding will improve mitigation and recovery efforts. Objective 1. Measure 2007 adult escapement and describe the age structure of the spawning run of naturally produced spring/summer Chinook salmon passing Lower Granite Dam. Objective 2. Monitor the juvenile production of Chinook salmon and steelhead trout for the major population groups (MPGs) within the Clearwater and Salmon subbasins. Objective 3. Evaluate life cycle survival and the freshwater productivity/production of Snake River spring/summer Chinook salmon. There are two components: update/refine a stock-recruit model and estimate aggregate smolt-to-adult survival. In this annual progress report, we present technical results for work done during 2007. Part 2 contains detailed results of INPMEP aging research and estimation of smolt-to-adult return rates for wild and naturally produced Chinook salmon (Objectives 1 and 3). Part 3 is a report on the ongoing development of a stock-recruit model for the freshwater phase of spring/summer Chinook salmon in the Snake River basin (Objective 3). Part 4 is a summary of the parr density data (Objective 2) collected in 2007 using the new site selection

  16. Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease.

    OpenAIRE

    Zeybel, Müjdat; Hardy, Timothy; Robinson, Stuart M.; Fox, Christopher; Anstee, Quentin M.; Ness, Thomas; Masson, Steven; Masson, Steven; French, Jeremy; White, Steve; Mann, Jelena

    2015-01-01

    RESEARCH Open Access Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease Müjdat Zeybel1, Timothy Hardy1, Stuart M Robinson1, Christopher Fox1, Quentin M Anstee1, Thomas Ness2, Steven Masson1, John C Mathers1, Jeremy French1, Steve White1 and Jelena Mann1* Abstract Background: Chronic liver injury can lead to the development of liver fibrosis and cirrhosis but only in a minority of patie...

  17. blue cheese Mutations Define a Novel, Conserved Gene Involved in Progressive Neural Degeneration

    National Research Council Canada - National Science Library

    Finley, Kim D; Edeen, Philip T; Cumming, Robert C; Mardahl-Dumesnil, Michelle D; Taylor, Barbara J; Rodriguez, Maria H; Hwang, Calvin E; Benedetti, Michael; McKeown, Michael

    2003-01-01

    .... The Drosophila blue cheese (bchs) gene defines such a novel degenerative pathway. bchs mutants have a reduced adult life span with the age-dependent formation of protein aggregates throughout the neuropil of the CNS...

  18. Prolactin as a Candidate Gene Controlling Molting and Egg Production of Duck

    Directory of Open Access Journals (Sweden)

    Triana Susanti

    2015-03-01

    Full Text Available Incidence of molting is a crucial problem in the local ducks that need to be handled from many aspects including genetic aspect. Handling of molting genetically can be done quickly and accurately when the control genes have been found. The search for marker genes of molting can be conducted in poultry through broodiness naturally, because its physiological processes are related to the continuity of egg production. This paper describes the mechanism of molting, the relationship of molting with prolactin hormone and the association of prolactin gene polymorphism with molting and egg production. Molting and egg production were influenced by the prolactin hormone, that may be controlled by the prolactin gene. High concentration of prolactin hormone will inhibit the function of pituitary gland, decreasing production of gonadotrophin hormone (follicle stimulating hormone and luteinizing hormone hence ovulation ceased. This will stop egg production and at the same time molting proccess occurred.

  19. Progress and problems with the use of viral vectors for gene therapy.

    Science.gov (United States)

    Thomas, Clare E; Ehrhardt, Anja; Kay, Mark A

    2003-05-01

    Gene therapy has a history of controversy. Encouraging results are starting to emerge from the clinic, but questions are still being asked about the safety of this new molecular medicine. With the development of a leukaemia-like syndrome in two of the small number of patients that have been cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go.

  20. [Enhancement of photoassimilate utilization by manipulation of ADP-glucose pyrophosphorylase gene]. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.

    1999-04-01

    Part 1 of this research focuses on patterns of gene expression of ADPG-pyrophosphorylase in native and transgenic potato plants. To elucidate the mechanism controlling AGP expression during plant development, the expression of the potato tuber AGP small subunit (sAGP) gene was analyzed in transgenic potato plants using a promoter-{beta}-glucuronidase expression system. Part II evaluated the structure-function relationships of AGP.

  1. Organization and control of genes encoding catabolic enzymes in Rhizobiaceae. Progress report, March 1993

    Energy Technology Data Exchange (ETDEWEB)

    Parke, D.; Ornston, L.N.

    1993-03-01

    Rhizobiaceae, a diverse bacterial group comprising rhizobia and agrobacteria, symbiotic partnership with plants form nitrogen-fixing nodules on plant roots or are plant pathogens. Phenolic compounds produced by plants serve as inducers of rhizobial nodulation genes and agrobacterial virulence genes reflect their capacity to utilize numerous aromatics, including phenolics, as a source of carbon and energy. In many microbes the aerobic degradation of numerous aromatic compounds to tricarboxylic acid cycle intermediates is achieved by the {beta}-ketoadipate pathway. Our initial studies focused on the organization and regulation of the ketoadipate pathway in Agrobacterium tumefaciens. We have cloned, identified and characterized a novel regulatory gene that modulates expression of an adjacent pca (protocatechuate) structural gene, pcaD. Regulation of pcaD is mediated by the regulatory gene, termed pcaQ, in concert with the intermediate {beta}-carboxy-cis,cis-muconate. {beta}-carboxy-cis,cismuconate is an unstable chemical, not marketed commercially, and it is unlikely to permeate Escherichia coli cells if supplied in media. Because of these factors, characterization of pcaQ in E. coli required an in vivo delivery system for {beta}-carboxycis,cis-muconate. This was accomplished by designing an E. coli strain that expressed an Acinetobacter calcoaceticus pcaA gene for conversion of protocatechuate to {beta}-carboxy-cis,cis-muconate.

  2. Aluminum oxide nanoparticles alter cell cycle progression through CCND1 and EGR1 gene expression in human mesenchymal stem cells.

    Science.gov (United States)

    Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Alshatwi, Ali A

    2016-05-01

    Aluminum oxide nanoparticles (Al2 O3 -NPs) are important ceramic materials that have been used in a variety of commercial and industrial applications. However, the impact of acute and chronic exposure to Al2 O3 -NPs on the environment and on human health has not been well studied. In this investigation, we evaluated the cytotoxic effects of Al2 O3 -NPs on human mesenchymal stem cells (hMSCs) by using a cell viability assay and observing cellular morphological changes, analyzing cell cycle progression, and monitoring the expression of cell cycle response genes (PCNA, EGR1, E2F1, CCND1, CCNC, CCNG1, and CYCD3). The Al2 O3 -NPs reduced hMSC viability in a dose- and time-dependent manner. Nuclear condensation and fragmentation, chromosomal DNA fragmentation, and cytoplasmic vacuolization were observed in Al2 O3 -NP-exposed cells. The nuclear morphological changes indicated that Al2 O3 -NPs alter cell cycle progression and gene expression. The cell cycle distribution revealed that Al2 O3 -NPs cause cell cycle arrest in the sub-G0-G1 phase, and this is associated with a reduction in the cell population in the G2/M and G0/G1 phases. Moreover, Al2 O3 -NPs induced the upregulation of cell cycle response genes, including EGR1, E2F1, and CCND1. Our results suggested that exposure to Al2 O3 -NPs could cause acute cytotoxic effects in hMSCs through cell cycle regulatory genes.

  3. Antiproliferative effect of ascorbic acid is associated with the inhibition of genes necessary to cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Sophie Belin

    Full Text Available BACKGROUND: Ascorbic acid (AA, or Vitamin C, is most well known as a nutritional supplement with antioxidant properties. Recently, we demonstrated that high concentrations of AA act on PMP22 gene expression and partially correct the Charcot-Marie-Tooth disease phenotype in a mouse model. This is due to the capacity of AA, but not other antioxidants, to down-modulate cAMP intracellular concentration by a competitive inhibition of the adenylate cyclase enzymatic activity. Because of the critical role of cAMP in intracellular signalling, we decided to explore the possibility that ascorbic acid could modulate the expression of other genes. METHODS AND FINDINGS: Using human pangenomic microarrays, we found that AA inhibited the expression of two categories of genes necessary for cell cycle progression, tRNA synthetases and translation initiation factor subunits. In in vitro assays, we demonstrated that AA induced the S-phase arrest of proliferative normal and tumor cells. Highest concentrations of AA leaded to necrotic cell death. However, quiescent cells were not susceptible to AA toxicity, suggesting the blockage of protein synthesis was mainly detrimental in metabolically-active cells. Using animal models, we found that high concentrations of AA inhibited tumor progression in nude mice grafted with HT29 cells (derived from human colon carcinoma. Consistently, expression of tRNA synthetases and ieF2 appeared to be specifically decreased in tumors upon AA treatment. CONCLUSIONS: AA has an antiproliferative activity, at elevated concentration that could be obtained using IV injection. This activity has been observed in vitro as well in vivo and likely results from the inhibition of expression of genes involved in protein synthesis. Implications for a clinical use in anticancer therapies will be discussed.

  4. Allele loss and down-regulation of heparanase gene are associated with the progression and poor prognosis of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Guo-Liang Huang

    Full Text Available OBJECTIVES: The role of heparanase (HPSE gene in cancers including hepatocellular carcinoma (HCC is currently controversial. This study was aimed at investigating the impact of genetic alteration and expression change of HPSE on the progression and prognosis of HCC. METHODS: The HPSE gene was studied in three different aspects: (1 loss of heterozygosity (LOH by a custom SNP microarray and DNA copy number by real-time PCR; (2 mRNA level by qRT-PCR; and (3 protein expression by immunohistochemistry. The clinical significances of allele loss and expression change of HPSE were analyzed. RESULTS: Microarray analysis showed that the average LOH frequency for 10 SNPs located within HPSE gene was 31.6%, three of which were significantly correlated with tumor grade, serum HBV-DNA level, and AFP concentration. In agreement with SNP LOH data, DNA copy number loss of HPSE was observed in 38.74% (43/111 of HCC cases. HPSE mRNA level was notably reduced in 74.1% (83/112 of tumor tissues compared with non-tumor liver tissues, which was significantly associated with DNA copy number loss, increased tumor size, and post-operative metastasis. HPSE protein level was also remarkably reduced in 66.3% (53/80 of tumor tissues, which was correlated with tumor grade. Patients with lower expression level of HPSE mRNA or protein had a significantly lower survival rate than those with higher expression. Cox regression analysis suggested that HPSE protein was an independent predictor of overall survival in HCC patients. CONCLUSIONS: The results in this study demonstrate that genetic alteration and reduction of HPSE expression are associated with tumor progression and poor prognosis of HCCs, suggesting that HPSE behaves like a tumor suppressor gene and is a potential prognostic marker for HCC patients.

  5. Product-induced gene expression, a product-responsive reporter assay used to screen metagenomic libraries for enzyme-encoding genes.

    Science.gov (United States)

    Uchiyama, Taku; Miyazaki, Kentaro

    2010-11-01

    A reporter assay-based screening method for enzymes, which we named product-induced gene expression (PIGEX), was developed and used to screen a metagenomic library for amidases. A benzoate-responsive transcriptional activator, BenR, was placed upstream of the gene encoding green fluorescent protein and used as a sensor. Escherichia coli sensor cells carrying the benR-gfp gene cassette fluoresced in response to benzoate concentrations as low as 10 μM but were completely unresponsive to the substrate benzamide. An E. coli metagenomic library consisting of 96,000 clones was grown in 96-well format in LB medium containing benzamide. The library cells were then cocultivated with sensor cells. Eleven amidase genes were recovered from 143 fluorescent wells; eight of these genes were homologous to known bacterial amidase genes while three were novel genes. In addition to their activity toward benzamide, the enzymes were active toward various substrates, including d- and l-amino acid amides, and displayed enantioselectivity. Thus, we demonstrated that PIGEX is an effective approach for screening novel enzymes based on product detection.

  6. Urinary collagen degradation products as early markers of progressive renal fibrosis.

    Science.gov (United States)

    Hijmans, Ryanne S; Rasmussen, Daniel Guldager Kring; Yazdani, Saleh; Navis, Gerjan; van Goor, Harry; Karsdal, Morten Asser; Genovese, Federica; van den Born, Jacob

    2017-03-20

    Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic S1P-receptor modulator FTY720 treatment. Proteinuria was induced in male Wistar rats by Adriamycin (ADR) injection (n = 16). Healthy rats served as controls (n = 12). Six weeks post-injection, all underwent renal biopsy, and FTY720-treatment started in ADR-rats (n = 8) and controls (n = 6). Others remained untreated. Rats were sacrificed after 12 weeks. Collagen type I (C1M) and III (C3M) degradation fragments were measured in blood and urine using ELISA. Kidneys were stained for various inflammatory and fibrotic markers. Six weeks post-injection proteinuria increased (versus controls, P < 0.001) and although no accumulation of interstitial renal collagen type III (iColl3) was observed at this time, urinary C3M (uC3M) and C1M (uC1M) were significantly increased (both P < 0.001). At 12 weeks, uC3M (P < 0.001) and uC1M (P < 0.01) further increased in ADR-rats versus controls, just as fibronectin, PDGF-β receptor, hyaluronan (all P < 0.01), iColl3, PAS, myofibroblasts, macrophages and T-cells (all P < 0.05). FTY720-treatment reduced accumulation of immune cells, α-SMA+ myofibroblasts and PAS-score, but not iColl3 and uC3M. Correlation analyses indicated that uC3M and uC1M reflected and predicted tubulointerstitial fibrogenesis. These data displayed urinary collagen breakdown products as sensitive early markers of interstitial fibrosis, preceding histological fibrotic changes, which might replace the invasive renal biopsy procedure to assess fibrosis. Anti-fibrotic FTY720 intervention reduced some fibrotic markers without affecting collagen type III metabolism.

  7. Gene expression profiling of R6/2 transgenic mice with different CAG repeat lengths reveals genes associated with disease onset and progression in Huntington's disease.

    Science.gov (United States)

    Tang, Bin; Seredenina, Tamara; Coppola, Giovanni; Kuhn, Alexandre; Geschwind, Daniel H; Luthi-Carter, Ruth; Thomas, Elizabeth A

    2011-06-01

    R6/2 transgenic mice with expanded CAG repeats (>300) have a surprisingly prolonged disease progression and longer lifespan than prototypical parent R6/2 mice (carrying 150 CAGs); however, the mechanism of this phenotype amelioration is unknown. We compared gene expression profiles in the striatum of R6/2 transgenic mice carrying ~300 CAG repeats (R6/2(Q300) transgenic mice) to those carrying ~150 CAG repeats (R6/2(Q150) transgenic mice) and littermate wildtype controls in order to identify genes that may play determinant roles in the time course of phenotypic expression in these mice. Of the top genes showing concordant expression changes in the striatum of both R6/2 lines, 85% were decreased in expression, while discordant expression changes were observed mostly for genes upregulated in R6/2(Q300) transgenic mice. Upregulated genes in the R6/2(Q300) mice were associated with the ubiquitin ligase complex, cell adhesion, protein folding, and establishment of protein localization. We qPCR-validated increases in expression of genes related to the latter category, including Lrsam1, Erp29, Nasp, Tap1, Rab9b, and Pfdn5 in R6/2(Q300) mice, changes that were not observed in R6/2 mice with shorter CAG repeats, even in late stages (i.e., 12 weeks of age). We further tested Lrsam1 and Erp29, the two genes showing the greatest upregulation in R6/2(Q300) transgenic mice, for potential neuroprotective effects in primary striatal cultures overexpressing a mutated human huntingtin (htt) fragment. Overexpression of Lrsam1 prevented the loss of NeuN-positive cell bodies in htt171-82Q cultures, concomitant with a reduction of nuclear htt aggregates. Erp29 showed no significant effects in this model. This is consistent with the distinct pattern of htt inclusion localization observed in R6/2(Q300) transgenic mice, in which smaller cytoplasmic inclusions represent the major form of insoluble htt in the cell, as opposed to large nuclear inclusions observed in R6/2(Q150) transgenic mice

  8. [Progress in genes related to seed-coat color in soybean].

    Science.gov (United States)

    Song, Jian; Guo, Yong; Yu, Li-Jie; Qiu, Li-Juan

    2012-06-01

    Seed-coat color has changed from black to yellow during natural and artificial selection of cultivated soybean from wild soybean, and it is also an important morphological marker. Therefore, discovering genes related to the soybean seed-coat color will play a very important role in breeding and evolutionary study. Different seed-coat colors caused by deposition of various anthocyanin pigments. Although pigmentation has been well dissected at molecular level in several plant species, the genes controlling natural variation of seed-coat color in soybean remain to be unknown. Genes related to seed-coat color in soybean were discussed in this paper, including 5 genetic loci (I, T, W1, R and O). Locus I is located in a region that riches in chalcone synthase (CHS) genes on chromosome 8. Gene CHS is a multi-gene family with highly conserved sequences in soybean. Locus T located on chromosome 6 has been cloned and verified, which encodes a flavon-oid-3'-hydroxylase. Mutant of F3'H can not interact with the heme-binding domain due to lack of conservative domain GGEK caused by a nucleotide deletion in the coding region of F3'H. Locus R is located between A668-1 and K387-1 on chromosome 9 (linkage group K). This locus may encode a R2R3 MYB transcription factor or a UDP flavonoid 3-O glyco-syltransferase. Locus O is located between Satt207 and Satt493 on chromosome 8 (linkage group A2) and its molecular characteristics has not been characterized. Locus W1 may be a homology of F3'5'H gene.

  9. Research Progress of Colon Cancer Related Genes%结肠癌相关基因研究进展

    Institute of Scientific and Technical Information of China (English)

    唐楠; 王媛媛

    2012-01-01

    结肠癌是常见的恶性肿瘤,在我国其发病率有上升趋势.近年来,从分子水平上研究结肠癌的发生、发展及预后,寻找更有效的治疗方法,已经成为热点.目前研究结果显示,与结肠癌发生、发展相关的基因有许多.现从癌基因、抑癌基因、与血管生成有关的基因、其他基因等几个方面对其研究进展予以综述,为更好地研究结肠癌提供一定的理论依据.%Colon cancer is a common malignant tumor,the incidence of which is in uptrend in China. In recent years, the research of the genesis, development and prognosis of colon cancer on molecular level to find more effective treatment has become the hotspot. Current studies showed that there were many genes related to the development of colon cancer. Here is to make a review on the research progress from the perspective of onco-genes,tumor suppressor genes,and angiogenesis-related genes etc. ,to provide a theoretical basis for better understanding of colon cancer.

  10. Progression of Gene Expression Changes following a Mechanical Injury to Articular Cartilage as a Model of Early Stage Osteoarthritis.

    Science.gov (United States)

    McCulloch, R S; Ashwell, M S; Maltecca, C; O'Nan, A T; Mente, P L

    2014-01-01

    An impact injury model of early stage osteoarthritis (OA) progression was developed using a mechanical insult to an articular cartilage surface to evaluate differential gene expression changes over time and treatment. Porcine patellae with intact cartilage surfaces were randomized to one of three treatments: nonimpacted control, axial impaction (2000 N), or a shear impaction (500 N axial, with tangential displacement to induce shear forces). After impact, the patellae were returned to culture for 0, 3, 7, or 14 days. At the appropriate time point, RNA was extracted from full-thickness cartilage slices at the impact site. Quantitative real-time PCR was used to evaluate differential gene expression for 18 OA related genes from four categories: cartilage matrix, degradative enzymes and inhibitors, inflammatory response and signaling, and cell apoptosis. The shear impacted specimens were compared to the axial impacted specimens and showed that shear specimens more highly expressed type I collagen (Col1a1) at the early time points. In addition, there was generally elevated expression of degradative enzymes, inflammatory response genes, and apoptosis markers at the early time points. These changes suggest that the more physiologically relevant shear loading may initially be more damaging to the cartilage and induces more repair efforts after loading.

  11. [Enhancement of photoassimilate utilization by manipulation of the ADPglucose pyrophosphorylase gene]. Summary of progress, [April 15, 1991--April 14, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.

    1992-12-31

    The long term aim of this project is to assess the feasibility of increasing the conversion of photosynthate into starch via manipulation of genes encoding enzymes that may be rate-limiting in starch biosynthesis. In developing storage tissues such as tubers, starch biosynthesis is regulated by the gene activation and expression of ADPglucose pyrophosphorylase, starch synthase, branching enzyme and other ancillary starch modifying enzymes, as well as the allosteric-controlled behavior of ADPglucose pyrophosphorylase activity. In view of the regulatory role of ADPglucose pyrophosphorylase in starch biosynthesis at both the genetic and biochemical level, we have focused our attention on the genes that encode for this enzyme in potato tubers. The proposed objectives of the grant were to (1) analyze the structure of the tuber enzyme, (2) isolate and characterize the structure of its genes, and (3) identify the regulatory elements controlling ADPglucose pyrophosphorylase during plant development. During the last two and 1/2 years we have met or have made considerable progress in achieving these objectives as discussed in more detail below.

  12. [Enhancement of photoassimilate utilization by manipulation of the ADPglucose pyrophosphorylase gene]. Summary of progress, [April 15, 1991--April 14, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Okita, T.W.

    1992-12-31

    The long term aim of this project is to assess the feasibility of increasing the conversion of photosynthate into starch via manipulation of genes encoding enzymes that may be rate-limiting in starch biosynthesis. In developing storage tissues such as tubers, starch biosynthesis is regulated by the gene activation and expression of ADPglucose pyrophosphorylase, starch synthase, branching enzyme and other ancillary starch modifying enzymes, as well as the allosteric-controlled behavior of ADPglucose pyrophosphorylase activity. In view of the regulatory role of ADPglucose pyrophosphorylase in starch biosynthesis at both the genetic and biochemical level, we have focused our attention on the genes that encode for this enzyme in potato tubers. The proposed objectives of the grant were to (1) analyze the structure of the tuber enzyme, (2) isolate and characterize the structure of its genes, and (3) identify the regulatory elements controlling ADPglucose pyrophosphorylase during plant development. During the last two and 1/2 years we have met or have made considerable progress in achieving these objectives as discussed in more detail below.

  13. Molecular Study on Differentiation-Associated Genes Involved in Both Malignant Progression of Glioma and Differentiation of Human Fetal Neural Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Jun Dong; Yinyan Wu; Qiang Huang; Fei Wang; Aidong Wang; Qing Lan

    2006-01-01

    OBJECTIVE It is unclear whether differentiation disturbances or deregulation of neural stem cells (NSCs) are the early key steps for gliomagenesis and tumor development. Furthermore, relevant molecular changes and gene-regulation pathways are unknown. This study focused on screening and validating differentiation-associated genes from both human NSCs and glioma cells with malignant progression, for the purpose of offering an experimental basis for the cellular origin of gilomas and molecular pathology of gliomagenesis.METHODS The differential-gene expression profiles of malignant progression of gliomas were established, then the differentiation related genes were screened out with a bioinformatics analysis. Expression levels of these genes was further analyzed in cultured human fetal NSCs undergoing differentiation processes with a semi-quantitative RT-PCR assay.RESULTS Eight genes were screened out from the gene-expression profiling of which the expression levels were associated with the differentiation processes of NSCs, namely CXCR4, TN-C, GLT1, IL1-RI, EGFR8, CDC2, Ndr3 and MAPKK4. Three of them, ie., GLT1, CDC2 and MAPKK4, were further analyzed, showing that expression levels decreased with the differentiation processes of NSCs, and increased with the malignant progression of ganglioglioma.CONCLUSION Three differentiation associated genes were found negatively associated with NSCs differentiation and positively associated with malignant progression of gliomas, suggesting that differentiation disturbances of neural stem ceils may be involved in oncogenesis, and that further studies on their roles in gliomagenesis should be conducted.

  14. Higher body mass index in adults at diagnosis of the slowly progressive form of type 1 diabetes mellitus is associated with lower risk HLA genes.

    Science.gov (United States)

    Fourlanos, S; Elkassaby, S; Varney, M D; Colman, P G; Harrison, L C

    2014-06-01

    We hypothesised that higher body weight, a proposed risk factor for type 1 diabetes mellitus, would be associated with increased penetrance of lower risk genes. In adults at diagnosis of the slowly progressive form of type 1 diabetes mellitus we found that higher body mass index was associated with the absence of the highest risk HLA genes.

  15. Cyclooxygenase product inhibition with acetylsalicylic acid slows disease progression in the Han:SPRD-Cy rat model of polycystic kidney disease.

    Science.gov (United States)

    Ibrahim, Naser H M; Gregoire, Melanie; Devassy, Jessay G; Wu, Yinhong; Yoshihara, Daisuke; Yamaguchi, Tamio; Nagao, Shizuko; Aukema, Harold M

    2015-01-01

    Renal cyclooxygenase (COX) derived eicosanoids are elevated and lipoxygenase (LOX) products are reduced in the Han:SPRD-Cy rat model of polycystic kidney disease (PKD). Selective COX2 inhibition reduces kidney disease progression, but COX1 levels also are elevated in this model. Since the effect of reducing the products of both COX isoforms and the role of LOX products is not known, weanling normal and diseased Han:SPRD-cy littermates were given either low dose acetylsalicylic acid (ASA), nordihydroguaiaretic (NDGA) or no treatment for eight weeks. Renal eicosanoids were altered in the diseased compared to normal cortex, with COX products being higher and LOX products being lower. ASA reduced COX products, cyst growth and kidney water content, while NDGA reduced LOX products without altering disease progression or kidney function. Hence, a human equivalent ASA dose equal to less than one regular strength aspirin per day slowed disease progression, while further reduction of LOX products did not worsen disease progression.

  16. 肥胖基因FTO的研究进展%Current progress on FTO gene

    Institute of Scientific and Technical Information of China (English)

    王辉; 孟雁

    2010-01-01

    Whole-genome association analysis makes Fro gene (fat mass and obesity associated gene) become the first candidate gene for obesity among general population.It is highly expressed in hypo-thalamus and is involved in the control of energy balance.FTO gene with single nucleotide polymorphism vari-ation is correlated with the choice of dietary intake which may influence body weight that result in obesity.In addition,it is also associated with type 2 diabetes, and has correlation with other genes.%全基因组关联分析使得FTO(fat mass and obesity associated)基因成为第一个普通人群肥胖候选基因,其在下丘脑核丰富表达,参与能量平衡的控制.FTO基因的不同单核苷酸多态性可影响饮食的摄取,从而影响人的体重,参与肥胖的发生.此外,FTO基因还与2型糖尿病等疾病密切相关,与其他基因发挥协同作用.

  17. Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size.

    Science.gov (United States)

    Chen, Jian-Fu; Zhang, Ying; Wilde, Jonathan; Hansen, Kirk C; Lai, Fan; Niswander, Lee

    2014-05-30

    Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly.

  18. Human Cpr (Cell Cycle Progression Restoration) Genes Impart a Far(-) Phenotype on Yeast Cells

    OpenAIRE

    Edwards, M. C.; Liegeois, N.; Horecka, J.; DePinho, R A; Sprague-Jr., G. F.; Tyers, M; Elledge, S J

    1997-01-01

    Regulated cell cycle progression depends on the proper integration of growth control pathways with the basic cell cycle machinery. While many of the central molecules such as cyclins, CDKs, and CKIs are known, and many of the kinases and phosphatases that modify the CDKs have been identified, little is known about the additional layers of regulation that impinge upon these molecules. To identify new regulators of cell proliferation, we have selected for human and yeast cDNAs that when overexp...

  19. Evaluation of gene expression and alginate production in response to oxygen transfer in continuous culture of Azotobacter vinelandii.

    Directory of Open Access Journals (Sweden)

    Alvaro Díaz-Barrera

    Full Text Available Alginates are polysaccharides used as food additives and encapsulation agents in biotechnology, and their functional properties depend on its molecular weight. In this study, different steady-states in continuous cultures of A. vinelandii were established to determine the effect of the dilution rate (D and the agitation rate on alginate production and expression of genes involved in alginate polymerization and depolymerization. Both, the agitation and dilution rates, determined the partitioning of the carbon utilization from sucrose into alginate and CO2 under oxygen-limiting conditions. A low D (0.07 h(-1 and 500 rpm resulted in the highest carbon utilization into alginate (25%. Quantitative real-time polymerase chain reaction was used to determine the transcription level of six genes involved in alginate polymerization and depolymerization. In chemostat cultures at 0.07 h(-1, the gene expression was affected by changes in the agitation rate. By increasing the agitation rate from 400 to 600 rpm, the algE7 gene expression decreased tenfold, whereas alyA1, algL and alyA2 gene expression increased between 1.5 and 2.8 times under similar conditions evaluated. Chemostat at 0.07 h(-1 showed a highest alginate molecular weight (580 kDa at 500 rpm whereas similar molecular weights (480 kDa were obtained at 400 and 600 rpm. The highest molecular weight was not explained by changes in the expression of alg8 and alg44 (genes involved in alginate polymerization. Nonetheless, a different expression pattern observed for lyases could explain the highest alginate molecular weight obtained. Overall, the results suggest that the control of alginate molecular weight in A. vinelandii cells growing in continuous mode is determined by a balance between the gene expression of intracellular and extracellular lyases in response to oxygen availability. These findings better our understanding of the biosynthesis of bacterial alginate and help us progress toward obtain

  20. Evaluation of Gene Expression and Alginate Production in Response to Oxygen Transfer in Continuous Culture of Azotobacter vinelandii

    Science.gov (United States)

    Díaz-Barrera, Alvaro; Martínez, Fabiola; Guevara Pezoa, Felipe; Acevedo, Fernando

    2014-01-01

    Alginates are polysaccharides used as food additives and encapsulation agents in biotechnology, and their functional properties depend on its molecular weight. In this study, different steady-states in continuous cultures of A. vinelandii were established to determine the effect of the dilution rate (D) and the agitation rate on alginate production and expression of genes involved in alginate polymerization and depolymerization. Both, the agitation and dilution rates, determined the partitioning of the carbon utilization from sucrose into alginate and CO2 under oxygen-limiting conditions. A low D (0.07 h−1) and 500 rpm resulted in the highest carbon utilization into alginate (25%). Quantitative real-time polymerase chain reaction was used to determine the transcription level of six genes involved in alginate polymerization and depolymerization. In chemostat cultures at 0.07 h−1, the gene expression was affected by changes in the agitation rate. By increasing the agitation rate from 400 to 600 rpm, the algE7 gene expression decreased tenfold, whereas alyA1, algL and alyA2 gene expression increased between 1.5 and 2.8 times under similar conditions evaluated. Chemostat at 0.07 h−1 showed a highest alginate molecular weight (580 kDa) at 500 rpm whereas similar molecular weights (480 kDa) were obtained at 400 and 600 rpm. The highest molecular weight was not explained by changes in the expression of alg8 and alg44 (genes involved in alginate polymerization). Nonetheless, a different expression pattern observed for lyases could explain the highest alginate molecular weight obtained. Overall, the results suggest that the control of alginate molecular weight in A. vinelandii cells growing in continuous mode is determined by a balance between the gene expression of intracellular and extracellular lyases in response to oxygen availability. These findings better our understanding of the biosynthesis of bacterial alginate and help us progress toward obtain tailor

  1. Progresses in Researches of the Application of Low-Amylose Content Rice Gene for Breeding

    Institute of Scientific and Technical Information of China (English)

    ZHU Chang-lan; SHEN Wen-biao; ZHAI Hu-qu; WAN Jian-min

    2004-01-01

    Amylose content is a key determinant of eating quality of rice. With the characteristics of fluffy texture, glossy appearance when cooked, remaining soft when cooled and excellent puffing ability, the low-amylose rice with amylose content 5-15% could be served as not only cooked rice directly, but also good material for convenience, mixed rice and puffing foods.Current status on characterization, inheritance, molecular mechanism and breeding of lowamylose content rice was reviewed in this paper, strategy of related researches in the era of glymics was mainly discussed furthermore. The future research should focus on screening and enhancing the germplasm, further elucidating the molecular mechanism on mutation of low amylose content, utilizing the genes independent of Wx on low-amylose content rice breeding program, and developing high quality functional rice cultivars for special usage through pyramiding low amylose gene and other special quality genes.

  2. Cell surface expression system for the display of heterologous gene products using chimeric flagellin fusions of bacillus halodurans isolate

    CSIR Research Space (South Africa)

    Du Plessis, A

    2006-10-01

    Full Text Available N-terminal sequencing gave rise to homology to flagellin protein, product of the hag gene. protein, product of the hag gene. Gene was cloned by using degenerate primers and inverse PCR. The gene sequence as well as the up- and down- stream regions...

  3. DNA sequence, products, and transcriptional pattern of the genes involved in production of the DNA replication inhibitor microcin B17.

    Science.gov (United States)

    Genilloud, O; Moreno, F; Kolter, R

    1989-02-01

    The 3.8-kilobase segment of plasmid DNA that contains the genes required for production of the DNA replication inhibitor microcin B17 was sequenced. The sequence contains four open reading frames which were shown to be translated in vivo by the construction of fusions to lacZ. The location of these open reading frames fits well with the location of the four microcin B17 production genes, mcbABCD, identified previously through genetic complementation. The products of the four genes have been identified, and the observed molecular weights of the proteins agree with those predicted from the nucleotide sequence. The transcription of these genes was studied by using fusions to lacZ and physical mapping of mRNA start sites. Three promoters were identified in this region. The major promoter for all the genes is a growth phase-regulated OmpR-dependent promoter located upstream of mcbA. A second promoter is located within mcbC and is responsible for a low-level basal expression of mcbD. A third promoter, located within mcbD, promotes transcription in the reverse direction starting within mcbD and extending through mcbC. The resulting mRNA appears to be an untranslated antisense transcript that could play a regulatory role in the expression of these genes.

