WorldWideScience

Sample records for prp gene argues

  1. Early embryonic gene expression profiling of zebrafish prion protein (Prp2 morphants.

    Directory of Open Access Journals (Sweden)

    Rasoul Nourizadeh-Lillabadi

    Full Text Available BACKGROUND: The Prion protein (PRNP/Prp plays a crucial role in transmissible spongiform encephalopathies (TSEs like Creutzfeldt-Jakob disease (CJD, scrapie and mad cow disease. Notwithstanding the importance in human and animal disease, fundamental aspects of PRNP/Prp function and transmission remains unaccounted for. METHODOLOGY/PRINCIPAL FINDINGS: The zebrafish (Danio rerio genome contains three Prp encoding genes assigned prp1, prp2 and prp3. Currently, the second paralogue is believed to be the most similar to the mammalian PRNP gene in structure and function. Functional studies of the PRNP gene ortholog was addressed by prp2 morpholino (MO knockdown experiments. Investigation of Prp2 depleted embryos revealed high mortality and apoptosis at 24 hours post fertilization (hpf as well as impaired brain and neuronal development. In order to elucidate the underlying mechanisms, a genome-wide transcriptome analysis was carried out in viable 24 hpf morphants. The resulting changes in gene expression profiles revealed 249 differently expressed genes linked to biological processes like cell death, neurogenesis and embryonic development. CONCLUSIONS/SIGNIFICANCE: The current study contributes to the understanding of basic Prp functions and demonstrates that the zebrafish is an excellent model to address the role of Prp in vertebrates. The gene knockdown of prp2 indicates an essential biological function for the zebrafish ortholog with a morphant phenotype that suggests a neurodegenerative action and gene expression effects which are apoptosis related and effects gene networks controlling neurogenesis and embryo development.

  2. Propionate catabolism in Salmonella typhimurium LT2: two divergently transcribed units comprise the prp locus at 8.5 centisomes, prpR encodes a member of the sigma-54 family of activators, and the prpBCDE genes constitute an operon.

    Science.gov (United States)

    Horswill, A R; Escalante-Semerena, J C

    1997-02-01

    We present the initial genetic and biochemical characterization of the propionate (prp) locus at 8.5 centisomes of the Salmonella typhimurium LT2 chromosome (T. A. Hammelman et al., FEMS Microbiol. Lett. 137: 233-239, 1996). In this paper, we report the nucleotide sequences of two divergently transcribed transcriptional units. One unit is comprised of the prpR gene (1,626 bp) encoding a member of the sigma-54 family of transcriptional activators; the second unit contains an operon of four genes designated prpB (888 bp), prpC (1,170 bp), prpD (1,452 bp), and prpE (1,923 bp). The heme biosynthetic gene hemB was shown by DNA sequencing to be located immediately downstream of the prpBCDE operon; hemB is divergently transcribed from prpBCDE and is separated from prpE by a 66-bp gap. In addition, we demonstrate the involvement of PrpB, PrpC, and PrpD in propionate catabolism by complementation analysis of mutants using plasmids carrying a single prp gene under the control of the arabinose-responsive P(BAD) promoter. Expression of prpB to high levels was deleterious to the growth of a prp+ strain on minimal medium supplemented with propionate as a carbon and energy source. We also report the cloning and overexpression of prpB, prpC, prpD, and prpE in the T7 system. PrpB, PrpC, PrpD, and PrpE had molecular masses of ca. 32, ca. 44, ca. 53, and ca. 70 kDa, respectively. PrpB showed homology to carboxyphosphonoenolpyruvate phosphonomutase of Streptomyces hygroscopicus and to its homolog in the carnation Dianthus caryophyllus; PrpC was homologous to both archaeal and bacterial citrate synthases; PrpD showed homology to yeast and Bacillus subtilis proteins of unknown function; PrpE showed homology to acetyl coenzyme A synthetases. We identified a sigma-54 (RpoN)-dependent promoter with a consensus RpoN binding site upstream of the initiating methionine codon of prpB, the promoter-proximal gene of the prp operon. Consistent with this finding, an rpoN prp+ mutant failed to use

  3. Cotton PRP5 gene encoding a proline-rich protein is involved in fiber development.

    Science.gov (United States)

    Xu, Wen-Liang; Zhang, De-Jing; Wu, Yan-Feng; Qin, Li-Xia; Huang, Geng-Qing; Li, Juan; Li, Long; Li, Xue-Bao

    2013-07-01

    Proline-rich proteins contribute to cell wall structure of specific cell types and are involved in plant growth and development. In this study, a fiber-specific gene, GhPRP5, encoding a proline-rich protein was functionally characterized in cotton. GhPRP5 promoter directed GUS expression only in trichomes of both transgenic Arabidopsis and tobacco plants. The transgenic Arabidopsis plants with overexpressing GhPRP5 displayed reduced cell growth, resulting in smaller cell size and consequently plant dwarfs, in comparison with wild type plants. In contrast, knock-down of GhPRP5 expression by RNA interference in cotton enhanced fiber development. The fiber length of transgenic cotton plants was longer than that of wild type. In addition, some genes involved in fiber elongation and wall biosynthesis of cotton were up-regulated or down-regulated in the transgenic cotton plants owing to suppression of GhPRP5. Collectively, these data suggested that GhPRP5 protein as a negative regulator participates in modulating fiber development of cotton.

  4. Sequence polymorphism of PrP exon 3 gene in Istrian and crossbred sheep

    Directory of Open Access Journals (Sweden)

    Ino Curik

    2010-01-01

    Full Text Available Polymorphisms in sheep PrP (prion protein gene are known for scrapie susceptibility. We sequenced part of PrP exon 3 gene in 92 autochthonous Istrian (IS and 38 crossbred sheep (CBS. ARQ, ARR and AHQ alleles were predominant with frequency of 0.674 (0.526, 0.228 (0.132 and 0.082 (0.263 in IS (CBS, respectively, while VRQ (0.011 in IS and ARH (0.005 in IS and 0.079 in CBS alleles were rare. We also found non-synonymous mutations at codons 112 (M→T, 127 (G→S and 143 (H→R, and synonymous mutations at codons 231 (R and 237 (L. Additional mutations were associated only with AHQ, ARH and ARQ alleles. The polymorphism of PrP gene in IS was not critical with respect to scrapie susceptibility and with some efforts number of “favourable” genotypes can be increased.

  5. Expression of the promoter of HyPRP, an embryo-specific gene from Zea mays in maize and tobacco transgenic plants.

    Science.gov (United States)

    José-Estanyol, Matilde; Pérez, Pascual; Puigdomènech, Pere

    2005-08-15

    zmHyPRP is a gene specifically expressed in maize immature embryos where its transcripts are mainly observed in the scutellum. It has been shown that zmHyPRP expression in the embryo is arrested when ABA levels increase at the beginning of the maturation stage. Here we report the ability of 2 Kb zmHyPRP promoter to reproduce the zmHyPRP gene specific expression pattern in the maize embryo and its repression by ABA at the end of the morphogenetic process. Three different approaches have been used, transient particle bombardment of maize immature excised embryos and stable transformation of maize and tobacco plants with a construct containing 2 Kb of zmHyPRP promoter fused to the GUS gene. This construct has shown to confer specific expression to maize and tobacco embryos but in tobacco expression in the embryo was very low. The same construct was also negatively regulated by ABA in embryos of both species. This suggests that 2 Kb of the zmHyPRP promoter contain all regulatory elements sufficient to confer the developmental expression patterns of the gene characterized to date.

  6. Hyperuricemic PRP in Tendon Cells

    Directory of Open Access Journals (Sweden)

    I. Andia

    2014-01-01

    Full Text Available Platelet-rich plasma (PRP is injected within tendons to stimulate healing. Metabolic alterations such as the metabolic syndrome, diabetes, or hyperuricemia could hinder the therapeutic effect of PRP. We hypothesise that tendon cells sense high levels of uric acid and this could modify their response to PRP. Tendon cells were treated with allogeneic PRPs for 96 hours. Hyperuricemic PRP did not hinder the proliferative actions of PRP. The gene expression pattern of inflammatory molecules in response to PRP showed absence of IL-1b and COX1 and modest expression of IL6, IL8, COX2, and TGF-b1. IL8 and IL6 proteins were secreted by tendon cells treated with PRP. The synthesis of IL6 and IL8 proteins induced by PRP is decreased significantly in the presence of hyperuricemia (P = 0.017 and P = 0.012, resp.. Concerning extracellular matrix, PRP-treated tendon cells displayed high type-1 collagen, moderate type-3 collagen, decorin, and hyaluronan synthase-2 expression and modest expression of scleraxis. Hyperuricemia modified the expression pattern of extracellular matrix proteins, upregulating COL1 (P = 0.036 and COMP (P = 0.012 and downregulating HAS2 (P = 0.012. Positive correlations between TGF-b1 and type-1 collagen (R = 0.905, P = 0.002 and aggrecan (R = 0.833, P = 0.010 and negative correlations between TGF-b1 and IL6 synthesis (R = −0.857, P = 0.007 and COX2 (R = −0.810, P = 0.015 were found.

  7. The MsPRP2 promoter enables strong heterologous gene expression in a root-specific manner and is enhanced by overexpression of Alfin 1.

    Science.gov (United States)

    Winicov, Ilga; Valliyodan, Babu; Xue, Lingru; Hoober, J Kenneth

    2004-10-01

    Promoter specificity and efficiency of utilization are essential for endogenous and transgene expression. Selective root expression remains to be defined in terms of both promoter elements and transcription factors that provide high levels of ubiquitous expression. We characterized expression from the MsPRP2 promoter with the green fluorescent protein (GFP) reporter transgene in alfalfa (Medicago sativa) and found that a promoter fragment (+1 to -652 bp) retained the root and callus specificity of the endogenous MsPRP2 gene and hence this promoter fragment contains elements necessary for root-specific expression. The strong ubiquitous expression obtained from this promoter was comparable to that of the CaMV 35S promoter in roots and was enhanced by transgenic overexpression of Alfin 1, a root- and callus-specific transcription factor in alfalfa. No transgenic expression was obtained in leaves with this promoter in the presence or absence of Alfin 1. The increased expression of GFP in alfalfa containing the Alfin 1 transgene confirms the function of Alfin 1 binding sites in the MsPRP2 promoter fragment and also indicates that Alfin 1 concentrations are limiting for maximal expression in calli and roots. These findings characterize the MsPRP2 promoter as a novel root- and callus-specific promoter of plant origin that can be used as an effective tool for strong root-directed gene expression. In addition, we have demonstrated that the signal sequence of MsPRP2 can be used for efficient secretion of transgene products from callus and roots.

  8. Arguing Against Security Communitarianism

    DEFF Research Database (Denmark)

    Bilgin, Pinar

    2016-01-01

    as a particular approach that seeks to limit the scope of security to one’s community – be it the ‘nation-state’ or ‘civilization’. I will suggest that arguing against ‘security communitarianism’ requires paying further attention to the postcolonial critique of cosmopolitanism.......Anthony Burke’s ‘security cosmopolitanism’ is a fresh and thought-provoking contribution to critical theorizing about security. In this discussion piece, I would like to join Burke’s call for ‘security cosmopolitanism’ by way of arguing against ‘security communitarianism’. I understand the latter...