  4. Transposon tagging of disease resistance genes. Progress report, May 1, 1988--1992

    Energy Technology Data Exchange (ETDEWEB)

    Michelmore, R.

    1994-06-01

    Our goal is to clone genes in lettuce determining resistance to downy mildew. One approach involves the mobilization of transposons into resistance genes to mutate and tag the target gene. Because transposons have yet to be isolated and characterized from lettuce, the majority of our experiments have involved Ac from corn as this is increasingly the best characterized transposon. Over the past several years, various labs have contributed to a detailed understanding of the biology of Ac in corn and heterologous plant species. We have collaborated closely with several of these labs, exchanged materials and incorporated their advances into our analysis of transposition in lettuce. The original proposal described the development of a transposon mutagenesis system for lettuce and its subsequent use to tag disease resistance genes. The development phase involved characterization and manipulation of Ac transposition, identification of suitable whole plant selectable markers for the construction of chimeric non-autonomous elements, and investigation of the stability of resistance genes. Investigation of Ac transposition in lettuce has received the majority of our attention. Initially, we made a simple construct with wildtype Ac and introduced it into lettuce. No transposition was observed; although other labs demonstrated that the same construct was functional in tomato. We then focused on assaying for Ac transposition with constructs of increasing sophistication that had been demonstrated by others to be functional in other species. The latest constructs for transposon mutagenesis clearly demonstrated transposition in lettuce. This allowed us to generate seed stocks that we will start to screen for insertional inactivation of resistance genes this year.

  5. Sites and gene products involved in lambdoid phage DNA packaging.

    Science.gov (United States)

    Smith, M P; Feiss, M

    1993-04-01

    21 is a temperate lambdoid coliphage, and the genes that encode the head proteins of lambda and 21 are descended from a common ancestral bacteriophage. The sequencing of terminase genes 1 and 2 of 21 was completed, along with that of a segment at the right end of 21 DNA that includes the R4 sequence. The R4 sequence, a site that is likely involved in termination of DNA packaging, was found to be very similar to the R4 sequences of lambda and phi 80, suggesting that R4 is a recognition site that is not phage specific. DNA packaging by 21 is dependent on a host protein, integration host factor. A series of mutations in gene 1 (her mutations), which allow integration host factor-independent DNA packaging by 21, were found to be missense changes that affect predicted alpha-helixes in gp1. gp2, the large terminase subunit, is predicted to contain an ATP-binding domain and, perhaps, a second domain important for the cos-cutting activity of terminase. orf1, an open reading frame analogous in position to FI, a lambda gene involved in DNA packaging, shares some sequence identity with FI. orf1 was inactivated with nonsense and insertion mutations; these mutations were found not to affect phage growth. 21 was also not able to complement a lambda FI mutant.

  6. Reporter gene imaging of immune responses to cancer: progress and challenges.

    Science.gov (United States)

    Dubey, Purnima

    2012-01-01

    Immune responses to cancer are dynamic processes which take place through the concerted activity of innate and adaptive cell populations. In order to fully understand the efficacy of immune therapies for cancer, it is critical to understand how the treatment modulates the function of each cell type involved in the anti-tumor immune response. Molecular imaging is a versatile method for longitudinal studies of cellular localization and function. The development of reporter genes for tracking cell movement and function was a powerful addition to the immunologist's toolbox. This review will highlight the advances and challenges in the use of reporter gene imaging to track immune cell localization and function in cancer.

  7. Inducible amplification of gene copy number and heterologous protein production in the yeast Kluyveromyces lactis.

    Science.gov (United States)

    Morlino, G B; Tizzani, L; Fleer, R; Frontali, L; Bianchi, M M

    1999-11-01

    Heterologous protein production can be doubled by increasing the copy number of the corresponding heterologous gene. We constructed a host-vector system in the yeast Kluyveromyces lactis that was able to induce copy number amplification of pKD1 plasmid-based vectors upon expression of an integrated copy of the plasmid recombinase gene. We increased the production and secretion of two heterologous proteins, glucoamylase from the yeast Arxula adeninivorans and mammalian interleukin-1beta, following gene dosage amplification when the heterologous genes were carried by pKD1-based vectors. The choice of the promoters for expression of the integrated recombinase gene and of the episomal heterologous genes are critical for the mitotic stability of the host-vector system.

  8. TVA/DOE integrated onfarm alcohol production system. Phase II. Progress report, October 1981-February 1982. Circular Z-134

    Energy Technology Data Exchange (ETDEWEB)

    Badger, P.C.; Pile, R.S.; Burch, D.W.; Mays, D.A.; Lewis, J.M.

    1982-03-01

    Equipment and procedures necessary for using a grain (corn) feedstock for onfarm alcohol production were refined and documented to provide benchmark data. Also, significant progress was made in developing technology to convert other agricultural crops into 190-proof alcohol with the farm-sized alcohol production facility. This was achieved by modifying the base alcohol-from-grain facility to process the nongrain feedstocks (Irish potatoes, sweet sorghum, sweet potatoes, sugar beets, fodder beets, and Jerusalem artichokes) being evaluated in field production trials by TVA. Alcohol production capacities of cull potatoes, water chestnuts, and cull apples were also tested. A computerized investment model was refined to predict rapidly the economic implications for alcohol production levels, feedstocks, and various system components.

  9. Chemoprevention in gastrointestinal physiology and disease. Targeting the progression of cancer with natural products: a focus on gastrointestinal cancer.

    Science.gov (United States)

    Khoogar, Roxane; Kim, Byung-Chang; Morris, Jay; Wargovich, Michael J

    2016-05-01

    The last decade has witnessed remarkable progress in the utilization of natural products for the prevention and treatment of human cancer. Many agents now in the pipeline for clinical trial testing have evolved from our understanding of how human nutritional patterns account for widespread differences in cancer risk. In this review, we have focused on many of these promising agents arguing that they may provide a new strategy for cancer control: natural products once thought to be only preventive in their mode of action now are being explored for efficacy in tandem with cancer therapeutics. Natural products may reduce off-target toxicity of therapeutics while making cancers more amenable to therapy. On the horizon is the use of certain natural products, in their own right, as mitigants of late-stage cancer, a new frontier for small-molecule natural product drug discovery.

  10. Improvement of gougerotin and nikkomycin production by engineering their biosynthetic gene clusters.

    Science.gov (United States)

    Du, Deyao; Zhu, Yu; Wei, Junhong; Tian, Yuqing; Niu, Guoqing; Tan, Huarong

    2013-07-01

    Nikkomycins and gougerotin are peptidyl nucleoside antibiotics with broad biological activities. The nikkomycin biosynthetic gene cluster comprises one pathway-specific regulatory gene (sanG) and 21 structural genes, whereas the gene cluster for gougerotin biosynthesis includes one putative regulatory gene, one major facilitator superfamily transporter gene, and 13 structural genes. In the present study, we introduced sanG driven by six different promoters into Streptomyces ansochromogenes TH322. Nikkomycin production was increased significantly with the highest increase in engineered strain harboring hrdB promoter-driven sanG. In the meantime, we replaced the native promoter of key structural genes in the gougerotin (gou) gene cluster with the hrdB promoters. The heterologous producer Streptomyces coelicolor M1146 harboring the modified gene cluster produced gougerotin up to 10-fold more than strains carrying the unmodified cluster. Therefore, genetic manipulations of genes involved in antibiotics biosynthesis with the constitutive hrdB promoter present a robust, easy-to-use system generally useful for the improvement of antibiotics production in Streptomyces.

  11. Progressive loss of CD3 expression after HTLV-I infection results from chromatin remodeling affecting all the CD3 genes and persists despite early viral genes silencing

    Directory of Open Access Journals (Sweden)

    Martiat Philippe

    2007-09-01

    Full Text Available Abstract Background HTLV-I infected CD4+ T-cells lines usually progress towards a CD3- or CD3low phenotype. In this paper, we studied expression, kinetics, chromatin remodeling of the CD3 gene at different time-points post HTLV-I infection. Results The onset of this phenomenon coincided with a decrease of CD3γ followed by the subsequent progressive reduction in CD3δ, then CD3ε and CD3ζ mRNA. Transient transfection experiments showed that the CD3γ promoter was still active in CD3- HTLV-I infected cells demonstrating that adequate amounts of the required transcription factors were available. We next looked at whether epigenetic mechanisms could be responsible for this progressive decrease in CD3 expression using DNase I hypersensitivity (DHS experiments examining the CD3γ and CD3δ promoters and the CD3δ enhancer. In uninfected and cells immediately post-infection all three DHS sites were open, then the CD3γ promoter became non accessible, and this was followed by a sequential closure of all the DHS sites corresponding to all three transcriptional control regions. Furthermore, a continuous decrease of in vivo bound transcription initiation factors to the CD3γ promoter was observed after silencing of the viral genome. Coincidently, cells with a lower expression of CD3 grew more rapidly. Conclusion We conclude that HTLV-I infection initiates a process leading to a complete loss of CD3 membrane expression by an epigenetic mechanism which continues along time, despite an early silencing of the viral genome. Whether CD3 progressive loss is an epiphenomenon or a causal event in the process of eventual malignant transformation remains to be investigated.

  12. Aberrant promoter methylation and gene expression of H-cadherin gene is associated with tumor progression and recurrence in epithelial ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Rahul Bhagat

    2014-01-01

    Full Text Available Background: Loss of expression of cadherins by promoter hypermethylation has been described in many epithelial cancers, and it may play a role in tumor cell invasion and metastasis. Previously, we reported that E-cadherin gene is frequently methylated in epithelial ovarian cancer. Aim: The aim of this study was to compare the promoter hypermethylation of H-cadherin gene in ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Materials and Methods: We examined the promoter methylation of the H-cadherin gene in 134 epithelial ovarian carcinomas (EOC, 23 low malignant potential (LMP tumors, 26 benign cystadenomas and 15 normal ovarian tissues. Methylation was investigated by methylation specific polymerase chain reaction (MSP and the results confirmed by bisulfite DNA sequencing. Relative gene expression of H-cadherin was done using quantitative reverse transcriptase PCR on 51 EOC cases, 9 LMP tumors, 7 benign cystadenomas with 5 normal ovarian tissues. Results: Aberrant methylation of H-cadherin was present in 20 of 134 (15% carcinoma cases, 2 of 23 (09% LMP tumors and 1 of 26 (4% benign cystadenomas. No methylation was observed in any of the normal ovarian tissues. The mRNA expression level of H-cadherin was significantly down-regulated in EOC and LMP tumors than the corresponding normal tissues, whereas the expression level was normal in benign cystadenomas. A significant correlation of H-cadherin promoter methylation was observed with reduced gene expression in EOC. The prevalence of H-cadherin methylation was associated significantly with stage, histopathological grade, and menopausal status of the patient. H-cadherin methylation also had significant association with recurrence and differentiation of tumor. Conclusion: Our findings suggest an association between H-cadherin methylation, tumor progression and recurrence in EOC.

  13. Gene delivery into plant cells for recombinant protein production

    National Research Council Canada - National Science Library

    Chen, Qiang; Lai, Huafang

    2015-01-01

    .... In recent years, the development of deconstructed virus-based vectors has allowed plants to become a viable platform for recombinant protein production, with advantages in versatility, speed, cost...

  14. Mobile antibiotic resistance - the spread of genes determining the resistance of bacteria through food products.

    Science.gov (United States)

    Godziszewska, Jolanta; Guzek, Dominika; Głąbski, Krzysztof; Wierzbicka, Agnieszka

    2016-07-07

    In recent years, more and more antibiotics have become ineffective in the treatment of bacterial nfections. The acquisition of antibiotic resistance by bacteria is associated with circulation of genes in the environment. Determinants of antibiotic resistance may be transferred to pathogenic bacteria. It has been shown that conjugation is one of the key mechanisms responsible for spread of antibiotic resistance genes, which is highly efficient and allows the barrier to restrictions and modifications to be avoided. Some conjugative modules enable the transfer of plasmids even between phylogenetically distant bacterial species. Many scientific reports indicate that food is one of the main reservoirs of these genes. Antibiotic resistance genes have been identified in meat products, milk, fruits and vegetables. The reason for such a wide spread of antibiotic resistance genes is the overuse of antibiotics by breeders of plants and animals, as well as by horizontal gene transfer. It was shown, that resistance determinants located on mobile genetic elements, which are isolated from food products, can easily be transferred to another niche. The antibiotic resistance genes have been in the environment for 30 000 years. Their removal from food products is not possible, but the risks associated with the emergence of multiresistant pathogenic strains are very large. The only option is to control the emergence, selection and spread of these genes. Therefore measures are sought to prevent horizontal transfer of genes. Promising concepts involve the combination of developmental biology, evolution and ecology in the fight against the spread of antibiotic resistance.

  15. Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production.

    Directory of Open Access Journals (Sweden)

    Kirrie J Ballard

    Full Text Available Differentiation of logopenic (lvPPA and nonfluent/agrammatic (nfvPPA variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r(2 = 0.47 with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word

  16. Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production.

    Science.gov (United States)

    Ballard, Kirrie J; Savage, Sharon; Leyton, Cristian E; Vogel, Adam P; Hornberger, Michael; Hodges, John R

    2014-01-01

    Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r(2) = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task

  17. Matrix Metalloproteinases: The Gene Expression Signatures of Head and Neck Cancer Progression

    Energy Technology Data Exchange (ETDEWEB)

    Iizuka, Shinji [Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Ishimaru, Naozumi; Kudo, Yasusei, E-mail: yasusei@tokushima-u.ac.jp [Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-8-15 Kuramoto, Tokushima 770-8504 (Japan)

    2014-02-13

    Extracellular matrix degradation by matrix metalloproteinases (MMPs) plays a pivotal role in cancer progression by promoting motility, invasion and angiogenesis. Studies have shown that MMP expression is increased in head and neck squamous cell carcinomas (HNSCCs), one of the most common cancers in the world, and contributes to poor outcome. In this review, we examine the expression pattern of MMPs in HNSCC by microarray datasets and summarize the current knowledge of MMPs, specifically MMP-1, -3, -7 -10, -12, -13, 14 and -19, that are highly expressed in HNSCCs and involved cancer invasion and angiogenesis.

  18. Idaho Natural Production Monitoring and Evaluation : Annual Progress Report February 1, 2007 - January 31, 2008.

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Timothy; Johnson, June; Putnam, Scott

    2008-12-01

    River stocks of steelhead and spring/summer Chinook salmon still have significant natural reproduction and thus are the focal species for this project's investigations. The overall goal is to monitor the abundance, productivity, distribution, and stock-specific life history characteristics of naturally produced steelhead trout and Chinook salmon in Idaho (IDFG 2007). We have grouped project tasks into three objectives, as defined in our latest project proposal and most recent statement of work. The purpose of each objective involves enumerating or describing individuals within the various life stages of Snake River anadromous salmonids. By understanding the transitions between life stages and associated controlling factors, we hope to achieve a mechanistic understanding of stock-specific population dynamics. This understanding will improve mitigation and recovery efforts. Objective 1. Measure 2007 adult escapement and describe the age structure of the spawning run of naturally produced spring/summer Chinook salmon passing Lower Granite Dam. Objective 2. Monitor the juvenile production of Chinook salmon and steelhead trout for the major population groups (MPGs) within the Clearwater and Salmon subbasins. Objective 3. Evaluate life cycle survival and the freshwater productivity/production of Snake River spring/summer Chinook salmon. There are two components: update/refine a stock-recruit model and estimate aggregate smolt-to-adult survival. In this annual progress report, we present technical results for work done during 2007. Part 2 contains detailed results of INPMEP aging research and estimation of smolt-to-adult return rates for wild and naturally produced Chinook salmon (Objectives 1 and 3). Part 3 is a report on the ongoing development of a stock-recruit model for the freshwater phase of spring/summer Chinook salmon in the Snake River basin (Objective 3). Part 4 is a summary of the parr density data (Objective 2) collected in 2007 using the new site selection

  19. Progress in Research of Vanillin Production Processes%香兰素生产工艺研究进展

    Institute of Scientific and Technical Information of China (English)

    赵元; 丁绍民; 宋华付

    2001-01-01

    综述了香兰素生产的各种工艺路线和合成路线的研究进展,并对各种生产工艺路线和合成路线的发展前景提出了观点。%A comprehensive review was given regarding the progress of vanillin production processes and synthetic routes.

  20. 香蕉抗寒相关功能基因研究进展%Research Progress on Banana Functional Genes Involved in Cold Resistance

    Institute of Scientific and Technical Information of China (English)

    李卫亮; 李茂富; 贺军虎; 赵小青; 冯顺; 周海兰; 李绍鹏

    2015-01-01

    As one of the three largest fruit producer, banana is also the fourth food crops in the world. Low temperature was one of the important factors affecting the banana production in China. In particular, the cold snap in winter and spring hit the banana production area throughout the year except Hainan and the southwest of Guangdong regions. In recent years, with the development of cold-resistant genetic engineering, the research on molecular level of cold resistance of banana has achieved great progress. This article started with the cold-resist functional genes of banana and summed up domestic and foreign researches about the related functional genes of cold-resist banana (such as: the cold stress-related protein gene, membrane lipid associated protein, antioxidant enzyme gene) and also put forward a prospect, which aims to provide some ideas to the excavation of banana cold-resistant main-effect gene resources and breeding of banana anti-cold variety.%香蕉是世界上产量最大的三大水果之一,也是世界上第四大粮食作物。低温是影响中国香蕉生产的重要因素之一,尤其是除海南和广东西南等地区外的香蕉产区常年遭遇冬春寒流侵袭。近年来随着抗寒基因工程的发展,有关香蕉抗寒性的分子水平研究得到了较大进展。本文从香蕉抗寒相关的功能基因入手,归纳了近几年国内外关于香蕉的抗寒相关功能基因(冷胁迫相关蛋白基因,膜脂相关蛋白基因,抗氧化酶基因等)研究并提出了展望,旨在为香蕉抗寒主效基因资源的发掘及香蕉抗寒品种的选育提供思路。

  1. Epigenetics in Apicomplexa: control of gene expression during cell cycle progression, differentiation and antigenic variation.

    Science.gov (United States)

    Hakimi, Mohamed-Ali; Deitsch, Kirk W

    2007-08-01

    Apicomplexan parasites are important disease causing organisms that infect both animals and humans, causing extensive health and economic damage to human populations, particularly those in the developing world. The ability to perform genetic crosses, to engineer transgenic parasites lines, and the wealth of information made available through recent genome sequencing projects have made the laboratory study of these parasites important not only for understanding the diseases that they cause, but also for gaining insights into basic biological processes. The control of gene expression and cellular differentiation are particularly interesting in these organisms, as the apparent lack of large families of recognizable transcription factors typically found in other eukaryotic organisms suggests that they may be unusually reliant on epigenetic mechanisms. Here we review recent advances in the study of epigenetic gene regulation in the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii.

  2. In Vivo Delivery of CRISPR/Cas9 for Therapeutic Gene Editing: Progress and Challenges.

    Science.gov (United States)

    Mout, Rubul; Ray, Moumita; Lee, Yi-Wei; Scaletti, Federica; Rotello, Vincent M

    2017-03-17

    The successful use of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-based gene editing for therapeutics requires efficient in vivo delivery of the CRISPR components. There are, however, major challenges on the delivery front. In this Topical Review, we will highlight recent developments in CRISPR delivery, and we will present hurdles that still need to be overcome to achieve effective in vivo editing.

  3. Research progress of production of bacterium cellulose%细菌纤维素的生产研究进展

    Institute of Scientific and Technical Information of China (English)

    范兆乾

    2013-01-01

    The special structure, function, physical and chemical properties, and application prospect of bacterial cellulose ( BC ) is presented briefly. The research progress of bacterial cellulose production, production method and raw material strains are summarized.%介绍了细菌纤维素(BC)的特殊结构、功能、物理和化学性质以及应用前景.综述了目前细菌纤维素的生产菌种、生产方式及原料的研究进展.

  4. [Iron regulation of gene expression in the Bradyrhizobium japonicum/soybean symbiosis]. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Guerinot, M.L.

    1992-06-01

    We wish to address the question of whether iron plays a regulatory role in the Bradyrhizobium japonicum/soybeam symbiosis. Iron may be an important regulatory signal in planta as the bacteria must acquire iron from their plant hosts and iron-containing proteins figure prominently in all nitrogen-fixing symbioses. For example, the bacterial partner is believed to synthesize the heme moiety of leghemoglobin, which may represent as much as 25--30% of the total soluble protein in an infected plant cell. For this reason, we have focused our attention on the regulation by iron of the first step in the bacterial heme biosynthetic pathway. The enzyme which catalyzes this step, 5-aminolevulinic acid synthase, is encoded by the hemA gene which we had previously cloned and sequenced. Specific objectives include: to define the cis-acting sequences which confer iron regulation on the B. japonicum hemA gene; to identify trans-acting factors which regulate the expression of hemA by iron; to identify new loci which are transcriptionally responsive to changes in iron availability; and to examine the effects of mutations in various known regulatory genes for their effect on the expression of hemA.

  5. Clonal rearrangements of immunoglobulin genes and progression to B cell lymphoma in cutaneous lymphoid hyperplasia.

    Science.gov (United States)

    Wood, G S; Ngan, B Y; Tung, R; Hoffman, T E; Abel, E A; Hoppe, R T; Warnke, R A; Cleary, M L; Sklar, J

    1989-07-01

    Cutaneous lymphoid hyperplasia (CLH) is a disorder characterized by the development of one or more skin lesions containing dense lymphoid infiltrates that exhibit the histopathologic features of a benign, reactive process. Nevertheless, some cases have been associated with the subsequent development of clinically overt lymphomas. This suggests that monoclonal populations may exist in some cases of CLH and that these cases may represent a subset more likely to evolve into lymphoma. To determine if such a subset of CLH can be distinguished, Southern blot analysis of DNA was used to study the immunogenotypic features of lesions from 14 patients with clinical, histopathologic, and immunopathologic findings characteristic of CLH. Five cases exhibited detectable clonal rearrangements of immunoglobulin genes. Furthermore, one of these five cases evolved into overt diffuse large cell lymphoma of B cell lineage during a 2-year follow-up of recurrent disease at the original cutaneous site. The immunoglobulin gene rearrangements of this lymphoma were identical to those of the prior CLH lesion. There was no evidence of detectable t(14;18) chromosomal translocations or clonal rearrangements of the beta gene of the T cell receptor in any case. It was concluded that CLH can be divided into two subsets based on the presence or absence of a clonal B cell population, and that overt lymphoma can arise from the former subset and contain the same B cell clone identified in the pre-existent CLH lesion.

  6. [Recent progress in gene mapping through high-throughput sequencing technology and forward genetic approaches].

    Science.gov (United States)

    Lu, Cairui; Zou, Changsong; Song, Guoli

    2015-08-01

    Traditional gene mapping using forward genetic approaches is conducted primarily through construction of a genetic linkage map, the process of which is tedious and time-consuming, and often results in low accuracy of mapping and large mapping intervals. With the rapid development of high-throughput sequencing technology and decreasing cost of sequencing, a variety of simple and quick methods of gene mapping through sequencing have been developed, including direct sequencing of the mutant genome, sequencing of selective mutant DNA pooling, genetic map construction through sequencing of individuals in population, as well as sequencing of transcriptome and partial genome. These methods can be used to identify mutations at the nucleotide level and has been applied in complex genetic background. Recent reports have shown that sequencing mapping could be even done without the reference of genome sequence, hybridization, and genetic linkage information, which made it possible to perform forward genetic study in many non-model species. In this review, we summarized these new technologies and their application in gene mapping.

  7. Regulation of lipid synthesis genes and milk fat production in human mammary epithelial cells during secretory activation.

    Science.gov (United States)

    Mohammad, Mahmoud A; Haymond, Morey W

    2013-09-15

    Expression of genes for lipid biosynthetic enzymes during initiation of lactation in humans is unknown. Our goal was to study mRNA expression of lipid metabolic enzymes in human mammary epithelial cell (MEC) in conjunction with the measurement of milk fatty acid (FA) composition during secretory activation. Gene expression from mRNA isolated from milk fat globule (MFG) and milk FA composition were measured from 6 h to 42 days postpartum in seven normal women. Over the first 96 h postpartum, daily milk fat output increased severalfold and mirrored expression of genes for all aspects of lipid metabolism and milk FA production, including lipolysis at the MEC membrane, FA uptake from blood, intracellular FA transport, de novo FA synthesis, FA and glycerol activation, FA elongation, FA desaturation, triglyceride synthesis, cholesterol synthesis, and lipid droplet formation. Expression of the gene for a key lipid synthesis regulator, sterol regulatory element-binding transcription factor 1 (SREBF1), increased 2.0-fold by 36 h and remained elevated over the study duration. Expression of genes for estrogen receptor 1, thyroid hormone-responsive protein, and insulin-induced 2 increased progressively to plateau by 96 h. In contrast, mRNA of peroxisome proliferator-activated receptor-γ decreased severalfold. With onset of lactation, increased de novo synthesis of FA was the most prominent change in milk FA composition and mirrored the expression of FA synthesis genes. In conclusion, milk lipid synthesis and secretion in humans is a complex process requiring the orchestration of a wide variety of pathways of which SREBF1 may play a primary role.

  8. Production of cloned pigs with targeted attenuation of gene expression.

    Directory of Open Access Journals (Sweden)

    Vilceu Bordignon

    Full Text Available The objective of this study was to demonstrate that RNA interference (RNAi and somatic cell nuclear transfer (SCNT technologies can be used to attenuate the expression of specific genes in tissues of swine, a large animal species. Apolipoprotein E (apoE, a secreted glycoprotein known for its major role in lipid and lipoprotein metabolism and transport, was selected as the target gene for this study. Three synthetic small interfering RNAs (siRNA targeting the porcine apoE mRNA were tested in porcine granulosa cells in primary culture and reduced apoE mRNA abundance ranging from 45-82% compared to control cells. The most effective sequence was selected for cloning into a short hairpin RNA (shRNA expression vector under the control of RNA polymerase III (U6 promoter. Stably transfected fetal porcine fibroblast cells were generated and used to produce embryos with in vitro matured porcine oocytes, which were then transferred into the uterus of surrogate gilts. Seven live and one stillborn piglet were born from three gilts that became pregnant. Integration of the shRNA expression vector into the genome of clone piglets was confirmed by PCR and expression of the GFP transgene linked to the expression vector. Analysis showed that apoE protein levels in the liver and plasma of the clone pigs bearing the shRNA expression vector targeting the apoE mRNA was significantly reduced compared to control pigs cloned from non-transfected fibroblasts of the same cell line. These results demonstrate the feasibility of applying RNAi and SCNT technologies for introducing stable genetic modifications in somatic cells for eventual attenuation of gene expression in vivo in large animal species.

  9. Nonlinear biosynthetic gene cluster dose effect on penicillin production by Penicillium chrysogenum.

    Science.gov (United States)

    Nijland, Jeroen G; Ebbendorf, Bjorg; Woszczynska, Marta; Boer, Rémon; Bovenberg, Roel A L; Driessen, Arnold J M

    2010-11-01

    Industrial penicillin production levels by the filamentous fungus Penicillium chrysogenum increased dramatically by classical strain improvement. High-yielding strains contain multiple copies of the penicillin biosynthetic gene cluster that encodes three key enzymes of the β-lactam biosynthetic pathway. We have analyzed the gene cluster dose effect on penicillin production using the high-yielding P. chrysogenum strain DS17690 that was cured from its native clusters. The amount of penicillin V produced increased with the penicillin biosynthetic gene cluster number but was saturated at high copy numbers. Likewise, transcript levels of the biosynthetic genes pcbAB [δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine synthetase], pcbC (isopenicillin N synthase), and penDE (acyltransferase) correlated with the cluster copy number. Remarkably, the protein level of acyltransferase, which localizes to peroxisomes, was saturated already at low cluster copy numbers. At higher copy numbers, intracellular levels of isopenicillin N increased, suggesting that the acyltransferase reaction presents a limiting step at a high gene dose. Since the number and appearance of the peroxisomes did not change significantly with the gene cluster copy number, we conclude that the acyltransferase activity is limiting for penicillin biosynthesis at high biosynthetic gene cluster copy numbers. These results suggest that at a high penicillin production level, productivity is limited by the peroxisomal acyltransferase import activity and/or the availability of coenzyme A (CoA)-activated side chains.

  10. Id-1 and Id-2 genes and products as markers of epithelial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Desprez, Pierre-Yves (El Cerrito, CA); Campisi, Judith (Berkeley, CA)

    2011-10-04

    A method for detection and prognosis of breast cancer and other types of cancer. The method comprises detecting expression, if any, for both an Id-1 and an Id-2 genes, or the ratio thereof, of gene products in samples of breast tissue obtained from a patient. When expressed, Id-1 gene is a prognostic indicator that breast cancer cells are invasive and metastatic, whereas Id-2 gene is a prognostic indicator that breast cancer cells are localized and noninvasive in the breast tissue.

  11. Id-1 and Id-2 genes and products as markers of epithelial cancer

    Science.gov (United States)

    Desprez, Pierre-Yves [El Cerrito, CA; Campisi, Judith [Berkeley, CA

    2011-10-04

    A method for detection and prognosis of breast cancer and other types of cancer. The method comprises detecting expression, if any, for both an Id-1 and an Id-2 genes, or the ratio thereof, of gene products in samples of breast tissue obtained from a patient. When expressed, Id-1 gene is a prognostic indicator that breast cancer cells are invasive and metastatic, whereas Id-2 gene is a prognostic indicator that breast cancer cells are localized and noninvasive in the breast tissue.

  12. Id-1 and Id-2 genes and products as markers of epithelial cancer

    Science.gov (United States)

    Desprez, Pierre-Yves; Campisi, Judith

    2008-09-30

    A method for detection and prognosis of breast cancer and other types of cancer. The method comprises detecting expression, if any, for both an Id-1 and an Id-2 genes, or the ratio thereof, of gene products in samples of breast tissue obtained from a patient. When expressed, Id-1 gene is a prognostic indicator that breast cancer cells are invasive and metastatic, whereas Id-2 gene is a prognostic indicator that breast cancer cells are localized and noninvasive in the breast tissue.

  13. Major genes and QTL influencing wool production and quality: a review

    Directory of Open Access Journals (Sweden)

    Purvis Ian

    2005-12-01

    Full Text Available Abstract The opportunity exists to utilise our knowledge of major genes that influence the economically important traits in wool sheep. Genes with Mendelian inheritance have been identified for many important traits in wool sheep. Of particular importance are genes influencing pigmentation, wool quality and the keratin proteins, the latter of which are important for the morphology of the wool fibre. Gene mapping studies have identified some chromosomal regions associated with variation in wool quality and production traits. The challenge now is to build on this knowledge base in a cost-effective way to deliver molecular tools that facilitate enhanced genetic improvement programs for wool sheep.

  14. Research Progress of Brown Planthopper Resistance Genes in Rice%水稻抗褐飞虱基因研究进展

    Institute of Scientific and Technical Information of China (English)

    祝莉莉; 胡亮; 杜波

    2011-01-01

    综述了水稻抗褐飞虱基因的研究进展.褐飞虱是对水稻为害最严重的害虫之一.它栖息于稻丛基部,吸食韧皮部汁液.褐飞虱具有不同的生物型.在抗性品种的选择压力下,将产生一种新的生物型褐飞虱群体克服该抗性品种.因此,寻找新的抗性基因是培育新的抗褐飞虱水稻品种的关键.合适的水稻抗褐飞虱的鉴定方法是克隆水稻抗褐飞虱基因的基础.常用的方法有苗期集团鉴定、蜜露量测定、电子取食监测系统等.迄今为止,科学家已经在栽培稻和野生稻中定位了21个水稻抗褐飞虱基因,并且Bph14基因已经被武汉大学生命科学学院杂交水稻国家重点实验室成功克隆.该结果为克隆其他水稻抗褐飞虱基因以及研究水稻抗褐飞虱的分子机制奠定了基础.%The research progresses on brown planthopper (Nilap arv ata lugens Stal, BPH) resistance genes in rice were summarized. BPH is one of the most destructive pests in crop production worldwide. They gather at the base part of rice plant and suck assimilates from the phloem. BPH has various biotypos. Under the selection pressure of resistant variety, a new biotype of BPH might come out to overcome the resistance of the variety. Exploring new resistance gene is critical for developing resistant rice variety. Appropriate evaluation of germplasm for BPH resistance is the key to identify resistance genes correctly.There are several types of screening methods such as the standard seodbex screening technique, honey dew test, electronic monitoring system and so on. To date, 21 BPH-resistance genes have been identified from cultivated and wild rice species.Bph14 is the fast report of BPH-resistance gene in rice. These results provide basis for the clone of more BPH resistance genes and the study on molecular mechanism of rice resistance to BPH.

  15. Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Malpass, Gloria E., E-mail: gloria.malpass@gmail.com [Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157 (United States); Arimilli, Subhashini, E-mail: sarimill@wakehealth.edu [Department of Microbiology and Immunology, Wake Forest University Health Sciences, Winston-Salem, NC 27157 (United States); Prasad, G.L., E-mail: prasadg@rjrt.com [R and D Department, R.J. Reynolds Tobacco Company, Winston-Salem, NC 27102 (United States); Howlett, Allyn C., E-mail: ahowlett@wakehealth.edu [Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157 (United States)

    2014-09-01

    Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1 h or 5 h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1 h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1 h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5 h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1 h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5 h), which was increased by nicotine but suppressed by other components of STE. Within 2 h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research. - Highlights: • Tobacco product preparations (TPPs) alter gene expression in dermal fibroblasts. • Some immediate early genes critical to the inflammatory process are affected. • Different TPPs produce differential responses in certain pro-inflammatory genes.

  16. Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger

    DEFF Research Database (Denmark)

    Meijer, Susan Lisette; Nielsen, Michael Lynge; Olsson, Lisbeth

    2009-01-01

    With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell...... factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which...... the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger....

  17. Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production

    Science.gov (United States)

    Bailey, Andy M.; Alberti, Fabrizio; Kilaru, Sreedhar; Collins, Catherine M.; de Mattos-Shipley, Kate; Hartley, Amanda J.; Hayes, Patrick; Griffin, Alison; Lazarus, Colin M.; Cox, Russell J.; Willis, Christine L.; O’Dwyer, Karen; Spence, David W.; Foster, Gary D.

    2016-05-01

    Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi.

  18. Calcitonin gene-related peptide targeted immunotherapy for migraine: progress and challenges in treating headache.

    Science.gov (United States)

    Peroutka, Stephen J

    2014-06-01

    A role for calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine has been established over the past 25 years. There have now been at least five different small-molecule CGRP antagonists that have demonstrated statistical proof of efficacy in the acute treatment of migraine. At present, multiple clinical trials are underway that are assessing the ability of long-acting antibodies against CGRP to prevent frequent migraine attacks. This review summarizes the existing data concerning the role of CGRP in migraine and attempts to highlight some possible outcomes from the ongoing anti-CGRP antibody trials.

  19. Rapid In Vivo Validation of Tumor Suppressor Gene Function in Prostate Cancer Progression

    Science.gov (United States)

    2016-07-01

    containing an mCherry cDNA fused to the sgRNA target. As predicted, we observed variable efficiencies between sgRNAs. Our assay facilitated the rapid...efficiently disrupted a heterologous gene construct containing an mCherry cDNA fused to the sgRNA target. As predicted, we observed variable ...o rm a li z e d M F I p53 Figure 1. A. Schematic of CRISPRv2Cre and CRISPRv2GFP. Each vector expresses sgRNA, Cas9, and either Cre or GFP. B

  20. Molecular characterization of a maize regulatory gene. Annual progress report, March 1990--November 1991

    Energy Technology Data Exchange (ETDEWEB)

    Wessler, S.R.

    1991-12-01

    Based on initial bombardment studies we have previously concluded that promoter diversity was responsible for the diversity of naturally occurring R alleles. During this period we have found that R is controlled at the level of translation initiation and intron 1 is alternatively spliced. The experiments described in Sections 1 and 2 sought to quantify these effects and to determine whether they contribute to the tissue specific expression of select R alleles. This study was done because very little is understood about the post-transcriptional regulation of plant genes. Section 3 and 4 describe experiments designed to identify important structural components of the R protein.

  1. Variations of Human DNA Polymerase Genes as Biomarkers of Prostate Cancer Progression

    Science.gov (United States)

    2013-07-01

    obtain the percentage of product formed. Time courses were linear for the chosen enzyme concentration and time interval. 2.8. Data analysis The...1] E.C. Friedberg DNA damage and repair, Nature 421 (2003) 436-440. [2] W.A. Beard, S.H. Wilson Structure and mechanism of DNA polymerase β, Chem

  2. Identification and distribution of products from novel tryptopyrokinin genes in the locust, Locusta migratoria.

    Science.gov (United States)

    Redeker, Jana; Bläser, Marcel; Neupert, Susanne; Predel, Reinhard

    2017-04-22

    A recent analysis of the genome of Locusta migratoria indicated the presence of four novel insect neuropeptide genes encoding for multiple tryptopyrokinin peptides (tryptoPKs); hitherto only known from pyrokinin or capa genes. In our study, mature products of tryptoPK genes 1 and 2 were identified by mass spectrometry; precursor sequences assigned to the tryptoPK genes 3 and 4 are likely partial sequences of a single precursor. The expression of tryptoPK genes 1 and 2 is restricted to two cells in the subesophageal ganglion, exhibiting not only a unique neuropeptidome but also a very distinctive axonal projection. Comparative neuroendocrinology revealed that homologous cells in other insects also produce tryptoPKs but use other genes to generate this pattern. Since capa and pyrokinin genes are discussed as ancestors of the tryptoPK genes, we completed the hitherto only partially known precursor sequences of these genes by means of transcriptome analyses. The distribution of mature products of CAPA and pyrokinin precursors in the CNS is compared with that of tryptoPKs. In addition, a novel pyrokinin-like precursor is described.

  3. Utility of the pat gene as a selectable marker gene in production of transgenic Dunaliella salina

    Directory of Open Access Journals (Sweden)

    Hyo Sun Jung

    2016-09-01

    Full Text Available Abstract Background The objective of this study was to develop an efficient selectable marker for transgenic Dunaliella salina. Results Tests of the sensitivity of D. salina to the antibiotic chloramphenicol and the herbicide Basta® showed that cells (1.0 × 106 cells/ml treated with 1000 or 1500 μg/ml chloramphenicol died in 8 or 6 days, respectively, whereas D. salina cells (1.0 × 106 cells/ml treated with 5, 10, 20, or 40 μg/ml Basta® died in 2 days. Therefore, D. salina is more sensitive to Basta® than to chloramphenicol. To examine the possibility of using the phosphinothricin N-acetyltransferase (pat gene as a selectable marker gene, we introduced the pat genes into D. salina with particle bombardment system under the condition of helium pressure of 900 psi from a distance of 3 cm. PCR analysis confirmed that the gene was stably inserted into the cells and that the cells survived in 5 μg/ml Basta®, the medium used to select the transformed cells. Conclusions The findings of this study suggest that the pat gene can be used as an efficient selectable marker when producing transgenic D. salina.

  4. Episomal Nonviral Gene Therapy Vectors Slow Progression of Atherosclerosis in a Model of Familial Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Alastair G Kerr

    2016-01-01

    Full Text Available Familial hypercholesterolemia (FH is a life-threatening genetic disorder characterized by elevated levels of plasma low-density lipoprotein cholesterol (LDL-cholesterol. Current attempts at gene therapy for FH have been limited by the use of strong heterologous promoters which lack genomic DNA elements essential for regulated expression. Here, we have combined a minigene vector expressing the human LDLR cDNA from a 10 kb native human LDLR locus genomic DNA promoter element, with an efficient miRNA targeting 3-hydroxy-3-methylgutaryl-coenzyme A reductase (Hmgcr, to further enhance LDLR expression. We show that the combined vector suppresses endogenous Hmgcr transcripts in vivo, leading to an increase in LDLR transgene expression. In a diet-induced Ldlr-/- mouse model of FH, we show that administration of the combined vector reduces atherogenic plasma lipids by ≃32%. Finally, we demonstrate that our episomal nonviral vectors are able to reduce atherosclerosis by ≃40% after 12 weeks in vivo. Taken together, the vector system we describe exploits the normal cellular regulation of the LDLR to provide prolonged expression of LDLR through targeted knockdown of Hmgcr. This novel gene therapy system could act alone, or in synergy with current therapies that modulate intracellular cholesterol, such as statins, greatly enhancing its therapeutic application for FH.

  5. Research Progress in GHR Gene%生长激素受体基因的研究进展

    Institute of Scientific and Technical Information of China (English)

    程胜利; 杨保平; 肖玉萍; 魏云霞

    2013-01-01

    Growth hormone receptor( GHR ) is one of the key genes modulating growth and development in animal. As an important candidate gene of livestock productivity, it becomes gradually research focus for improving meat and milk production in recent years. These further researches could lead to breakthrough of candidate gene studies in livestock breeding and production, but also contribute to application of marker assisted selection in practice. This paper reviewed mainly the GHR structure, signal transduction pathway, specificity expression of GHR in tissue, the relationship between GHR polymorphism and production performance, and development change of GHR mRNA expression in animal.%生长激素受体(GHR)是调控动物生长发育的关键基因之一.近年来,将GHR基因作为家畜生产力的候选基因来探讨提高动物奶肉产量等方面的报道不断增加,已逐渐成为研究热点.该领域的深入探讨可能产生家畜育种和生产中候选基因研究的突破性进展,而且有助于标记辅助选择的实施.文章主要从GHR基因的结构、信号传导途径、GHR表达的组织特异性、GHR多态性与生产性能的关系以及GHR表达的发育性变化等方面进行了综述.

  6. The paf gene product modulates asexual development in Penicillium chrysogenum.

    Science.gov (United States)

    Hegedüs, Nikoletta; Sigl, Claudia; Zadra, Ivo; Pócsi, Istvan; Marx, Florentine

    2011-06-01

    Penicillium chrysogenum secretes a low molecular weight, cationic and cysteine-rich protein (PAF). It has growth inhibitory activity against the model organism Aspergillus nidulans and numerous zoo- and phytopathogenic fungi but shows only minimal conditional antifungal activity against the producing organism itself. In this study we provide evidence for an additional function of PAF which is distinct from the antifungal activity against putative ecologically concurrent microorganisms. Our data indicate that PAF enhances conidiation in P. chrysogenum by modulating the expression of brlA, the central regulatory gene for mitospore development. A paf deletion strain showed a significant impairment of mitospore formation which sustains our hypothesis that PAF plays an important role in balancing asexual differentiation in P. chrysogenum.

  7. Alphavirus vectors for vaccine production and gene therapy.

    Science.gov (United States)

    Lundstrom, Kenneth

    2003-06-01

    Alphavirus vectors demonstrate high expression of heterologous proteins in a broad range of host cells. Replication-deficient as well as replication-competent variants exist. Systemic delivery of many viral antigens has elicited strong antibody responses in immunized mice and primates, and protection against challenges with lethal viruses was obtained. Similarly, prophylactic vaccination was established against tumor challenges. Attention has been paid to the engineering of improved targeting to immunologically active cells, such as dendritic cells. In the area of gene therapy, intratumoral injections of alphavirus vectors have resulted in potentially promising tumor rejection. Moreover, encapsulation of alphavirus particles into liposomes demonstrated efficient tumor targeting in mice with severe combined immunodeficiency, which permitted the initiation of clinical trials for patients with advanced kidney carcinoma and melanoma.

  8. Systems Pharmacology‐Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes

    Science.gov (United States)

    Fang, J; Cai, C; Wang, Q; Lin, P

    2017-01-01

    Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration‐approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products. PMID:28294568

  9. Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1)

    Energy Technology Data Exchange (ETDEWEB)

    Lalioti, M.D.; Mirotsou, M.; Rossier, C. [Univ. Hospital of Geneva (Switzerland)] [and others

    1997-02-01

    Progressive myoclonus epilepsy (EPM1) is an autosomal recessive disorder, characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The EPM1 locus was mapped to within 0.3 cM from PFKL in chromosome 21q22.3. The gene for the proteinase inhibitor cystatin B was recently localized in the EPM1 critical region, and mutations were identified in two EPM1 families. We have identified six nucleotide changes in the cystatin B gene of non-Finnish EPM1 families from northern Africa and Europe. The 426G{r_arrow}C change in exon 1 results in a Gly4Arg substitution and is the first missense mutation described that is associated with EPM1. Molecular modeling predicts that this substitution severely affects the contact of cystatin B with papain. Mutations in the invariant AG dinucleotides of the acceptor sites of introns 1 and 2 probably result in abnormal splicing. A deletion of two nucleotides in exon 3 produces a frameshift and truncates the protein. Therefore, these four mutations are all predicted to impair the production of functional protein. These mutations were found in 7 of the 29 unrelated EPM1 patients analyzed, in homozygosity in 1, and in heterozygosity in the others. The remaining two sequence changes, 431G{r_arrow}T and 2575A{r_arrow}G, probably represent polymorphic variants. In addition, a tandem repeat in the 5{prime} UTR (CCCCGCCCCGCG) is present two or three times in normal alleles. It is peculiar that in the majority of patients no mutations exist within the exons and splice sites of the cystatin B gene. 23 refs., 5 figs., 3 tabs.

  10. Progress achieved in restricting the marketing of high-fat, sugary and salty food and beverage products to children.

    Science.gov (United States)

    Kraak, Vivica I; Vandevijvere, Stefanie; Sacks, Gary; Brinsden, Hannah; Hawkes, Corinna; Barquera, Simón; Lobstein, Tim; Swinburn, Boyd A

    2016-07-01

    In May 2010, 192 Member States endorsed Resolution WHA63.14 to restrict the marketing of food and non-alcoholic beverage products high in saturated fats, trans fatty acids, free sugars and/or salt to children and adolescents globally. We examined the actions taken between 2010 and early 2016 - by civil society groups, the World Health Organization (WHO) and its regional offices, other United Nations (UN) organizations, philanthropic institutions and transnational industries - to help decrease the prevalence of obesity and diet-related noncommunicable diseases among young people. By providing relevant technical and policy guidance and tools to Member States, WHO and other UN organizations have helped protect young people from the marketing of branded food and beverage products that are high in fat, sugar and/or salt. The progress achieved by the other actors we investigated appears variable and generally less robust. We suggest that the progress being made towards the full implementation of Resolution WHA63.14 would be accelerated by further restrictions on the marketing of unhealthy food and beverage products and by investing in the promotion of nutrient-dense products. This should help young people meet government-recommended dietary targets. Any effective strategies and actions should align with the goal of WHO to reduce premature mortality from noncommunicable diseases by 25% by 2025 and the aim of the UN to ensure healthy lives for all by 2030.

  11. Comparative analysis of meiotic progression in female mice bearing mutations in genes of the DNA mismatch repair pathway.

    Science.gov (United States)

    Kan, Rui; Sun, Xianfei; Kolas, Nadine K; Avdievich, Elena; Kneitz, Burkhard; Edelmann, Winfried; Cohen, Paula E

    2008-03-01

    The DNA mismatch repair (MMR) family functions in a variety of contexts to preserve genome integrity in most eukaryotes. In particular, members of the MMR family are involved in the process of meiotic recombination in germ cells. MMR gene mutations in mice result in meiotic disruption during prophase I, but the extent of this disruption often differs between male and female meiocytes. To address the role of MMR proteins specifically in female meiosis, we explored the progression of oocytes through prophase I and the meiotic divisions in mice harboring deletions in members of the MMR pathway (Mlh1, Mlh3, Exo1, and an ATPase-deficient variant of Mlh1, Mlh1(G67R)). The colocalization of MLH1 and MLH3, key proteins involved in stabilization of nascent crossovers, was dependent on intact heterodimer formation and was highly correlated with the ability of oocytes to progress through to metaphase II. The exception was Exo1(-/-) oocytes, in which normal MLH1/MLH3 localization was observed followed by failure to proceed to metaphase II. All mutant oocytes were able to resume meiosis after dictyate arrest, but they showed a dramatic decline in chiasmata (to less than 25% of normal), accompanied by varied progression through metaphase I. Taken together, these results demonstrate that MMR function is required for the formation and stabilization of crossovers in mammalian oocytes and that, in the absence of a functional MMR system, the failure to maintain chiasmata results in a reduced ability to proceed normally through the first and second meiotic divisions, despite near-normal levels of meiotic resumption after dictyate arrest.

  12. Association of pituitary tumor transforming gene expression with early oral tumorigenesis and malignant progression of precancerous lesions.

    Science.gov (United States)

    Liao, Li-Jen; Hsu, Yi-Hsin; Yu, Chuan-Hang; Chiang, Chun-Pin; Jhan, Jing-Ru; Chang, Lien-Cheng; Lin, Jing-Jer; Lou, Pei-Jen

    2011-05-01

    Pituitary tumor transforming gene (PTTG1) is overexpressed in many types of human cancers and is involved in late-stage tumor progression. The role of PTTG1 in initiating tumorigenesis is unclear. PTTG1 expression was assessed in precancerous lesions and squamous cell carcinomas of the oral cavity (OSCC). The association between the protein expression and clinicopathologic parameters was analyzed. The expression level of PTTG1 upon carcinogen treatment was also investigated. PTTG1 was overexpressed in both precancerous lesions and OSCC. The expression of PTTG1 was associated with carcinogen exposure in vivo and in vitro. PTTG1 overexpression was an independent factor for oral cancer development in precancerous lesions. This study provides the first evidence that PTTG1 is involved in the early stages of oral tumorigenesis. Carcinogen exposure may cause the initial induction of PTTG1 expression in oral precancerous lesions. PTTG1 overexpression is a potential prognosticator for malignant progression of oral precancerous lesions. Copyright © 2010 Wiley Periodicals, Inc.

  13. Differential expression of genes encoding CD30L and P-selectin in cattle with Johne's disease: Progress toward a diagnostic gene expression signature

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Grell, S. N.; Heegaard, Peter M. H.;

    2006-01-01

    Mycobacterium avium subspecies paratuberculosis (Mycobacterium paratuberculosis), the causative agent of paratuberculosis (paraTB) or Johne's disease in ruminants, is a health problem for the global cattle industry with significant economic losses related to decreased milk production and reduced...... fertility. Commonly paraTB in cattle is diagnosed by antibody detection by serum enzyme-linked immunosorbent assay (ELISA), by detection of the pathogen by cultivation of individual faecal samples, or by in vitro measurement of cell mediated immune responses using the IFN-gamma test. There is an ongoing...... included cattle (Holstein) from two locations (Denmark and USA) for the microarray experiment. Our results indicate that expression profiles of at least 52 genes are different in leukocytes from M. paratuberculosis infected cattle compared to control cattle. Gene expression differences were verified...

  14. A Study on Promotion and Implementation of Cleaner Production Practices in Malaysian Industry - Development of a National Program and Action Plan for Promotion of Cleaner Production. Progress Report 1

    DEFF Research Database (Denmark)

    Wangel, Arne

    This Progress Report presents the initial findings of the research project 'A Study on Promotion and Implementation of Cleaner Production Practices in Malaysian Industry - Development of a National Program and Action Plan for Promotion of Cleaner Production. Progress Report' funded...... by the Department of Environment, Malaysia...

  15. Altered cortical expression of GABA-related genes in schizophrenia: illness progression vs developmental disturbance.

    Science.gov (United States)

    Hoftman, Gil D; Volk, David W; Bazmi, H Holly; Li, Siyu; Sampson, Allan R; Lewis, David A

    2015-01-01

    Schizophrenia is a neurodevelopmental disorder with altered expression of GABA-related genes in the prefrontal cortex (PFC). However, whether these gene expression abnormalities reflect disturbances in postnatal developmental processes before clinical onset or arise as a consequence of clinical illness remains unclear. Expression levels for 7 GABA-related transcripts (vesicular GABA transporter [vGAT], GABA membrane transporter [GAT1], GABAA receptor subunit α1 [GABRA1] [novel in human and monkey cohorts], glutamic acid decarboxylase 67 [GAD67], parvalbumin, calretinin, and somatostatin [previously reported in human cohort, but not in monkey cohort]) were quantified in the PFC from 42 matched pairs of schizophrenia and comparison subjects and from 49 rhesus monkeys ranging in age from 1 week postnatal to adulthood. Levels of vGAT and GABRA1, but not of GAT1, messenger RNAs (mRNAs) were lower in the PFC of the schizophrenia subjects. As previously reported, levels of GAD67, parvalbumin, and somatostatin, but not of calretinin, mRNAs were also lower in these subjects. Neither illness duration nor age accounted for the levels of the transcripts with altered expression in schizophrenia. In monkey PFC, developmental changes in expression levels of many of these transcripts were in the opposite direction of the changes observed in schizophrenia. For example, mRNA levels for vGAT, GABRA1, GAD67, and parvalbumin all increased with age. Together with published reports, these findings support the interpretation that the altered expression of GABA-related transcripts in schizophrenia reflects a blunting of normal postnatal development changes, but they cannot exclude a decline during the early stages of clinical illness. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Regulation of a novel gene cluster involved in secondary metabolite production in Streptomyces coelicolor.

    Science.gov (United States)

    Hindra; Pak, Patricia; Elliot, Marie A

    2010-10-01

    Antibiotic biosynthesis in the streptomycetes is a complex and highly regulated process. Here, we provide evidence for the contribution of a novel genetic locus to antibiotic production in Streptomyces coelicolor. The overexpression of a gene cluster comprising four protein-encoding genes (abeABCD) and an antisense RNA-encoding gene (α-abeA) stimulated the production of the blue-pigmented metabolite actinorhodin on solid medium. Actinorhodin production also was enhanced by the overexpression of an adjacent gene (abeR) encoding a predicted Streptomyces antibiotic regulatory protein (SARP), while the deletion of this gene impaired actinorhodin production. We found the abe genes to be differentially regulated and controlled at multiple levels. Upstream of abeA was a promoter that directed the transcription of abeABCD at a low but constitutive level. The expression of abeBCD was, however, significantly upregulated at a time that coincided with the initiation of aerial development and the onset of secondary metabolism; this expression was activated by the binding of AbeR to four heptameric repeats upstream of a promoter within abeA. Expressed divergently to the abeBCD promoter was α-abeA, whose expression mirrored that of abeBCD but did not require activation by AbeR. Instead, α-abeA transcript levels were subject to negative control by the double-strand-specific RNase, RNase III.

  17. Physiological evaluation of the filamentous fungus Trichoderma reesei in production processes by marker gene expression analysis

    Directory of Open Access Journals (Sweden)

    Penttilä Merja

    2007-05-01

    Full Text Available Abstract Background Biologically relevant molecular markers can be used in evaluation of the physiological state of an organism in biotechnical processes. We monitored at high frequency the expression of 34 marker genes in batch, fed-batch and continuous cultures of the filamentous fungus Trichoderma reesei by the transcriptional analysis method TRAC (TRanscript analysis with the aid of Affinity Capture. Expression of specific genes was normalised either with respect to biomass or to overall polyA RNA concentration. Expressional variation of the genes involved in various process relevant cellular functions, such as protein production, growth and stress responses, was related to process parameters such as specific growth and production rates and substrate and dissolved oxygen concentrations. Results Gene expression of secreted cellulases and recombinant Melanocarpus albomyces laccase predicted the trends in the corresponding extracellular enzyme production rates and was highest in a narrow "physiological window" in the specific growth rate (μ range of 0.03 – 0.05 h-1. Expression of ribosomal protein mRNAs was consistent with the changes in μ. Nine starvation-related genes were found as potential markers for detection of insufficient substrate feed for maintaining optimal protein production. For two genes induced in anaerobic conditions, increasing transcript levels were measured as dissolved oxygen decreased. Conclusion The data obtained by TRAC supported the usefulness of focused and intensive transcriptional analysis in monitoring of biotechnical processes providing thus tools for process optimisation purposes.

  18. Reciprocal regulation of pyoluteorin production with membrane transporter gene expression in Pseudomonas fluorescens Pf-5.

    Science.gov (United States)

    Brodhagen, Marion; Paulsen, Ian; Loper, Joyce E

    2005-11-01

    Pyoluteorin is a chlorinated polyketide antibiotic secreted by the rhizosphere bacterium Pseudomonas fluorescens Pf-5. Genes encoding enzymes and transcriptional regulators involved in pyoluteorin production are clustered in the genome of Pf-5. Sequence analysis of genes adjacent to the known pyoluteorin biosynthetic gene cluster revealed the presence of an ABC transporter system. We disrupted two putative ABC transporter genes by inserting transcriptional fusions to an ice nucleation reporter gene. Mutations in pltI and pltJ, which are predicted to encode a membrane fusion protein and an ATP-binding cassette of the ABC transporter, respectively, greatly reduced pyoluteorin production by Pf-5. During the transition from exponential growth to stationary phase, populations of a pltI mutant were lower than those of a pltI+ strain in a culture medium containing pyoluteorin, suggesting a role for the transport system in efflux and the resistance of Pf-5 to the antibiotic. Although pltI or pltJ mutant strains displayed low pyoluteorin production, they did not accumulate proportionately more of the antibiotic intracellularly, indicating that pltI and pltJ do not encode an exclusive exporter for pyoluteorin. Transcription of the putative pyoluteorin efflux genes pltI and pltJ was enhanced by exogenous pyoluteorin. These new observations parallel an earlier finding that pyoluteorin enhances the transcription of pyoluteorin biosynthesis genes and pyoluteorin production in Pf-5. This report provides evidence of a coordination of pyoluteorin production and the transcription of genes encoding a linked transport apparatus, wherein each requires the other for optimal expression.

  19. Postnatal development of protein gene product 9.5 and calcitonin gene-related peptide immunoreactive nerve fibres in rat temporomandibular joint disc.

    Science.gov (United States)

    Ueki, N; Tanaka, E; Watanabe, M; Wakida, K; Takahashi, O; Uchida, T; Tanne, K

    2003-02-01

    Protein gene product 9.5 (PGP 9.5), an immunohistochemical marker of whole nerve fibres, and calcitonin gene-related peptide (CGRP), a marker of thin nerve fibres, were used to elucidate the postnatal development of nerve fibres in rat temporomandibular joint (TMJ) disc. At birth, PGP 9.5-immunoreactive nerve fibres exhibited running towards the central area of the disc, invading by approximately 95 m from the disc attachment. The nerve fibres existing inside the disc became longer during postnatal development. The number of nerve fibres in the disc increased in a progressive manner up to 40 days after birth. CGRP-immunoreactive nerve fibres also presented changes essentially similar to those of PGP 9.5-immunoreactive nerve fibres. However, the proportion of CGRP-immunoreactive nerve fibres to PGP 9.5-immunoreactive ones was approximately 80%, and remained constant up to 40 days after birth. In conclusion, the distribution and the number of nerve fibres are variable during postnatal development, although the ratio of thin nerve fibres remains invariable. It is emphasized that these changes of innervation in the TMJ are associated with the development of masticatory function.

  20. Cloning large natural product gene clusters from the environment: Piecing environmental DNA gene clusters back together with TAR

    OpenAIRE

    Kim, Jeffrey H.; Feng, Zhiyang; Bauer, John D.; Kallifidas, Dimitris; Calle, Paula Y.; Brady, Sean F

    2010-01-01

    A single gram of soil can contain thousands of unique bacterial species, of which only a small fraction is regularly cultured in the laboratory. Although the fermentation of cultured microorganisms has provided access to numerous bioactive secondary metabolites, with these same methods it is not possible to characterize the natural products encoded by the uncultured majority. The heterologous expression of biosynthetic gene clusters cloned from DNA extracted directly from environmental sample...

  1. Research progress on natural products from traditional Chinese medicine in treatment of Alzheimer's disease.

    Science.gov (United States)

    Gao, Jianjun; Inagaki, Yoshinori; Li, Xuan; Kokudo, Norihiro; Tang, Wei

    2013-04-01

    Alzheimer's disease (AD) is a severe condition in aging societies. Although research on this disease is advancing rapidly, thus far few very effective drugs are available for AD patients. The currently widely used medicines such as donepezil and galantamine transiently improve the symptoms of patients with mild to moderate AD. They are hardly capable of preventing, halting or reversing the progression of this disease. In the long history of development of traditional Chinese medicine, many herbs have been discovered and employed to treat dementia diseases in clinics in China. In recent decades, a number of agents were isolated from these herbs and their efficacies against AD were tested. Some flavonoids, alkaloids, phenylpropanoids, triterpenoid saponins, and polysaccharides were demonstrated to have potential efficacies against AD via targeting multiple pathological changes of this disease. In this article, we reviewed research progress on the efficacies and underlying mechanisms of these agents.

  2. The FRIABLE1 gene product affects cell adhesion in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Lutz Neumetzler

    Full Text Available Cell adhesion in plants is mediated predominantly by pectins, a group of complex cell wall associated polysaccharides. An Arabidopsis mutant, friable1 (frb1, was identified through a screen of T-DNA insertion lines that exhibited defective cell adhesion. Interestingly, the frb1 plants displayed both cell and organ dissociations and also ectopic defects in organ separation. The FRB1 gene encodes a Golgi-localized, plant specific protein with only weak sequence similarities to known proteins (DUF246. Unlike other cell adhesion deficient mutants, frb1 mutants do not have reduced levels of adhesion related cell wall polymers, such as pectins. Instead, FRB1 affects the abundance of galactose- and arabinose-containing oligosaccharides in the Golgi. Furthermore, frb1 mutants displayed alteration in pectin methylesterification, cell wall associated extensins and xyloglucan microstructure. We propose that abnormal FRB1 action has pleiotropic consequences on wall architecture, affecting both the extensin and pectin matrices, with consequent changes to the biomechanical properties of the wall and middle lamella, thereby influencing cell-cell adhesion.

  3. Advanced Turbine Systems (ATS) program conceptual design and product development. Quarterly progress report, December 1, 1995--February 29, 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    This report describes the overall program status of the General Electric Advanced Gas Turbine Development program, and reports progress on three main task areas. The program is focused on two specific products: (1) a 70-MW class industrial gas turbine based on the GE90 core technology, utilizing a new air cooling methodology; and (2) a 200-MW class utility gas turbine based on an advanced GE heavy-duty machine, utilizing advanced cooling and enhancement in component efficiency. The emphasis for the industrial system is placed on cycle design and low emission combustion. For the utility system, the focus is on developing a technology base for advanced turbine cooling while achieving low emission combustion. The three tasks included in this progress report are on: conversion to a coal-fueled advanced turbine system, integrated program plan, and design and test of critical components. 13 figs., 1 tab.

  4. Methylation of the miR-126 gene associated with glioma progression.

    Science.gov (United States)

    Cui, Hongwei; Mu, Yongping; Yu, Lei; Xi, Ya-guang; Matthiesen, Rune; Su, Xiulan; Sun, Wenjie

    2016-04-01

    Gliomas are the most common and the most malignant brain tumors, accouting for 45-55% of all intracranial tumors. The incidence of glioma worldwide is about 6-12 per 100,000. Recently, several studies showed that the activation of the oncogenes and the inactivation and/or loss of the tumor suppressor genes, especially for miRNA-21, let-7 and so on, are the most primary molecule event in gliomas. MicroRNAs (miRNAs) are a class of endogenously expressed small noncoding RNAs which are usually 21-23 nucleotides long. miRNAs regulate gene expression and play important roles in a variety of physiological and pathological processes, such as cell proliferation, differentiation and apoptosis. To date, Growing evidence has shown that mi RNAs are frequently dysregulated in human cancers and can act as both tumor suppressors and oncogenes. Along with the discovery of micro RNA, more and more research focusing on its relationship with glioma was carried out to investigate the biological features of glioma and to provide experimental evidence for glioma mechanism. In the present study, we aimed to verify the miRNA-126 down-regulation which showed in the results of glioma tissue miRNAs chip and discuss the miRNA-126 methylation in patients with glioma. A total of 50 samples from patients with glioma and 20 control samples from patients with cerebral trauma were included in this study. The expression levels of the miR-126 gene were detected using quantitative polymerase chain reaction (PCR), and the methylation status of miR-126 was examined using methylation-specific PCR-denaturing high-performance liquid chromatography (MSP-DHPLC). The expression level of miRNA-126 was found to be significantly higher in the control group (0.6134 ± 0.1214) than in the glioma group (0.2771 ± 0.1529; P < 0.05). The expression was also significantly elevated in low-grade gliomas (0.3117 ± 0.1474) compared with high-grade gliomas (0.1582 ± 0.1345; P < 0.05). In addition, increased methylation of

  5. Split-gene system for hybrid wheat seed production.

    Science.gov (United States)

    Kempe, Katja; Rubtsova, Myroslava; Gils, Mario

    2014-06-24

    Hybrid wheat plants are superior in yield and growth characteristics compared with their homozygous parents. The commercial production of wheat hybrids is difficult because of the inbreeding nature of wheat and the lack of a practical fertility control that enforces outcrossing. We describe a hybrid wheat system that relies on the expression of a phytotoxic barnase and provides for male sterility. The barnase coding information is divided and distributed at two loci that are located on allelic positions of the host chromosome and are therefore "linked in repulsion." Functional complementation of the loci is achieved through coexpression of the barnase fragments and intein-mediated ligation of the barnase protein fragments. This system allows for growth and maintenance of male-sterile female crossing partners, whereas the hybrids are fertile. The technology does not require fertility restorers and is based solely on the genetic modification of the female crossing partner.

  6. 植物中SAMMtases基因研究进展%Progress of SAM Mtases Gene Study in Plants

    Institute of Scientific and Technical Information of China (English)

    穆红梅; 夏冰; 高俊平; 张秀省; 汪仁; 彭峰; 何树兰

    2012-01-01

    SAM Mtases是从多种植物中分离到的一类S-腺苷-L-甲硫氨酸依赖性氧位甲基转移酶基因,该基因对植物体内木质素、类苯基丙烷、类黄酮类、生物碱和脂肪族化合物等许多次生代谢产物合成有直接的影响,并且在植物抗病、抗紫外线、杀虫、抗菌、植物激素生长和信号调节、植物共生、花粉管伸长和花粉生长等生理过程中起重要作用.该文总结了国内外已经克隆到的SAM Mtases同源基因的分离、分类及其功能,为进一步研究SAM Mtases 基因在植物生理代谢调控中的地位及在植物抗性及药用成分育种上的应用提供参考.%SAMMtases was S-adenosyl-L-methionine dependent Omethyltransferase gene. The gene has a direct effect on plant lignin, class of phenyl propane, flavonoids, alkaloids and aliphatic compounds and many other secondary metabolite syntheses. It involved ir. plant disease resistance,UV resistance,insecticide, antiseptic, plant hormones,growth and signal conditioning,symbionts of plants,pollen tube elongation and pollen growth of plant allelopathy reaction. This review provides an overview on the research progress in separation,classification,and functions of SAM Mtases gene. It is helpful for better understanding of its position in plant physiological and metabolic regulation. We also highlight SAM Mtases gene as a candidate gene for plant resistance and plant secondary metabolism improvement.