  9. Arguing with the cognitivists.

    Science.gov (United States)

    Lee, C

    1996-12-01

    A number of cognitivists have claimed that it is somehow illegitimate for those people who do not accept that cognitions are the only cause of human behavior to enter into debate on the issue. Their argument appears to be that it is not possible to develop an argument without making use of the sort of cognition described by Bandura [Bandura (1995) Comments on the crusade against the causal efficacy of human thought, Journal of Behavior Therapy and Experimental Psychiatry, 26, 179-190] and others, nor is it possible to influence other people without attempting to change their cognitive model of the topic, and therefore the mere fact of arguing is enough to disprove the non-cognitivists' position. This paper argues that argument is not dependent on an inner monologue but is a behavioral process; and attempting to persuade others does not necessitate a belief in a central causal role for cognitions. It is quite possible to engage in academic debate without adopting a dualist model of the human being, and, by extension, it is quite possible to explain a wide range of complex human activities without recourse to the limiting models of contemporary cognitive psychology.

  10. Changes in allele and genotype frequencies of PrP gene in breeds of sheep in Slovakia between 2004 and 2015

    Directory of Open Access Journals (Sweden)

    Milan Margetín

    2016-09-01

    Full Text Available The objective of the study was to analyze the changes in allele and genotype frequencies of PrP gene in auction purebred rams of various breeds in Slovakia between 2004 and 2015. Male genotyping was done within the National Scrapie Eradication Programme by the certified laboratories. Positive changes in all breeds were found during the analyzed period. As a result of strict positive selection for ARR allele and strict negative selection for VRQ and ARQ alleles in most numerous Improved Valachian (IV and Tsigai (TS breeds, 94.7 % (IV and 95.7 % (TS of animals were included in the first and second risk (R1 and R2 groups in 2015. Frequencies of ARR allele were above 0.9 in specialized meat breeds. In Lacaune breed, frequencies of ARR, ARQ and VRQ alleles were 0.896, 0.117 and 0.003 in 2015. All purebred East Friesian males were included in R1 and R2 groups in 2015.

  11. Identification of a key recombinant narrows the CADASIL gene region to 8 cM and argues against allelism of CADASIL and familial hemiplegic migraine

    Energy Technology Data Exchange (ETDEWEB)

    Dichgans, M.; Mayer, M.; Straube, A. [Univ. of Munich (Germany)] [and others

    1996-02-15

    This article reports on new information regarding the genetic mapping of the human CADASIL gene region. Previously, the gene had been mapped to human chromosome 19q12. Using the identification of a chromosomal crossover, the region has been refined to an 8-cM interval. 11 refs., 2 figs., 1 tab.

  12. Can PRP effectively treat injured tendons?

    Science.gov (United States)

    Wang, James H-C

    2014-01-01

    PRP is widely used to treat tendon and other tissue injuries in orthopaedics and sports medicine; however, the efficacy of PRP treatment on injured tendons is highly controversial. In this commentary, I reason that there are many PRP- and patient-related factors that influence the outcomes of PRP treatment on injured tendons. Therefore, more basic science studies are needed to understand the mechanism of PRP on injured tendons. Finally, I suggest that better understanding of the PRP action mechanism will lead to better use of PRP for the effective treatment of tendon injuries in clinics.

  13. Consistency argued students of fluid

    Science.gov (United States)

    Viyanti; Cari; Suparmi; Winarti; Slamet Budiarti, Indah; Handika, Jeffry; Widyastuti, Fatma

    2017-01-01

    Problem solving for physics concepts through consistency arguments can improve thinking skills of students and it is an important thing in science. The study aims to assess the consistency of the material Fluid student argmentation. The population of this study are College students PGRI Madiun, UIN Sunan Kalijaga Yogyakarta and Lampung University. Samples using cluster random sampling, 145 samples obtained by the number of students. The study used a descriptive survey method. Data obtained through multiple-choice test and interview reasoned. Problem fluid modified from [9] and [1]. The results of the study gained an average consistency argmentation for the right consistency, consistency is wrong, and inconsistent respectively 4.85%; 29.93%; and 65.23%. Data from the study have an impact on the lack of understanding of the fluid material which is ideally in full consistency argued affect the expansion of understanding of the concept. The results of the study as a reference in making improvements in future studies is to obtain a positive change in the consistency of argumentations.

  14. HGF mediates the anti-inflammatory effects of PRP on injured tendons.

    Directory of Open Access Journals (Sweden)

    Jianying Zhang

    Full Text Available Platelet-rich plasma (PRP containing hepatocyte growth factor (HGF and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2.

  15. Polymorphism of the PrP prion protein gene in Polish Merino and old-type Polish Merino from Brylewo flock

    Directory of Open Access Journals (Sweden)

    Niżnikowski Roman

    2015-06-01

    Full Text Available The study was conducted on Polish Merino (143♀ and 39♂ and old-type Polish Merino sheep (176♀ and 61♂ in Brylewo flock (Wielkopolskie Province. The examined sheep were at the age of one year. Prion protein (PrP genotype was determined in all animals. In both breeds four alleles (ARR, ARQ, AHQ, VRQ were found. Highly significant effect of breed and insignificant impact of gender within breed was observed in regard to the frequency of occurrence of alleles and genotypes susceptible to classical scrapie in the sheep. Eight different PrP genotypes in Polish Merino and nine genotypes in old-type Polish Merino were identified. Very high frequency of ARR/ARR genotype in old-type Polish Merino and high frequency of ARR/ARQ genotype in Polish Merino were found, with relatively significant frequency of occurrence of the genotypes containing VRQ allele. In old-type Polish Merino, three animals (of both genders had VRQ/VRQ genotype. Breeding work involving elimination of animals encoding valine at codon 136, and introduction of rams with ARR allele to the population increased the frequency of occurrence of ARR/ARR genotype and ARR allele in the population of old-type Polish Merino. To improve the distribution of the genotypes genetically resistant to scrapie in the flock of Polish Merino only rams with ARR/ARR genotype were left. This guarantees an increase in the frequency of occurrence of genotypes genetically resistant to scrapie in the offspring.

  16. PRP and Articular Cartilage: A Clinical Update

    Directory of Open Access Journals (Sweden)

    Antonio Marmotti

    2015-01-01

    Full Text Available The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory.

  17. Portable Radiation Package (PRP) Instrument Handbook

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, R Michael [Remote Measurements and Research Company, Seattle, WA (United States)

    2017-08-03

    The Portable Radiation Package (PRP) was developed to provide basic radiation information in locations such as ships at sea where proper exposure is remote and difficult, the platform is in motion, and azimuth alignment is not fixed. Development of the PRP began at Brookhaven National Laboratory (BNL) in the mid-1990s and versions of it were deployed on ships in the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility’s Nauru-99 project. The PRP was deployed on ships in support of the National Aeronautics and Space Administration (NASA) Sensor Intercomparison for Marine Biological and Interdisciplinary Ocean Studies (SIMBIOS) program. Over the years the measurements have remained the same while the post-processing data analysis, especially for the FRSR, has evolved. This document describes the next-generation Portable Radiation Package (PRP2) that was developed for the DOE ARM Facility, under contract no. 9F-31462 from Argonne National Laboratory (ANL). The PRP2 has the same scientific principles that were well validated in prior studies, but has upgraded electronic hardware. The PRP2 approach is completely modular, both in hardware and software. Each sensor input is treated as a separate serial stream into the data collection computer. In this way the operator has complete access to each component of the system for purposes of error checking, calibration, and maintenance. The resulting system is more reliable, easier to install in complex situations, and more amenable to upgrade.

  18. How to argue against active euthanasia.

    Science.gov (United States)

    Boonin, D

    2000-01-01

    Most arguments against active euthanasia, as do most arguments in applied ethics generally, take place within the framework of what can broadly be referred to as a modern, as opposed to an ancient, approach to moral theory. In this paper, I argue that this fact works to the disadvantage of opponents of active euthanasia, and that if there is a successful argument against active euthanasia, it will be of the latter sort. In Part I, I attempt to clarify the distinction between modern and ancient approaches with which I am concerned. In Part II, I attempt to show that any argument against active euthanasia that is of the first sort is bound to fail. In Part III, I propose an argument against active euthanasia of the second sort that I believe has a better chance for success. In Part IV, I consider some objections that can be raised against this argument and attempt to show how they can be overcome.

  19. Pigeonpea Hybrid-Proline-Rich Protein (CcHyPRP) Confers Biotic and Abiotic Stress Tolerance in Transgenic Rice

    Science.gov (United States)

    Mellacheruvu, Sunitha; Tamirisa, Srinath; Vudem, Dashavantha Reddy; Khareedu, Venkateswara Rao

    2016-01-01

    In this study, we report the overexpression of Cajanus cajan hybrid-proline-rich protein encoding gene (CcHyPRP) in rice which resulted in increased tolerance to both abiotic and biotic stresses. Compared to the control plants, the transgenic rice lines, expressing CcHyPRP, exhibited high-level tolerance against major abiotic stresses, viz., drought, salinity, and heat, as evidenced by increased biomass, chlorophyll content, survival rate, root, and shoot growth. Further, transgenic rice lines showed increased panicle size and grain number compared to the control plants under different stress conditions. The CcHyPRP transgenics, as compared to the control, revealed enhanced activities of catalase and superoxide dismutase (SOD) enzymes and reduced malondialdehyde (MDA) levels. Expression pattern of CcHyPRP::GFP fusion-protein confirmed its predominant localization in cell walls. Moreover, the CcHyPRP transgenics, as compared to the control, exhibited increased resistance to the fungal pathogen Magnaporthe grisea which causes blast disease in rice. Higher levels of bZIP and endochitinase transcripts as well as endochitinase activity were observed in transgenic rice compared to the control plants. The overall results demonstrate the intrinsic role of CcHyPRP in conferring multiple stress tolerance at the whole-plant level. The multipotent CcHyPRP seems promising as a prime candidate gene to fortify crop plants for enhanced tolerance/resistance to different stress factors. PMID:26834756

  20. Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent.

    OpenAIRE

    Sakaguchi, S; Katamine, S.; Shigematsu, K.; Nakatani, A; Moriuchi, R.; Nishida, N.; Kurokawa, K; Nakaoke, R; Sato, H; Jishage, K

    1995-01-01

    Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative disease of humans caused by an unidentified infectious agent, the prion. To determine whether there was an involvement of the host-encoded prion protein (PrPc) in CJD development and prion propagation, mice heterozygous (PrP+/-) or homozygous (PrP-/-) for a disrupted PrP gene were established and inoculated with the mouse-adapted CJD agent. In keeping with findings of previous studies using other lines of PrP-less mice inocu...