  7. Reduced Representation Bisulfite Sequencing Determination of Distinctive DNA Hypermethylated Genes in the Progression to Colon Cancer in African Americans

    Directory of Open Access Journals (Sweden)

    Hassan Ashktorab

    2016-01-01

    Full Text Available Background and Aims. Many studies have focused on the determination of methylated targets in colorectal cancer. However, few analyzed the progressive methylation in the sequence from normal to adenoma and ultimately to malignant tumors. This is of utmost importance especially in populations such as African Americans who generally display aggressive tumors at diagnosis and for whom markers of early neoplasia are needed. We aimed to determine methylated targets in the path to colon cancer in African American patients using Reduced Representation Bisulfite Sequencing (RRBS. Methods. Genomic DNA was isolated from fresh frozen tissues of patients with different colon lesions: normal, a tubular adenoma, a tubulovillous adenoma, and five cancers. RRBS was performed on these DNA samples to identify hypermethylation. Alignment, mapping, and confirmed CpG methylation analyses were performed. Preferential hypermethylated pathways were determined using Ingenuity Pathway Analysis (IPA. Results. We identified hypermethylated CpG sites in the following genes: L3MBTL1, NKX6-2, PREX1, TRAF7, PRDM14, and NEFM with the number of CpG sites being 14, 17, 10, 16, 6, and 6, respectively, after pairwise analysis of normal versus adenoma, adenoma versus cancer, and normal versus cancer. IPA mapped the above-mentioned hypermethylated genes to the Wnt/β-catenin, PI3k/AKT, VEGF, and JAK/STAT3 signaling pathways. Conclusion. This work provides insight into novel differential CpGs hypermethylation sites in colorectal carcinogenesis. Functional analysis of the novel gene targets is needed to confirm their roles in their associated carcinogenic pathways.

  8. Association of renin-angiotensin system genes polymorphism with progression of diabetic nephropathy in patients with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ilić Vesna

    2014-01-01

    Full Text Available Background/Aim. Diabetic nephropathy (DN as a major microvascular complication of diabetes mellitus (DM include a progressive increase in urinary albumin excretion in association with an increase in blood pressure and to end stage renal failure. Hypertension connected with renin-angiotensin system (RAS hyperactivity and corresponding genotypes, angiotensinogen (AGT, angiotensine-converting enzyme (ACE and angiotensin II type 1 receptor (AT1R, predispose the increasing risk of DN. The aim of this study was to assess the distribution of AGT, ACE and AT1R gene polymorphisms in patients with type 1 DM according to the level of DN and patients clinical characteristics. Methods. The study included 79 type 1 diabetic patients. Inclusion criteria were: age between 20-40, duration of diabetes > 5 years, and no other severe diseases. Clinical characteristics were gained from interviewing the patients. Polymorphism was detected by polymerase chain reaction (PCR and restriction fragment length polymorphism using restriction enzymes Psy I (Tth 111 I and Hae III. Results. The patients with proteinuria compared with normo- and microalbuminuric patients, highly differed in age, diabetes duration, blood pressure level, hypertension, rethynopathy and urinary albumin excretion values (p < 0.001. No statistically significant difference between the groups was found for the ACE and AT1R gene polymorphisms distribution. The presence of TT genotype of the M235T polymorphism was significantly higher in the group with proteinuria (p < 0.05. The patients with hypertension raised nephropathy 5.2 times higher (OR = 5.20, p < 0.05 while carriers of TT allel developed nephropathy 28.38 times higher (OR = 28.389, p < 0.01 than those with MM genotype. Conclusion. Increased association of hypertension and TT angiotensinogen gene polymorphism in patients with diabetes mellitus with proteinuria could be a significant marker of diabetic nephropathy.

  9. Progress in the design of manufacturing plan and planning new product development in indefinite situations

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ How to embed those indefinite situations and nonlinear factors derived from a complicated industry environment into the production planning and new product development (NPD) planning, and the further establishment of fuzzy decision models, are very important issues in decision-making in manufacturing and operation administration.

  10. Enhanced validamycin production and gene expression at elevated temperature in Streptomyces hygroscopicus subsp. Jingangensis 5008

    Institute of Scientific and Technical Information of China (English)

    LI Lei; BAI LinQuan; ZHOU XiuFen; DENG ZiXin

    2009-01-01

    Cultivation shift from 30℃ to 37℃ significantly enhanced validamycin (VAL) production. Analyzed by reverse-transcripUon PCR, the transcription of three val genes, valA, valK and valG, representing the three operons of the cluster was simultaneously increased at elevated temperature. Furthermore, the transcription of valP and valQ, a pair of two-component regulators in validamycin biosynthetic gene cluster, was also increased at 37℃. Inactivation of valPand valQ reduced validamycin production at 37℃ to the yield level of wild type strain at 30℃, and the val genes showed reduced expression in the mutant LL-8 at 37℃. These results revealed that the two-component regulator valP and valQ contribute to the elevated validamycin production.

  11. Genetic resources for advanced biofuel production described with the Gene Ontology.

    Science.gov (United States)

    Torto-Alalibo, Trudy; Purwantini, Endang; Lomax, Jane; Setubal, João C; Mukhopadhyay, Biswarup; Tyler, Brett M

    2014-01-01

    Dramatic increases in research in the area of microbial biofuel production coupled with high-throughput data generation on bioenergy-related microbes has led to a deluge of information in the scientific literature and in databases. Consolidating this information and making it easily accessible requires a unified vocabulary. The Gene Ontology (GO) fulfills that requirement, as it is a well-developed structured vocabulary that describes the activities and locations of gene products in a consistent manner across all kingdoms of life. The Microbial ENergy processes Gene Ontology () project is extending the GO to include new terms to describe microbial processes of interest to bioenergy production. Our effort has added over 600 bioenergy related terms to the Gene Ontology. These terms will aid in the comprehensive annotation of gene products from diverse energy-related microbial genomes. An area of microbial energy research that has received a lot of attention is microbial production of advanced biofuels. These include alcohols such as butanol, isopropanol, isobutanol, and fuels derived from fatty acids, isoprenoids, and polyhydroxyalkanoates. These fuels are superior to first generation biofuels (ethanol and biodiesel esterified from vegetable oil or animal fat), can be generated from non-food feedstock sources, can be used as supplements or substitutes for gasoline, diesel and jet fuels, and can be stored and distributed using existing infrastructure. Here we review the roles of genes associated with synthesis of advanced biofuels, and at the same time introduce the use of the GO to describe the functions of these genes in a standardized way.

  12. Genetic Resources for Advanced Biofuel Production Described with the Gene Ontology

    Directory of Open Access Journals (Sweden)

    Trudy eTorto-Alalibo

    2014-10-01

    Full Text Available Dramatic increases in research in the area of microbial biofuel production coupled with high-throughput data generation on bioenergy-related microbes has led to a deluge of information in the scientific literature and in databases. Consolidating this information and making it easily accessible requires a unified vocabulary. The Gene Ontology (GO fulfills that requirement, as it is a well-developed structured vocabulary that describes the activities and locations of gene products in a consistent manner across all kingdoms of life. The Microbial Energy Gene Ontology (MENGO: http://www.mengo.biochem.vt.edu project is extending the GO to include new terms to describe microbial processes of interest to bioenergy production. Our effort has added over 600 bioenergy related terms to the Gene Ontology. These terms will aid in the comprehensive annotation of gene products from diverse energy-related microbial genomes. An area of microbial energy research that has received a lot of attention is microbial production of advanced biofuels. These include alcohols such as butanol, isopropanol, isobutanol, and fuels derived from fatty acids, isoprenoids, and polyhydroxyalkanoates. These fuels are superior to first generation biofuels (ethanol and biodiesel esterified from vegetable oil or animal fat, can be generated from non-food feedstock sources, can be used as supplements or substitutes for gasoline, diesel and jet fuels, and can be stored and distributed using existing infrastructure. Here we review the roles of genes associated with synthesis of advanced biofuels, and at the same time introduce the use of the GO to describe the functions of these genes in a standardized way.

  13. Acetic acid production from marine algae. Progress report No. 2, September 30--December 31, 1977

    Energy Technology Data Exchange (ETDEWEB)

    1977-01-01

    Preliminary results on the production of acetic acid from marine algae by anaerobic fermentation indicate that the rate is quite fast. First order rate constants of 0.77 day/sup -1/ were observed. This rate constant gives a half-life of less than one day. In other words, with a properly designed product removal system a five day retention time would yield 98% of theoretical conversion. Determination of the theoretical conversion of marine algae to acetic acid is the subject of much experimentation. The production of one acetic acid molecule (or equivalent in higher organic acids) for each three carbon atoms in the substrate has been achieved; but it is possible that with a mixed culture more than one acetic acid molecule may be produced for each three carbons in the substrate. Work is continuing to improve the yield of acetic acid from marine algae. Marine algae have been found to be rather low in carbon, but the carbon appears to be readily available for fermentation. It, therefore, lends itself to the production of higher value chemicals in relatively expensive equipment, where the rapid conversion rate is particularly cost effective. Fixed packed bed fermenters appear to be desirable for the production of liquid products which are inhibitory to the fermentation from coarse substrates. The inhibitory products may be removed from the fermentation by extraction during recirculation. This technique lends itself to either conventional processing or low capital processing of substrates which require long retention times.

  14. Progress in the epidemiological understanding of gene-environment interactions in major diseases: cancer.

    Science.gov (United States)

    Clavel, Jacqueline

    2007-04-01

    Cancer epidemiology has undergone marked development since the 1950s. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking on the occurrence of lung, larynx, and bladder cancer. Major chemical, physical, and biological carcinogenic agents have been identified in the working environment and in the overall environment. The chain of events from environmental exposures to cancer requires hundreds of polymorphic genes coding for proteins involved in the transport and metabolism of xenobiotics, or in repair, or in an immune or inflammatory response. The multifactorial and multistage characteristics of cancer create the theoretical conditions for statistical interactions that have been exceptionally detected. Over the last two decades, a considerable mass of data has been generated, mostly addressing the interactions between smoking and xenobiotic-metabolizing enzymes in smoking-related cancers. They were sometimes considered disappointing, but they actually brought a lot of information and raised many methodological issues. In parallel, the number of polymorphisms that can be considered candidate per function increased so much that multiple testing has become a major issue, and genome wide-screening approaches have more and more gained in interest. Facing the resulting complexity, some instruments are being set up: our studies are now equipped with carefully sampled biological collections, high-throughput genotyping systems are becoming available, work on statistical methodologies is ongoing, bioinformatics databases are growing larger and access to them is becoming simpler; international consortiums are being organized. The roles of environmental and genetic factors are being jointly elucidated. The basic rules of epidemiology, which are demanding with respect to sampling, with respect to the histological and molecular criteria for cancer classification, with respect to the evaluation of environmental exposures

  15. Livin与肿瘤的研究进展%Research progress of Livin gene in tumors

    Institute of Scientific and Technical Information of China (English)

    薛栋; 张扬; 成丕光; 李新军; 张同军; 陈雨信

    2013-01-01

    Livin,as a novel member of human inhibitor of apoptosis protein family,is highly expressed in many malignant tumors.Livin plays critical role in apoptosis inhibition,regulating the cell cycle,participating in tumor angiogenesis.Livin is also significant to chemoresistance.The majority of the current data suggests that Livin expression in cancer appears to be associated with unfavorable clinico-pathological parameters,such as disease relapse and shorter patient survival.In recent years,immunotherapy and gene therapy for the targeting of Livin have become a hot research field,which provides new strategy and direction for tumor therapy.%凋亡抑制因子Livin是凋亡抑制蛋白家族的新成员.Livin在多种肿瘤组织中高表达,在细胞凋亡、细胞增生、细胞周期调控及参与肿瘤血管生成等过程中发挥重要作用,并且与化疗耐药性相关.大量研究表明,在许多恶性肿瘤组织中Livin异常表达与患者的预后密切相关,如肿瘤复发、生存期较短等.因此,以Livin为靶点的基因与免疫治疗也成为热点研究之一,为肿瘤的综合治疗提供了新的策略和方向.

  16. Candidate genes for drought tolerance and improved productivity in rice (Oryza sativa L.)

    Indian Academy of Sciences (India)

    M S Vinod; Naveen Sharma; K Manjunatha; Adnan Kanbar; N B Prakash; H E Shashidhar

    2006-03-01

    Candidate genes are sequenced genes of known biological action involved in the development or physiology of a trait. Twenty-one putative candidate genes were designed after an exhaustive search in the public databases along with an elaborate literature survey for candidate gene products and/or regulatory sequences associated with enhanced drought resistance. The downloaded sequences were then used to design primers considering the flanking sequences as well. Polymerase chain reaction (PCR) performed on 10 diverse cultivars that involved Japonica, Indica and local accessions, revealed 12 polymorphic candidate genes. Seven polymorphic candidate genes were then utilized to genotype 148 individuals of CT9993 × IR62266 doubled haploid (DH) mapping population. The segregation data were tested for deviation from the expected Mendelian ratio (1:1) using a Chi-square test (<1%). Based on this, four candidate genes were assessed to be significant and the remaining three, as non-significant. All the significant candidate genes were biased towards CT9993, the female parent in the DH mapping population. Single-marker analysis strongly associated ( < 1%) them to different traits under both well-watered and low-moisture stress conditions. Two candidate genes, EXP15 and EXP13, were found to be associated with root number and silicon content in the stem respectively, under both well-watered and low-moisture stress conditions.

  17. 虾青素生产方法研究进展%Research Progress of Astaxanthin's Production Process

    Institute of Scientific and Technical Information of China (English)

    肖素荣; 李京东

    2011-01-01

    虾青素作为一种具有特殊生理功效的物质,其抗氧化作用和着色作用在食品、药片、饲料以及化妆品行业有着广阔前景.本文主要论述了虾青素生产方法的研究进展.%Because of its special physiological function antioxidant ability and pigmentation ability, astaxanthin has broad prospects in food industries, medicine, feedstuffs as well as in cosmetics line. This thesis mainly discussed the research progress of astaxanthin's production process.

  18. ROS production during symbiotic infection suppresses pathogenesis-related gene expression.

    Science.gov (United States)

    Peleg-Grossman, Smadar; Melamed-Book, Naomi; Levine, Alex

    2012-03-01

    Leguminous plants have exclusive ability to form symbiotic relationship with soil bacteria of the genus Rhizobium. Symbiosis is a complex process that involves multiple molecular signaling activities, such as calcium fluxes, production of reactive oxygen species (ROS) and synthesis of nodulation genes. We analyzed the role of ROS in defense gene expression in Medicago truncatula during symbiosis and pathogenesis. Studies in Arabidopsis thaliana showed that the induction of pathogenesis-related (PR) genes during systemic acquired resistance (SAR) is regulated by NPR1 protein, which resides in the cytoplasm as an oligomer. After oxidative burst and return of reducing conditions, the NPR1 undergoes monomerization and becomes translocated to the nucleus, where it functions in PR genes induction. We show that ROS production is both stronger and longer during symbiotic interactions than during interactions with pathogenic, nonhost or common nonpathogenic soil bacteria. Moreover, root cells inoculated with Sinorhizobium meliloti accumulated ROS in the cytosol but not in vacuoles, as opposed to Pseudomonas putida inoculation or salt stress treatment. Furthermore, increased ROS accumulation by addition of H₂O₂ reduced the PR gene expression, while catalase had an opposite effect, establishing that the PR gene expression is opposite to the level of cytoplasmic ROS. In addition, we show that salicylic acid pretreatment significantly reduced ROS production in root cells during symbiotic interaction.

  19. Products of lipid, protein and RNA oxidation as signals and regulators of gene expression in plants

    Directory of Open Access Journals (Sweden)

    Jagna eChmielowska-Bąk

    2015-06-01

    Full Text Available Reactive oxygen species (ROS are engaged in several processes essential for normal cell functioning, such as differentiation, anti-microbial defense, stimulus sensing and signaling. Interestingly, recent studies imply that cellular signal transduction and gene regulation are mediated not only directly by ROS but also by the molecules derived from ROS-mediated oxidation. Lipid peroxidation leads to non-enzymatic formation of oxylipins. These molecules were shown to modulate expression of signaling associated genes including genes encoding phosphatases, kinases and transcription factors. Oxidized peptides derived from protein oxidation might be engaged in organelle-specific ROS signaling. In turn, oxidation of particular mRNAs leads to decrease in the level of encoded proteins and thus, contributes to the post-transcriptional regulation of gene expression. Present mini review summarizes latest findings concerning involvement of products of lipid, protein and RNA oxidation in signal transduction and gene regulation.

  20. Progress in treatment of tumor suicide gene%肿瘤自杀基因治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    刘志; 王汝娜

    2003-01-01

    Suicide gene therapy at present is an effective therapy for tumors. The presentpaper introduces the latest advances of suicide gene therapy in aspects ofwork system, bystander effect, bisuicide gene and suicide gene combmingother therapies etc.

  1. Engineering validamycin production by tandem deletion of γ-butyrolactone receptor genes in Streptomyces hygroscopicus 5008.

    Science.gov (United States)

    Tan, Gao-Yi; Peng, Yao; Lu, Chenyang; Bai, Linquan; Zhong, Jian-Jiang

    2015-03-01

    Paired homologs of γ-butyrolactone (GBL) biosynthesis gene afsA and GBL receptor gene arpA are located at different positions in genome of Streptomyces hygroscopicus 5008. Inactivation of afsA homologs dramatically decreased biosynthesis of validamycin, an important anti-fungal antibiotic and a critical substrate for antidiabetic drug synthesis, and the deletion of arpA homologs increased validamycin production by 26% (ΔshbR1) and 20% (ΔshbR3). By double deletion, the ΔshbR1/R3 mutant showed higher transcriptional levels of adpA-H (the S. hygroscopicus ortholog of the global regulatory gene adpA) and validamycin biosynthetic genes, and validamycin production increased by 55%. Furthermore, by engineering a high-producing industrial strain via tandem deletion of GBL receptor genes, validamycin production and productivity were enhanced from 19 to 24 g/L (by 26%) and from 6.7 to 9.7 g/L(-1) d(-1) (by 45%), respectively, which was the highest ever reported. The strategy demonstrated here may be useful to engineering other Streptomyces spp. with multiple pairs of afsA-arpA homologs.

  2. Inflammatory cues modulate the expression of secretory product genes, Golgi sulfotransferases and sulfomucin production in LS174T cells.

    Science.gov (United States)

    Croix, Jennifer A; Bhatia, Shikha; Gaskins, H Rex

    2011-12-01

    The signals that mediate goblet cell expression of specific mucin chemotypes are poorly defined. Animal and in vitro studies show that acidomucin chemotypes may be altered by inflammation and changes in intestinal microbiota. To examine factors that may elicit this response, human adenocarcinoma-derived LS174T cells, which have a goblet cell-like phenotype and produce both sulfo- and sialomucins, were used to examine the effects of selected microbial and host factors on expression of goblet cell secretory product genes, sulfotransferases and sulfomucin production. Expression of genes encoding mucin 2 (MUC2), resistin-like molecule β (RETNLB), and trefoil factor 3 (TFF3) and Golgi sulfotransferases, carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 5 (CHST5) and galactose-3-O-sulfotransferase 2 (GAL3ST2), was measured by quantitative reverse transcriptase-polymerase chain reaction following treatment with bacterial flagellin, tumor necrosis factor α (TNF-α) or the mucogenic cytokine interleukin-13 (IL-13). Expression of the toll-like receptor 5 (TLR5) gene was also analysed. Sulfomucin expression was examined via high-iron diamide/alcian blue (HID/AB) histochemistry and immunofluorescent staining for the Sulfo Le(a) antigen, which is synthesized in part by GAL3ST2. Flagellin, IL-13 and TNF-α all significantly increased GAL3ST2, MUC2, TFF3 and TLR5 expression, while only IL-13 increased RETNLB and CHST5 expression. Based on HID/AB histochemistry, mucin sulfation was significantly increased in response to both flagellin and IL-13 but not TNF-α. Only treatment with flagellin increased the expression of the Sulfo Le(a) antigen. Collectively, these results indicate that bacterial flagellin, IL-13 and TNF-α differentially modulate the expression of goblet cell secretory product genes, sulfotransferases and sulfomucin production.

  3. Final Progress Report on Model-Based Diagnosis of Soil Limitations to Forest Productivity

    Energy Technology Data Exchange (ETDEWEB)

    Luxmoore, R.J.

    2004-08-30

    This project was undertaken in support of the forest industry to link modeling of nutrients and productivity with field research to identify methods for enhancing soil quality and forest productivity and for alleviating soil limitations to sustainable forest productivity. The project consisted of a series of related tasks, including (1) simulation of changes in biomass and soil carbon with nitrogen fertilization, (2) development of spreadsheet modeling tools for soil nutrient availability and tree nutrient requirements, (3) additional modeling studies, and (4) evaluation of factors involved in the establishment and productivity of southern pine plantations in seasonally wet soils. This report also describes the two Web sites that were developed from the research to assist forest managers with nutrient management of Douglas-fir and loblolly pine plantations.

  4. Secondary production in wetlands of the Lacreek National Wildlife refuge : 2002 progress report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Productivity of prairie wetlands is maintained through the natural wet/dry climatic cycles of the region. Periodic drying is required to oxidize sediments and...

  5. Secondary production in wetlands of the Lacreek National Wildlife refuge : 2003 progress report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Productivity of prairie wetlands is maintained through the natural wet/dry climatic cycles of the region. Periodic drying is required to oxidize sediments and...

  6. Progress in the uitilization and promotion of South African indigenous goats for cashmere production

    CSIR Research Space (South Africa)

    Braun, AL

    2004-01-01

    Full Text Available . Utilization of the fibres as an addition source of income would make the goat flocks more profitable Cashmere production is labour intensive and ideally suited for farmers with small number of goats Supports rural and economic development...

  7. Research Progress of Hydrogen Production fromOrganic Wastes in Microbial Electrolysis Cell(MEC

    Directory of Open Access Journals (Sweden)

    YU Yin-sheng

    2015-08-01

    Full Text Available Microbial electrolysis cell(MECtechnology as an emerging technology, has achieved the target of hydrogen production from different substrates such as waste water, forestry wastes, activated sludge by simultaneous enzymolysis and fermentation, which can effectively improve the efficiency of resource utilization. This paper described the working principle of MEC and analyzed these factors influencing the process of hydrogen production from organic waste in MEC.

  8. Investigation of genes involved in nisin production in Enterococcus spp. strains isolated from raw goat milk.

    Science.gov (United States)

    Perin, Luana Martins; Todorov, Svetoslav Dimitrov; Nero, Luís Augusto

    2016-09-01

    Different strains of Lactococcus lactis are capable of producing the bacteriocin nisin. However, genetic transfer mechanisms allow the natural occurrence of genes involved in nisin production in members of other bacterial genera, such as Enterococcus spp. In a previous study, nisA was identified in eight enterococci capable of producing antimicrobial substances. The aim of this study was to verify the presence of genes involved in nisin production in Enterococcus spp. strains, as well as nisin expression. The nisA genes from eight Enterococcus spp. strains were sequenced and the translated amino acid sequences were compared to nisin amino-acid sequences previously described in databases. Although containing nisin structural and maturation related genes, the enterococci strains tested in the present study did not present the immunity related genes (nisFEG and nisI). The translated sequences of nisA showed some point mutations, identical to those presented by Lactococcus strains isolated from goat milk. All enterococci were inhibited by nisin, indicating the absence of immunity and thus that nisin cannot be expressed. This study demonstrated for the first time the natural occurrence of nisin structural genes in Enterococcus strains and highlights the importance of providing evidence of a link between the presence of bacteriocin genes and their expression.

  9. Perception of products by progressive multisensory integration. A study on hammers.

    Science.gov (United States)

    Vergara, Margarita; Mondragón, Salvador; Sancho-Bru, Joaquín Luis; Company, Pedro; Agost, María-Jesús

    2011-07-01

    The aim of this work is to determine the influence of multisensory (visual-haptic) integration and the level of interaction (seeing photographs, seeing the actual product, touching it and using it) on the perception of products, including perceived ergonomics. The product selected for the experiment was the hammer, as this will help to establish whether emotional design studies can also apply to 'commercial' products. Subjective opinions of users were evaluated through semantic differential tests. A factor analysis identified six semantic factors or axes (Quality/Robustness, Ergonomics/Appearance, Innovation, Lightness, Dynamic Effects, and Efficacy). Results show that Lightness and Dynamic Effects are quite sensitive to the level of interaction, while Ergonomics/Appearance is partially affected. However, the perceptions of Innovation, Quality/Robustness and Efficacy are not so affected and they could be detected through a lower level of interaction (i.e. seeing photographs). This suggests that commercial products seem sensitive to emotional design studies and that multisensory integration enhances the perception of the factors that are clearly linked with physical interaction between users and tools, i.e. Ergonomics/Appearance, Lightness and Dynamic Effects. Additionally, it should be highlighted that some aspects related with the ergonomics and ease of use of products are also perceived at different stages of interaction. Copyright © 2010 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  10. Production of indole antibiotics induced by exogenous gene derived from sponge metagenomes.

    Science.gov (United States)

    Takeshige, Yuya; Egami, Yoko; Wakimoto, Toshiyuki; Abe, Ikuro

    2015-05-01

    Sponge metagenomes are accessible genetic sources containing genes and gene clusters responsible for the biosynthesis of sponge-derived bioactive natural products. In this study, we obtained the clone pDC112, producing turbomycin A and 2,2-di(3-indolyl)-3-indolone, based on the functional screening of the metagenome library derived from the marine sponge Discodermia calyx. The subcloning experiment identified ORF 25, which is homologous to inosine 5'-monophosphate dehydrogenase and required for the production of 2,2-di(3-indolyl)-3-indolone in Escherichia coli.

  11. Characterization of the mammalian DNA polymerase gene and protein. Annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, N.C.

    1992-01-01

    We have purified and characterized at least three DNA polymerases from Chinese hamster ovary (CHO) cell line Kl in order to evaluate the roles of different polymerases in eukaryotic DNA replication. Pol {alpha} was the most abundant among different polymerase activities and it was neutralized by a monoclonal antibody raised against human pol {alpha}. Pol {var_epsilon} was separated from pol {alpha} and pol {delta} activities using DEAE Sephacell, phosphocellulose and hydroxylapatite columns. The enzyme proved to be sensitive to aphidicolin and carbonyldiphosphonate and was not stimulated by PCNA- Pol {delta} was the least abundant among the three enzymes. It was sensitive to aphidicolin and carbonyidiphosphonate and was stimulated by PCNA. it had a preference for template/primer poly (dA-dT). Based on DNA sequence data of different eukaryotic polymerases PCR primers complementary to two neighboring synthesized. In PCR experiments several products were obtained which are assumed to be specific for the CHO polymerases. We have also analyzed a large number of aphidicolin resistant mutants of CHO to identify mutants with altered DNA polymerases.

  12. Waterfowl populations, production and habitat ecology on the Yukon-Kuskokwim Delta, Alaska: Population and ecology of cackling geese: Progress report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This is a progress report on the waterfowl populations, production and habitat ecology on the Yukon-Kuskokwim Delta, Alaska, specifically the populations and ecology...

  13. GeneViTo: Visualizing gene-product functional and structural features in genomic datasets

    Directory of Open Access Journals (Sweden)

    Promponas Vasilis J

    2003-10-01

    Full Text Available Abstract Background The availability of increasing amounts of sequence data from completely sequenced genomes boosts the development of new computational methods for automated genome annotation and comparative genomics. Therefore, there is a need for tools that facilitate the visualization of raw data and results produced by bioinformatics analysis, providing new means for interactive genome exploration. Visual inspection can be used as a basis to assess the quality of various analysis algorithms and to aid in-depth genomic studies. Results GeneViTo is a JAVA-based computer application that serves as a workbench for genome-wide analysis through visual interaction. The application deals with various experimental information concerning both DNA and protein sequences (derived from public sequence databases or proprietary data sources and meta-data obtained by various prediction algorithms, classification schemes or user-defined features. Interaction with a Graphical User Interface (GUI allows easy extraction of genomic and proteomic data referring to the sequence itself, sequence features, or general structural and functional features. Emphasis is laid on the potential comparison between annotation and prediction data in order to offer a supplement to the provided information, especially in cases of "poor" annotation, or an evaluation of available predictions. Moreover, desired information can be output in high quality JPEG image files for further elaboration and scientific use. A compilation of properly formatted GeneViTo input data for demonstration is available to interested readers for two completely sequenced prokaryotes, Chlamydia trachomatis and Methanococcus jannaschii. Conclusions GeneViTo offers an inspectional view of genomic functional elements, concerning data stemming both from database annotation and analysis tools for an overall analysis of existing genomes. The application is compatible with Linux or Windows ME-2000-XP operating

  14. Microbial production of aliphatic hydrocarbons. Progress report, February 1, 1979-September 30, 1979. [Optimization for commercial oily hydrocarbon production

    Energy Technology Data Exchange (ETDEWEB)

    Tornabene, T G

    1979-09-01

    The neutral lipids of nine species of methanogenic bacteria, two thermoacidophiles, two alkalinophiles and 20 algal samples were analyzed. The major components were C/sub 30/, C/sub 25/, and/or C/sub 20/ acyclic isoprenoid hydrocarbons with a continuous range of hydroisoprenoid homologues. The range or acyclic isoprenoids detected were from C/sub 14/ to C/sub 30/. The neutral lipid composition from these bacteria resembles the isoprenoid distribution isolated from ancient sediments and petroleum. Therefore, these findings may have major implications to biological and biogeochemical evolution. In this connection, samples and cores from ancient sediments and future fossil fuel source beds are being analyzed for these neutral lipids as well as the more polar isopranyl glycerol-ether lipids. The derivation of fossil fuels and the biomass accumulations are the focal points of this phase of the study. Ancient and recent sediments, future source beds, and local esturaries are being enriched for microorganisms to establish a range and capability profile for hydrocarbon production. Only a relatively small percent of the microorganisms isolated demonstrated the ability to synthesize hydrocarbons; however, one particular algal isolate demonstrated that it can synthesize hydrocarbons while in a green physiological stage. Greater production is expected in the brown phase of growth. Hydrocarbon biosynthesis studies were conducted in an attempt to better understand the conditions required to maximize hydrocarbon production. The program involved physical and chemical parameters as well as assays of specifically labelled precusors with a cell free enzyme system to measure their conversions to hydrocarbons. The results have indicated a complex one enzyme system is involved in condensation and reduction of two fatty acids into hydrocarbons.

  15. Biofilm formation, phenotypic production of cellulose and gene expression in Salmonella enterica decrease under anaerobic conditions.

    Science.gov (United States)

    Lamas, A; Miranda, J M; Vázquez, B; Cepeda, A; Franco, C M

    2016-12-05

    Salmonella enterica subsp. enterica is one of the main food-borne pathogens. This microorganism combines an aerobic life outside the host with an anaerobic life within the host. One of the main concerns related to S. enterica is biofilm formation and cellulose production. In this study, biofilm formation, morphotype, cellulose production and transcription of biofilm and quorum sensing-related genes of 11 S. enterica strains were tested under three different conditions: aerobiosis, microaerobiosis, and anaerobiosis. The results showed an influence of oxygen levels on biofilm production. Biofilm formation was significantly higher (Pbiofilm and quorum sensing-related genes. Thus, the results from this study indicate that biofilm formation and cellulose production are highly influenced by atmospheric conditions. This must be taken into account as contamination with these bacteria can occur during food processing under vacuum or modified atmospheres.

  16. Energy biomass tree seedling production study. Fuels from woody biomass. Progress report, September 1978-January 1980

    Energy Technology Data Exchange (ETDEWEB)

    Foote, K.R.

    1980-03-01

    The research to date has centered around the establishment of baseline growing conditions for a number of species of tree seedlings, primarily deciduous hardwoods. As these baseline conditions were established for each specie, the shoot and root environments were manipulated in an attempt to establish techniques to increase seedling growth and reduce production times. Seedlings were outplanted in an attempt to establish baseline survival rates for seedlings grown in totally controlled environments. Studies to determine the optimum container for tree seedling production have been run and will continue as other containers are identified and made available. The most significant of the research results has been in the maximization of seedling growth. Seedling production times have been decreased in some species by as much as 50% under the baseline production times. Controlled environment production techniques provide for plant densities as high as 144 seedlings per square foot of growing space. Investigations of growing media indicate a significant species specific responses. Preliminary results of outplanting indicate survival rates as high as 90% plus.

  17. Recent progress on industrial fermentative production of acetone-butanol-ethanol by Clostridium acetobutylicum in China.

    Science.gov (United States)

    Ni, Ye; Sun, Zhihao

    2009-06-01

    China is one of the few countries, which maintained the fermentative acetone-butanol-ethanol (ABE) production for several decades. Until the end of the last century, the ABE fermentation from grain was operated in a few industrial scale plants. Due to the strong competition from the petrochemical industries, the fermentative ABE production lost its position in the 1990s, when all the solvent fermentation plants in China were closed. Under the current circumstances of concern about energy limitations and environmental pollution, new opportunities have emerged for the traditional ABE fermentation industry since it could again be potentially competitive with chemical synthesis. From 2006, several ABE fermentation plants in China have resumed production. The total solvent (acetone, butanol, and ethanol) production capacity from ten plants reached 210,000 tons, and the total solvent production is expected to be extended to 1,000,000 tons (based on the available data as of Sept. 2008). This article reviews current work in strain development, the continuous fermentation process, solvent recovery, and economic evaluation of ABE process in China. Challenges for an economically competitive ABE process in the future are also discussed.

  18. 1,3-Propanediol production by Escherichia coli using genes from Citrobacter freundii atcc 8090.

    Science.gov (United States)

    Przystałowska, Hanna; Zeyland, Joanna; Kośmider, Alicja; Szalata, Marlena; Słomski, Ryszard; Lipiński, Daniel

    2015-01-01

    Compared with chemical synthesis, fermentation has the advantage of mass production at low cost, and has been used in the production of various industrial chemicals. As a valuable organic compound, 1,3-propanediol (1,3-PDO) has numerous applications in the production of polymers, lubricants, cosmetics and medicines. Here, conversion of glycerol (a renewable substrate and waste from biodiesel production) to 1,3-PDO by E. coli bacterial strain carrying altered glycerol metabolic pathway was investigated. Two gene constructs containing the 1,3-PDO operon from Citrobacter freundii (pCF1 and pCF2) were used to transform the bacteria. The pCF1 gene expression construct contained dhaBCE genes encoding the three subunits of glycerol dehydratase, dhaF encoding the large subunit of the glycerol dehydratase reactivation factor and dhaG encoding the small subunit of the glycerol dehydratase reactivating factor. The pCF2 gene expression construct contained the dhaT gene encoding the 1,3-propanediol dehydrogenase. Expression of the genes cloned in the above constructs was under regulation of the T7lac promoter. RT-PCR, SDS-PAGE analyses and functional tests confirmed that 1,3-PDO synthesis pathway genes were expressed at the RNA and protein levels, and worked flawlessly in the heterologous host. In a batch flask culture, in a short time applied just to identify the 1,3-PDO in a preliminary study, the recombinant E. coli bacteria produced 1.53 g/L of 1,3-PDO, using 21.2 g/L of glycerol in 72 h. In the Sartorius Biostat B Plus reactor, they produced 11.7 g/L of 1,3-PDO using 24.2 g/L of glycerol, attaining an efficiency of 0.58 [mol1,3-PDO/molglycerol].

  19. Identification and engineering of regulation-related genes toward improved kasugamycin production.

    Science.gov (United States)

    Zhu, Chenchen; Kang, Qianjin; Bai, Linquan; Cheng, Lin; Deng, Zixin

    2016-02-01

    Kasugamycin, produced by Streptomyces kasugaensis and Streptomyces microaureus, is an important amino-glycoside family antibiotic and widely used for veterinary and agricultural applications. In the left flanking region of the previously reported kasugamycin gene cluster, four additional genes (two-component system kasW and kasX, MerR-family kasV, and isoprenylcysteine carboxyl methyltransferase kasS) were identified both in the low-yielding S. kasugaensis BCRC12349 and high-yielding S. microaureus XM301. Deletion of regulatory gene kasT abolished kasugamycin production, and its overexpression in BCRC12349 resulted in an increased titer by 186 %. Deletion of kasW, kasX, kasV, and kasS improved kasugamycin production by 12, 19, 194, and 22 %, respectively. qRT-PCR analysis demonstrated that the transcription of kas genes was significantly increased in all the four mutants. Similar gene inactivation was performed in the high-yielding strain S. microaureus XM301. As expected, the deletion of kasW/X resulted in a 58 % increase of the yield from 6 to 9.5 g/L. However, the deletion of kasV and over-expression of kasT had no obvious effect, and the disruption of kasS surprisingly decreased kasugamycin production. In addition, trans-complementation of the kasS mutant with a TTA codon-mutated kasS increased the kasugamycin yield by 20 %. A much higher transcription of kas genes was detected in the high-yielding XM301 than in the low-yielding BCRC12349, which may partially account for the discrepancy of gene inactivation effects between them. Our work not only generated engineered strains with improved kasugamycin yield, but also pointed out that different strategies on manipulating regulatory-related genes should be considered for low-yielding or high-yielding strains.

  20. Acetic acid production from marine algae. Progress report No. 2, September 30 to December 31, 1977

    Energy Technology Data Exchange (ETDEWEB)

    Sanderson, J E; Wise, D L

    1978-03-10

    Preliminary results on the production of acetic acid from marine algae by anaerobic fermentation indicates that the rate is quite fast. First order rate constants of 0.77 day/sup -1/ have been observed. This rate constant gives a half-life of less than one day. In other words, with a properly designed product removal system a five day retention time would yield 98% of theoretical conversion. Determination of the theoretical conversion of marine algae to acetic acid is the subject of much experimentation. The production of one acetic acid molecule (or equivalent in higher organic acids) for each three carbon atoms in the substrate has been achieved; but it is possible that with a mixed culture more than one acetic acid molecule may be produced for each three carbons in the substrate.

  1. Heterotrophic microalgae cultivation to synergize biodiesel production with waste remediation: progress and perspectives.

    Science.gov (United States)

    Venkata Mohan, S; Rohit, M V; Chiranjeevi, P; Chandra, Rashmi; Navaneeth, B

    2015-05-01

    Microalgae are inexhaustible feedstock for synthesis of biodiesel rich in polyunsaturated fatty acids (PUFA) and valuable bioactive compounds. Their cultivation is critical in sustaining the global economy in terms of human consumption of food and fuel. When compared to autotrophic cultivation, heterotrophic systems are more suitable for producing high cell densities of microalgae for accumulation of large quantities of lipids (triacylglycerols) which can be converted into biodiesel. Consorted efforts are made in this communication to converge recent literature on heterotrophic cultivation systems with simultaneous wastewater treatment and algal oil production. Challenges faced during large scale production and limiting factors which hinder the microalgae growth are enumerated. A strategic deployment of integrated closed loop biorefinery concept with multi-product recovery is proposed to exploit the full potential of algal systems. Sustainable algae cultivation is essential to produce biofuels leading to green future.

  2. Recent progress in synthetic biology for microbial production of C3-C10 alcohols

    Directory of Open Access Journals (Sweden)

    Edna N. Lamsen

    2012-06-01

    Full Text Available The growing need to address current energy and environmental problems has sparked an interest in developing improved biological methods to produce liquid fuels from renewable sources. While microbial ethanol production is well established, higher chain alcohols possess chemical properties that are more similar to gasoline. Unfortunately, these alcohols (except 1-butanol are not produced efficiently in natural microorganisms, and thus economical production in industrial volumes remains a challenge. Synthetic biology, however, offers additional tools to engineer synthetic pathways in user-friendly hosts to help increase titers and productivity of these advanced biofuels. This review concentrates on recent developments in synthetic biology to produce higher-chain alcohols as viable renewable replacements for traditional fuel.

  3. Regulatory structures for gene therapy medicinal products in the European Union.

    Science.gov (United States)

    Klug, Bettina; Celis, Patrick; Carr, Melanie; Reinhardt, Jens

    2012-01-01

    Taking into account the complexity and technical specificity of advanced therapy medicinal products: (gene and cell therapy medicinal products and tissue engineered products), a dedicated European regulatory framework was needed. Regulation (EC) No. 1394/2007, the "ATMP Regulation" provides tailored regulatory principles for the evaluation and authorization of these innovative medicines. The majority of gene or cell therapy product development is carried out by academia, hospitals, and small- and medium-sized enterprises (SMEs). Thus, acknowledging the particular needs of these types of sponsors, the legislation also provides incentives for product development tailored to them. The European Medicines Agency (EMA) and, in particular, its Committee for Advanced Therapies (CAT) provide a variety of opportunities for early interaction with developers of ATMPs to enable them to have early regulatory and scientific input. An important tool to promote innovation and the development of new medicinal products by micro-, small-, and medium-sized enterprises is the EMA's SME initiative launched in December 2005 to offer financial and administrative assistance to smaller companies. The European legislation also foresees the involvement of stakeholders, such as patient organizations, in the development of new medicines. Considering that gene therapy medicinal products are developed in many cases for treatment of rare diseases often of monogenic origin, the involvement of patient organizations, which focus on rare diseases and genetic and congenital disorders, is fruitful. Two such organizations are represented in the CAT. Research networks play another important role in the development of gene therapy medicinal products. The European Commission is funding such networks through the EU Sixth Framework Program.

  4. Progress of succinic acid production from renewable resources: Metabolic and fermentative strategies.

    Science.gov (United States)

    Jiang, Min; Ma, Jiangfeng; Wu, Mingke; Liu, Rongming; Liang, Liya; Xin, Fengxue; Zhang, Wenming; Jia, Honghua; Dong, Weiliang

    2017-06-03

    Succinic acid is a four-carbon dicarboxylic acid, which has attracted much interest due to its abroad usage as a precursor of many industrially important chemicals in the food, chemicals, and pharmaceutical industries. Facing the shortage of crude oil supply and demand of sustainable development, biological production of succinic acid from renewable resources has become a topic of worldwide interest. In recent decades, robust producing strain selection, metabolic engineering of model strains, and process optimization for succinic acid production have been developed. This review provides an overview of succinic acid producers and cultivation technology, highlight some of the successful metabolic engineering approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Progress on macrophage’s proinflammatory products as markers of acute endometriosis

    Institute of Scientific and Technical Information of China (English)

    Alicja Ziętek; Konrad Futyma; Łukasz Nowakowski; Marek Gogacz; Tomasz Rechberger

    2015-01-01

    To provide the review of the macrophage activity products as pathophysiological markers of endometriosis by literature survey (PubMed, Cochrane). Immunoreactive cells and several of their synthesis products concentrations are elevated in the serum and peritoneal fluid in patients with endometriosis.The enhanced reactive proteins contributed to local inflammation and aggregation of endometriotic lesions. Immune response and immune surveillance of tissue play an important role in pathogenesis of endometriosis. Activated macrophages in peritoneal environment secrete immunoreactive cytokines which are responsible for inflammatory cascade of reactions. The immunoreactive cytokines should be a target not only as a disease marker but also as a part of therapeutic protocol.

  6. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lin Yang; Li-Ge Kuang; Hua-Chuan Zheng; Jin-Yi Li; Dong-Ying Wu; Su-Min Zhang; Yan Xin

    2003-01-01

    AIM: To detect the expression of PTEN encoding productin normal mucosa, intestinal metaplasia (IM), dysplasia andcarcinoma of the stomach, and to investigate its clinicalimplication in tumorigenesis and progression of gastriccarcinoma.METHODS: Formalin-fixed paraffin embedded specimens from184 cases of gastric carcinoma, their adjacent normal mucosa,IM and dysplasia were evaluated for PTEN protein expressionby SABC immunohistochemistry. PTEN expression wascompared with tumor stage, lymph node metastasis, Lauren'sand WHO's histological classification of gastric carcinoma.Expression of VEGF was also detected in 60 cases of gastriccarcinoma and its correlation with PTEN was concerned.RESULTS: The positive rates of PTEN protein were 100 %(102/102), 98.5 %(65/66), 66.7 % (4/6) and 47.8 %(88/184)in normal mucosa, IM, dysplasia and carcinoma of the stomach,respectively. The positive rates in dysplasia and carcinomawere lower than in normal mucosa and IM (P<0.01).Advanced gastric cancers expressed less frequent PTEN thanearly gastric cancer (42.9 % v567.6 %, P<0.01). The positiverate of PTEN protein was lower in gastric cancer with thanwithout lymph node metastasis (40.3 % v563.3 %, P<0.01).PTEN was less expressed in diffuse-type than in intestinal-type gastric cancer (41.5 % v557.8 %,P<0.05). Signet ringcell carcinoma showed the expression of PTEN at the lowestlevel (25.0 %, 7/28); less than well and moderatelydifferentiated ones (P<0.01). Expression of PTEN was notcorrelated with expression of VEGF (P>0.05).CONCLUSION: Loss or reduced expression of PTEN proteinoccures commonly in tumorigenesis and progression of gastriccarcinoma. It is suggested that PTEN can be an objective markerfor pathologically biological behaviors of gastric carcinoma.

  7. Isolated fungal promoters and gene transcription terminators and methods of protein and chemical production in a fungus

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Ziyu; Lasure, Linda L; Magnuson, Jon K

    2014-05-27

    The present invention encompasses isolated gene regulatory elements and gene transcription terminators that are differentially expressed in a native fungus exhibiting a first morphology relative to the native fungus exhibiting a second morphology. The invention also encompasses a method of utilizing a fungus for protein or chemical production. A transformed fungus is produced by transforming a fungus with a recombinant polynucleotide molecule. The recombinant polynucleotide molecule contains an isolated polynucleotide sequence linked operably to another molecule comprising a coding region of a gene of interest. The gene regulatory element and gene transcription terminator may temporally and spatially regulate expression of particular genes for optimum production of compounds of interest in a transgenic fungus.

  8. Isolated fungal promoters and gene transcription terminators and methods of protein and chemical production in a fungus

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Ziyu; Lasure, Linda L; Magnuson, Jon K

    2014-05-27

    The present invention encompasses isolated gene regulatory elements and gene transcription terminators that are differentially expressed in a native fungus exhibiting a first morphology relative to the native fungus exhibiting a second morphology. The invention also encompasses a method of utilizing a fungus for protein or chemical production. A transformed fungus is produced by transforming a fungus with a recombinant polynucleotide molecule. The recombinant polynucleotide molecule contains an isolated polynucleotide sequence linked operably to another molecule comprising a coding region of a gene of interest. The gene regulatory element and gene transcription terminator may temporally and spatially regulate expression of particular genes for optimum production of compounds of interest in a transgenic fungus.

  9. Isolated Fungal Promoters and Gene Transcription Terminators and Methods of Protein and Chemical Production in a Fungus

    Science.gov (United States)

    Dai, Ziyu; Lasure, Linda L.; Magnuson, Jon K.

    2008-11-11

    The present invention encompasses isolated gene regulatory elements and gene transcription terminators that are differentially expressed in a native fungus exhibiting a first morphology relative to the native fungus exhibiting a second morphology. The invention also encompasses a method of utilizing a fungus for protein or chemical production. A transformed fungus is produced by transforming a fungus with a recombinant polynucleotide molecule. The recombinant polynucleotide molecule contains an isolated polynucleotide sequence linked operably to another molecule comprising a coding region of a gene of interest. The gene regulatory element and gene transcription terminator may temporally and spatially regulate expression of particular genes for optimum production of compounds of interest in a transgenic fungus.

  10. Effects of medium composition on the production of plasmid DNA vector potentially for human gene therapy

    Institute of Scientific and Technical Information of China (English)

    XU Zhi-nan; SHEN Wen-he; CHEN Hao; CEN Pei-lin

    2005-01-01

    Plasmid vector is increasingly applied to gene therapy or gene vaccine. The production of plasmid pCMV-AP3 for cancer gene therapy was conducted in a modified MBL medium using a recombinant E. coli BL21 system. The effects of different MMBL components on plasmid yield, cell mass and specific plasmid DNA productivity were evaluated on shake-flask scale. The results showed that glucose was the optimal carbon source. High plasmid yield (58.3 mg/L) was obtained when 5.0 g/L glucose was added to MMBL. Glycerol could be chosen as a complementary carbon source because of the highest specific plasmid productivity (37.9 mg DNA/g DCW). After tests of different levels of nitrogen source and inorganic phosphate, a modified MMBL medium was formulated for optimal plasmid production. Further study showed that the initial acetate addition (less than 4.0 g/L) in MMBL improved plasmid production significantly, although it inhibited cell growth. The results will be useful for large-scale plasmid production using recombinant E. coli system.

  11. Reducing the acrylamide content of processed potato products through germplasm improvement: opportunities, challenges and progress

    Science.gov (United States)

    Processed potato products, including french fries and potato chips, make a substantial contribution to total dietary acrylamide. Health safety concerns raised by acrylamide in food increase financial risks to the potato industry and have encouraged industry to take a proactive response toward acryla...

  12. Recent progress in supercritical fluid science for biofuel production from woody biomass

    Institute of Scientific and Technical Information of China (English)

    Shiro Saka

    2006-01-01

    Owing to an environment-friendly utilization of resources, increased attention has been focused on fuels and chemicals from biomass as an alternative to fossil resources. In addition, supercritical fluid technology has been considered to be an environmentally-benign treatment. Therefore, its technology was applied for a conversion of biomass to useful fuels and chemicals in order to mitigate environmental loading. For example, supercritical water treatment has demonstrated that lignocellulosics can be hydrolyzed to become lignin-derived products for useful aromatic chemicals and carbohydrate-derived products, such as polysaccharides,oligosaccharides and monosaccharides of glucose, mannose and xylose used for subsequent ethanol fermentation. If this treatment is prolonged, lignocellulosics were found to be converted to organic acids such as formic, acetic, glycolic and lactic acids which can be converted to methane for biofuel. When alcohols, such as methanol and ethanol, were used instead of water, some other useful products were achieved, and its liquefied products were found to have a potential for liquid biofuel. In this study, therefore, our research achievements in supercritical fluid science of woody biomass will be introduced for clean and green chemistry for a sustainable environment.

  13. Prolactin (PRL) and prolactin receptor (PRLR) genes and their role in poultry production traits.

    Science.gov (United States)

    Wilkanowska, Anna; Mazurowski, Artur; Mroczkowski, Sławomir; Kokoszyński, Dariusz

    2014-01-01

    Prolactin (PRL), secreted from the anterior pituitary, plays extensive roles in osmoregulation, corpus luteum formation, mammogenesis, lactogenesis, lactopoiesis, and production of crop milk. In birds, prolactin (PRL) is generally accepted as crucial to the onset and maintenance of broodiness. All the actions of prolactin (PRL) hormone are mediated by its receptor (PRLR), which plays an important role in the PRL signal transduction cascade. It has been well established that the PRL gene is closely associated to the onset and maintenance of broody behavior, and could be a genetic marker in breeding against broodiness in chickens. Meanwhile, the prolactin receptor (PRLR) gene is regarded as a candidate genetic marker for reproductive traits. PRLR is also an important regulator gene for cell growth and differentiation. The identified polymorphism of this gene is mainly viewed in terms of egg production traits. Due to different biological activities attributed to PRL and PRLR, they can be used as major candidate genes in molecular animal breeding programs. Characterization of PRL and PRLR genes helps to elucidate their roles in birds and provides insights into the regulatory mechanisms of PRL and PRLR expression conserved in birds and mammals.

  14. Polyhydroxyalkanoate production from sucrose by Cupriavidus necator strains harboring csc genes from Escherichia coli W.

    Science.gov (United States)

    Arikawa, Hisashi; Matsumoto, Keiji; Fujiki, Tetsuya

    2017-09-09

    Cupriavidus necator H16 is the most promising bacterium for industrial production of polyhydroxyalkanoates (PHAs) because of their remarkable ability to accumulate them in the cells. With genetic modifications, this bacterium can produce poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), which has better physical properties, as well as poly(3-hydroxybutyrate) (PHB) using plant oils and sugars as a carbon source. Considering production cost, sucrose is a very attractive raw material because it is inexpensive; however, this bacterium cannot assimilate sucrose. Here, we used the sucrose utilization (csc) genes of Escherichia coli W to generate C. necator strains that can assimilate sucrose. Especially, glucose-utilizing recombinant C. necator strains harboring the sucrose hydrolase gene (cscA) and sucrose permease gene (cscB) of E. coli W grew well on sucrose as a sole carbon source and accumulated PHB. In addition, strains introduced with a crotonyl-CoA reductase gene (ccr), ethylmalonyl-CoA decarboxylase gene (emd), and some other genetic modifications besides the csc genes and the glucose-utilizing mutations produced PHBHHx with a 3-hydroxyhexanoate (3HHx) content of maximum approximately 27 mol% from sucrose. Furthermore, when one of the PHBHHx-producing strains was cultured with sucrose solution in a fed-batch fermentation, PHBHHx with a 3HHx content of approximately 4 mol% was produced and reached 113 g/L for 65 h, which is approximately 1.5-fold higher than that produced using glucose solution.

  15. The dam replacing gene product enhances Neisseria gonorrhoeae FA1090 viability and biofilm formation.

    Science.gov (United States)

    Kwiatek, Agnieszka; Bacal, Pawel; Wasiluk, Adrian; Trybunko, Anastasiya; Adamczyk-Poplawska, Monika

    2014-01-01

    Many Neisseriaceae do not exhibit Dam methyltransferase activity and, instead of the dam gene, possess drg (dam replacing gene) inserted in the leuS/dam locus. The drg locus in Neisseria gonorrhoeae FA1090 has a lower GC-pairs content (40.5%) compared to the whole genome of N. gonorrhoeae FA1090 (52%). The gonococcal drg gene encodes a DNA endonuclease Drg, with GmeATC specificity. Disruption of drg or insertion of the dam gene in gonococcal genome changes the level of expression of genes as shown by transcriptome analysis. For the drg-deficient N. gonorrhoeae mutant, a total of 195 (8.94% of the total gene pool) genes exhibited an altered expression compared to the wt strain by at least 1.5 fold. In dam-expressing N. gonorrhoeae mutant, the expression of 240 genes (11% of total genes) was deregulated. Most of these deregulated genes were involved in translation, DNA repair, membrane biogenesis and energy production as shown by cluster of orthologous group analysis. In vivo, the inactivation of drg gene causes the decrease of the number of live neisserial cells and long lag phase of growth. The insertion of dam gene instead of drg locus restores cell viability. We have also shown that presence of the drg gene product is important for N. gonorrhoeae FA1090 in adhesion, including human epithelial cells, and biofilm formation. Biofilm produced by drg-deficient strain is formed by more dispersed cells, compared to this one formed by parental strain as shown by scanning electron and confocal microscopy. Also adherence assays show a significantly smaller biomass of formed biofilm (OD570 = 0.242 ± 0.038) for drg-deficient strain, compared to wild-type strain (OD570 = 0.378 ± 0.057). Dam-expressing gonococcal cells produce slightly weaker biofilm with cells embedded in an extracellular matrix. This strain has also a five times reduced ability for adhesion to human epithelial cells. In this context, the presence of Drg is more advantageous for N. gonorrhoeae biology than

  16. Epigenetic modification regulates both expression of tumor-associated genes and cell cycle progressing in human colon cancer cell lines:Colo-320 and SW1116

    Institute of Scientific and Technical Information of China (English)

    Jing Yuan FANG; Ying Xuan CHEN; Juan LU; Rong LU; Li YANG; Hong Yin ZHU; Wei Qi GU; Lun Gen LU

    2004-01-01

    The aim of this study is to assess the effects of DNA methylation and histone acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established human colon cancer cell lines: Colo-320 and SW1116. Treatments with 5-aza-2'-deoxycytidine (5-aza-dC) and trichostatin A, alone or in combination, were applied respectively. The methylation status of the CDKN2A promoter was determined by methylation-specific PCR, and the acetylated status of the histones associated with the p21wAF1 and CDKN2A genes was examined by chromatin immunoprecipitation. The expression of the CDKN2A, p21WAF1, p53, p73, APC, c-myc, c-Ki-ras and survivin genes was detected by real-time RT-PCR and RT-PCR. The cell cycle profile was established by flow cytometry.We found that along with the demethylation of the CDKN2A gene promoter in both cell lines induced by 5-aza-dC alone or in combination with TSA, the expression of both CDKN2A and APC genes increased. The treatment of TSA or sodium butyrate up-regulated the transcription of p21 WAF1 significantly by inducing the acetylation of histones H4 and H3, but failed to alter the acetylation level of CDKN2A-associated histones. No changes in transcription of p53, p73,c-myc, c-Ki-ras and survivin genes were observed. In addition, TSA or sodium butyrate was shown to arrest cells at the G1 phase. However, 5-aza-dC was not able to affect the cell cycle progression. In conclusion, regulation by epigenetic modification of the transcription of tumor-associated genes and the cell cycle progression in both human colon cancer cell lines Colo-320 and SW1116 is gene-specific.

  17. Ethanol production by Escherichia coli strains co-expressing Zymomonas PDC and ADH genes

    Energy Technology Data Exchange (ETDEWEB)

    Ingram, Lonnie O. (Gainesville, FL); Conway, Tyrrell (Lincoln, NE); Alterthum, Flavio (Gainesville, FL)

    1991-01-01

    A novel operon and plasmids comprising genes which code for the alcohol dehydrogenase and pyruvate decarboxylase activities of Zymomonas mobilis are described. Also disclosed are methods for increasing the growth of microorganisms or eukaryotic cells and methods for reducing the accumulation of undesirable metabolic products in the growth medium of microorganisms or cells.

  18. Assembly of Highly Standardized Gene Fragments for High-Level Production of Porphyrins in E. coli

    DEFF Research Database (Denmark)

    Nielsen, Morten Thrane; Madsen, Karina Marie; Seppala, Susanna;

    2015-01-01

    to formulate a molecular cloning pipeline and iteratively assemble and optimize a six-gene pathway for protoporphyrin IX synthesis in Escherichia coli. State of the art production levels were achieved through two simple cycles of engineering and screening. The principles defined here are generally applicable...

  19. ALOX5 gene variants affect eicosanoid production and response to fish oil supplementation

    Science.gov (United States)

    The objective of this study was to determine whether 5-lipoxygenase (ALOX5) gene variants associated with cardiovascular disease affect eicosanoid production by monocytes. The study was a randomized, double-masked, parallel intervention trial with fish oil (5.0 g of fish oil daily, containing 2.0 g ...

  20. Functional analysis of Photosystem I light-harvesting complexes (Lhca) gene products of Chlamydomonas reinhardtii

    NARCIS (Netherlands)

    Mozzo, Milena; Mantelli, Manuela; Passarini, Francesca; Caffarri, Stefano; Croce, Roberta; Bassi, Roberto

    2010-01-01

    The outer antenna system of Chlamydomonas reinhardtii Photosystem I is composed of nine gene products, but due to difficulty in purification their individual properties are not known. In this work, the functional properties of the nine Lhca antennas of Chlamydomonas, have been investigated upon expr

  1. A positive feedback-based gene circuit to increase the production of a membrane protein

    Directory of Open Access Journals (Sweden)

    Gennis Robert B

    2010-05-01

    Full Text Available Abstract Background Membrane proteins are an important class of proteins, playing a key role in many biological processes, and are a promising target in pharmaceutical development. However, membrane proteins are often difficult to produce in large quantities for the purpose of crystallographic or biochemical analyses. Results In this paper, we demonstrate that synthetic gene circuits designed specifically to overexpress certain genes can be applied to manipulate the expression kinetics of a model membrane protein, cytochrome bd quinol oxidase in E. coli, resulting in increased expression rates. The synthetic circuit involved is an engineered, autoinducer-independent variant of the lux operon activator LuxR from V. fischeri in an autoregulatory, positive feedback configuration. Conclusions Our proof-of-concept experiments indicate a statistically significant increase in the rate of production of the bd oxidase membrane protein. Synthetic gene networks provide a feasible solution for the problem of membrane protein production.

  2. Polymorphic genes of detoxification and mitochondrial enzymes and risk for progressive supranuclear palsy: a case control study

    Directory of Open Access Journals (Sweden)

    Potts Lisa F

    2012-03-01

    Full Text Available Abstract Background There are no known causes for progressive supranuclear palsy (PSP. The microtubule associated protein tau (MAPT H1 haplotype is the major genetic factor associated with risk of PSP, with both oxidative stress and mitochondrial dysfunction also implicated. We investigated whether specific single nucleotide polymorphisms (SNPs in genes encoding enzymes of xenobiotic detoxification, mitochondrial functioning, or oxidative stress response, including debrisoquine 4-hydroxylase, paraoxonase 1 and 2, N-acetyltransferase 1 and 2 (NAT2, superoxide dismutase 1 and 2, and PTEN-induced putative kinase are associated with PSP. Methods DNA from 553 autopsy-confirmed Caucasian PSP cases (266 females, 279 males; age at onset 68 ± 8 years; age at death 75 ± 8 from the Society for PSP Brain Bank and 425 clinical control samples (197 females, 226 males; age at draw 72 ± 11 years from healthy volunteers were genotyped using Taqman PCR and the SequenomiPLEX Gold assay. Results The proportion of NAT2 rapid acetylators compared to intermediate and slow acetylators was larger in cases than in controls (OR = 1.82, p MAPT (p Conclusions Our results show that NAT2 rapid acetylator phenotype is associated with PSP, suggesting that NAT2 may be responsible for activation of a xenobiotic whose metabolite is neurotoxic. Although our results need to be further confirmed in an independent sample, NAT2 acetylation status should be considered in future genetic and epidemiological studies of PSP.

  3. Interleukin-6 Gene Promoter-572 C Allele May Play a Role in Rate of Disease Progression in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Judith M. Greer

    2012-10-01

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. One important mediator of immune responses and inflammation is interleukin-6 (IL-6. Previously, elevated levels of IL-6 in mononuclear cells in blood and in brain tissue from MS patients have been reported. Various polymorphisms in the promoter region of the IL6 gene have also been linked with IL-6 protein levels. In MS, several small studies have investigated whether two IL6 promoter polymorphisms (−597 G>A and −174 G>C correlate with MS susceptibility, but with varying results. In the present study, we analyzed these polymorphisms, together with an additional polymorphism (−572 G>C in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different −597 or −174 IL6 promoter alleles or genotypes. There was a slight reduction in the percentage of individuals with MS who carried a C allele at position −572, although this was not significant after correction for multiple comparisons. Interestingly, however, the −572 C allele showed a significant correlation with the MS severity score, suggesting a possible role in disease progression.

  4. Progress on 241Am Production for Use in Radioisotope Power Systems

    Science.gov (United States)

    Baker, S. R.; Bell, K. J.; Brown, J.; Carrigan, C.; Carrott, M. J.; Gregson, C.; Clough, M.; Maher, C. J.; Mason, C.; Rhodes, C. J.; Rice, T. G.; Sarsfield, M. J.; Stephenson, K.; Taylor, R. J.; Tinsley, T. P.; Woodhead, D. A.; Wiss, T.

    2014-08-01

    Electrical power sources used in outer planet missions are a key enabling technology for data acquisition and communications. Power sources generate electricity from the thermal energy from alpha decay of the radioisotope 238Pu via thermo-electric conversion. Production of 238Pu requires specialist facilities including a nuclear reactor and reprocessing plants that are expensive to build and operate, so naturally, a more economical alternative is attractive to the industry. Within Europe 241Am is a feasible alternative to 238Pu that can provide a heat source for radioisotope thermoelectric generators (RTGs) and radioisotope heating units (RHUs). As a daughter product of 241Pu decay, 241Am is present at 1000s kg levels within the UK civil plutonium stockpile.A chemical separation process is required to extract the 241Am in a pure form and this paper describes such a process, successfully developed to the proof of concept stage.

  5. PROGRESS IN CATALYST AND PROCESS DEVELOPMENT FOR LOW SULFUR AND LOW AROMATICS DIESEL PRODUCTION

    Institute of Scientific and Technical Information of China (English)

    ZHOUYong; HANChong-ren

    2003-01-01

    The article includes three parts:①The development and performance of FH-DS catalyst for deep and ultra -deep distillate HDS;②The single stage HDS/HDA hydrotreating process for the production of low sulfur and low aromatics diesels from straight run and coker AGO by using highly active base metal catalyst at moderate pressure;③A two-stage aromatics saturation system utilizing noble metal catalyst in the second stage developed for production of low sulfur and low aromatics diesel from LCO.FDA catalyst developed by FRIPP has high activity for aromatics saturation together with high tolerance for sulfur and nitrogen in the feed.The process is effective in reducing density and increasing cetane number.

  6. Characterization of TMI-type wastes and solid products. Quarterly progress report, April-September 1981

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, A.J.

    1981-12-01

    A research program is under way to systematically characterize the type of radwastes which may be generated in cleanup procedures following off-normal reactor operations. Specifically, the program is presently investigating how the properties of wastes containing ion-exchange media may be modified by heavy doses of irradiation from sorbed radionuclides. Special effort is being devoted toward quantifying the effects of factors such as radiation dose rate, chemical loading on the ion exchangers, moisture content and composition of external media, etc., which may inflence the relation between laboratory test results and field performance. Initial irradation damage measurements have been carried out on organic cation resin IRN-77 in both hydrogen and sodium forms. Gamma irradiation of both of these materials produces water soluble acidic decomposition products; the acid product yields depend on the chemical loading and are lower for the sodium form.

  7. Progress in live food production and use in fish and shellfish hatcheries

    OpenAIRE

    Sorgeloos, P

    1998-01-01

    Different species of microalgae, the rotifer, Brachionus spp., and the brine shrimp, Artemia spp., are essential live food in the farming of several species of molluscs (e.g. oyster, clam, scallop), crustaceans (e.g. marine shrimp, freshwater prawn, crabs) and fish (e.g. bass, bream, grouper, turbot, flounder, halibut, ayu). A brief overview is given of the latest developments in their production and use in industrial hatcheries.

  8. [Research progress of chemistry and anti-cancer activities of natural products from Chinese Garcinia plants].

    Science.gov (United States)

    Fu, Wen-Wei; Tan, Hong-Sheng; Xu, Hong-Xi

    2014-02-01

    Garcinia plants are one of the rich sources of natural xanthones and benzophenones which have attracted a great deal of attention from the scientists in the fields of chemistry and pharmacology. Recently, many structurally unique constituents with various bioactivities, especially anti-tumor activity, have been isolated from Garcinia plants. This concise review focused on the anti-cancer activity natural products isolated from Chinese Garcinia plants, and the research finding by authors and collaborators over the past several years were cited.

  9. Hematological- and Neurological-Expressed Sequence 1 Gene Products in Progenitor Cells during Newt Retinal Development

    Directory of Open Access Journals (Sweden)

    Tatsushi Goto

    2012-01-01

    Full Text Available Urodele amphibians such as Japanese common newts have a remarkable ability to regenerate their injured neural retina, even as adults. We found that hematological- and neurological-expressed sequence 1 (Hn1 gene was induced in depigmented retinal pigment epithelial (RPE cells, and its expression was maintained at later stages of newt retinal regeneration. In this study, we investigated the distribution of the HN1 protein, the product of the Hn1 gene, in the developing retinas. Our immunohistochemical analyses suggested that the HN1 protein was highly expressed in an immature retina, and the subcellular localization changed during this retinogenesis as observed in newt retinal regeneration. We also found that the expression of Hn1 gene was not induced in mouse after retinal removal. Our results showed that Hn1 gene can be useful for detection of undifferentiated and dedifferentiated cells during both newt retinal development and regeneration.