  1. PRP8 inteins in species of the genus Botrytis and other ascomycetes.

    Science.gov (United States)

    Bokor, Annika A M; Kohn, Linda M; Poulter, Russell T M; van Kan, Jan A L

    2012-03-01

    The mobile elements termed inteins have a sporadic distribution in microorganisms. It is unclear how these elements are maintained. Inteins are intervening protein sequences that autocatalytically excise themselves from a precursor. Excision is a post-translational process referred to as 'protein splicing' in which the sequences flanking the intein are ligated, reforming the mature host protein. Some inteins contain a homing endonuclease domain (HEG) that is proposed to facilitate propagation of the intein element within a gene pool. We have previously demonstrated that the HEG of the PRP8 intein is highly active during meiosis in Botrytis cinerea. Here we analysed the Prp8 gene status in 21 additional Botrytis species to obtain insight into the mode of intein inheritance within the Botrytis lineage. Of the 21 species, 15 contained a PRP8 intein whereas six did not. The analysis was extended to closely related (Sclerotiniaceae) and distantly related (Ascomycota) taxa, focussing on evolutionary diversification of the PRP8 intein, including their possible acquisition by horizontal transfer and loss by deletion. Evidence was obtained for the occurrence of genetic footprints of previous intein occupation. There is no compelling evidence of horizontal transfer among species. Three distinct states of the Prp8 allele were identified, distributed over different orders within the Ascomycota: an occupied allele; an empty allele that was never occupied; an empty allele that was presumably previously occupied, from which the intein was precisely deleted. The presence of the genetic footprint identifies 20 species (including Neurospora crassa, Magnaporthe oryzae and Fusarium oxysporum) that previously contained the intein but have lost it entirely, while only 18 species (including Podospora anserina and Fusarium graminearum) appear never to have contained a PRP8 intein. The analysis indicates that inteins may be maintained in an equilibrium state. Copyright © 2012 Elsevier

  2. GmPRP2 promoter drives root-preferential expression in transgenic Arabidopsis and soybean hairy roots.

    Science.gov (United States)

    Chen, Li; Jiang, Bingjun; Wu, Cunxiang; Sun, Shi; Hou, Wensheng; Han, Tianfu

    2014-09-16

    Promoters play important roles in gene expression and function. There are three basic types of promoters: constitutive, specific, and inducible. Constitutive promoters are widely used in genetic engineering, but these promoters have limitations. Inducible promoters are activated by specific inducers. Tissue-specific promoters are a type of specific promoters that drive gene expression in specific tissues or organs. Here, we cloned and characterized the GmPRP2 promoter from soybean. The expression pattern indicated that this promoter is root-preferential in transgenic Arabidopsis and the hairy roots of soybean. It can be used to improve the root resistance or tolerance to pathogens, pests, malnutrition and other abiotic stresses which cause extensive annual losses in soybean production. The GmPRP2 promoter (GmPRP2p-1062) was isolated from soybean cv. Williams 82. Sequence analysis revealed that this promoter contains many cis-acting elements, including root-specific motifs. The GmPRP2p-1062 and its 5'-deletion fragments were fused with the GUS reporter gene and introduced into Arabidopsis and the hairy roots of soybean to further determine promoter activity. Histochemical analysis in transgenic Arabidopsis showed that GUS activity was mainly detected in roots and hypocotyls in all deletion fragments except GmPRP2p-471 (a 5'-deletion fragment of GmPRP2p-1062 with 471 bp length). GUS activity was higher in transgenic Arabidopsis and hairy roots with GmPRP2p-1062 and GmPRP2p-852 (a 5'-deletion fragment of GmPRP2p-1062 with 852 bp length) constructs than the other two constructs. GUS activity was enhanced by NaCl, PEG, IAA and JM treatments and decreased by SA, ABA and GA treatments in transgenic Arabidopsis. GmPRP2p-1062 is a root-preferential promoter, and its core fragment for root-preferential expression might lie between -369 and +1. GmPRP2p-852 may be useful in the genetic engineering of novel soybean cultivars in the future.

  3. Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges.

    Science.gov (United States)

    Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

    2015-10-20

    Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group.

  4. Nuclear Weapon Personnel Reliability Program (PRP)

    Science.gov (United States)

    1993-05-25

    amphetamines, barbiturates, or other narcotic drugs not prescribed by proper medical authorities, and anabolic steroids shall render an individual...Hallucinogens e. Cannabis f Anabolic Steroids Total C.3. Serious offense decertifications by type (continued) PRP Position Category Crit Cont Crit Cont Crit...States Code (c) DoD Directive 1010.4, "Alcohol and Drug Abuse by C TE. DoD Personnel," August 25, 1980 NO02 1 9 9 3 (d) DoD Directive 5210.56, "Use of

  5. Platlet Rich Plasma (PRP) Improves Fat Grafting Outcomes.

    Science.gov (United States)

    Modarressi, Ali

    2013-01-01

    Autologous fat transfer offers many qualities of a ideal soft tissue filler. Main advantages of fat grafting ensue from the fact that the lipoaspirate tissue is an abundant source of regenerative pluripotential cells. However, the reported rates of fat cell survival vary greatly in the medical literature (10-90%). Different techniques of harvesting, processing, and reinjecting the fat cells are so claimed to be responsible for these differences, without any agreement concerning the best way to process. To address this important disadvantage, we propose the addition of autologous platelet rich plasma (PRP) which is known as a natural reservoir of growth factors stimulating tissue repair and regeneration. This approach is completely autologous and immediately employed without any type of preconditioning. Platelets rich plasma (PRP) preparation included bleeding of 8 ml of blood from patient's peripheral vein in Regen Lab© tubes containing sodium citrate anticoagulant. The whole blood was centrifugated at 1500 g during 3 min. As Regen-tubes contained a special gel separator, 99 % of red blood cells were discarded from the plasma at the bottom of the gel, and >90% of platelets were harvested in 4 ml of plasma on the top of the gel, called the platelet-rich plasma (PRP). The purified fat prepared by Coleman technique was mixed with different amount of PRP for in vitro, in vivo (mice) and clinical experiments: >50% of PRP for skin rejuvenation, superficial scars correction, infraorbital region, ..., and for 20% of PRP with 80% of purified fat for deep filler indication (nasolabial folds, lips, or soft tissue defect). In vitro studies demonstrated that PRP increased fat cells survival rate and stem cells differentiation. Animal models showed that fat graft survival rate was significantly increased by addition of PRP. Several clinical cases confirmed the improvement of wound healing and fat grafting survival in facial reconstruction and aesthetic cases by association of

  6. ArguBlogging: An Application for the Argument Web

    NARCIS (Netherlands)

    Bex, Floris; Snaith, Mark; Lawrence, John; Reed, Chris

    2014-01-01

    In this paper, we present a software tool for ‘ArguBlogging’, which allows users to construct debate and discussions across blogs, linking existing and new online resources to form distributed, structured conversations. Arguments and counterarguments can be posed by giving opinions on one’s own blog

  7. Level of Skill Argued Students on Physics Material

    Science.gov (United States)

    Viyanti, V.; Cari, C.; Sunarno, W.; Prasetyo, Z. K.

    2017-09-01

    This study aims to analyze the prior knowledge of students to map the level of skills to argue floating and sinking material. Prior knowledge is the process of concept formation in cognitive processes spontaneously or based on student experience. The study population is high school students of class XI. The sample selection using cluster random sampling, obtained the number of sampel as many as 50 student. The research used descriptive survey method. The data were obtained through a multiple choice test both grounded and interviewed. The data analyzed refers to: alignment the concept and the activity of developing the skill of the argument. The result obtained by the average level of skill argue in terms of the prior knowladge of on “Level 2”. The data show that students have difficulty expressing simple arguments consisting of only one statement. This indicates a lack of student experience in cultivating argumentative skills in their learning. The skill level mapping argued in this study to be a reference for researchers to provide feedback measures to obtain positive change in cognitive conflict argued.

  8. Arguing with Adversaries: Aikido, Rhetoric, and the Art of Peace

    Science.gov (United States)

    Kroll, Barry M.

    2008-01-01

    The Japanese martial art of aikido affords a framework for understanding argument as harmonization rather than confrontation. Two movements, circling away ("tenkan") and entering in ("irimi"), suggest tactics for arguing with adversaries. The ethical imperative of aikido involves protecting one's adversary from harm, using the least force…

  9. Bathrooms without Borders: Transgender Students Argue Separate Is Not Equal

    Science.gov (United States)

    Watkins, Paul J.; Moreno, Edward

    2017-01-01

    Title IX guidelines governing equal access to collide with state legislation around gender identity and multiple use bathrooms and changing facilities. This policy review of literature argues for a stronger voice from Washington, protecting the rights of all students to feel safe using private spaces at school. The many court rulings offer a fair…

  10. Who's arguing? A call for reflexivity in bioethics.

    Science.gov (United States)

    Ives, Jonathan; Dunn, Michael

    2010-06-01

    In this paper we set forth what we believe to be a relatively controversial argument, claiming that 'bioethics' needs to undergo a fundamental change in the way it is practised. This change, we argue, requires philosophical bioethicists to adopt reflexive practices when applying their analyses in public forums, acknowledging openly that bioethics is an embedded socio-cultural practice, shaped by the ever-changing intuitions of individual philosophers, which cannot be viewed as a detached intellectual endeavour. This said, we argue that in order to manage the personal, social and cultural embeddedness of bioethics, philosophical bioethicists should openly acknowledge how their practices are constructed and should, in their writing, explicitly deal with issues of bias and conflict of interest, just as empirical scientists are required to do.

  11. Familial CJD associated PrP mutants within transmembrane region induced Ctm-PrP retention in ER and triggered apoptosis by ER stress in SH-SY5Y cells.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available BACKGROUND: Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C to the pathogenic one (PrP(Sc. The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. METHODOLOGY/PRINCIPAL FINDINGS: To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER, the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL and PrP with three amino acids exchange in transmembrane region (PrP-3AV were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and caspase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K failed. CONCLUSIONS/SIGNIFICANCE: The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them

  12. Prp22 and spliceosome components regulate chromatin dynamics in germ-line polyploid cells.

    Directory of Open Access Journals (Sweden)

    Stephen Klusza

    Full Text Available During Drosophila oogenesis, the endopolyploid nuclei of germ-line nurse cells undergo a dramatic shift in morphology as oogenesis progresses; the easily-visible chromosomes are initially polytenic during the early stages of oogenesis before they transiently condense into a distinct '5-blob' configuration, with subsequent dispersal into a diffuse state. Mutations in many genes, with diverse cellular functions, can affect the ability of nurse cells to fully decondense their chromatin, resulting in a '5-blob arrest' phenotype that is maintained throughout the later stages of oogenesis. However, the mechanisms and significance of nurse-cell (NC chromatin dispersal remain poorly understood. Here, we report that a screen for modifiers of the 5-blob phenotype in the germ line isolated the spliceosomal gene peanuts, the Drosophila Prp22. We demonstrate that reduction of spliceosomal activity through loss of peanuts promotes decondensation defects in NC nuclei during mid-oogenesis. We also show that the Prp38 spliceosomal protein accumulates in the nucleoplasm of nurse cells with impaired peanuts function, suggesting that spliceosomal recycling is impaired. Finally, we reveal that loss of additional spliceosomal proteins impairs the full decondensation of NC chromatin during later stages of oogenesis, suggesting that individual spliceosomal subcomplexes modulate expression of the distinct subset of genes that are required for correct morphology in endopolyploid nurse cells.

  13. Prp22 and Spliceosome Components Regulate Chromatin Dynamics in Germ-Line Polyploid Cells

    Science.gov (United States)

    Klusza, Stephen; Novak, Amanda; Figueroa, Shirelle; Palmer, William; Deng, Wu-Min

    2013-01-01

    During Drosophila oogenesis, the endopolyploid nuclei of germ-line nurse cells undergo a dramatic shift in morphology as oogenesis progresses; the easily-visible chromosomes are initially polytenic during the early stages of oogenesis before they transiently condense into a distinct ‘5-blob’ configuration, with subsequent dispersal into a diffuse state. Mutations in many genes, with diverse cellular functions, can affect the ability of nurse cells to fully decondense their chromatin, resulting in a ‘5-blob arrest’ phenotype that is maintained throughout the later stages of oogenesis. However, the mechanisms and significance of nurse-cell (NC) chromatin dispersal remain poorly understood. Here, we report that a screen for modifiers of the 5-blob phenotype in the germ line isolated the spliceosomal gene peanuts, the Drosophila Prp22. We demonstrate that reduction of spliceosomal activity through loss of peanuts promotes decondensation defects in NC nuclei during mid-oogenesis. We also show that the Prp38 spliceosomal protein accumulates in the nucleoplasm of nurse cells with impaired peanuts function, suggesting that spliceosomal recycling is impaired. Finally, we reveal that loss of additional spliceosomal proteins impairs the full decondensation of NC chromatin during later stages of oogenesis, suggesting that individual spliceosomal subcomplexes modulate expression of the distinct subset of genes that are required for correct morphology in endopolyploid nurse cells. PMID:24244416

  14. PRP: The Proven Solution for Cleaning Up Oil Spills

    Science.gov (United States)

    2006-01-01

    The basic technology behind PRP is thousands of microcapsules, tiny balls of beeswax with hollow centers. Water cannot penetrate the microcapsule s cell, but oil is absorbed right into the beeswax spheres as they float on the water s surface. This way, the contaminants, chemical compounds that originally come from crude oil such as fuels, motor oils, or petroleum hydrocarbons, are caught before they settle. PRP works well as a loose powder for cleaning up contaminants in lakes and other ecologically fragile areas. The powder can be spread over a contaminated body of water or soil, and it will absorb contaminants, contain them in isolation, and dispose of them safely. In water, it is important that PRP floats and keeps the oil on the surface, because, even if oil exposure is not immediately lethal, it can cause long-term harm if allowed to settle. Bottom-dwelling fish exposed to compounds released after oil spills may develop liver disease, in addition to reproductive and growth problems. This use of PRP is especially effective for environmental cleanup in sensitive areas like coral reefs and mangroves.

  15. The Prp19 complex directly functions in mitotic spindle assembly.

    Science.gov (United States)

    Hofmann, Jennifer C; Tegha-Dunghu, Justus; Dräger, Stefanie; Will, Cindy L; Lührmann, Reinhard; Gruss, Oliver J

    2013-01-01

    The conserved Prp19 (pre-RNA processing 19) complex is required for pre-mRNA splicing in eukaryotic nuclei. Recent RNAi screens indicated that knockdown of Prp19 complex subunits strongly delays cell proliferation. Here we show that knockdown of the smallest subunit, BCAS2/Spf27, destabilizes the entire complex and leads to specific mitotic defects in human cells. These could result from splicing failures in interphase or reflect a direct function of the complex in open mitosis. Using Xenopus extracts, in which cell cycle progression and spindle formation can be reconstituted in vitro, we tested Prp19 complex functions during a complete cell cycle and directly in open mitosis. Strikingly, immunodepletion of the complex either before or after interphase significantly reduces the number of intact spindles, and increases the percentage of spindles with lower microtubule density and impaired metaphase alignment of chromosomes. Our data identify the Prp19 complex as the first spliceosome subcomplex that directly contributes to mitosis in vertebrates independently of its function in interphase.

  16. The Prp19 complex directly functions in mitotic spindle assembly.

    Directory of Open Access Journals (Sweden)

    Jennifer C Hofmann

    Full Text Available The conserved Prp19 (pre-RNA processing 19 complex is required for pre-mRNA splicing in eukaryotic nuclei. Recent RNAi screens indicated that knockdown of Prp19 complex subunits strongly delays cell proliferation. Here we show that knockdown of the smallest subunit, BCAS2/Spf27, destabilizes the entire complex and leads to specific mitotic defects in human cells. These could result from splicing failures in interphase or reflect a direct function of the complex in open mitosis. Using Xenopus extracts, in which cell cycle progression and spindle formation can be reconstituted in vitro, we tested Prp19 complex functions during a complete cell cycle and directly in open mitosis. Strikingly, immunodepletion of the complex either before or after interphase significantly reduces the number of intact spindles, and increases the percentage of spindles with lower microtubule density and impaired metaphase alignment of chromosomes. Our data identify the Prp19 complex as the first spliceosome subcomplex that directly contributes to mitosis in vertebrates independently of its function in interphase.

  17. Platelet-rich plasma (PRP) for knee disorders

    Science.gov (United States)

    Shahid, Mohammad; Kundra, Rik

    2017-01-01

    Platelet-rich plasma (PRP) is an autologous blood product with platelet concentrations above baseline values. The process involves the extraction of blood from the patient which is then centrifuged to obtain a concentrated suspension of platelets by plasmapheresis. It then undergoes a two-stage centrifugation process to separate the solid and liquid components of the anticoagulated blood. PRP owes its therapeutic use to the growth factors released by the platelets which are claimed to possess multiple regenerative properties. In the knee, PRP has been used in patients with articular cartilage pathology, ligamentous and meniscal injuries. There is a growing body of evidence to support its use in selected indications and this review looks at the most recent evidence. We also look at the current UK National Institute of Health & Clinical Excellence (NICE) guidelines with respect to osteoarthritis and the use of PRP in the knee. Cite this article: EFORT Open Rev 2017;2:28–34. DOI: 10.1302/2058-5241.2.160004. PMID:28607768

  18. Do autologous blood and PRP injections effectively treat tennis elbow?

    Science.gov (United States)

    Widstrom, Luke; Slattengren, Andrew

    2016-09-01

    Both approaches reduce pain, but the improvement with platelet-rich plasma (PRP) is not clinically meaningful. Autologous blood injections (ABIs) are more effective than corticosteroid injections for reducing pain and disability in patients with tennis elbow in both the short and long term.

  19. Human prion protein (PrP) 219K is converted to PrPSc but shows heterozygous inhibition in variant Creutzfeldt-Jakob disease infection.

    Science.gov (United States)

    Hizume, Masaki; Kobayashi, Atsushi; Teruya, Kenta; Ohashi, Hiroaki; Ironside, James W; Mohri, Shirou; Kitamoto, Tetsuyuki

    2009-02-06

    Prion protein gene (PRNP) E219K is a human polymorphism commonly occurring in Asian populations but is rarely found in patients with sporadic Creutzfeldt-Jakob disease (CJD). Thus the polymorphism E219K has been considered protective against sporadic CJD. The corresponding mouse prion protein (PrP) polymorphism variant (mouse PrP 218K) is not converted to the abnormal isoform (PrP(Sc)) and shows a dominant negative effect on wild-type PrP conversion. To define the conversion activity of this human molecule, we herein established knock-in mice with human PrP 219K and performed a series of transmission experiments with human prions. Surprisingly, the human PrP 219K molecule was converted to PrP(Sc) in variant CJD infection, and the conversion occurred more efficiently than PrP 219E molecule. Notably the knock-in mice with PRNP codon 219E/K showed the least efficient conversion compared with their hemizygotes with PRNP codon 219E/0 or codon 219K/0, or homozygotes with PRNP codon 219E/E or codon 219K/K. This phenomenon indicated heterozygous inhibition. This heterozygous inhibition was observed also in knock-in mice with PRNP codon 129M/V genotype. In addition to variant CJD infection, the human PrP 219K molecule is conversion-competent in transmission experiments with sporadic CJD prions. Therefore, the protective effect of PRNP E219K against sporadic CJD might be due to heterozygous inhibition.

  20. Decreased hernia recurrence using autologous platelet-rich plasma (PRP) with Strattice™ mesh in a rodent ventral hernia model.

    Science.gov (United States)

    Van Eps, Jeffrey; Fernandez-Moure, Joseph; Cabrera, Fernando; Wang, Xin; Karim, Azim; Corradetti, Bruna; Chan, Paige; Dunkin, Brian; Tasciotti, Ennio; Weiner, Bradley; Ellsworth, Warren

    2016-08-01

    Recurrence after ventral hernia repair (VHR) remains a multifactorial problem still plaguing surgeons today. Some of the many contributing factors include mechanical strain, poor tissue-mesh integration, and degradation of matrices. The high recurrence rate witnessed with the use of acellular dermal matrices (ADM) for definitive hernia repair has reduced their use largely to bridging repair and breast reconstruction. Modalities that improve classic cellular metrics of successful VHR could theoretically result in improved rates of hernia recurrence; autologous platelet-rich plasma (PRP) may represent one such tool, but has been underinvestigated for this purpose. Lewis rats (32) had chronic ventral hernias created surgically and then repaired with Strattice™ mesh alone (control) or mesh + autologous PRP. Samples were harvested at 3 and 6 months postoperatively and compared for gross, histologic, and molecular outcomes of: neovascularization, tissue incorporation, peritoneal adhesions, hernia recurrence, and residual mesh thickness. Compared to control at 3 months postoperatively, PRP-treated rats displayed significantly more neovascularization of implanted mesh and considerable upregulation of both angiogenic genes (vEGF 2.73-fold, vWF 2.21-fold) and myofibroblastic genes (αSMA 9.68-fold, FSP-1 3.61-fold, Col1a1 3.32-fold, Col31a1 3.29-fold). Histologically, they also showed enhanced tissue deposition/ingrowth and diminished chronic immune cell infiltration. Peritoneal adhesions were less severe at both 3 (1.88 vs. 2.94) and 6 months (1.63 vs. 2.75) by Modified Hopkins Adhesion Scoring. PRP-treated rats experienced decreased hernia recurrence at 6 months (0/10 vs. 7/10) and had significantly improved ADM preservation as evidenced by quantification of residual mesh thickness. PRP is an autologous source of pro-regenerative growth factors and chemokines uniquely suited to soft tissue wound healing. When applied to a model of chronic VHR, it incites enhanced

  1. Protecting effect of PrP codons M142 and K222 in goats orally challenged with bovine spongiform encephalopathy prions

    NARCIS (Netherlands)

    Fast, C.; Goldmann, W.; Berthon, P.; Tauscher, Kerstin; Andréoletti, O.; Lantier, I.; Rossignol, C.; Bossers, A.; Jacobs, J.G.; Hunter, N.; Groschup, Martin H.; Lantier, F.; Langeveld, J.P.M.

    2017-01-01

    Breeding towards genetic resistance to prion disease is effective in eliminating scrapie. In sheep, classical forms of scrapie have been eradicated almost completely in several countries by breeding programs using a prion protein (PrP) gene (PRNP) amino acid polymorphism. For goats, field and

  2. PrP0\\0 mice show behavioral abnormalities that suggest PrPC has a role in maintaining the cytoskeleton.

    Science.gov (United States)

    Background/Introduction. PrPC is highly conserved among mammals, but its natural function is unclear. Prnp ablated mice (PrP0/0) appear to develop normally and are able to reproduce. These observations seem to indicate that the gene is not essential for viability, in spite of it being highly conse...

  3. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    Science.gov (United States)

    Yuan, Gonglin; Duan, Xiabin; Liu, Wenjie; Wang, Xiaoliang; Cui, Zengru; Sheng, Zhou

    2015-01-01

    Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1) βk ≥ 0 2) the search direction has the trust region property without the use of any line search method 3) the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

  4. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    Directory of Open Access Journals (Sweden)

    Gonglin Yuan

    Full Text Available Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1 βk ≥ 0 2 the search direction has the trust region property without the use of any line search method 3 the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

  5. Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation.

    Directory of Open Access Journals (Sweden)

    Jia Shao

    Full Text Available Prion protein PrP is a central player in several devastating neurodegenerative disorders, including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels of PrP are regulated is poorly understood. Human PrP is known to be degraded by the proteasome, but the specific proteolytic pathway responsible for PrP destruction remains elusive. Here, we demonstrate that the ubiquitin ligase gp78, known for its role in protein quality control, is critical for unglycosylated PrP ubiquitylation and degradation. Furthermore, C-terminal sequences of PrP protein are crucial for its ubiquitylation and degradation. Our study reveals the first ubiquitin ligase specifically involved in prion protein PrP degradation and PrP sequences crucial for its turnover. Our data may lead to a new avenue to control PrP level and pathogenesis.

  6. Effectiveness of polyene antibiotics in treatment of transmissible spongiform encephalopathy in transgenic mice expressing Syrian hamster PrP only in neurons.