  10. Recent Progress in Liposome Production, Relevance to Drug Delivery and Nanomedicine.

    Science.gov (United States)

    Koynova, Rumiana; Tenchov, Boris

    2015-01-01

    From their discovery half a century ago and the subsequent appreciation of their clinical utility, liposomes currently hold a recognized position in the mainstream of drug delivery systems. Conventional techniques for liposome preparation and size reduction are simple to implement and do not require sophisticated equipment. However, most of them are not easy to scale-up for industrial liposome production. With several liposomal formulations already on the market, and more in final clinical trials, the industrial scale production of liposomes has become reality, and so the range of liposome preparation methods has been extended by a number of techniques which are increasingly attractive, such as microfluidic hydrodynamic focusing, supercritical fluid processing, freeze-drying and spray-drying. Some of these new techniques generally represent advancements of the conventional methods allowing for scale-up, better reproducibility and process control. This review summarizes patents in the last decade offering new techniques for production of liposomes as related to their application in drug delivery.

  11. Increasing the biomass production of short rotation coppice forests. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Steinbeck, K.; Brown, C.L.

    1978-03-01

    Progress is reported in research to increase biomass yields from coppice forests by admixing the nitrogen fixing tree Alnus glutinosa to plantations of Plantanus occidentalis and Liquidambar styraciflua. Plantations to compare growth rates of pure and mixed plots of the three species have been established on two sites in Georgia. Locations were selected on the basis of physiographic province (Piedmont and Coastal Plain) on soils which probably will be available for short rotation forestry. Propagation techniques for mass-cloning Platanus occidentalis using single buds and internodes of dormant or active twigs from young trees were developed. Tissue culture procedures were used to induce bud and root formation in callus cultures of Robinia and Gleditsia. Research dealing with fluctuations in starch and sugar levels in coppiced root systems of sycamore during the winter is reported. Total available carbohydrates ranged from 15 to 26 percent of root dry weight and starch to sugar conversion was detected. However, more starch disappeared than could be accounted for by the concomitant rise of sugar levels. There were some differences between annually coppiced root systems and those cut every two years. (JGB)

  12. The Use of Alternative Raw Material in Production of Pastry Products as a Progressive Direction in Creating the Products of High Biological Value

    Directory of Open Access Journals (Sweden)

    Janа Bachinska

    2017-02-01

    Full Text Available This paper examines the impact of the use of alternative vegetable raw materials in the manufacture of pastry products with high biological value; it presents the results of evaluation of commodity of the developed products and compares them with the main samples presented in Kharkiv trade network. The feasibility of using a mixture of fiber and pumpkin seeds in the technology of pastry production to extend the range of confectionery products of high biological value and products with reduced calories has been proved. Adding the mixture of fiber and pumpkin seeds to biscuits and cakes positively affected the chemical composition of the ready-made product, saturating it with useful and necessary to human body mineral elements, vitamins, dietary fiber.

  13. The Gene bldA, a regulator of morphological differentiation and antibiotic production in streptomyces.

    Science.gov (United States)

    Hackl, Stefanie; Bechthold, Andreas

    2015-07-01

    Streptomyces species are well known for their particular features of morphological differentiation. On solid agar, a mold-like aerial mycelium is formed and spores are produced, in which the bld genes play a crucial role. In S. coelicolor, mutations in one specific bld gene called bldA led to a "naked" phenotype lacking aerial hyphae and spores. This peculiar behavior became a major interest for scientific research in the past and it was revealed that bldA is coding for a unique tRNA able to translate a UUA codon into the amino acid leucine. UUA codons are a very rare property of G + C-rich Streptomyces genomes. The impact of bldA on morphology can in parts be attributed to the regulatory effect of bldA on the translational level, because TTA-containing genes can only be translated into their corresponding protein in the presence of a fully functioning bldA gene. In addition to the visible effect of bldA expression on the phenotype of S. coelicolor, bldA mutants were also deficient in antibiotic production. This led to the assumption that the role of bldA must exceed translational control. Many TTA-containing genes are coding for transcriptional regulators which are activating or repressing the transcription of many more genes. Proteomics and transcriptomics are two powerful methods for identifying bldA target genes and it was possible to assign also post-translational regulation to bldA. This review wants to give a short overview on the importance of bldA as a regulator of morphological differentiation and antibiotic production by switching on "silent" gene clusters in Streptomyces.

  14. Aerobic conditions increase isoprenoid biosynthesis pathway gene expression levels for carotenoid production in Enterococcus gilvus.

    Science.gov (United States)

    Hagi, Tatsuro; Kobayashi, Miho; Nomura, Masaru

    2015-06-01

    Some lactic acid bacteria that harbour carotenoid biosynthesis genes (crtNM) can produce carotenoids. Although aerobic conditions can increase carotenoid production and crtNM expression levels, their effects on the pathways that synthesize carotenoid precursors such as mevalonate and isoprene are not completely understood. In this study, we investigated whether aerobic conditions affected gene expression levels involved in the isoprenoid biosynthesis pathway that includes the mevalonate and isoprene biosynthesis pathways in Enterococcus gilvus using real-time quantitative reverse transcription PCR. NADH oxidase (nox) and superoxide dismutase (sod) gene expression levels were investigated as controls for aerobic conditions. The expression levels of nox and sod under aerobic conditions were 7.2- and 8.0-fold higher, respectively, than those under anaerobic conditions. Aerobic conditions concomitantly increased the expression levels of crtNM carotenoid biosynthesis genes. HMG-CoA synthase gene expression levels in the mevalonate pathway were only slightly increased under aerobic conditions, whereas the expression levels of HMG-CoA reductase and five other genes in the isoprene biosynthesis pathways were 1.2-2.3-fold higher than those under anaerobic conditions. These results demonstrated that aerobic conditions could increase the expression levels of genes involved in the isoprenoid biosynthesis pathway via mevalonate in E. gilvus.

  15. Increasing cocoa butter-like lipid production of Saccharomyces cerevisiae by expression of selected cocoa genes

    DEFF Research Database (Denmark)

    Wei, Yongjun; Gossing, Michael; Bergenholm, David

    2017-01-01

    Cocoa butter (CB) extracted from cocoa beans mainly consists of three different kinds of triacylglycerols (TAGs), 1,3-dipalmitoyl-2-oleoyl-glycerol (POP, C16:0-C18:1-C16:0), 1-palmitoyl-3-stearoyl-2-oleoyl-glycerol(POS,C16:0C18:1-C18:0) and 1,3-distearoyl-2-oleoyl-glycerol (SOS, C18:0-C18:1-C18....... TAG synthesis is mainly catalyzed by three enzymes: glycerol-3-phosphate acyltransferase (GPAT), lysophospholipid acyltransferase (LPAT) and diacylglycerol acyltransferase (DGAT). In order to produce CBL in S. cerevisiae, we selected six cocoa genes encoding GPAT, LPAT and DGAT potentially responsible...... for CB biosynthesis from the cocoa genome using a phylogenetic analysis approach. By expressing the selected cocoa genes in S. cerevisiae, we successfully increased total fatty acid production, TAG production and CBL production in some S. cerevisiae strains. The relative CBL content in three yeast...

  16. Effect of Different Carbon Source on Expression of Carotenogenic Genes and Astaxanthin Production in Xanthophyllomyces dendrorhous

    Directory of Open Access Journals (Sweden)

    Wei Wu

    2013-10-01

    Full Text Available The present research gives an insight into astaxanthin production, as well as transcription differences of four key carotenogenic genes, in Xanthophyllomyces dendrorhous when cultured with various carbon sources and soybean oil as co-substrates. Glucose was found to be the carbon source with best culture growth and astaxanthin production and the addition of 2% (v/v soybean oil resulted in even higher astaxanthin producing. In addition, four carotenogenic genes encoding geranylgeranyl diphosphate synthase (crtE, phytoene desaturase (crtl, phytoene synthase lycopene cyclase(crtYB, and astaxanthin synthetase (ast, respectively, were demonstrated to be associated with different transcription levels under various substrates. The present study suggests the effectiveness of manipulating the metabolic regulation by using different carbon sources, in order to improve the production of astaxanthin.

  17. Correlation of gene expression and protein production rate - a system wide study

    Directory of Open Access Journals (Sweden)

    Arvas Mikko

    2011-12-01

    Full Text Available Abstract Background Growth rate is a major determinant of intracellular function. However its effects can only be properly dissected with technically demanding chemostat cultivations in which it can be controlled. Recent work on Saccharomyces cerevisiae chemostat cultivations provided the first analysis on genome wide effects of growth rate. In this work we study the filamentous fungus Trichoderma reesei (Hypocrea jecorina that is an industrial protein production host known for its exceptional protein secretion capability. Interestingly, it exhibits a low growth rate protein production phenotype. Results We have used transcriptomics and proteomics to study the effect of growth rate and cell density on protein production in chemostat cultivations of T. reesei. Use of chemostat allowed control of growth rate and exact estimation of the extracellular specific protein production rate (SPPR. We find that major biosynthetic activities are all negatively correlated with SPPR. We also find that expression of many genes of secreted proteins and secondary metabolism, as well as various lineage specific, mostly unknown genes are positively correlated with SPPR. Finally, we enumerate possible regulators and regulatory mechanisms, arising from the data, for this response. Conclusions Based on these results it appears that in low growth rate protein production energy is very efficiently used primarly for protein production. Also, we propose that flux through early glycolysis or the TCA cycle is a more fundamental determining factor than growth rate for low growth rate protein production and we propose a novel eukaryotic response to this i.e. the lineage specific response (LSR.

  18. Commercialization of bacterial cell factories for the sustainable production of polyhydroxyalkanoate thermoplastics: progress and prospects.

    Science.gov (United States)

    Kumar, Abhishek; Srivastava, Janmejai K; Mallick, Nirupama; Singh, Akhilesh K

    2015-01-01

    Ubiquitous conventional plastics, generally manufactured from finite, nonsustainable fossil fuels are non-biodegradable wonder entities but their ill effect on Mother Nature has subsequently raised major environmental concerns like their safe disposal, solid waste management and several potential hazards. Such concerns have fuelled initiatives for research globally towards development of sustainable and eco-friendly bioplastics. The new generation of plastics called 'bioplastics' are polymers of long chain of repeating monomer units that are classified as photodegradable, semi-biodegradable, chemically synthesized and polyhydroxyalkanoates (PHAs). The commonly emerged novel bioplastics are polyesters of hydroxyalkanoates (HAs) called PHAs, which are lipoidic storage materials found in the cytosol of vast and diverse forms of bacteria. Among 150 different PHAs known so far, poly- 3-hydroxybutyrate is the most common and comprehensively characterized PHA. Interestingly, PHAs are only completely biodegradable plastics with material properties comparable to conventional plastics that can be achieved by regulating the co-monomers incorporation into PHAs backbone. PHA bioplastics are exploited in the form of user-friendly goods viz. films, absorbable sutures, bone plates, drug carriers, etc. Besides advantages, such useful entity(s) has major shortcomings as well like high production cost compared to conventional plastics. Precisely, in PHAs production, about fifty percent of the overall price is due to the carbon substrates. Consequently, exploring novel cost-effective substrates is a major compulsion for successful commercialization of this bioplastic, which is anticipated to reduce the cost of production as a result of advancing and intensifying research work. This review presents an insight and patent developments in the field of PHAs bioplastics.

  19. Recent Progress on Enyne Metathesis: Its Application to Syntheses of Natural Products and Related Compounds

    Directory of Open Access Journals (Sweden)

    Miwako Mori

    2010-03-01

    Full Text Available Olefin metathesis using ruthenium carbene complexes is a useful method in synthetic organic chemistry. Enyne metathesis is also catalyzed by these complexes and various carbo- and heterocycles could be synthesized from the corresponding enynes. Dienyne metathesis, cross enyne metathesis and ring-opening enyne metathesis have been further developed. Various complicated compounds, such as the natural products and the related biologically active substances, could be synthesized using these metatheses reactions. Skeletal reorganization using the transition metals and metallotropic rearrangement are also discussed.

  20. Liquid fuels production from biomass. Progress report No. 5, July 1-September 30, 1978

    Energy Technology Data Exchange (ETDEWEB)

    Sanderson, J.E.; Wise, D.L.

    1978-01-01

    The current program to convert biomass into liquid hydrocarbon fuels is an extension of the previous program to ferment marine algae to acetic acid. In that study, it was found that marine algae could be converted to higher aliphatic organic acids and that these acids could be readily removed from the fermentation both by membrane or liquid-liquid extraction. It was then proposed to convert these higher organic acids to aliphatic hydrocarbons via Kolbe Electrolysis, which may be used as a diesel fuel. The specific goals for the current program are: (1) Establish conditions under which substrates other than marine algae may be converted in good yield to organic acids. The primary task in this regard is methane suppression. (2) Modify the current 300 liter fixed packed bed batch fermenter to operate in a continuous mode. (3) Change from membrane extraction of organic acids to liquid-liquid extraction. (4) Optimize the energy balance of the electrolytic oxidation process. The primary task in this regard is to reduce the working potential required for the electrolysis while maintaining an adequate current density. (5) Scale the entire process up to match the output of the 300 liter fermenter. The accomplishments in this program are on schedule. Substantial progress has been made on the problem of methane suppression through the use of sulfide addition and the identification of bromoethane-sulfonic acid as a specific inhibitor of methanogenesis. A conceptual design of a continuously fed fixed packed bed fermenter is presented. Experimental results show that the electrolysis of organic acids produced by fermentation to liquid hydrocarbon fuels already have a favorable energy balance of 6/1 based on the applied potential and over 10/1 based on the working potential.

  1. Low VOC drying of lumber and wood panel products. Progress report No. 7

    Energy Technology Data Exchange (ETDEWEB)

    Hui Yan; Hooda, Usha; Banerjee, Sujit [and others

    1998-03-01

    Green pine blocks (2x1x 1) were dried to different moisture levels at 120 degrees C. They were immersed in D{sub 2}O (greater than 99% isotopic Content) for different periods at room temperature, and were then cut in halves. One piece from each set was then wrapped in plastic, and microwaved at 110 W, for 30 minutes, with the field being cycled to keep the wood surface at 90-100 degrees C. Fibers taken from just inside the wet surface from five regions along the length of the piece were then analysed by mass spectrometry with a direct insertion probe. The m/e profiles of the three isotopic forms of water, namely H{sub 2}O, HOD, and D{sub 2}O, remained unchanged as the wood was heated inside the spectrometer, indicating that they were bound equally strongly to the wood. The water released from the green wood had the same isotopic composition regardless of whether or not the wood was microwaved (Table 1), indicating that the exchangeable protons in wood were not affected by microwaving. However, as the wood progressively dried, the water released from the microwaved wood was of lower isotopic content, which means that microwaving increases access of the exchangeable protons in wood tissue to water. The only exchangeable protons in dried wood are those sited on hydroxyl groups, and the difference in isotopic exchange is the greatest for dried wood. This must mean that as wood dries, internal hydrogen bonding restricts access of D{sub 2}O to the hydroxyl protons. Presumably the energy transferred to water upon microwaving is sufficient to at least partially overcome this barrier. The effect is akin to the hysteresis that occurs for moisture sorption to green and dried wood. Similar isotope exchange work with D{sub 2}O has been previously conducted to determine the accessibility of cellulose to water.

  2. Production of 2-ketoisocaproate with Corynebacterium glutamicum strains devoid of plasmids and heterologous genes.

    Science.gov (United States)

    Vogt, Michael; Haas, Sabine; Polen, Tino; van Ooyen, Jan; Bott, Michael

    2015-03-01

    2-Ketoisocaproate (KIC), the last intermediate in l-leucine biosynthesis, has various medical and industrial applications. After deletion of the ilvE gene for transaminase B in l-leucine production strains of Corynebacterium glutamicum, KIC became the major product, however, the strains were auxotrophic for l-isoleucine. To avoid auxotrophy, reduction of IlvE activity by exchanging the ATG start codon of ilvE by GTG was tested instead of an ilvE deletion. The resulting strains were indeed able to grow in glucose minimal medium without amino acid supplementation, but at the cost of lowered growth rates and KIC production parameters. The best production performance was obtained with strain MV-KICF1, which carried besides the ilvE start codon exchange three copies of a gene for a feedback-resistant 2-isopropylmalate synthase, one copy of a gene for a feedback-resistant acetohydroxyacid synthase and deletions of ltbR and iolR encoding transcriptional regulators. In the presence of 1 mM l-isoleucine, MV-KICF1 accumulated 47 mM KIC (6.1 g l(-1)) with a yield of 0.20 mol/mol glucose and a volumetric productivity of 1.41 mmol KIC l(-1)  h(-1). Since MV-KICF1 is plasmid free and lacks heterologous genes, it is an interesting strain for industrial application and as platform for the production of KIC-derived compounds, such as 3-methyl-1-butanol.

  3. Increase of Clavulanic acid production by using recombinant Streptomyces clavuligerus strain including claR gene

    Directory of Open Access Journals (Sweden)

    Maryam Kay

    2014-07-01

    Full Text Available   Introduction : Clavulanic acid is a major β-lactam antibiotic which is produced by Streptomyces clavuligerus. Clavulanic acid is used in combination of strong but sensitive to β-lactamase antibiotics. The claR gene has an important role in regulation of clavulanic acid production and is needed for the expression of the genes in final step of clavulanic acid biosynthesis.   Materials and methods: The recombinant construct pMTclaR which contains claR gene is obtained from Isfahan University and plasmid extraction was done from Streptomyces lividans for next steps. The Streptomyces clavuligerus protoplast was prepared and transformation was done by using polyethylene glycol. Transformation was confirmed by plasmid extraction and PCR. Finally, bioassay method was used to survey the effect of extra copy of claR on clavulanic acid production .   Results : The typical chalky white colony of Streptomyces clavuligerus was seen on GYME plates containing thiostrepton antibiotic. Plasmid extraction was initially carried out. Furthermore, PCR reaction was done by claR specific primers and the 1334 bp band which was belonging to claR was detected. Finally, the bioassay was done and the diameters of zone of inhibition in control and sample were compared. The results of the bioassay show that amplification of the claR gene in multicopy plasmids resulted in a 2.5 fold increase in clavulanic acid production .   Discussion and conclusion : In this study the 3.3 fold increase in clavulanic acid production was obtained by using an expression vector containing claR. According to the clinical use of clavulanic acid, production of bacterial strains which are able to produce high level of antibiotic can help significantly in customization of antibiotic production.

  4. Research Progress of Meat Product with Low Nitrite%低硝肉制品研究进展

    Institute of Scientific and Technical Information of China (English)

    孙迪; 张志国

    2016-01-01

    Nitrite is a common kind of food additive.In meat production,nitrite is responsible for the development of cured color,flavor and texture of meat products.More importantly,nitrite acts as a strong antimicrobial agent to control Clostridium botulinum outgrowth.But nitrite is responsible for the issues concerning the safety of using nitrite for cured meat,which include chemical toxicity and formation of N-nitrosamines.Therefore,research on the problems of nitrite substitute is urgent. Summarize the important role of nitrite in meat products and safety problems;also introduce the research progress of low-nitrite meat product,especially the research progress of antibacterial activity of nitrite,and the development prospect of low-nitrite meat product.%亚硝酸盐是一种常用的食品添加剂,在肉制品加工中,亚硝酸盐具有发色、呈味及改善肉制品质构的作用,更为重要的是对肉毒梭状芽孢杆菌有抑制作用。但亚硝酸盐性质活泼,添加过量可引起中毒,同时又能与胺类物质生成强致癌物亚硝胺。因此,亚硝酸盐替代物的研究问题亟待解决。文章总结了亚硝酸盐在肉制品中的重要作用及其带来的安全性问题,同时介绍了低硝肉制品的研究进展,尤其是亚硝酸盐抑菌作用的研究进展,还对低硝肉制品的发展前景做了展望。

  5. VIIRS Reflective Solar Bands Calibration Progress and Its Impact on Ocean Color Products

    Directory of Open Access Journals (Sweden)

    Junqiang Sun

    2016-02-01

    Full Text Available The radiometric calibration for the reflective solar bands (RSB of the Visible Infrared Imaging Radiometer Suite (VIIRS on board the Suomi National Polar-orbiting Partnership (SNPP platform has reached a mature stage after four years since its launch. The characterization of the vignetting effect of the attenuation screens, the bidirectional reflectance factor of the solar diffuser, the degradation performance of the solar diffuser, and the calibration coefficient of the RSB have all been made robust. Additional investigations into the time-dependent out-of-band relative spectral response and the solar diffuser degradation non-uniformity effect have led to newer insights. In particular, it has been demonstrated that the solar diffuser (SD degradation non-uniformity effect induces long-term bias in the SD-calibration result. A mitigation approach, the so-called Hybrid Method, incorporating lunar-based calibration results, successfully restores the calibration to achieve ~0.2% level accuracy. The successfully calibrated RSB data record significantly impacts the ocean color products, whose stringent requirements are especially sensitive to calibration accuracy, and helps the ocean color products to reach maturity.

  6. Technology progress of EO production%环氧乙烷生产技术进展

    Institute of Scientific and Technical Information of China (English)

    王海蔷; 刘昱

    2012-01-01

    EO is able to derive many kinds of fine chemicals.such as:glycol,non-ionic surfactant,etha nol amino,glycol ether amine and so on,and can be extended to produce synthetic detergent,emulsifi-er,antifreeze agent, plasticizer, lubricants, pesticides, fumigants, Its application field is extremely extensive. This paper introduced EO production technology development, put forward the development proposal of EO in our country,such as developing large-scale reactor,expanding the development and application of its down-stream products.%环氧乙烷能够衍生出乙二醇、非离子表面活性剂、乙醇胺、乙二醇醚等多种精细化工产品,进而可以延伸生产合成洗涤剂、乳化剂、抗冻剂、增塑剂、润滑剂、杀虫剂、熏蒸剂等五千余种产品,应用领域极其广泛.作者对国内外环氧乙烷生产技术发展现状进行了分析,并提出了我国环氧乙烷的发展建议,即开发大型反应器,加大其下游产品的开发与应用等.

  7. Biological production of organic solvents from cellulosic wastes. Progress report, September 15, 1976--September 14, 1977

    Energy Technology Data Exchange (ETDEWEB)

    Pye, E.K.; Humphrey, A.E.; Forro, J.R.

    1977-06-01

    The objectives of this project are to optimize a modular process to convert cellulosic wastes to butanol and other oil-sparing chemicals. Research to date has focused on developing analytical methods, establishing a good data base and improving cellulase yields. Reliable assay methods for the Thermoactinomyces cellulase complex have been developed, measuring glucose and reducing sugar from filter paper and Avicel for total cellulase activity, viscosity change with carboxymethyl cellulose for the endoglucanase activity, and fluorescence change with methylumbelliferyl-..beta..-D-glucopyranoside for ..beta..-glucosidase activity. Isoelectric focusing within the range pH 3.5 to 6.0 has proved to be a quick and useful means of determining effective cellulase complex composition. About 10 different proteins are present in the fermentation broth. Detailed procedures for uv and near uv plus 8-methoxy-psoralen mutagenesis have been developed, and four mutants having 50% greater activity than the parent YX strain have been isolated. Cellulase production by Thermoactinomyces is growth related and is maximum when growth stops at 12 to 16 hours with 1 to 5% Avicel at pH 7.0 to 7.2 and 55/sup 0/C. A multistage fermenter has been assembled for optimization of butanol versus acetone production by Cl. acetobutylicum. A preliminary economic assessment, currently indicating butanol at just above 30 cents/lb, is being continuously updated.

  8. Gene Discovery for Synthetic Biology: Exploring the Novel Natural Product Biosynthetic Capacity of Eukaryotic Microalgae.

    Science.gov (United States)

    O'Neill, E C; Saalbach, G; Field, R A

    2016-01-01

    Eukaryotic microalgae are an incredibly diverse group of organisms whose sole unifying feature is their ability to photosynthesize. They are known for producing a range of potent toxins, which can build up during harmful algal blooms causing damage to ecosystems and fisheries. Genome sequencing is lagging behind in these organisms because of their genetic complexity, but transcriptome sequencing is beginning to make up for this deficit. As more sequence data becomes available, it is apparent that eukaryotic microalgae possess a range of complex natural product biosynthesis capabilities. Some of the genes concerned are responsible for the biosynthesis of known toxins, but there are many more for which we do not know the products. Bioinformatic and analytical techniques have been developed for natural product discovery in bacteria and these approaches can be used to extract information about the products synthesized by algae. Recent analyses suggest that eukaryotic microalgae produce many complex natural products that remain to be discovered.

  9. The Umatilla Basin Natural Production Monitoring and Evaluation Project, 2008 Annual Progress Report.

    Energy Technology Data Exchange (ETDEWEB)

    Contor, Craig R.; Harris, Robin; King, Marty [Confederated Tribes of the Umatilla Indian Reservation

    2009-06-10

    The Umatilla Basin Natural Production Monitoring and Evaluation Project (UBNPMEP) is funded by Bonneville Power Administration (BPA) as directed by section 4(h) of the Pacific Northwest Electric Power Planning and Conservation Act of 1980 (P.L.96-501). This project is in accordance with and pursuant to measures 4.2A, 4.3C.1, 7.1A.2, 7.1C.3, 7.1C.4 and 7.1D.2 of the Northwest Power Planning Council's (NPPC) Columbia River Basin Fish and Wildlife Program (NPPC 1994). Work was conducted by the Fisheries Program of the Confederated Tribes of the Umatilla Indian Reservation (CTUIR). The UBNPMEP is coordinated with two Oregon Department of Fish and Wildlife (ODFW) research projects that also monitor and evaluate the success of the Umatilla Fisheries Restoration Plan. This project deals with the natural production component of the plan, and the ODFW projects evaluate hatchery operations (project No. 1990-005-00, Umatilla Hatchery M & E) and smolt outmigration (project No. 1989-024-01, Evaluation of Juvenile Salmonid Outmigration and Survival in the Lower Umatilla River). Collectively these three projects monitor and evaluate natural and hatchery salmonid production in the Umatilla River Basin. The need for natural production monitoring has been identified in multiple planning documents including Wy-Kan-Ush-Mi Wa-Kish-Wit Volume I, 5b-13 (CRITFC 1996), the Umatilla Hatchery Master Plan (CTUIR & ODFW 1990), the Umatilla Basin Annual Operation Plan, the Umatilla Subbasin Summary (CTUIR & ODFW 2001), the Subbasin Plan (CTUIR & ODFW 2004), and the Comprehensive Research, Monitoring, and Evaluation Plan (CTUIR and ODFW 2006). Natural production monitoring and evaluation is also consistent with Section III, Basinwide Provisions, Strategy 9 of the 2000 Columbia River Basin Fish and Wildlife Program (NPPC 1994, NPCC 2004). The Umatilla Basin M&E plan developed along with efforts to restore natural populations of spring and fall Chinook salmon, (Oncorhynchus tshawytsha), coho

  10. 1,3-Propanediol production by new recombinant Escherichia coli containing genes from pathogenic bacteria.

    Science.gov (United States)

    Przystałowska, Hanna; Zeyland, Joanna; Szymanowska-Powałowska, Daria; Szalata, Marlena; Słomski, Ryszard; Lipiński, Daniel

    2015-02-01

    1,3-Propanediol (1,3-PDO) is an organic compound, which is a valuable intermediate product, widely used as a monomer for synthesizing biodegradable polymers, increasing their strength; as well as an ingredient of textile, cosmetic and medical products. 1,3-PDO is mostly synthesized chemically. Global companies have developed technologies for 1,3-PDO synthesis from petroleum products such as acrolein and ethylene oxide. A potentially viable alternative is offered by biotechnological processes using microorganisms capable of synthesizing 1,3-PDO from renewable substrates (waste glycerol, a by-product of biofuel production, or glucose). In the present study, genes from Citrobacter freundii and Klebsiella pneumoniae were introduced into Escherichia coli bacteria to enable the synthesis of 1,3-PDO from waste glycerol. These strains belong to the best 1,3-PDO producers, but they are pathogenic, which restricts their application in industrial processes. The present study involved the construction of two gene expression constructs, containing a total of six heterologous glycerol catabolism pathway genes from C. freundii ATCC 8090 and K. pneumoniae ATCC 700721. Heterologous genes encoding glycerol dehydratase (dhaBCE) and the glycerol dehydratase reactivation factor (dhaF, dhaG) from C. freundii and gene encoding 1,3-PDO oxidoreductase (dhaT) from K. pneumoniae were expressed in E. coli under the control of the T7lac promoter. An RT-PCR analysis and overexpression confirmed that 1,3-PDO synthesis pathway genes were expressed on the RNA and protein levels. In batch fermentation, recombinant E. coli bacteria used 32.6gl(-1) of glycerol to produce 10.6 gl(-1) of 1,3-PDO, attaining the efficiency of 0.4 (mol₁,₃-PDO molglycerol(-1)). The recombinant E. coli created is capable of metabolizing glycerol to produce 1,3-PDO, and the efficiency achieved provides a significant research potential of the bacterium. In the face of shortage of fossil fuel supplies and climate warming

  11. Effects of a Community-Based Progressive Resistance Training Program on the Work Productivity of Adolescents with Moderate to Severe Intellectual Disabilities.

    Science.gov (United States)

    Zetts, Raymond A.; And Others

    1995-01-01

    Effects of a community-based progressive resistance physical training program on simulated work productivity were evaluated with six students (mean age 17 years) having moderate to severe intellectual disabilities. Strength values increased from preprogram to postprogram assessment. Mean values for all work productivity tasks increased during the…

  12. Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer.

    Science.gov (United States)

    Xu, J; Li, Y; Wang, F; Wang, X; Cheng, B; Ye, F; Xie, X; Zhou, C; Lu, W

    2013-02-21

    MicroRNAs (miRNAs) act as important gene regulators in human genomes and their aberrant expression links to many malignancies. We previously identified a different characteristic miRNA expression profile in cervical cancer from that in cervical normal tissues, including the downregulated miR-424. However, the role and mechanism of miR-424 in cervical cancer still remain unknown. Here, we focused on identifying the tumor-suppressive function and clinical significance of miR-424 and exploring the mechanistic relevance by characterizing its target. We showed a significantly decreased expression of miR-424 in 147 cervical cancer tissues versus 74 cervical normal tissues by performing quantitative RT-PCR. In 147 cervical cancer tissue samples, low-level expression of miR-424 was positively correlated with poor tumor differentiation, advanced clinical stage, lymph node metastasis and other poor prognostic clinicopathological parameters. Further in vitro observations showed that enforced expression of miR-424 inhibited cell growth by both enhancing apoptosis and blocking G1/S transition, and suppressed cell migration and invasion in two human cervical cancer cell lines, SiHa and CaSki, implying that miR-424 functions as a tumor suppressor in the progression of cervical cancer. Interestingly, overexpression of miR-424 inhibited the expression of protein checkpoint kinase 1 (Chk1) and phosphorylated Chk1 (p-Chk1) at residues Ser345 and decreased the activity of luciferase-reporter containing the 3'-untranslated region (UTR) of Chk1 with predicted miR-424-binding site. Moreover, miR-424 expression levels were inversely correlated with Chk1 and p-Chk1 protein levels in both cervical cancer and normal tissues. Furthermore, RNAi-mediated knockdown of Chk1 decreased matrix metalloproteinase 9 expression and phenocopied the tumor suppressive effects of miR-424 in cell models. Taken together, our results identify a crucial tumor suppressive role of miR-424 in the progression of

  13. Prevalence of Campylobacter species in milk and milk products, their virulence gene profile and antibiogram

    Directory of Open Access Journals (Sweden)

    Shivani Modi

    2015-01-01

    Full Text Available Aim: During the last decades, number of food poisoning cases due to Campylobacter occurred, immensely. After poultry, raw milk acts as a second main source of Campylobacter. Therefore, the present study was undertaken to detect the prevalence of Campylobacters in milk and milk products and to know the antibiotic sensitivity and virulence gene profile of Campylobacter spp. in Anand city, Gujarat, India. Materials and Methods: A total of 240 samples (85 buffalo milk, 65 cow milk, 30 cheese, 30 ice-cream and 30 paneer were collected from the different collection points in Anand city. The samples were processed by microbiological culture method, and presumptive isolates were further confirmed by genus and species-specific polymerase chain reaction using previously reported primer. The isolates were further subjected to antibiotic susceptibility assay and virulence gene detection. Result: Campylobacter species were detected in 7 (2.91% raw milk samples whereas none of the milk product was positive. All the isolate identified were Campylobacter jejuni. Most of the isolates showed resistance against nalidixic acid, ciprofloxacin, and tetracyclin. All the isolates have three virulence genes cadF, cdtB and flgR whereas only one isolate was positive for iamA gene and 6 isolates were positive for fla gene. Conclusion: The presence of Campylobacter in raw milk indicates that raw milk consumption is hazardous for human being and proper pasteurization of milk and adaptation of hygienic condition will be necessary to protect the consumer from this zoonotic pathogen.

  14. Decarboxylase gene expression and cadaverine and putrescine production by Serratia proteamaculans in vitro and in beef.