    Science.gov (United States)

    Demaimay, R; Race, R; Chesebro, B

    1999-04-01

    To date very few drugs have favorably influenced the course of transmissible spongiform encephalopathies. In previous studies, the polyene antibiotics amphotericin B (AmB) and MS-8209 prolonged the incubation time in Syrian hamsters of the 263K strain of scrapie, but AmB had no effect against other scrapie strains in Syrian hamsters. In the present experiments using transgenic mice expressing Syrian hamster PrP in neurons only, MS-8209 extended the life spans of animals infected with the 263K strain but not the DY strain. AmB was effective against both 263K and DY and prevented death in 18% of DY-infected animals. The AmB effect against strain 263K was more prominent in mice whose endogenous PrP gene had been inactivated by homologous recombination. It was unclear whether this difference was due to a change in the duration of the disease or to possible interactive effects between the mouse PrP gene and the drugs themselves. The effectiveness of treatment after intracerebral scrapie infection in transgenic mice expressing PrP only in neurons suggested that neurons are important sites of action for these drugs.

  7. Prp19 Arrests Cell Cycle via Cdc5L in Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Huang, Renzheng; Xue, Ruyi; Qu, Di; Yin, Jie; Shen, Xi-Zhong

    2017-04-07

    Pre-mRNA processing factor 19 (Prp19) is involved in many cellular events including pre-mRNA processing and DNA damage response. Recently, it has been identified as a candidate oncogene in hepatocellular carcinoma (HCC). However, the role of Prp19 in tumor biology is still elusive. Here, we reported that Prp19 arrested cell cycle in HCC cells via regulating G2/M transition. Mechanistic insights revealed that silencing Prp19 inhibited the expression of cell division cycle 5-like (Cdc5L) via repressing the translation of Cdc5L mRNA and facilitating lysosome-mediated degradation of Cdc5L in HCC cells. Furthermore, we found that silencing Prp19 induced cell cycle arrest could be partially resumed by overexpressing Cdc5L. This work implied that Prp19 participated in mitotic progression and thus could be a promising therapeutic target of HCC.

  8. Intraarticular Injections of Platelet-rich Plasma (PRP) in the Management of Knee Osteoarthritis

    OpenAIRE

    E. Carlos RODRIGUEZ-MERCHAN

    2013-01-01

      The clinical use of PRP therapy in the practical setting of orthopaedic fields is increasing partly because of the accessibility of devices that are used in outpatient preparation and delivery. Another reason is the strong advertisement of PRP procedures as the ultimate treatment and novel technology for knee problems by a few orthopaedic surgeons based on claims of abundant scientific evidence. Hence, PubMed articles related to the clinical use of PRP in knee osteoarthritis were searched u...

  9. The Splicing Factor Prp43p, a DEAH Box ATPase, Functions in Ribosome Biogenesis

    Science.gov (United States)

    Leeds, Nina B.; Small, Eliza C.; Hiley, Shawna L.; Hughes, Timothy R.; Staley, Jonathan P.

    2006-01-01

    Biogenesis of the small and large ribosomal subunits requires modification, processing, and folding of pre-rRNA to yield mature rRNA. Here, we report that efficient biogenesis of both small- and large-subunit rRNAs requires the DEAH box ATPase Prp43p, a pre-mRNA splicing factor. By steady-state analysis, a cold-sensitive prp43 mutant accumulates 35S pre-rRNA and depletes 20S, 27S, and 7S pre-rRNAs, precursors to the small- and large-subunit rRNAs. By pulse-chase analysis, the prp43 mutant is defective in the formation of 20S and 27S pre-rRNAs and in the accumulation of 18S and 25S mature rRNAs. Wild-type Prp43p immunoprecipitates pre-rRNAs and mature rRNAs, indicating a direct role in ribosome biogenesis. The Prp43p-Q423N mutant immunoprecipitates 27SA2 pre-rRNA threefold more efficiently than the wild type, suggesting a critical role for Prp43p at the earliest stages of large-subunit biogenesis. Consistent with an early role for Prp43p in ribosome biogenesis, Prp43p immunoprecipitates the majority of snoRNAs; further, compared to the wild type, the prp43 mutant generally immunoprecipitates the snoRNAs more efficiently. In the prp43 mutant, the snoRNA snR64 fails to methylate residue C2337 in 27S pre-rRNA, suggesting a role in snoRNA function. We propose that Prp43p promotes recycling of snoRNAs and biogenesis factors during pre-rRNA processing, similar to its recycling role in pre-mRNA splicing. The dual function for Prp43p in the cell raises the possibility that ribosome biogenesis and pre-mRNA splicing may be coordinately regulated. PMID:16382143

  10. Why Argue?

    Science.gov (United States)

    Ehrenworth, Mary

    2017-01-01

    With the massive amounts of conflicting information and opinion bombarding us from all sides today, it has never been more important to teach young people to suspend judgment, to weigh evidence, and to consider multiple perspectives. Teaching students the craft of argument writing--not only in language arts classes, but also in social studies,…

  11. Reconstrucción mamaria mediante lipoinfiltrado enriquecido con PRP

    Directory of Open Access Journals (Sweden)

    A. Jarrah

    2013-12-01

    Full Text Available Presentamos una serie de pacientes con mastectomía a las que hemos realizado reconstrucción mamaria con infiltraciones de grasa (lipoinfiltrado enriquecida con plasma rico en plaquetas (PRP como único procedimiento, o como paso previo a la colocación de un implante mamario. El objetivo de este trabajo es presentar una alternativa a la reconstrucción mamaria con colgajos libres o pediculados en mamas sometidas a radioterapia; también, una revisión detallada de los pasos a seguir para la realización de este procedimiento, que van desde la extracción de sangre para la posterior obtención del PRP, hasta la técnica de infiltración de grasa enriquecida con dichos factores en la mama intervenida. Con esta técnica de enriquecimiento de la grasa hemos logrado mejores resultados y mayor permanencia de los injertos grasos. Evaluando los postoperatorios de las pacientes sometidas a este procedimiento, hemos observado que se necesitan de 2 a 3 tiempos de lipoinfiltrado para obtener buena cobertura y mejoría de la calidad de piel como paso previo a la colocación del implante en este tipo de pacientes.

  12. Prp43p Is a DEAH-Box Spliceosome Disassembly Factor Essential for Ribosome Biogenesis

    Science.gov (United States)

    Combs, D. Joshua; Nagel, Roland J.; Ares, Manuel; Stevens, Scott W.

    2006-01-01

    The known function of the DEXH/D-box protein Prp43p is the removal of the U2, U5, and U6 snRNPs from the postsplicing lariat-intron ribonucleoprotein complex. We demonstrate that affinity-purified Prp43p-associated material includes the expected spliceosomal components; however, we also identify several preribosomal complexes that are specifically purified with Prp43p. Conditional prp43 mutant alleles confer a 35S pre-rRNA processing defect, with subsequent depletion of 27S and 20S precursors. Upon a shift to a nonpermissive temperature, both large and small-ribosomal-subunit proteins accumulate in the nucleolus of prp43 mutants. Pulse-chase analysis demonstrates delayed kinetics of 35S, 27S, and 20S pre-rRNA processing with turnover of these intermediates. Microarray analysis of pre-mRNA splicing defects in prp43 mutants shows a very mild effect, similar to that of nonessential pre-mRNA splicing factors. Prp43p is the first DEXH/D-box protein shown to function in both RNA polymerase I and polymerase II transcript metabolism. Its essential function is in its newly characterized role in ribosome biogenesis of both ribosomal subunits, positioning Prp43p to regulate both pre-mRNA splicing and ribosome biogenesis. PMID:16382144

  13. Recommendations for the Involvement of Patient Research Partners (PRP) in OMERACT Working Groups. A Report from the OMERACT 2014 Working Group on PRP.

    Science.gov (United States)

    Cheung, Peter P; de Wit, Maarten; Bingham, Clifton O; Kirwan, John R; Leong, Amye; March, Lyn M; Montie, Pam; Scholte-Voshaar, Marieke; Gossec, Laure

    2016-01-01

    Patient participation in research is increasing; however, practical guidelines to enhance this participation are lacking. Specifically within the Outcome Measures in Rheumatology (OMERACT) organization, although patients have participated in OMERACT meetings since 2002, consensus about the procedures for involving patients in working groups has not been formalized. The objective is to develop a set of recommendations regarding patient research partner (PRP) involvement in research working groups. We conducted a systematic literature review on recommendations/guidelines of PRP involvement in research; elaborated a structured consensus process involving multiple participants to develop a set of recommendations; and sought endorsement of recommendations by OMERACT. In the 18 articles included in the literature review, there was general agreement on the broad concepts for recommendations covering PRP involvement in research although they were heterogeneous in detail. Most considered PRP involvement in all phases of research with early engagement, training, and support important, but details on the content were scarce. This review informed a larger consensus-building process regarding PRP inclusion in OMERACT research. Three overarching principles and 8 recommendations were developed, discussed, and refined at OMERACT 2014. The guiding principles were endorsed during the OMERACT plenary session. These recommendations for PRP involvement in OMERACT research reinforce the importance of patient participation throughout the research process as integral members. Although the applicability of the recommendations in other research contexts should be assessed, the generalizability is expected to be high. Future research should evaluate their implementation and their effect on outcome development.

  14. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

    Directory of Open Access Journals (Sweden)

    Mohssen Hakimi

    Full Text Available One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC. The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group. In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG, whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

  15. Structural and functional analysis of the human spliceosomal DEAD-box helicase Prp28

    Energy Technology Data Exchange (ETDEWEB)

    Möhlmann, Sina [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Mathew, Rebecca [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Neumann, Piotr; Schmitt, Andreas [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Lührmann, Reinhard [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Ficner, Ralf, E-mail: rficner@uni-goettingen.de [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany)

    2014-06-01

    The crystal structure of the helicase domain of the human spliceosomal DEAD-box protein Prp28 was solved by SAD. The binding of ADP and ATP by Prp28 was studied biochemically and analysed with regard to the crystal structure. The DEAD-box protein Prp28 is essential for pre-mRNA splicing as it plays a key role in the formation of an active spliceosome. Prp28 participates in the release of the U1 snRNP from the 5′-splice site during association of the U5·U4/U6 tri-snRNP, which is a crucial step in the transition from a pre-catalytic spliceosome to an activated spliceosome. Here, it is demonstrated that the purified helicase domain of human Prp28 (hPrp28ΔN) binds ADP, whereas binding of ATP and ATPase activity could not be detected. ATP binding could not be observed for purified full-length hPrp28 either, but within an assembled spliceosomal complex hPrp28 gains ATP-binding activity. In order to understand the structural basis for the ATP-binding deficiency of isolated hPrp28, the crystal structure of hPrp28ΔN was determined at 2.0 Å resolution. In the crystal the helicase domain adopts a wide-open conformation, as the two RecA-like domains are extraordinarily displaced from the productive ATPase conformation. Binding of ATP is hindered by a closed conformation of the P-loop, which occupies the space required for the γ-phosphate of ATP.

  16. Arguing from Nature: The role of 'nature' in students' argumentations on a socio-scientific issue

    DEFF Research Database (Denmark)

    Nielsen, J. A.

    2012-01-01

    the students in this study invoked nature at key places in a variety of dialectical contexts in the discussions, these invocations were often uncritical appeals and rarely involved science factual content. Even when an argument from nature was challenged, the author of that argument would often shift the sense......This paper explores how students invoked different conceptions of 'nature' in eight socio-scientific group discussions about human gene therapy. The paper illustrates and discusses how the students articulated nature and to what extent they elicited science factual content in the process. While...... of nature rather than elaborate upon the argumentation. It is argued that if students were properly introduced to the evaluative character of the term 'nature' it would not just be conducive to the quality of their argumentation, but also invite them to foreground science factual content at key places...

  17. Intraarticular Injections of Platelet-rich Plasma (PRP) in the Management of Knee Osteoarthritis.

    Science.gov (United States)

    Rodriguez-Merchan, E Carlos

    2013-09-01

    The clinical use of PRP therapy in the practical setting of orthopaedic fields is increasing partly because of the accessibility of devices that are used in outpatient preparation and delivery. Another reason is the strong advertisement of PRP procedures as the ultimate treatment and novel technology for knee problems by a few orthopaedic surgeons based on claims of abundant scientific evidence. Hence, PubMed articles related to the clinical use of PRP in knee osteoarthritis were searched using the key words: PRP, knee and osteoarthritis in order to study these claims. A total of 20 reports were found directly related to the topic. The aforementioned clinical studies suggest that intraarticular injections of PRP could have preventive effects against osteoarthritis progression. However, presently there is no clear evidence from well-designed clinical trials that intraarticular injections of PRP are efficacious in osteoarthritis. Therefore, at this time the efficacy of PRP requires more investigation, wherein better scientific studies should be performed that include high powered randomized controlled trials.

  18. Augmenting tendon and ligament repair with platelet-rich plasma (PRP)

    Science.gov (United States)

    Yuan, Ting; Zhang, Chang-Qing; Wang, James H-C.

    2013-01-01

    Summary Tendon and ligament injuries (TLI) commonly occur in athletes and non-athletes alike, and remarkably debilitate patients’ athletic and personal abilities. Current clinical treatments, such as reconstruction surgeries, do not adequately heal these injuries and often result in the formation of scar tissue that is prone to re-injury. Platelet-rich plasma (PRP) is a widely used alternative option that is also safe because of its autologous nature. PRP contains a number of growth factors that are responsible for its potential to heal TLIs effectively. In this review, we provide a comprehensive report on PRP. While basic science studies in general indicate the potential of PRP to treat TLIs effectively, a review of existing literature on the clinical use of PRP for the treatment of TLIs indicates a lack of consensus due to varied treatment outcomes. This suggests that current PRP treatment protocols for TLIs may not be optimal, and that not all TLIs may be effectively treated with PRP. Certainly, additional basic science studies are needed to develop optimal treatment protocols and determine those TLI conditions that can be treated effectively. PMID:24367773

  19. Myc-oncogene inactivating effect by proline rich polypeptide (PRP-1) in chondrosarcoma JJ012 cells.

    Science.gov (United States)

    Galoian, Karina; Scully, Sean; Galoyan, Armen

    2009-02-01

    Proline rich polypeptide (PRP-1) produced by NPV and NSO cells is released into the general circulation and exerts its effect on the activity of immunocompetent and neuronal cells. PRP-1 is a unique regulator of hematopoiesis, stimulator of bone-marrow hematogenesis. Taking into consideration our preliminary data on antitumor and unique diverse biological properties of PRP-1 previously described by Galoyan et al., we proceeded with investigation of the PRP-1 effect on chondrosarcoma, the second most common malignancy in bone, which tends to be locally invasive and then metastatic. Currently it does not have any effective treatment and does not respond either to radiation or chemotherapy, leaving surgical resection as the only option. Our experimental results of PRP-1 action on human chondrosarcoma JJ012 cells demonstrated inactivation, abolishment of Myc oncogene activity usually upregulated in chondrosarcoma cells and other malignancies. The fact that addition of PRP-1 caused drastic inactivation of Myc-luc response element to the control level in human chondrosarcoma JJ012 cell line prompts to investigate further this neuropeptides powerful antioncogenic potential, opening up possibilities to consider PRP-1 as a potential therapeutic tool for chondrosarcoma treatment.

  20. Crystallographic Studies of Prion Protein (PrP) Segments Suggest How Structural Changes Encoded by Polymorphism at Residue 129 Modulate Susceptibility to Human Prion Disease

    Energy Technology Data Exchange (ETDEWEB)

    Apostol, Marcin I.; Sawaya, Michael R.; Cascio, Duilio; Eisenberg, David (UCLA)

    2010-09-23

    A single nucleotide polymorphism (SNP) in codon 129 of the human prion gene, leading to a change from methionine to valine at residue 129 of prion protein (PrP), has been shown to be a determinant in the susceptibility to prion disease. However, the molecular basis of this effect remains unexplained. In the current study, we determined crystal structures of prion segments having either Met or Val at residue 129. These 6-residue segments of PrP centered on residue 129 are 'steric zippers,' pairs of interacting {beta}-sheets. Both structures of these 'homozygous steric zippers' reveal direct intermolecular interactions between Met or Val in one sheet and the identical residue in the mating sheet. These two structures, plus a structure-based model of the heterozygous Met-Val steric zipper, suggest an explanation for the previously observed effects of this locus on prion disease susceptibility and progression.

  1. The N-terminal domain of the thermo-regulated surface protein PrpA of Enterococcus faecium binds to fibrinogen, fibronectin and platelets.

    Science.gov (United States)

    Guzmán Prieto, Ana M; Urbanus, Rolf T; Zhang, Xinglin; Bierschenk, Damien; Koekman, C Arnold; van Luit-Asbroek, Miranda; Ouwerkerk, Janneke P; Pape, Marieke; Paganelli, Fernanda L; Wobser, Dominique; Huebner, Johannes; Hendrickx, Antoni P A; Bonten, Marc J M; Willems, Rob J L; van Schaik, Willem

    2015-12-17

    Enterococcus faecium is a commensal of the mammalian gastrointestinal tract, but is also found in non-enteric environments where it can grow between 10 °C and 45 °C. E. faecium has recently emerged as a multi-drug resistant nosocomial pathogen. We hypothesized that genes involved in the colonization and infection of mammals exhibit temperature-regulated expression control and we therefore performed a transcriptome analysis of the clinical isolate E. faecium E1162, during mid-exponential growth at 25 °C and 37 °C. One of the genes that exhibited differential expression between 25 °C and 37 °C, was predicted to encode a peptidoglycan-anchored surface protein. The N-terminal domain of this protein is unique to E. faecium and closely related enterococci, while the C-terminal domain is homologous to the Streptococcus agalactiae surface protein BibA. This region of the protein contains proline-rich repeats, leading us to name the protein PrpA for proline-rich protein A. We found that PrpA is a surface-exposed protein which is most abundant during exponential growth at 37 °C in E. faecium E1162. The heterologously expressed and purified N-terminal domain of PrpA was able to bind to the extracellular matrix proteins fibrinogen and fibronectin. In addition, the N-terminal domain of PrpA interacted with both non-activated and activated platelets.

  2. The use of monoclonal antibody epitopes for tagging PrP in conversion experiments.

    Science.gov (United States)

    Vorberg, I; Pfaff, E; Groschup, M H

    2000-01-01

    The key event in the pathogenesis of spongiform encephalopathies is a conformational transition of a normal cellular protein, PrPsen, to its pathological isoform, PrPres. The mechanism of PrPres formation is unknown but is likely to involve a direct interaction between PrPsen and PrPres. The molecular basis of PrPres formation has been studied extensively using transgenic mice and scrapie-infected tissue cultures that express heterologous PrP molecules. However, these experiments are dependant on the discrimination of endogenous host PrP and exogenous PrP molecules. Here we give a short review on the PrP-specific epitopes that have been used for tagging exogenous PrP molecules and present a novel PrP-specific epitope that is well suitable for in vivo and in vitro conversion experiments.

  3. Role of Ultrasound Guided Platelet-Rich Plasma (PRP Injection in Treatment of Lateral Epicondylitis

    Directory of Open Access Journals (Sweden)

    Enass M. Khattab

    2017-06-01

    Conclusion: We concluded that US-guided platelet-rich plasma (PRP injection for treatment of lateral epicondylitis was a safe, minimally invasive and effective procedure in improving the sonographic and pathological changes of common extensor tendon (CET.

  4. An improved freeze-dried PRP-coated biodegradable material suitable for connective tissue regenerative therapy.

    Science.gov (United States)

    Horimizu, Makoto; Kawase, Tomoyuki; Nakajima, Yu; Okuda, Kazuhiro; Nagata, Masaki; Wolff, Larry F; Yoshie, Hiromasa

    2013-06-01

    We previously published an investigation indicating freeze-dried platelet-rich plasma (PRP)-coated polyglactin mesh was a promising wound-dressing material. However, one of its disadvantages was the inflammatory nature due to degradation of the polyglactin. Therefore, in this study, we investigated the use of a collagen sponge as the carrier for PRP. When implanted subcutaneously in nude mice, the PRP-coated sponge alone rapidly induced angiogenesis and infiltration of surrounding connective tissue without inducing appreciable inflammation. Moreover, addition of periosteal fibroblastic cells substantially augmented the angiogenic response. With in vitro studies, the PRP-coated sponge provided various major growth factors at high levels to stimulate the proliferation of cells cultured on plastic dishes, but did not stimulate the proliferation of cells inoculated into the PRP-coated sponge. Cells were embedded in the fibrin mesh and maintained their spherical shape without stretching. The atomic force microscopic analysis demonstrated that the fibrin gel formed on the PRP-coated sponge was much softer (approx. 22 kPa) than the cross-linked collagen that formed the sponge base (appox. 1.9 MPa). Because insoluble matrices have recently and increasingly been considered important regulatory factors of cellular behavior, as are soluble growth factors, it is suggested that this soft fibrin mesh possibly suppresses cell survival. Overall, our investigation has successfully demonstrated improved wound-healing and regenerative potential of the PRP-coated mesh by combining it with the collagen sponge. In the clinical setting, this PRP-coated collagen sponge is a promising material for connective tissue regenerative therapy, such as periodontal therapy, burn victim treatment and in cosmetic or plastic surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. The Effects of Platelet-Rich-Plasma (PRP Injection on Ligament Injury

    Directory of Open Access Journals (Sweden)

    Yudhistira Pradnyan Kloping

    2016-04-01

    Full Text Available Background: Soft tissue injuries are becoming a problem especially among active people and athletes, thus doctors are focusing on PRP injection however variety of study results are making the beneficial effects of PRP towards soft tissue healing unclear. The purpose of this study is to clarify the effects of PRP injection on the healing aspect of a ligament injury. Methods: The experimental study used European rabbit (Oryctolagus cuniculus, which was divided into the control and treated group. The 22 samples, ankle ligaments were injured. The treated group was injected with 4 ml PRP taken autologously. On the 2nd day the samples were examined for hematoma. 4 samples from each group were also examined histopathologically. On the 2nd week, the ligament thickness of the remaining samples from each group was examined ultrasonographically. Results: The clinical result showed lower presence of hematoma on the group injected with PRP compared to the control group. The Capillary dilation was less on the treated group compared to the control group. The Inflammatory cells were less on the treated group compared to the control group. The Fibroblasts Cells was less on the treated group compared to the control group. The fibrocytes was more abundant on the treated group compared to the control group. The average of Ligament Thickness was thicker on the treated group compared to the control group. Conclusion: The Injection of PRP is beneficial to a ligament injury based on its effect on enhancing healing on the inflammation, regeneration, and remodeling phases.