    Science.gov (United States)

    De Filippis, Francesca; Pennacchia, Carmela; Di Pasqua, Rosangela; Fiore, Alberto; Fogliano, Vincenzo; Villani, Francesco; Ercolini, Danilo

    2013-08-01

    Studies of the molecular basis of microbial metabolic activities that are important for the changes in food quality are valuable in order to help in understanding the behavior of spoiling bacteria in food. The growth of a psychrotrophic Serratia proteamaculans strain was monitored in vitro and in artificially inoculated raw beef. Two growth temperatures (25°C and 4°C) were tested in vitro, while growth at 15°C and 4°C was monitored in beef. During growth, the expression of inducible lysine and ornithine-decarboxylase genes was evaluated by quantitative reverse transcription-PCR (qRT-PCR), while the presence of cadaverine and putrescine was quantified by LC-ESI-MS/MS. The expression of the decarboxylase genes, and the consequent production of cadaverine and putrescine were shown to be influenced by the temperature, as well as by the complexity of the growth medium. Generally, the maximum gene expression and amine production took place during the exponential and early stationary phase, respectively. In addition, lower temperatures caused slower growth and gene downregulation. Higher amounts of cadaverine compared to putrescine were found during growth in beef with the highest concentrations corresponding to microbial loads of ca. 9CFU/g. The differences found in gene expression evaluated in vitro and in beef suggested that such activities are more reliably investigated in situ in specific food matrices.

  15. Dairy Product Consumption Interacts with Glucokinase (GCK Gene Polymorphisms Associated with Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Marine S. Da Silva

    2017-08-01

    Full Text Available Dairy product intake and a person’s genetic background have been reported to be associated with the risk of type 2 diabetes (T2D. The objective of this study was to examine the interaction between dairy products and genes related to T2D on glucose-insulin homeostasis parameters. A validated food frequency questionnaire, fasting blood samples, and glucokinase (GCK genotypes were analyzed in 210 healthy participants. An interaction between rs1799884 in GCK and dairy intake on the homeostasis model assessment of insulin resistance was identified. Secondly, human hepatocellular carcinoma cells (HepG2 were grown in a high-glucose medium and incubated with either 1-dairy proteins: whey, caseins, and a mixture of whey and casein; and 2-four amino acids (AA or mixtures of AA. The expression of GCK-related genes insulin receptor substrate-1 (IRS-1 and fatty acid synthase (FASN was increased with whey protein isolate or hydrolysate. Individually, leucine increased IRS-1 expression, whereas isoleucine and valine decreased FASN expression. A branched-chain AA mixture decreased IRS-1 and FASN expression. In conclusion, carriers of the A allele for rs1799884 in the GCK gene may benefit from a higher intake of dairy products to maintain optimal insulin sensitivity. Moreover, the results show that whey proteins affect the expression of genes related to glucose metabolism.

  16. A shortest-path graph kernel for estimating gene product semantic similarity

    Directory of Open Access Journals (Sweden)

    Alvarez Marco A

    2011-07-01

    Full Text Available Abstract Background Existing methods for calculating semantic similarity between gene products using the Gene Ontology (GO often rely on external resources, which are not part of the ontology. Consequently, changes in these external resources like biased term distribution caused by shifting of hot research topics, will affect the calculation of semantic similarity. One way to avoid this problem is to use semantic methods that are "intrinsic" to the ontology, i.e. independent of external knowledge. Results We present a shortest-path graph kernel (spgk method that relies exclusively on the GO and its structure. In spgk, a gene product is represented by an induced subgraph of the GO, which consists of all the GO terms annotating it. Then a shortest-path graph kernel is used to compute the similarity between two graphs. In a comprehensive evaluation using a benchmark dataset, spgk compares favorably with other methods that depend on external resources. Compared with simUI, a method that is also intrinsic to GO, spgk achieves slightly better results on the benchmark dataset. Statistical tests show that the improvement is significant when the resolution and EC similarity correlation coefficient are used to measure the performance, but is insignificant when the Pfam similarity correlation coefficient is used. Conclusions Spgk uses a graph kernel method in polynomial time to exploit the structure of the GO to calculate semantic similarity between gene products. It provides an alternative to both methods that use external resources and "intrinsic" methods with comparable performance.

  17. Enhanced hydrogen production by insertional inactivation of adhE gene in Klebsiella oxytoca HP1

    Institute of Scientific and Technical Information of China (English)

    ZHU JunBo; LONG MinNan; XU FangCheng; WU XiaoBing; XU HuiJuan

    2007-01-01

    Ethanol is the main byproduct of anaerobic H2-producing fermentation in Klebsiella oxytoca HP1. Two moles of NAD(P)H are consumed to yield one mole of ethanol that may decrease bacterial hydrogen production. In this article the adhE gene that codes for acetaldehyde dehydrogenase was disrupted for the first time. A homologous recombination vector pTA-Str was constructed in which the adhE gene was disrupted by inserting an aminoglycoside-3'-adenyltransferase (aadA) gene. As expected, the vector includes the insertion 5'-adhE-aadA-adhE-3'. The amplified DNA fragment 5'-adhE-aadA-adhE-3' from pTA-Str was transformed into K. Oxytoca HP1 and one recombinant was obtained. PCR analysis of the resulting genomic DNA indicated the appropriate deletion and insertion. Compared with the H2-production of wild type K. Oxytoca HP1, the hydrogen yield of the mutant increased by 16.07% and ethanol concentration decreased by 77.47%, suggesting that inactivation of the adhE gene in K. Oxytoca HP1 is a potential method for enhancing bacterial H2-production.

  18. Correlation of methane production and functional gene transcriptional activity in a peat soil.

    Science.gov (United States)

    Freitag, Thomas E; Prosser, James I

    2009-11-01

    The transcription dynamics of subunit A of the key gene in methanogenesis (methyl coenzyme M reductase; mcrA) was studied to evaluate the relationship between process rate (methanogenesis) and gene transcription dynamics in a peat soil ecosystem. Soil methanogen process rates were determined during incubation of peat slurries at temperatures from 4 to 37 degrees C, and real-time quantitative PCR was applied to quantify the abundances of mcrA genes and transcripts; corresponding transcriptional dynamics were calculated from mcrA transcript/gene ratios. Internal standards suggested unbiased recovery of mRNA abundances in comparison to DNA levels. In comparison to those in pure-culture studies, mcrA transcript/gene ratios indicated underestimation by 1 order of magnitude, possibly due to high proportions of inactive or dead methanogens. Methane production rates were temperature dependent, with maxima at 25 degrees C, but changes in abundance and transcription of the mcrA gene showed no correlation with temperature. However, mcrA transcript/gene ratios correlated weakly (regression coefficient = 0.76) with rates of methanogenesis. Methanogen process rates increased over 3 orders of magnitude, while the corresponding maximum transcript/gene ratio increase was only 18-fold. mcrA transcript dynamics suggested steady-state expression in peat soil after incubation for 24 and 48 h, similar to that in stationary-phase cultures. mcrA transcript/gene ratios are therefore potential in situ indicators of methanogen process rate changes in complex soil systems.

  19. New Insights about Antibiotic Production by Pseudomonas aeruginosa: A Gene Expression Analysis

    Directory of Open Access Journals (Sweden)

    Bárbara Gionco

    2017-09-01

    Full Text Available The bacterial resistance for antibiotics is one of the most important problems in public health and only a small number of new products are in development. Antagonistic microorganisms from soil are a promising source of new candidate molecules. Products of secondary metabolism confer adaptive advantages for their producer, in the competition for nutrients in the microbial community. The biosynthesis process of compounds with antibiotic activity is the key to optimize their production and the transcriptomic study of microorganisms is of great benefit for the discovery of these metabolic pathways. Pseudomonas aeruginosa LV strain growing in the presence of copper chloride produces a bioactive organometallic compound, which has a potent antimicrobial activity against various microorganisms. The objective of this study was to verify overexpressed genes and evaluate their relation to the organometallic biosynthesis in this microorganism. P. aeruginosa LV strain was cultured in presence and absence of copper chloride. Two methods were used for transcriptomic analysis, genome reference-guided assembly and de novo assembly. The genome referenced analysis identified nine upregulated genes when bacteria were exposed to copper chloride, while the De Novo Assembly identified 12 upregulated genes. Nineteen genes can be related to an increased microbial metabolism for the extrusion process of exceeding intracellular copper. Two important genes are related to the biosynthesis of phenazine and tetrapyrroles compounds, which can be involved in the bioremediation of intracellular copper and we suggesting that may involve in the biosynthesis of the organometallic compound. Additional studies are being carried out to further prove the function of the described genes and relate them to the biosynthetic pathway of the organometallic compound.

  20. Association of methionine synthase gene polymorphisms with wool production and quality traits in Chinese Merino population.

    Science.gov (United States)

    Rong, E G; Yang, H; Zhang, Z W; Wang, Z P; Yan, X H; Li, H; Wang, N

    2015-10-01

    Methionine synthase (MTR) plays a crucial role in maintaining homeostasis of intracellular methionine, folate, and homocysteine, and its activity correlates with DNA methylation in many mammalian tissues. Our previous genomewide association study identified that 1 SNP located in the gene was associated with several wool production and quality traits in Chinese Merino. To confirm the potential involvement of the gene in sheep wool production and quality traits, we performed sheep tissue expression profiling, SNP detection, and association analysis with sheep wool production and quality traits. The semiquantitative reverse transcription PCR analysis showed that the gene was differentially expressed in skin from Merino and Kazak sheep. The sequencing analysis identified a total of 13 SNP in the gene from Chinese Merino sheep. Comparison of the allele frequencies revealed that these 13 identified SNP were significantly different among the 6 tested Chinese Merino strains ( < 0.001). Linkage disequilibrium analysis showed that SNP 3 to 11 were strongly linked in a single haplotype block in the tested population. Association analysis showed that SNP 2 to 11 were significantly associated with the average wool fiber diameter and the fineness SD and that SNP 4 to 11 were significantly associated with the CV of fiber diameter trait ( < 0.05). Single nucleotide polymorphism 2 and SNP 5 to 12 were weakly associated with wool crimp. Similarly, the haplotypes derived from these 13 identified SNP were also significantly associated with the average wool fiber diameter, fineness SD, and the CV of fiber diameter ( < 0.05). Our results suggest that is a candidate gene for sheep wool production and quality traits, and the identified SNP might be used in sheep breeding.

  1. Low VOC drying of lumber and wood panel products. Progress report No. 8

    Energy Technology Data Exchange (ETDEWEB)

    Su, W.; Yan, H.; Hooda, U.; Wild, M.P.; Banerjee, S. [Inst. of Paper Science and Technology, Atlanta, GA (United States); Shmulsky, R.; Thompson, A.; Ingram, L.; Conners, T. [Mississippi State Univ., MS (United States)

    1998-07-01

    This study was initiated by an Institute of Paper Science and Technology finding that heating softwood in a low-headspace environment removed much of the VOCs without removing the water. This offered the possibility of removing VOCs from wet wood, capturing them as a product, and then drying the VOC-depleted wood conventionally with little or no VOC controls. Two means of low-headspace heating were explored: steam and radiofrequency (RF). It was found in the previous year, that while both steam and RF were able to drive out VOCs, steam was impracticably slow for lumber. Hence the effect of RF or microwave on wood was the principal focus of the work reported here. Finally, in order to understand the mechanism of VOC release, the transport of the VOCs in wood was studied, together with the seasonal effects that influence VOC concentration in trees.

  2. Application of ionic liquids in actinide and fission product separations: progress and prospects.

    Energy Technology Data Exchange (ETDEWEB)

    Stepinski, D. C.; Young, B. A.; Jensen, M. P.; Rickert, P. G.; Dzielawa, J. A.; Dilger, A. A.; Rausch, D. J.; Dietz, M. L.; Chemistry

    2006-01-01

    Ionic liquids (ILs), particularly those that are liquid at room temperature, have attracted intense interest as alternatives to conventional organic solvents in a host of synthetic, catalytic, and electrochemical applications. Recently, growing attention has been devoted to their use in separations, typically as replacements for the organic diluents employed in traditional liquid-liquid extraction or membrane-based separations of organic solutes or metal ions. Although studies of the extraction of metal ions into various ILs indicate that these solvents frequently provide extraction efficiencies far greater than those obtained with conventional solvents, other work suggests that they suffer from various drawbacks that could limit their utility as extraction solvents. In this chapter, we examine the viability of ionic liquids as the basis for extraction systems for the separation of actinides and fission products from acidic media and consider approaches by which their limitations may be overcome.

  3. Recent Progress At The Idaho National Laboratory In High Temperature Electrolysis For Hydrogen And Syngas Production

    Energy Technology Data Exchange (ETDEWEB)

    C. Stoots; J. O' Brien; J. Herring; J. Hartvigsen

    2008-11-01

    This paper presents the most recent results of experiments conducted at the Idaho National Laboratory (INL) studying electrolysis of steam and coelectrolysis of steam / carbon dioxide in solid-oxide electrolysis stacks. Single button cell tests as well as multi-cell stack testing have been conducted. Multi-cell stack testing used 10 x 10 cm cells (8 x 8 cm active area) supplied by Ceramatec, Inc (Salt Lake City, Utah, USA) and ranged from 10 cell short stacks to 240 cell modules. Tests were conducted either in a bench-scale test apparatus or in a newly developed 5 kW Integrated Laboratory Scale (ILS) test facility. Gas composition, operating voltage, and operating temperature were varied during testing. The tests were heavily instrumented, and outlet gas compositions were monitored with a gas chromatograph. The ILS facility is currently being expanded to 15 kW testing capacity (H2 production rate based upon lower heating value).

  4. The Walla Walla Basin Natural Production Monitoring and Evaluation Project : Progress Report, 1999-2002.

    Energy Technology Data Exchange (ETDEWEB)

    Contor, Craig R.; Sexton, Amy D.

    2003-06-02

    The Walla Walla Basin Natural Production Monitoring and Evaluation Project (WWNPME) was funded by Bonneville Power Administration (BPA) as directed by section 4(h) of the Pacific Northwest Electric Power Planning and Conservation Act of 1980 (P. L. 96-501). This project is in accordance with and pursuant to measures 4.2A, 4.3C.1, 7.1A.2, 7.1C.3, 7.1C.4 and 7.1D.2 of the Northwest Power Planning Council's (NPPC) Columbia River Basin Fish and Wildlife Program (NPPC 1994). Work was conducted by the Fisheries Program of the Confederated Tribes of the Umatilla Indian Reservation (CTUIR) under the Walla Walla Basin Natural Production Monitoring and Evaluation Project (WWNPME). Chapter One provides an overview of the entire report and how the objectives of each statement of work from 1999, 2000, 2001, and 2002 contract years are organized and reported. Chapter One also provides background information relevant to the aquatic resources of the Walla Walla River Basin. Objectives are outlined below for the statements of work for the 1999, 2000, 2001 and 2002 contract years. The same objectives were sometimes given different numbers in different years. Because this document is a synthesis of four years of reporting, we gave objectives letter designations and listed the objective number associated with the statement of work for each year. Some objectives were in all four work statements, while other objectives were in only one or two work statements. Each objective is discussed in a chapter. The chapter that reports activities and findings of each objective are listed with the objective below. Because data is often interrelated, aspects of some findings may be reported or discussed in more than one chapter. Specifics related to tasks, approaches, methods, results and discussion are addressed in the individual chapters.

  5. Ethanol production via fungal decomposition and fermentation of biomass. Phase II (FY 1981) annual progress report

    Energy Technology Data Exchange (ETDEWEB)

    Antonopoulos, A. A.; Wene, E. G.

    1981-10-01

    This program has as its main goal the isolation and development of Fusarium strains that can efficiently and economically decompose plant polysaccharides to pentoses and hexoses and ferment them to ethanol for fuel purposes. During Phase II (FY 1981) of this program, more than 800 new Fusarium isolates were isolated and screened. All showed cellulolytic activity. The Fusarium mutant ANL 3-72181 (derived after uv exposure of ANL 22 isolate) produced 2.45 iu cellulase after 14 days. This cellulase activity was achieved in the presence of 0.7 mg/mL extracellular protein. In separate tests, the use of both proteose peptone and yeast extract with 1% cellulose increased the production of extracellular protein three times over that on cellulose alone. Initial fermentation by Fusarium strains on 1% glucose produced up to 4.2 mg/mL ethanol in 48 hours. All Fusarium isolates and mutants found during this period were screened for xylose fermentation. Ethanol production during early experimentation required from 120 to 144 hours to yield 4.0 to 4.5 mg/mL ethanol from 1% xylose solutions. Through continuous selection of isolates, this time was reduced to 66 hours. By recycling Fusarium cell mass, fermentations of 1% xylose yielded 4.0 to 4.3 mg/mL ethanol in 48 hours. Consecutive fermentations of 2% xylose produced an average of 8.1 mg/mL ethanol in 48 hours. Fermentation of a 4.5% xylose + 2% glucose solution produced 21 mg/mL ethanol and 0.8 mg/mL acetic acid, while fermentation of a 7% xylose + 2% glucose solution yielded 25.5 mg/mL ethanol and 0.85 mg/mL acetic acid; these fermentations were aerated at a rate of 0.03 v/v-min.

  6. STAPHYLOCOCCUS AUREUS ISOLATES FROM CAMELS DIFFER IN COAGULASE PRODUCTION, GENOTYPE AND METHICILLIN RESISTANCE GENE PROFILES

    Directory of Open Access Journals (Sweden)

    Ziad Jaradat

    2013-06-01

    Full Text Available Accurate and rapid typing of S. aureus is crucial to the control of its infections and minimizing its leakage to the food chain. The primary purpose of this research was to isolate S. aureus from camels’ meat and nasal swabs and to characterize the isolates for coagulase production and the presence of methicillin gene using PCR-RFLP of coagulase gene. A total of 264 camel’s meat and nasal swabs were collected from abattoirs or meat markets and were used in the study. Ninety two percent of samples showed typical colonies of S. aureus on Baird-Parker agar with a mean count 2.5 × 104 ± 1.8 × 104 CFU g-1. Upon confirmation of the isolates using S. aureus specific thermonuclease gene (nuc PCR primers, only 64 isolates contained the specific product and thus were confirmed as S. aureus. However, when tested for the presence of coagulase gene, only 48 of them were positive while the other 16 were coagulase negative. Coagulase gene-RFLP revealed 19 distinct patterns when the gene was digested with Alu I and Cfo I. The typing revealed that the 48 classified isolates were genetically diverse and comprised a heterogeneous population with 14 genotypes at a 44.4% similarity level. When the coagulase positive isolates were tested for the presence of methicillin resistance (mec A gene, 37 of the isolates were positive while the other 11 isolates were negative. The high heterogeneity among S. aureus isolates might be due to cross contamination between camel carcasses in slaughter houses and from handlers and their utensils.

  7. Four gene products are required for the fungal synthesis of the indole-diterpene, paspaline.

    Science.gov (United States)

    Saikia, Sanjay; Parker, Emily J; Koulman, Albert; Scott, Barry

    2006-03-06

    Paspaline belongs to a large, structurally and functionally diverse group of indole-diterpenes synthesized by filamentous fungi. However, the identity of the gene products required for the biosynthesis of paspaline, a key intermediate for the synthesis of paxilline and other indole-diterpenes, is not known. Transfer of constructs containing different pax gene combinations into a paxilline negative deletion derivative of Penicillium paxilli demonstrated that just four proteins, PaxG, a geranylgeranyl diphosphate synthase, PaxM, a FAD-dependent monooxygenase, PaxB, a putative membrane protein, and PaxC, a prenyl transferase, are required for the biosynthesis of paspaline.

  8. Overproduction and purification of the luxR gene product: Transcriptional activator of the Vibrio fischeri luminescence system

    OpenAIRE

    1987-01-01

    Expression of Vibrio fischeri luminescence genes requires an inducer, termed autoinducer, and a positive regulatory element, the luxR gene product. A plasmid containing luxR under control of a tac promoter was engineered to overproduce this gene product. The overproduced luxR gene product was active in vivo, and its apparent monomeric molecular weight was indistinguishable from that of the protein encoded by luxR under control of its own promoter (Mr 27,000). The new tac-luxR construct direct...

  9. Glutamic acid promotes monacolin K production and monacolin K biosynthetic gene cluster expression in Monascus.

    Science.gov (United States)

    Zhang, Chan; Liang, Jian; Yang, Le; Chai, Shiyuan; Zhang, Chenxi; Sun, Baoguo; Wang, Chengtao

    2017-12-01

    This study investigated the effects of glutamic acid on production of monacolin K and expression of the monacolin K biosynthetic gene cluster. When Monascus M1 was grown in glutamic medium instead of in the original medium, monacolin K production increased from 48.4 to 215.4 mg l(-1), monacolin K production increased by 3.5 times. Glutamic acid enhanced monacolin K production by upregulating the expression of mokB-mokI; on day 8, the expression level of mokA tended to decrease by Reverse Transcription-polymerase Chain Reaction. Our findings demonstrated that mokA was not a key gene responsible for the quantity of monacolin K production in the presence of glutamic acid. Observation of Monascus mycelium morphology using Scanning Electron Microscope showed glutamic acid significantly increased the content of Monascus mycelium, altered the permeability of Monascus mycelium, enhanced secretion of monacolin K from the cell, and reduced the monacolin K content in Monascus mycelium, thereby enhancing monacolin K production.

  10. A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

    Directory of Open Access Journals (Sweden)

    Cigudosa Juan C

    2011-05-01

    Full Text Available Abstract Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs, will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents. With the extension of this analysis to an Array-CGH dataset (glioblastomas from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.

  11. Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat

    Energy Technology Data Exchange (ETDEWEB)

    Kenney, S.; Kamine, J.; Markovitz, D.; Fenrick, R.; Pagano, J.

    1988-03-01

    Acquired immunodeficiency syndrome patients are frequently coinfected with Epstein-Barr virus (EBV). In this report, the authors demonstrate that an EBV immediate-early gene product, BamHI MLF1, stimulates expression of the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the human immunodeficiency virus (HIV) promoter. The HIV promoter sequences necessary for trans-activation by EBV do not include the tat-responsive sequences. In addition, in contrast to the other herpesvirus trans-activators previously studied, the EBV BamHI MLF1 gene product appears to function in part by a posttranscriptional mechanism, since it increases pHIV-CAT protein activity more than it increases HIV-CAT mRNA. This ability of an EBV gene product to activate HIV gene expression may have biologic consequences in persons coinfected with both viruses.

  12. Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters.

    Science.gov (United States)

    Schorn, Michelle A; Alanjary, Mohammad M; Aguinaldo, Kristen; Korobeynikov, Anton; Podell, Sheila; Patin, Nastassia; Lincecum, Tommie; Jensen, Paul R; Ziemert, Nadine; Moore, Bradley S

    2016-12-01

    Traditional natural product discovery methods have nearly exhausted the accessible diversity of microbial chemicals, making new sources and techniques paramount in the search for new molecules. Marine actinomycete bacteria have recently come into the spotlight as fruitful producers of structurally diverse secondary metabolites, and remain relatively untapped. In this study, we sequenced 21 marine-derived actinomycete strains, rarely studied for their secondary metabolite potential and under-represented in current genomic databases. We found that genome size and phylogeny were good predictors of biosynthetic gene cluster diversity, with larger genomes rivalling the well-known marine producers in the Streptomyces and Salinispora genera. Genomes in the Micrococcineae suborder, however, had consistently the lowest number of biosynthetic gene clusters. By networking individual gene clusters into gene cluster families, we were able to computationally estimate the degree of novelty each genus contributed to the current sequence databases. Based on the similarity measures between all actinobacteria in the Joint Genome Institute's Atlas of Biosynthetic gene Clusters database, rare marine genera show a high degree of novelty and diversity, with Corynebacterium, Gordonia, Nocardiopsis, Saccharomonospora and Pseudonocardia genera representing the highest gene cluster diversity. This research validates that rare marine actinomycetes are important candidates for exploration, as they are relatively unstudied, and their relatives are historically rich in secondary metabolites.

  13. Identification of Drosophila gene products required for phagocytosis of Candida albicans.

    Directory of Open Access Journals (Sweden)

    Shannon L Stroschein-Stevenson

    2006-01-01

    Full Text Available Phagocytosis is a highly conserved aspect of innate immunity. We used Drosophila melanogaster S2 cells as a model system to study the phagocytosis of Candida albicans, the major fungal pathogen of humans, by screening an RNAi library representing 7,216 fly genes conserved among metazoans. After rescreening the initial genes identified and eliminating certain classes of housekeeping genes, we identified 184 genes required for efficient phagocytosis of C. albicans. Diverse biological processes are represented, with actin cytoskeleton regulation, vesicle transport, signaling, and transcriptional regulation being prominent. Secondary screens using Escherichia coli and latex beads revealed several genes specific for C. albicans phagocytosis. Characterization of one of those gene products, Macroglobulin complement related (Mcr, shows that it is secreted, that it binds specifically to the surface of C. albicans, and that it promotes its subsequent phagocytosis. Mcr is closely related to the four Drosophila thioester proteins (Teps, and we show that TepII is required for efficient phagocytosis of E. coli (but not C. albicans or Staphylococcus aureus and that TepIII is required for the efficient phagocytosis of S. aureus (but not C. albicans or E. coli. Thus, this family of fly proteins distinguishes different pathogens for subsequent phagocytosis.

  14. Progress in Hydrogen Production from Water%水制氢技术研究进展

    Institute of Scientific and Technical Information of China (English)

    于娇娇; 苏伟; 孙艳

    2012-01-01

    氢能是一种高效、清洁的能源,其热值比石油还要高3倍.目前,大部分氢气都来自于化石燃料,如天然气、石油和煤等.这些方法不具有可再生性.以水为氢源的制氢技术因其可再生性而具有很好的应用前景.以水为氢源的制氢技术主要包括电解水制氢、光催化分解水制氢、直接热分解水制氢和热化学循环裂解水制氢技术.其中,电解水制氢技术最为成熟,其不足之处在于能耗过高;对光催化分解水制氢技术已经进行了系统研究,催化剂的性能是影响该方法的关键因素;对于直接热分解的研究相对较少;热化学循环制氢技术的优势在于反应效率高、利于放大,如何保持反应中间媒介物的高温循环稳定性则是该方法急需解决的技术难题.%Hydrogen is a clean energy, and has a heating value three times higher than petroleum. Presently it is mostly produced from fossil fuels (natural gas, oil and coal). However, water-splitting has been regarded as a promising way to produce hydrogen because it is renewable and water is abundant on Earth. Different methods of hydrogen production from water have been, or are being developed, such as electrolysis, photocatalysis, direct thermal decomposition, thermochemical processes and so on. Production of hydrogen by water electrolysis is a mature technology. The key problem of this method is how to reduce its cost. The performance of photocatalysis has been studied extensively both in theory and in practice. As a result, the activity of catalyst is very important for this method. Few reports on direct thermal decomposition have been presented for its high reaction temperature. Thermochemical hydrogen production is a means of splitting water via a series of chemical reactions and the advantage of this method is efficient and scaleable. However, material problems at the high temperatures have hindered the practical implementation of thermochemical cycles.

  15. 5q14.3 deletion neurocutaneous syndrome: Contiguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C: A progressive disease.

    Science.gov (United States)

    Ilari, Rita; Agosta, Guillermo; Bacino, Carlos

    2016-03-01

    We report the case of a young girl who was presented with complex clinical symptoms caused by the deletion of contiguous genes: RASA1 and MEF2C, located on chromosome 5q14.3. Specifically, the diagnosis of her skin disorder and vascular malformations involving central nervous system is consistent with a RASopathy. The child's neurological manifestations are observed in most patients suffering from 5q14.3 by deletion or mutation of the MEF2C gene. A review of the literature allowed us to conclude that the contiguous deletion of genes RASA1 and MEF2C fulfills the criteria for the diagnosis of a Neurocutaneous syndrome as proposed by Carr et al. [2011]. We also assessed the penetrance of RASA1 and clinical manifestations of MEF2C according to the type of deletion. This child described presents the complete symptomatology of both deleted genes. We would also like to highlight the progression of the disorder.

  16. Stable disruption of ethanol production by deletion of the genes encoding alcohol dehydrogenase isozymes in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ida, Yoshihiro; Furusawa, Chikara; Hirasawa, Takashi; Shimizu, Hiroshi

    2012-02-01

    We analyzed the effects of the deletions of genes encoding alcohol dehydrogenase (ADH) isozymes of Saccharomyces cerevisiae. The decrease in ethanol production by ADH1 deletion alone could be partially compensated by the upregulation of other isozyme genes, while the deletion of all known ADH isozyme genes stably disrupted ethanol production. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Re-examination of regulatory opinions in Europe: possible contribution for the approval of the first gene therapy product Glybera

    OpenAIRE

    2015-01-01

    The first commercially approved human gene therapy in the Western world is Glybera (alipogene tiparvovec), which is an adenoassociated viral vector encoding the lipoprotein lipase gene. Glybera was recommended for marketing authorization by the European Medicines Agency in 2012. The European Medicines Agency had only ever reviewed three marketing authorization applications for gene therapy medicinal products. Unlike in the case of Glybera, the applications of the first two products, Cerepro a...

  18. Progressive Image Transmission Based on Joint Source-Channel Decoding Using Adaptive Sum-Product Algorithm

    Directory of Open Access Journals (Sweden)

    David G. Daut

    2007-03-01

    Full Text Available A joint source-channel decoding method is designed to accelerate the iterative log-domain sum-product decoding procedure of LDPC codes as well as to improve the reconstructed image quality. Error resilience modes are used in the JPEG2000 source codec making it possible to provide useful source decoded information to the channel decoder. After each iteration, a tentative decoding is made and the channel decoded bits are then sent to the JPEG2000 decoder. The positions of bits belonging to error-free coding passes are then fed back to the channel decoder. The log-likelihood ratios (LLRs of these bits are then modified by a weighting factor for the next iteration. By observing the statistics of the decoding procedure, the weighting factor is designed as a function of the channel condition. Results show that the proposed joint decoding methods can greatly reduce the number of iterations, and thereby reduce the decoding delay considerably. At the same time, this method always outperforms the nonsource controlled decoding method by up to 3 dB in terms of PSNR.

  19. Solar thermal hydrogen production process. Annual technical progress report, January-December, 1979

    Energy Technology Data Exchange (ETDEWEB)

    Parker, G.H.

    1979-01-01

    Westinghouse is currently under contract to DOE for technology development of the Sulfur Cycle, a hybrid thermochemical-electrochemical process for the production of hydrogen and oxygen from water. Operational studies have been conducted and have resulted in definitions of operating modes for solar/hydrogen plants and in assessments of the day/night and annual variations in performance that will influence the operating modes and the sizing of plant subsystems. Conceptual design studies have been conducted for process components that interface with the solar receiver. From related trade-off studies, a preferred configuration emerged that involves an intermediate working fluid (e.g., hot gas) between the solar receiver and the sulfuric acid decomposition reactor. The design of the reactor has been based on a shell and tube type heat exchanger configuration with catalyst placement on the shell side. A number of candidate materials for structural use in the acid decomposition reactor also have been evaluated experimentally. Screening tests and endurance tests with potential catalysts (to accelerate the rate of sulfur trioxide cracking) have been conducted with encouraging results. Approximately three dozen candidate materials for use in constructing the acid vaporizer have been tested for corrosion resistance to the expected environment. Detailed discussions of the results obtained during 1979 are presented.

  20. Acetic acid production from marine algae. Progress report No. 4, April 1-June 30, 1978

    Energy Technology Data Exchange (ETDEWEB)

    Sanderson, J. E.; Wise, D. L.

    1978-08-28

    To date fermentations of marine algal species run at a controlled pH of 5.5 to 6.0 have exhibited essentially complete conversion to organic acids in as little as 16 days. (By complete conversion is meant conversion of each hexose unit to three acetic acid molecules or higher organic acids on a reducing equivalent basis.) As a result of these rapid rates and high conversions economic calculations have shown that processing costs are sufficiently low to encourage commercial development of this process. In the course of this work a diffusion membrane extraction system has been developed for removing organic acids from the fermentation broth. In addition, a fixed packed bed fermenter with a capacity of approximately 300 liters has been constructed and operated for a six month period. Another significant result is that fermentation at thermophilic temperatures (55/sup 0/C) gives higher ratios of acetic acid to total acid product than at mesophilic temperatures (37/sup 0/C). Manuscripts of two technical presentations based on this work are attached.

  1. Low VOC drying of lumber and wood panel products. Progress report No. 4, annual summary

    Energy Technology Data Exchange (ETDEWEB)

    Boerner, J.; Su, Wei; Yan, Hui [and others

    1997-07-01

    Heating softwood in a low-headspace environment draws out the VOCs from the wood, without removing the water. The VOCs can be collected from the headspace, and represent a valuable product. The VOC-depleted wood can then be dried conventionally with much reduced emissions. Heating can be accomplished through radiofrequency (RF) or steam. For lumber, steam is inefficient, but brief RF treatment under low-headspace conditions draws out 80% of the VOCs. The power used is quite low, since the RF energy is not used to remove water, but only to maintain the wood at a set temperature. The technology is now at the pre-pilot stage. Either steam or RF can be used for particle, OSB, and veneer, again under low-headspace conditions. Increasing steam temperature facilitates VOC removal. In order to understand the mechanism of VOC release in lumber, the transport of water and VOCs to the surface is being studied as a function of sample size and orientation. Characterization of the terpenes and resin/fatty acids from a control set of trees is underway in order to define the seasonal influence on VOCs.