  6. Polymorphisms at Amino Acid Residues 141 and 154 Influence Conformational Variation in Ovine PrP

    Directory of Open Access Journals (Sweden)

    Sujeong Yang

    2014-01-01

    Full Text Available Polymorphisms in ovine PrP at amino acid residues 141 and 154 are associated with susceptibility to ovine prion disease: Leu141Arg154 with classical scrapie and Phe141Arg154 and Leu141His154 with atypical scrapie. Classical scrapie is naturally transmissible between sheep, whereas this may not be the case with atypical scrapie. Critical amino acid residues will determine the range or stability of structural changes within the ovine prion protein or its functional interaction with potential cofactors, during conversion of PrPC to PrPSc in these different forms of scrapie disease. Here we computationally identified that regions of ovine PrP, including those near amino acid residues 141 and 154, displayed more conservation than expected based on local structural environment. Molecular dynamics simulations showed these conserved regions of ovine PrP displayed genotypic differences in conformational repertoire and amino acid side-chain interactions. Significantly, Leu141Arg154 PrP adopted an extended beta sheet arrangement in the N-terminal palindromic region more frequently than the Phe141Arg154 and Leu141His154 variants. We supported these computational observations experimentally using circular dichroism spectroscopy and immunobiochemical studies on ovine recombinant PrP. Collectively, our observations show amino acid residues 141 and 154 influence secondary structure and conformational change in ovine PrP that may correlate with different forms of scrapie.

  7. No associations between PrP genotypes and reproduction traits in INRA 401 sheep.

    Science.gov (United States)

    Vitezica, Z G; Moreno, C R; Bodin, L; François, D; Barillet, F; Brunel, J C; Elsen, J M

    2006-06-01

    In this study, the potential association of PrP genotypes with ewe reproductive traits and lamb growth traits was investigated. Data were included on ewes and lambs of the INRA 401 breed from the Bourges-La Sapinière INRA experimental farm. This breed was chosen because of good breeding (prolificacy and maternal abilities) and carcass qualities, and the large number of available animals with performance records and PrP genotypes. Ewes were categorized into 3 PrP genotype classes: ARR homozygous, ARR heterozygous, and animals without any ARR haplotype. Two analyses differing in the traits considered were carried out. Firstly, the potential association of the PrP genotype of ewes with their reproduction traits (fertility, litter size, and ovulation rate) was studied. The data included 801, 779, and 587 genotyped ewes for fertility, litter size, and ovulation rate, respectively. Secondly, the association of the PrP genotype of the ewes with growth traits of their lambs (birth weight, ADG between 10 and 30 d of age) was investigated. The data included 3,749 and 3,512 lambs for birth weight and ADG, respectively. The different traits were analyzed using an animal model, where the PrP genotype effect was included as a fixed effect. The reproductive traits were modeled under a probit or a threshold approach. The results of this study indicate no evidence of an association between PrP genotypes and reproductive and growth traits. It is unlikely that selection for scrapie resistance will have an effect on the reproductive or performance traits studied in the INRA 401 breed.

  8. Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie

    Science.gov (United States)

    Sarradin, Pierre; Viglietta, Céline; Limouzin, Claude; Andréoletti, Olivier; Daniel-Carlier, Nathalie; Barc, Céline; Leroux-Coyau, Mathieu; Berthon, Patricia; Chapuis, Jérôme; Rossignol, Christelle; Gatti, Jean-Luc; Belghazi, Maya; Labas, Valérie; Vilotte, Jean-Luc; Béringue, Vincent; Lantier, Frédéric; Laude, Hubert; Houdebine, Louis-Marie

    2015-01-01

    Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting a wide range of mammalian species. They are caused by prions, a proteinaceous pathogen essentially composed of PrPSc, an abnormal isoform of the host encoded cellular prion protein PrPC. Constrained steric interactions between PrPSc and PrPC are thought to provide prions with species specificity, and to control cross-species transmission into other host populations, including humans. Transgenetic expression of foreign PrP genes has been successfully and widely used to overcome the recognized resistance of mouse to foreign TSE sources. Rabbit is one of the species that exhibit a pronounced resistance to TSEs. Most attempts to infect experimentally rabbit have failed, except after inoculation with cell-free generated rabbit prions. To gain insights on the molecular determinants of the relative resistance of rabbits to prions, we generated transgenic rabbits expressing the susceptible V136R154Q171 allele of the ovine PRNP gene on a rabbit wild type PRNP New Zealand background and assessed their experimental susceptibility to scrapie prions. All transgenic animals developed a typical TSE 6–8 months after intracerebral inoculation, whereas wild type rabbits remained healthy more than 700 days after inoculation. Despite the endogenous presence of rabbit PrPC, only ovine PrPSc was detectable in the brains of diseased animals. Collectively these data indicate that the low susceptibility of rabbits to prion infection is not enciphered within their non-PrP genetic background. PMID:26248157

  9. Crystal Structure of the C-terminal Domain of Splicing Factor Prp8 Carrying Retinitis Pigmentosa Mutants

    Energy Technology Data Exchange (ETDEWEB)

    Zhang,L.; Shen, J.; Guarnieri, M.; Heroux, A.; Yang, K.; Zhao, R.

    2007-01-01

    Prp8 is a critical pre-mRNA splicing factor. Prp8 is proposed to help form and stabilize the spliceosome catalytic core and to be an important regulator of spliceosome activation. Mutations in human Prp8 (hPrp8) cause a severe form of the genetic disorder retinitis pigmentosa, RP13. Understanding the molecular mechanism of Prp8's function in pre-mRNA splicing and RP13 has been hindered by its large size (over 2000 amino acids) and remarkably low-sequence similarity with other proteins. Here we present the crystal structure of the C-terminal domain (the last 273 residues) of Caenorhabditis elegans Prp8 (cPrp8). The core of the C-terminal domain is an / structure that forms the MPN (Mpr1, Pad1 N-terminal) fold but without Zn{sup 2+} coordination. We propose that the C-terminal domain is a protein interaction domain instead of a Zn{sup 2+}-dependent metalloenzyme as proposed for some MPN proteins. Mapping of RP13 mutants on the Prp8 structure suggests that these residues constitute a binding surface between Prp8 and other partner(s), and the disruption of this interaction provides a plausible molecular mechanism for RP13.

  10. The influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of Platelet Rich Plasma (PRP

    Directory of Open Access Journals (Sweden)

    Lilies Anggarwati Astuti

    2016-06-01

    Full Text Available Platelet Rich Plasma (PRP is a blood concentrate that has a thrombocytes concentration several time higher than normal concentration of thrombocytes in normal human blood. PRP is a promising alternative to surgery with a safe and natural healing. The standard protocol for PRP preparation must be determined to get the right quantity and quality of the matrix of fibrin, leukocytes, platelets and growth factors. It could not be separated from the number of PRP produced. The use of PRP in the success of periodontal treatment would not be separated from methods to obtain it. To detect the influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of PRP. There are 41 subjects studied by taking 21 ml of venous blood in each of the seven tubes. Centrifugation performed twice with different speed, duration, use of anticoagulants then analyzed. This quantity between the two groups differed significantly between the PRP in EDTA group is higher 322.2 ml rather than citrate acid 3.8% group, then control group is higher 329.5 ml rather than citrate acid 3.8% group, while there is no difference between EDTA and control group. There is effect of the use of anticoagulants EDTA compared with citrate acid 3.8% in the quantity of PRP, and there was no effect using citrate acid 3.8% as anticoagulants in quantity of PRP.

  11. Brucella alters the immune response in a prpA-dependent manner

    Science.gov (United States)

    Spera, Juan M.; Comerci, Diego J.; Ugalde, Juan E.

    2014-01-01

    Brucellosis, a disease caused by the gram-negative bacterium Brucella sp, is a widespread zoonosis that inflicts important animal and human health problems, especially in developing countries. One of the hallmarks of Brucella infection is its capacity to establish a chronic infection, characteristic that depends on a wide repertoire of virulence factors among which are immunomodulatory proteins such as PrpA (encoding the proline racemase protein A or hydroxyproline-2-epimerase), involved in the establishment of the chronic phase of the infectious process that we have previously identified and characterized. We report here that, in vivo, B. abortus prpA is responsible for an increment in the B-cell number and in the specific antibody response and that these antibodies promote cell infection. We additionally found that Brucella alters the cytokine levels of IFN-γ, IL-10, TGFβ1 and TNFα during the acute phase of the infectious process in a prpA dependent manner. PMID:24508400

  12. Functions for fission yeast splicing factors SpSlu7 and SpPrp18 in alternative splice-site choice and stress-specific regulated splicing.

    Directory of Open Access Journals (Sweden)

    Geetha Melangath

    Full Text Available Budding yeast spliceosomal factors ScSlu7 and ScPrp18 interact and mediate intron 3'ss choice during second step pre-mRNA splicing. The fission yeast genome with abundant multi-intronic transcripts, degenerate splice signals and SR proteins is an apt unicellular fungal model to deduce roles for core spliceosomal factors in alternative splice-site choice, intron retention and to study the cellular implications of regulated splicing. From our custom microarray data we deduce a stringent reproducible subset of S. pombe alternative events. We examined the role of factors SpSlu7 or SpPrp18 for these splice events and investigated the relationship to growth phase and stress. Wild-type log and stationary phase cells showed ats1+ exon 3 skipped and intron 3 retained transcripts. Interestingly the non-consensus 5'ss in ats1+ intron 3 caused SpSlu7 and SpPrp18 dependent intron retention. We validated the use of an alternative 5'ss in dtd1+ intron 1 and of an upstream alternative 3'ss in DUF3074 intron 1. The dtd1+ intron 1 non-canonical 5'ss yielded an alternative mRNA whose levels increased in stationary phase. Utilization of dtd1+ intron 1 sub-optimal 5' ss required functional SpPrp18 and SpSlu7 while compromise in SpSlu7 function alone hampered the selection of the DUF3074 intron 1 non canonical 3'ss. We analysed the relative abundance of these splice isoforms during mild thermal, oxidative and heavy metal stress and found stress-specific splice patterns for ats1+ and DUF3074 intron 1 some of which were SpSlu7 and SpPrp18 dependent. By studying ats1+ splice isoforms during compromised transcription elongation rates in wild-type, spslu7-2 and spprp18-5 mutant cells we found dynamic and intron context-specific effects in splice-site choice. Our work thus shows the combinatorial effects of splice site strength, core splicing factor functions and transcription elongation kinetics to dictate alternative splice patterns which in turn serve as an additional

  13. Arguing as Trying to Show That a Target-claim is Correct

    Directory of Open Access Journals (Sweden)

    David Hitchcock

    2011-10-01

    Full Text Available In Giving Reasons, Bermejo-Luque rightly claims that a normative model of the speech act of argumentation is more defensible if it rests on an internal aim that is constitutive of the act of arguing than if it rests, as she claims existing normative models do, on an aim that one need not pursue when one argues. She rightly identifies arguing with trying to justify something. But it is not so clear that she has correctly identified the internal aim of arguing as showing that a target-claim is correct on the basis that a reason offered in its support is correct. First, if arguing is as she claims an attempt to justify, it is best construed as an attempt to justify the action or emotion expressed in its conclusion. Second, it is doubtful that qualified reasons and conclusions can always be reasonably reconstructed as unqualified claims, and even more doubtful that non-constative reasons and conclusions can always be reasonably reconstructed as indirect claims. Third, she needs to explain and justify her introduction of the concepts of showing and correctness in her analysis of the act of arguing.