  2. Idaho Habitat/Natural Production Monitoring, Pt. I: General Monitoring Subproject : Annual Progress Report 1990.

    Energy Technology Data Exchange (ETDEWEB)

    Rich, Bruce A.; Scully, Richard J.; Petrosky, Charles Edward

    1992-01-01

    The Idaho Department of Fish and Game (IDFG) has been monitoring and evaluating proposed and existing habitat improvement projects for rainbow-steelhead trout Oncorhynchus mykiss, hereafter called steelhead, and chinook salmon O. tshawytscha, hereafter called chinook, in the Clearwater and Salmon River drainages for the past seven years. Projects included in the evaluation are funded by, or proposed for funding by, the Bonneville Power Administration (BPA) under the Northwest Power Planning Act as off-site mitigation for downstream hydropower development on the Snake and Columbia rivers. This evaluation project is also funded under the same authority (Fish and Wildlife Program, Northwest Power Planning Council). A mitigation record is being developed using increased carrying capacity and/or survival as the best measure of benefit from a habitat enhancement project. Determination of full benefit from a project depends on completion or maturation of the project and presence of adequate numbers of fish to document actual increases in fish production. The depressed status of upriver anadromous stocks has precluded measuring full benefits of any habitat project in Idaho. Partial benefit is credited to the mitigation record in the interim period of run restoration.

  3. Progressive Image Transmission Based on Joint Source-Channel Decoding Using Adaptive Sum-Product Algorithm

    Directory of Open Access Journals (Sweden)

    Liu Weiliang

    2007-01-01

    Full Text Available A joint source-channel decoding method is designed to accelerate the iterative log-domain sum-product decoding procedure of LDPC codes as well as to improve the reconstructed image quality. Error resilience modes are used in the JPEG2000 source codec making it possible to provide useful source decoded information to the channel decoder. After each iteration, a tentative decoding is made and the channel decoded bits are then sent to the JPEG2000 decoder. The positions of bits belonging to error-free coding passes are then fed back to the channel decoder. The log-likelihood ratios (LLRs of these bits are then modified by a weighting factor for the next iteration. By observing the statistics of the decoding procedure, the weighting factor is designed as a function of the channel condition. Results show that the proposed joint decoding methods can greatly reduce the number of iterations, and thereby reduce the decoding delay considerably. At the same time, this method always outperforms the nonsource controlled decoding method by up to 3 dB in terms of PSNR.

  4. Accurate kinetic parameter estimation during progress curve analysis of systems with endogenous substrate production.

    Science.gov (United States)

    Goudar, Chetan T

    2011-10-01

    We have identified an error in the published integral form of the modified Michaelis-Menten equation that accounts for endogenous substrate production. The correct solution is presented and the error in both the substrate concentration, S, and the kinetic parameters Vm , Km , and R resulting from the incorrect solution was characterized. The incorrect integral form resulted in substrate concentration errors as high as 50% resulting in 7-50% error in kinetic parameter estimates. To better reflect experimental scenarios, noise containing substrate depletion data were analyzed by both the incorrect and correct integral equations. While both equations resulted in identical fits to substrate depletion data, the final estimates of Vm , Km , and R were different and Km and R estimates from the incorrect integral equation deviated substantially from the actual values. Another observation was that at R = 0, the incorrect integral equation reduced to the correct form of the Michaelis-Menten equation. We believe this combination of excellent fits to experimental data, albeit with incorrect kinetic parameter estimates, and the reduction to the Michaelis-Menten equation at R = 0 is primarily responsible for the incorrectness to go unnoticed. However, the resulting error in kinetic parameter estimates will lead to incorrect biological interpretation and we urge the use of the correct integral form presented in this study.

  5. Idaho Habitat/Natural Production Monitoring, Pt. I: General Monitoring Subproject : Annual Progress Report 1990.

    Energy Technology Data Exchange (ETDEWEB)

    Rich, Bruce A.; Scully, Richard J.; Petrosky, Charles Edward

    1992-01-01

    The Idaho Department of Fish and Game (IDFG) has been monitoring and evaluating proposed and existing habitat improvement projects for rainbow-steelhead trout Oncorhynchus mykiss, hereafter called steelhead, and chinook salmon O. tshawytscha, hereafter called chinook, in the Clearwater and Salmon River drainages for the past seven years. Projects included in the evaluation are funded by, or proposed for funding by, the Bonneville Power Administration (BPA) under the Northwest Power Planning Act as off-site mitigation for downstream hydropower development on the Snake and Columbia rivers. This evaluation project is also funded under the same authority (Fish and Wildlife Program, Northwest Power Planning Council). A mitigation record is being developed using increased carrying capacity and/or survival as the best measure of benefit from a habitat enhancement project. Determination of full benefit from a project depends on completion or maturation of the project and presence of adequate numbers of fish to document actual increases in fish production. The depressed status of upriver anadromous stocks has precluded measuring full benefits of any habitat project in Idaho. Partial benefit is credited to the mitigation record in the interim period of run restoration.

  6. Increasing the biomass production of short rotation coppice forests. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Steinbeck, K.; Brown, C. L.

    1980-09-01

    The objective of the project is to increase biomass yields from coppice forests by admixing tree species (Alnus glutinosa, Robinia pseudoacacia and others) to plantations of Platanus occidentalis and Liquidambar styraciflua. Yield increases due to intensive cultivation, especially fertilization and irrigation, will be documented. A genetic improvement program of promising candidate species both through the identification of superior genotypes and mass cloning with tissue culture is also included. Three plantings have been established successfully to screen candidate species on various sites and to test the effects of weed control, fertilization and irrigation on short rotation forests. Two plantations in Georgia are in their 2nd and 3rd growing seasons while one in South Carolina is in its 1st growing season. A two acre plantation has been established to test development of geographic seed source material for sycamore. A nursery is in operation to develop seedling production methods for new species and to grow and maintain genetic material. Mass cloning of selected material by tissue culture techniques has produced material for testing in outplantings.

  7. Progress and challenges in the computational prediction of gene function using networks [v1; ref status: indexed, http://f1000r.es/SqmJUM

    Directory of Open Access Journals (Sweden)

    Paul Pavlidis

    2012-09-01

    Full Text Available In this opinion piece, we attempt to unify recent arguments we have made that serious confounds affect the use of network data to predict and characterize gene function. The development of computational approaches to determine gene function is a major strand of computational genomics research. However, progress beyond using BLAST to transfer annotations has been surprisingly slow. We have previously argued that a large part of the reported success in using "guilt by association" in network data is due to the tendency of methods to simply assign new functions to already well-annotated genes. While such predictions will tend to be correct, they are generic; it is true, but not very helpful, that a gene with many functions is more likely to have any function. We have also presented evidence that much of the remaining performance in cross-validation cannot be usefully generalized to new predictions, making progressive improvement in analysis difficult to engineer. Here we summarize our findings about how these problems will affect network analysis, discuss some ongoing responses within the field to these issues, and consolidate some recommendations and speculation, which we hope will modestly increase the reliability and specificity of gene function prediction.

  8. Research Progress of the cry Gene of Bacillus thuringiensis%苏云金芽胞杆菌cry基因研究进展

    Institute of Scientific and Technical Information of China (English)

    郑琦; 唐玉明; 关雄

    2012-01-01

    从cry基因的分类、鉴定、遗传特性以及应用概况等4个方面综述了苏云金芽胞杆菌cry基因的研究进展,并对cry基因的研究进行展望.%The research and progress of the cry genes of Bacillus thuringiensis were reviewed from the following aspects; gene classification, identification methods, genetic characteristics, application survey. And the prospect of researching was expected simultaneously.

  9. Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jonathan A Ewald

    Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

  10. Synthesis of bacteriophage-coded gene products during infection of Escherichia coli with amber mutants of T3 and T7 defective in gene 1

    DEFF Research Database (Denmark)

    Issinger, O G; Hausmann, R

    1973-01-01

    During nonpermissive infection by a T7 amber mutant in gene 1 (phage RNA polymerase-deficient), synthesis of the products of the phage genes 3 (endonuclease), 3, 5 (lysozyme), 5 (DNA polymerase), and 17 (serum blocking power) was shown to occur at about half the rate as during wild-type infection...

  11. Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters.

    Science.gov (United States)

    Montiel, Daniel; Kang, Hahk-Soo; Chang, Fang-Yuan; Charlop-Powers, Zachary; Brady, Sean F

    2015-07-21

    Large-scale sequencing of prokaryotic (meta)genomic DNA suggests that most bacterial natural product gene clusters are not expressed under common laboratory culture conditions. Silent gene clusters represent a promising resource for natural product discovery and the development of a new generation of therapeutics. Unfortunately, the characterization of molecules encoded by these clusters is hampered owing to our inability to express these gene clusters in the laboratory. To address this bottleneck, we have developed a promoter-engineering platform to transcriptionally activate silent gene clusters in a model heterologous host. Our approach uses yeast homologous recombination, an auxotrophy complementation-based yeast selection system and sequence orthogonal promoter cassettes to exchange all native promoters in silent gene clusters with constitutively active promoters. As part of this platform, we constructed and validated a set of bidirectional promoter cassettes consisting of orthogonal promoter sequences, Streptomyces ribosome binding sites, and yeast selectable marker genes. Using these tools we demonstrate the ability to simultaneously insert multiple promoter cassettes into a gene cluster, thereby expediting the reengineering process. We apply this method to model active and silent gene clusters (rebeccamycin and tetarimycin) and to the silent, cryptic pseudogene-containing, environmental DNA-derived Lzr gene cluster. Complete promoter refactoring and targeted gene exchange in this "dead" cluster led to the discovery of potent indolotryptoline antiproliferative agents, lazarimides A and B. This potentially scalable and cost-effective promoter reengineering platform should streamline the discovery of natural products from silent natural product biosynthetic gene clusters.

  12. Fuel gas production from animal and agricultural residues and biomass. Quarterly coordination meeting, March 15-16, 1979, Tampa, Florida. Third quarterly progress report

    Energy Technology Data Exchange (ETDEWEB)

    Wise, D L; Ashare, E; Wentworth, R L

    1979-04-24

    The eleventh quarterly coordination meeting of the methane production group of the Fuels From Biomass Systems Branch, US Department of Energy was held at Tampa, Florida, March 15-16, 1979. Progress reports were presented by the contractors and a site visit was made to Kaplan Industries, Bartow, Florida to see the Hamilton Standard demonstration facility for digestion of environmental feedlot residue to methane. A meeting agenda, a list of attendees, and progress reports are presented.

  13. Association of the WFS1 gene with disease progression in children with new onset T1D. Results from the Hvidoere study group on childhood diabetes

    DEFF Research Database (Denmark)

    Nielsen, L.B.; Andersen, M.L.M.; Svensson, Jannete

    2010-01-01

    variants the Wolfram syndrome. The aim of this study was to investigate the impact of a common genetic variant (rs10010131) of the WFS1 gene on disease progression in a group of children newly diagnosed with T1D. Methods: The study is a multicenter longitudinal investigation with 18 participating...... paediatric centres from 15 countries. Clinical information and blood samples were collected from 275 children less than 16 years at diagnosis and at 1, 6, and 12 months after onset. Genotyping of the rs10010131 variant was done by KBioscience using an in-house KASPar assay system. Statistics: C-peptide, HbA1...... with proinsulin (est.: 1.55, P = 0.005) the first 12 month after disease onset compared to the AA genotype carriers. Conclusions: A common variant of the WFS1 gene is highly associated with better residual beta-cell function and corresponding better metabolic control during disease progression in new onset T1D...

  14. Disruption of ubiquitin-related genes in laboratory yeast strains enhances ethanol production during sake brewing.

    Science.gov (United States)

    Wu, Hong; Watanabe, Tomoko; Araki, Yoshio; Kitagaki, Hiroshi; Akao, Takeshi; Takagi, Hiroshi; Shimoi, Hitoshi

    2009-06-01

    Sake yeast can produce high levels of ethanol in concentrated rice mash. While both sake and laboratory yeast strains belong to the species Saccharomyces cerevisiae, the laboratory strains produce much less ethanol. This disparity in fermentation activity may be due to the strains' different responses to environmental stresses, including ethanol accumulation. To obtain more insight into the stress response of yeast cells under sake brewing conditions, we carried out small-scale sake brewing tests using laboratory yeast strains disrupted in specific stress-related genes. Surprisingly, yeast strains with disrupted ubiquitin-related genes produced more ethanol than the parental strain during sake brewing. The elevated fermentation ability conferred by disruption of the ubiquitin-coding gene UBI4 was confined to laboratory strains, and the ubi4 disruptant of a sake yeast strain did not demonstrate a comparable increase in ethanol production. These findings suggest different roles for ubiquitin in sake and laboratory yeast strains.

  15. The SKP1-like gene family of Arabidopsis exhibits a high degree of differential gene expression and gene product interaction during development.

    Directory of Open Access Journals (Sweden)

    Mohammad H Dezfulian

    Full Text Available The Arabidopsis thaliana genome encodes several families of polypeptides that are known or predicted to participate in the formation of the SCF-class of E3-ubiquitin ligase complexes. One such gene family encodes the Skp1-like class of polypeptide subunits, where 21 genes have been identified and are known to be expressed in Arabidopsis. Phylogenetic analysis based on deduced polypeptide sequence organizes the family of ASK proteins into 7 clades. The complexity of the ASK gene family, together with the close structural similarity among its members raises the prospect of significant functional redundancy among select paralogs. We have assessed the potential for functional redundancy within the ASK gene family by analyzing an expanded set of criteria that define redundancy with higher resolution. The criteria used include quantitative expression of locus-specific transcripts using qRT-PCR, assessment of the sub-cellular localization of individual ASK:YFP auto-fluorescent fusion proteins expressed in vivo as well as the in planta assessment of individual ASK-F-Box protein interactions using bimolecular fluorescent complementation techniques in combination with confocal imagery in live cells. The results indicate significant functional divergence of steady state transcript abundance and protein-protein interaction specificity involving ASK proteins in a pattern that is poorly predicted by sequence-based phylogeny. The information emerging from this and related studies will prove important for defining the functional intersection of expression, localization and gene product interaction that better predicts the formation of discrete SCF complexes, as a prelude to investigating their molecular mode of action.

  16. The SKP1-like gene family of Arabidopsis exhibits a high degree of differential gene expression and gene product interaction during development.

    Science.gov (United States)

    Dezfulian, Mohammad H; Soulliere, Danielle M; Dhaliwal, Rajdeep K; Sareen, Madhulika; Crosby, William L

    2012-01-01

    The Arabidopsis thaliana genome encodes several families of polypeptides that are known or predicted to participate in the formation of the SCF-class of E3-ubiquitin ligase complexes. One such gene family encodes the Skp1-like class of polypeptide subunits, where 21 genes have been identified and are known to be expressed in Arabidopsis. Phylogenetic analysis based on deduced polypeptide sequence organizes the family of ASK proteins into 7 clades. The complexity of the ASK gene family, together with the close structural similarity among its members raises the prospect of significant functional redundancy among select paralogs. We have assessed the potential for functional redundancy within the ASK gene family by analyzing an expanded set of criteria that define redundancy with higher resolution. The criteria used include quantitative expression of locus-specific transcripts using qRT-PCR, assessment of the sub-cellular localization of individual ASK:YFP auto-fluorescent fusion proteins expressed in vivo as well as the in planta assessment of individual ASK-F-Box protein interactions using bimolecular fluorescent complementation techniques in combination with confocal imagery in live cells. The results indicate significant functional divergence of steady state transcript abundance and protein-protein interaction specificity involving ASK proteins in a pattern that is poorly predicted by sequence-based phylogeny. The information emerging from this and related studies will prove important for defining the functional intersection of expression, localization and gene product interaction that better predicts the formation of discrete SCF complexes, as a prelude to investigating their molecular mode of action.

  17. The PKS4 gene in Fusarium graminearum is essential for zearalenone production

    DEFF Research Database (Denmark)

    Lysøe, E.; Klemsdal, S. S.; Bone, K.R.

    2006-01-01

    protocol was used to replace the central part of the PKS4 gene with a hygB resistance gene through double homologous recombination in an F. graminearum strain producing a high level of ZON. PCR and Southern analysis of transformants were used to identify isolates with single insertional replacements of PKS......4. High-performance liquid chromatography analysis showed that the PKS4 replacement mutant did not produce ZON. Thus, PKS4 encodes an enzyme required for the production of ZON in F. graminearum. Barley root infection studies revealed no alteration in the pathogenicity of the PKS4 mutant compared......-encoded protein or its product stimulates expression of PKS13. Furthermore, both the lack of aurofusarin and ZON influenced the expression of other polyketide synthases, demonstrating that one polyketide can influence the expression of others....

  18. Gene Disruption Technologies Have the Potential to Transform Stored Product Insect Pest Control

    Science.gov (United States)

    Perkin, Lindsey C.; Adrianos, Sherry L.; Oppert, Brenda

    2016-01-01

    Stored product insects feed on grains and processed commodities manufactured from grain post-harvest, reducing the nutritional value and contaminating food. Currently, the main defense against stored product insect pests is the pesticide fumigant phosphine. Phosphine is highly toxic to all animals, but is the most effective and economical control method, and thus is used extensively worldwide. However, many insect populations have become resistant to phosphine, in some cases to very high levels. New, environmentally benign and more effective control strategies are needed for stored product pests. RNA interference (RNAi) may overcome pesticide resistance by targeting the expression of genes that contribute to resistance in insects. Most data on RNAi in stored product insects is from the coleopteran genetic model, Tribolium castaneum, since it has a strong RNAi response via injection of double stranded RNA (dsRNA) in any life stage. Additionally, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology has been suggested as a potential resource for new pest control strategies. In this review we discuss background information on both gene disruption technologies and summarize the advances made in terms of molecular pest management in stored product insects, mainly T. castaneum, as well as complications and future needs. PMID:27657138

  19. Enterotoxin A Gene Barrier Staphylococcus aureus Within Traditionally Dairy Products of Tehran

    Directory of Open Access Journals (Sweden)

    Solmaz Hassani

    2014-11-01

    Full Text Available Background: Staphylococcus aureusis a serious agent that often colonize dairy products all over the world. Staphylococcal enterotoxins are the essential causes of food poisoningin human societies. Enterotoxin type A is an importantstaphylococcal exotoxin. Objectives: The aim of present study was to detect the enterotoxin producing Staphylococcus.aureus within different dairy products collected from Tehran, Iran. Materials and Methods: Two hundreds twenty dairy products samples were collected from local dealers across the city. The samples were first screened for S. aureus contaminations. All isolated strains of S. aureus were then investigated for enterotoxin a gene, usind spesific primer sets. Results: Staphylococcus aureus was isolated from 43% of dairy samples: 22% from milk and 18% from cheese samples. The SEA genes were detected in 10 isolates (22% originated from raw milk and in two isolates (25% from domestic cheese. Conclusions: Since, the staphylococcal enterotoxins are heat stable, heat had no effect on the toxicity of the enterotoxins within positive samples. Our primer stets confirmed previous studies that introduced PCR as rapid, sensitive, and specific method for dairy products screening system. Our data showed that routine screening and surveillance is vital for different food materials including dairy products.

  20. Gene Disruption Technologies Have the Potential to Transform Stored Product Insect Pest Control.

    Science.gov (United States)

    Perkin, Lindsey C; Adrianos, Sherry L; Oppert, Brenda

    2016-09-19

    Stored product insects feed on grains and processed commodities manufactured from grain post-harvest, reducing the nutritional value and contaminating food. Currently, the main defense against stored product insect pests is the pesticide fumigant phosphine. Phosphine is highly toxic to all animals, but is the most effective and economical control method, and thus is used extensively worldwide. However, many insect populations have become resistant to phosphine, in some cases to very high levels. New, environmentally benign and more effective control strategies are needed for stored product pests. RNA interference (RNAi) may overcome pesticide resistance by targeting the expression of genes that contribute to resistance in insects. Most data on RNAi in stored product insects is from the coleopteran genetic model, Tribolium castaneum, since it has a strong RNAi response via injection of double stranded RNA (dsRNA) in any life stage. Additionally, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology has been suggested as a potential resource for new pest control strategies. In this review we discuss background information on both gene disruption technologies and summarize the advances made in terms of molecular pest management in stored product insects, mainly T. castaneum, as well as complications and future needs.

  1. Gene Disruption Technologies Have the Potential to Transform Stored Product Insect Pest Control

    Directory of Open Access Journals (Sweden)

    Lindsey C. Perkin

    2016-09-01

    Full Text Available Stored product insects feed on grains and processed commodities manufactured from grain post-harvest, reducing the nutritional value and contaminating food. Currently, the main defense against stored product insect pests is the pesticide fumigant phosphine. Phosphine is highly toxic to all animals, but is the most effective and economical control method, and thus is used extensively worldwide. However, many insect populations have become resistant to phosphine, in some cases to very high levels. New, environmentally benign and more effective control strategies are needed for stored product pests. RNA interference (RNAi may overcome pesticide resistance by targeting the expression of genes that contribute to resistance in insects. Most data on RNAi in stored product insects is from the coleopteran genetic model, Tribolium castaneum, since it has a strong RNAi response via injection of double stranded RNA (dsRNA in any life stage. Additionally, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR technology has been suggested as a potential resource for new pest control strategies. In this review we discuss background information on both gene disruption technologies and summarize the advances made in terms of molecular pest management in stored product insects, mainly T. castaneum, as well as complications and future needs.

  2. Genome Wide Association Analysis Reveals New Production Trait Genes in a Male Duroc Population.

    Directory of Open Access Journals (Sweden)

    Kejun Wang

    Full Text Available In this study, 796 male Duroc pigs were used to identify genomic regions controlling growth traits. Three production traits were studied: food conversion ratio, days to 100 KG, and average daily gain, using a panel of 39,436 single nucleotide polymorphisms. In total, we detected 11 genome-wide and 162 chromosome-wide single nucleotide polymorphism trait associations. The Gene ontology analysis identified 14 candidate genes close to significant single nucleotide polymorphisms, with growth-related functions: six for days to 100 KG (WT1, FBXO3, DOCK7, PPP3CA, AGPAT9, and NKX6-1, seven for food conversion ratio (MAP2, TBX15, IVL, ARL15, CPS1, VWC2L, and VAV3, and one for average daily gain (COL27A1. Gene ontology analysis indicated that most of the candidate genes are involved in muscle, fat, bone or nervous system development, nutrient absorption, and metabolism, which are all either directly or indirectly related to growth traits in pigs. Additionally, we found four haplotype blocks composed of suggestive single nucleotide polymorphisms located in the growth trait-related quantitative trait loci and further narrowed down the ranges, the largest of which decreased by ~60 Mb. Hence, our results could be used to improve pig production traits by increasing the frequency of favorable alleles via artificial selection.

  3. Recombinant Streptomyces clavuligerus strain including cas2 gene production and analysis its antibiotic overproduction by bioassay

    Directory of Open Access Journals (Sweden)

    Zohreh Hojati

    2014-03-01

    Full Text Available Background: Streptomyces clavuligerus is one of the most important strain that produce clavulanic acid that wildly used in combination of strong but sensitive to β-lactamase antibiotics in clinics. The cas2 is one of the important genes in the biosynthesis pathway of clavulanic acid. Materials and Methods: The recombinant construct pMTcas2 which contain cas2 gene is obtained from Isfahan University. Recombinant plasmid extracts from streptomyces lividans and confirm by enzyme digestion. The streptomyces clavuligerus protoplast was prepared and transformation was done by using polyethylene glycol. Transformation was confirmed by plasmid extraction and PCR using cas2 specific primers. Finally, bioassay method was used to survey the effect of extra copy of cas2 on clavulanic acid production. Result: Plasmid extraction was initially carried out and the structure of plasmid was confirmed by digestion. The typical white colony was seen on protoplast recovery culture containing thiostrepton antibiotic and gray spores were detected after one week. Plasmid extraction was done from transformed strain and transformation was confirmed by PCR. The results of the bioassay show that amplification of the cas2 gene in multicopy plasmids resulted in a 4.1 fold increase in clavulanic acid production. Conclusion: The bioassay was done and the diameters of zone of inhibition in control and sample were compared. The results of the bioassay show that amplification of the cas2 gene in multicopy plasmids resulted in a 4.1 fold increase in clavulanic acid production. Overproduction of clavulanic acid decreases the cost of its dependent drug production.

  4. Expression of Clostridium acetobutylicum ATCC 824 Genes in Escherichia coli for Acetone Production and Acetate Detoxification

    OpenAIRE

    Bermejo, Lourdes L.; Welker, Neil E.; Papoutsakis, Eleftherios T.

    1998-01-01

    A synthetic acetone operon (ace4) composed of four Clostridium acetobutylicum ATCC 824 genes (adc, ctfAB, and thl, coding for the acetoacetate decarboxylase, coenzyme A transferase, and thiolase, respectively) under the control of the thl promoter was constructed and was introduced into Escherichia coli on vector pACT. Acetone production demonstrated that ace4 is expressed in E. coli and resulted in the reduction of acetic acid levels in the fermentation broth. Since different E. coli strains...

  5. Increasing cocoa butter-like lipid production of Saccharomyces cerevisiae by expression of selected cocoa genes.

    Science.gov (United States)

    Wei, Yongjun; Gossing, Michael; Bergenholm, David; Siewers, Verena; Nielsen, Jens

    2017-12-01

    Cocoa butter (CB) extracted from cocoa beans mainly consists of three different kinds of triacylglycerols (TAGs), 1,3-dipalmitoyl-2-oleoyl-glycerol (POP, C16:0-C18:1-C16:0), 1-palmitoyl-3-stearoyl-2-oleoyl-glycerol (POS, C16:0-C18:1-C18:0) and 1,3-distearoyl-2-oleoyl-glycerol (SOS, C18:0-C18:1-C18:0), but CB supply is limited. Therefore, CB-like lipids (CBL, which are composed of POP, POS and SOS) are in great demand. Saccharomyces cerevisiae produces TAGs as storage lipids, which are also mainly composed of C16 and C18 fatty acids. However, POP, POS and SOS are not among the major TAG forms in yeast. TAG synthesis is mainly catalyzed by three enzymes: glycerol-3-phosphate acyltransferase (GPAT), lysophospholipid acyltransferase (LPAT) and diacylglycerol acyltransferase (DGAT). In order to produce CBL in S. cerevisiae, we selected six cocoa genes encoding GPAT, LPAT and DGAT potentially responsible for CB biosynthesis from the cocoa genome using a phylogenetic analysis approach. By expressing the selected cocoa genes in S. cerevisiae, we successfully increased total fatty acid production, TAG production and CBL production in some S. cerevisiae strains. The relative CBL content in three yeast strains harboring cocoa genes increased 190, 230 and 196% over the control strain, respectively; especially, the potential SOS content of the three yeast strains increased 254, 476 and 354% over the control strain. Moreover, one of the three yeast strains had a 2.25-fold increased TAG content and 6.7-fold higher level of CBL compared with the control strain. In summary, CBL production by S. cerevisiae were increased through expressing selected cocoa genes potentially involved in CB biosynthesis.

  6. Genetic resources for methane production from biomass described with gene ontology

    Directory of Open Access Journals (Sweden)

    Endang ePurwantini

    2014-12-01

    Full Text Available Methane (CH4 is a valuable fuel, constituting 70-95% of natural gas, and a potent greenhouse gas. Release of CH4 into the atmosphere contributes to climate change. Biological CH4 production or methanogenesis is mostly performed by methanogens, a group of strictly anaerobic archaea. The direct substrates for methanogenesis are H2 plus CO2, acetate, formate, methylamines, methanol, methyl sulfides, and ethanol or a secondary alcohol plus CO2. In numerous anaerobic niches in nature, methanogenesis facilitates mineralization of complex biopolymers such as carbohydrates, lipids and proteins generated by primary producers. Thus, methanogens are critical players in the global carbon cycle. The same process is used in anaerobic treatment of municipal, industrial and agricultural wastes, reducing the biological pollutants in the wastes and generating methane. It also holds potential for commercial production of natural gas from renewable resources. This process operates in digestive systems of many animals, including cattle, and humans. In contrast, in deep-sea hydrothermal vents methanogenesis is a primary production process, allowing chemosynthesis of biomaterials from H2 plus CO2. In this report we present Gene Ontology (GO terms that can be used to describe processes, functions and cellular components involved in methanogenic biodegradation and biosynthesis of specialized coenzymes that methanogens use. Some of these GO terms were previously available and the rest were generated in our Microbial Energy Gene Ontology (MENGO project. A recently discovered non-canonical CH4 production process is also described. We have performed manual GO annotation of selected methanogenesis genes, based on experimental evidence, providing gold standards for machine annotation and automated discovery of methanogenesis genes or systems in diverse genomes. Most of the GO-related information presented in this report is available at the MENGO website (http://www.mengo.biochem.vt.edu/.

  7. Tumor Progression Locus 2 Promotes Induction of IFNλ, Interferon Stimulated Genes and Antigen-Specific CD8+ T Cell Responses and Protects against Influenza Virus.

    Directory of Open Access Journals (Sweden)

    Teneema Kuriakose

    2015-08-01

    Full Text Available Mitogen-activated protein kinase (MAP cascades are important in antiviral immunity through their regulation of interferon (IFN production as well as virus replication. Although the serine-threonine MAP kinase tumor progression locus 2 (Tpl2/MAP3K8 has been implicated as a key regulator of Type I (IFNα/β and Type II (IFNγ IFNs, remarkably little is known about how Tpl2 might contribute to host defense against viruses. Herein, we investigated the role of Tpl2 in antiviral immune responses against influenza virus. We demonstrate that Tpl2 is an integral component of multiple virus sensing pathways, differentially regulating the induction of IFNα/β and IFNλ in a cell-type specific manner. Although Tpl2 is important in the regulation of both IFNα/β and IFNλ, only IFNλ required Tpl2 for its induction during influenza virus infection both in vitro and in vivo. Further studies revealed an unanticipated function for Tpl2 in transducing Type I IFN signals and promoting expression of interferon-stimulated genes (ISGs. Importantly, Tpl2 signaling in nonhematopoietic cells is necessary to limit early virus replication. In addition to early innate alterations, impaired expansion of virus-specific CD8+ T cells accompanied delayed viral clearance in Tpl2-/- mice at late time points. Consistent with its critical role in facilitating both innate and adaptive antiviral responses, Tpl2 is required for restricting morbidity and mortality associated with influenza virus infection. Collectively, these findings establish an essential role for Tpl2 in antiviral host defense mechanisms.

  8. Recombinant hepatitis B surface antigen production in Aspergillus niger: evaluating the strategy of gene fusion to native glucoamylase

    CSIR Research Space (South Africa)

    James, ER

    2012-10-01

    Full Text Available Microbiology and Biotechnology October 2012/ Vol. 96, No.2 Recombinant hepatitis B surface antigen production in Aspergillus niger: evaluating the strategy of gene fusion to native glucoamylase ER James a,c & WH van Zyl b & PJ van Zyl c & JF Görgens..., Pretoria 0001, South Africa Abstract This study demonstrates the potential of Aspergillus niger as a candidate expression system for virus- like particle production using gene fusion. Hepatitis B surface antigen (HBsAg) production, targeted...

  9. Characterization of the Expression of Basigin Gene Products Within the Pineal Gland of Mice.

    Science.gov (United States)

    Tokar, Derek; van Ekeris, Leslie; Linser, Paul J; Ochrietor, Judith D

    2016-11-04

    The expression of Basigin gene products and monocarboxylate transporter-1 (MCT1) has been investigated within the mammalian neural retina and suggests a role for these proteins in cellular metabolism within that tissue. The purpose of the present study was to investigate the expression of these same proteins in the pineal gland of the mouse brain. Mouse pineal gland and neural retina RNA and protein were subjected to quantitative reverse transcription-polymerase chain reaction and immunoblotting analyses. In addition, paraffin-embedded sections of each tissue were analyzed for expression of Basigin gene products and MCT1 via immunohistochemistry. The results indicate that MCT1 and Basigin variant-2, but not Basigin variant-1, are expressed within the mouse pineal gland. The expression of Basigin variant-2 and MCT1 was localized to the capsule surrounding the gland. The position and relative amounts of the gene products suggest that they play a much less prominent role within the pineal gland than in the neural retina.

  10. Diversity of Streptococcus thermophilus in bacteriocin production; inhibitory spectrum and occurrence of thermophilin genes.

    Science.gov (United States)

    Rossi, Franca; Marzotto, Marta; Cremonese, Silvia; Rizzotti, Lucia; Torriani, Sandra

    2013-08-01

    The bacteriocin-producing Streptococcus thermophilus strains that can dominate in natural dairy ecosystems, may also enhance safety in products obtained from natural cultures. In this study, we sought to identify bacteriocin production and bacteriocin genes in 75 strains of dairy and plant origin. The strains were tested for antimicrobial activity against pathogens or pathogen models, spoiling bacteria, and lactic acid bacteria associated with dairy products. All strains moderately inhibited Staphylococcus aureus P310, none inhibited Listeria innocua LMG 11387(T) or Clostridium tyrobutyricum LMG 1285(T). In addition, 14 were active against one or more indicators in addition to S. aureus P310. Inhibition of other starter bacteria was more common than the inhibition of unwanted microorganisms. The involvement of a proteinaceous compound was ascertained in all cases. Results suggested that the selection of bacteriocinogenic S. thermophilus strains for use in biopreservation must take into account the effects exerted on other lactic acid bacteria. PCR detection of thermophilin genes proved unreliable in predicting antimicrobial activity. For S. thermophilus PRI36 and PRI45, with relevant inhibitory features, the identity of the bacteriocin genes present in the thermophilin 9 cluster was defined, thus revealing novel variants for this genome region.

  11. Association of polymorphisms of Nrampl gene with immune function and production performance of large white pig

    Institute of Scientific and Technical Information of China (English)

    Hongmei Wu; Duxue Cheng; Lixian Wang

    2008-01-01

    The present research was designed to study the association of polymorphism of natural resistance-associated macrophage protein 1 (Nrampl) with some immune function and the production performance in Large White pig. The PCR-RFLP technique was applied to analyze the correlation between the polymorphisms of Nrampl gene and immune function [value of Polymorphonuclear Leukocytes (PMN) obtained by Nitroblue Tetrazolium (NBT) Reduction and effect of Cytotoxin in Monocyte] and