  14. Anaesthetics, steroids and platelet-rich plasma (PRP) in ultrasound-guided musculoskeletal procedures

    Science.gov (United States)

    La Marra, Alice; Arrigoni, Francesco; Mariani, Silvia; Zugaro, Luigi; Splendiani, Alessandra; Di Cesare, Ernesto; Reginelli, Alfonso; Zappia, Marcello; Brunese, Luca; Duka, Ejona; Carrafiello, Giampaolo; Masciocchi, Carlo

    2016-01-01

    This review aims to evaluate the role of anaesthetics, steroids and platelet-rich plasma (PRP) employed with ultrasound-guided injection in the management of musculoskeletal pathology of the extremities. Ultrasound-guided injection represents an interesting and minimally invasive solution for the treatment of tendon and joint inflammatory or degenerative diseases. The availability of a variety of new drugs such as hyaluronic acid and PRP provides expansion of the indications and therapeutic possibilities. The clinical results obtained in terms of pain reduction and functional recovery suggest that the use of infiltrative procedures can be a good therapeutic alternative in degenerative and inflammatory joint diseases. PMID:27302491

  15. IMPACT OF NATURAL FERTILIZATION USING PRP FIX ON SOME SOIL FERTILITY INDICATORS

    OpenAIRE

    Ewa Możdżer; Justyna Chudeka

    2017-01-01

    The field experiment was carried out at The Experimental Station of Plant Varieties Protection in Szczecin Dąbie. The experiment aimed at evaluating the influence of slurry with and without increasing doses of PRP FIX preparation on some soil fertility indicators after test plants harvest. Contents of determined macronutrients in the soil were higher in objects where slurry was applied with addition of 8 kg or 12 kg of PRP FIX per 1 m3 as compared to those with exclusively mineral fertiliz...

  16. The telomerase inhibitor Gno1p/PINX1 activates the helicase Prp43p during ribosome biogenesis.

    Science.gov (United States)

    Chen, Yan-Ling; Capeyrou, Régine; Humbert, Odile; Mouffok, Saïda; Kadri, Yasmine Al; Lebaron, Simon; Henras, Anthony K; Henry, Yves

    2014-06-01

    We provide evidence that a central player in ribosome synthesis, the ribonucleic acid helicase Prp43p, can be activated by yeast Gno1p and its human ortholog, the telomerase inhibitor PINX1. Gno1p and PINX1 expressed in yeast interact with Prp43p and the integrity of their G-patch domain is required for this interaction. Moreover, PINX1 interacts with human PRP43 (DHX15) in HeLa cells. PINX1 directly binds to yeast Prp43p and stimulates its adenosine triphosphatase activity, while alterations of the G patch abolish formation of the PINX1/Prp43p complex and the stimulation of Prp43p. In yeast, lack of Gno1p leads to a decrease in the levels of pre-40S and intermediate pre-60S pre-ribosomal particles, defects that can be corrected by PINX1 expression. We show that Gno1p associates with 90S and early pre-60S pre-ribosomal particles and is released from intermediate pre-60S particles. G-patch alterations in Gno1p or PINX1 that inhibit their interactions with Prp43p completely abolish their function in yeast ribosome biogenesis. Altogether, our results suggest that activation of Prp43p by Gno1p/PINX1 within early pre-ribosomal particles is crucial for their subsequent maturation. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. The DExD/H-box ATPase Prp2p destabilizes and proofreads the catalytic RNA core of the spliceosome.

    Science.gov (United States)

    Wlodaver, Alissa M; Staley, Jonathan P

    2014-03-01

    After undergoing massive RNA and protein rearrangements during assembly, the spliceosome undergoes a final, more subtle, ATP-dependent rearrangement that is essential for catalysis. This rearrangement requires the DEAH-box protein Prp2p, an RNA-dependent ATPase. Prp2p has been implicated in destabilizing interactions between the spliceosome and the protein complexes SF3 and RES, but a role for Prp2p in destabilizing RNA-RNA interactions has not been explored. Using directed molecular genetics in budding yeast, we have found that a cold-sensitive prp2 mutation is suppressed not only by mutations in SF3 and RES components but also by a range of mutations that disrupt the spliceosomal catalytic core element U2/U6 helix I, which is implicated in juxtaposing the 5' splice site and branch site and in positioning metal ions for catalysis within the context of a putative catalytic triplex; indeed, mutations in this putative catalytic triplex also suppressed a prp2 mutation. Remarkably, we also found that prp2 mutations rescue lethal mutations in U2/U6 helix I. These data provide evidence that RNA elements that comprise the catalytic core are already formed at the Prp2p stage and that Prp2p destabilizes these elements, directly or indirectly, both to proofread spliceosome activation and to promote reconfiguration of the spliceosome to a fully competent, catalytic conformation.

  18. A comparison between platelet-rich plasma (PRP and hyaluronate acid on the healing of cartilage defects.

    Directory of Open Access Journals (Sweden)

    Ji Liu

    Full Text Available Platelet-rich plasma (PRP has offered great promise for the treatment of cartilage degradation, and has been proved to have positive effects on the restoration of cartilage lesions. But no comparative work has been done between PRP and hyaluronate acid (HA concerning their restoring effect on cartilage defect, especially by means of animal experiments and histologic assessments. The purpose of the study was to compare the therapeutic effects of P-PRP and HA on osteoarthritis in rabbit knees. Thirty rabbits were used to establish the animal models by creating a cartilage defect of 5 mm in diameter on the condyles of the femurs, and were randomly divided into three groups: the P-PRP group, HA group and the control group. Then each group was treated with P-PRP, HA or saline solution, respectively. Six and twelve weeks later the rabbits were sacrificed and the samples were collected. The platelet number, the concentrations of growth factors of P-PRP and whole blood, and the IL-1β concentration in the joint fluid were investigated, and the histological assessment of the cartilage were performed according to Mankin's scoring system. Micro-CT was also used to evaluate the restoration of subchondral bone. The platelet concentration in P-PRP is 6.8 fold of that in the whole blood. The IL-1β level in the P-PRP group was lower than in the HA group (p<0.01 and in the control group (p<0.01. The restoration of the defected cartilage as well as the subchondral bone was better in the P-PRP group than in the HA group or the control group (P<0.05. Our data showed that P-PRP is better than HA in promoting the restoration of the cartilage and alleviating the arthritis caused by cartilage damage.

  19. Clinical effect of PRP combined with calcium dobesilate in treatment of patients with DR

    Directory of Open Access Journals (Sweden)

    Li-Bo Wang

    2017-09-01

    Full Text Available AIM: To investigate the clinical effect of panretinal photocoagulation(PRPcombined with calcium dobesilate in treatment of diabetic retinopathy(DR. METHODS: Selected 120 cases(240 eyesof DR diagnosed in our hospital from January 2011 to January 2016 were retrospectively analyzed. According to whether calcium dobesilate was used, the treatment group was divided into two groups. Sixty cases were treated with PRP combined with calcium dobesilate, and 60 cases in the control group were treated with PRP only. The BCVA, CMT and clinical efficacy of the two groups were compared. RESULTS: Before treatment, there was no significant difference on BCVA between combined group and control group(P>0.05. After treatment, BCVA of combined group was higher than that of the control group(PP>0.05; after treatment, the combination group on CMT, neovascularization and fluorescein leakage area value were less than the control group(PPCONCLUSION:PRP combined with calcium dobesilate in treatment of DR has a more significant clinical effect than PRP alone.

  20. The use of autologous PRP gel as an aid in the management of acute trauma wounds.

    Science.gov (United States)

    Kazakos, K; Lyras, D N; Verettas, D; Tilkeridis, K; Tryfonidis, M

    2009-08-01

    Autologous platelet-rich plasma (PRP) gel is increasingly used in the treatment of a variety of soft and bony tissue defects, such as accelerating bone formation and in the management of chronic non-healing wounds. We performed this study to assess the benefits of using autologous PRP gel in the treatment of acute limb soft tissue wounds. 59 patients with acute wounds (open fractures, closed fractures with skin necrosis and friction burns) were randomised into two groups. Group A (32 patients) were treated with conventional dressings and Group B (27 patients) were managed with local application of PRP gel. Gustillo grade IIIb or IIIc open fractures were not included in this study, as these injuries required coverage with flap. The clinical endpoints were the healing rate and/or the time required to bring about adequate tissue regeneration in order to undergo reconstructive plastic surgery. The rate of wound healing rate was significantly faster in Group B at week 1, 2 and 3 (p=0.003, p<0.001 and p<0.001, respectively). The mean time to plastic reconstruction in Group B was 21.26 days, S.D.=1.35 vs 40.6 days in Group A, S.D.=5.27 (p<0.001). This study has shown that PRP gel treatment can be a valuable and effective aid in the management of acute trauma wounds.

  1. Quantitating PrP polymorphisms present in prions from heterozygous scrapie-infected sheep

    Science.gov (United States)

    Scrapie is a prion (PrPSc) disease of sheep. The incubation period of sheep scrapie is strongly influenced by polymorphisms at positions 136, 154, and 171 of a sheep’s normal cellular prion protein (PrPC). Chymotrypsin was used to digest sheep recombinant PrP to identify a set of characteristic pept...

  2. Immunological mimicry of PrPC-PrPSc interactions: antibody-induced PrP misfolding.

    Science.gov (United States)

    Li, Li; Guest, Will; Huang, Alan; Plotkin, Steven S; Cashman, Neil R

    2009-08-01

    Prion diseases are associated with the conversion of cellular prion protein (PrP(C)) to an abnormal protease-resistant conformational isoform (PrP(Sc)) by template-directed conversion. The interaction between PrP(C) and PrP(Sc) is mediated by specific sites which have been mapped to six putative 'binding and conversion domains' (PrP-BCD) through peptide and antibody competition studies. Monoclonal antibodies (mAbs) directed against the bityrosine motif Tyr-Tyr-Arg (YYR) specifically recognize PrP(Sc) and other misfolded PrP species. Here, we report that select bead-bound PrP-BCD mAbs induce exposure of bityrosine epitopes on mouse brain PrP. By competition immunoprecipitation, we show that PrP-BCD mAb-induced bityrosine exposure occurs at alpha-helices 1 and 3. However, PrP-BCD mAb-induced PrP(C) misfolding is not accompanied by beta-sheet dissociation, a key event in PrP(C) conversion to PrP(Sc), and is not associated with acquisition of protease resistance, or the capacity to recruit additional molecules of PrP. Our data suggest that mAb mimics of the physical interaction of PrP(C) with PrP(Sc) can induce unfolding of specific PrP domains, but that subsequent processes (including the energetically unfavorable beta-sheet dissociation) effect isoform conversion in prion disease.

  3. Exceptions to the PRP Effect? A Comparison of Prepared and Unconditioned Reflexes

    Science.gov (United States)

    Janczyk, Markus; Pfister, Roland; Wallmeier, Gloria; Kunde, Wilfried

    2014-01-01

    Psychological research has documented again and again marked performance decrements whenever humans perform 2 or more tasks at the same time. In fact, the available evidence seems to suggest that any type of behavior is subject to such limitations. The present experiments employed the psychological refractory period (PRP) paradigm to identify a…

  4. No associations between PrP genotypes and reproduction traits in INRA 401 sheep

    National Research Council Canada - National Science Library

    Vitezica, Z. G; Moreno, C. R; Bodin, L; Francois, D; Barillet, F; Brunel, J. C; Elsen, J. M

    2006-01-01

    ...; and and INRA, Domaine de la Sapinière, 18390 Osmoy, France 2 Corresponding author: vitezica{at}germinal.toulouse.inra.fr In this study, the potential association of PrP genotypes with ewe reproductive traits and lamb growth traits was investigated...

  5. In vitro study of the role of thrombin in platelet rich plasma (PRP) preparation: utility for gel formation and impact in growth factors release

    Science.gov (United States)

    Huber, Stephany Cares; Cunha Júnior, José Luiz Rosenberis; Montalvão, Silmara; da Silva, Letícia Queiroz; Paffaro, Aline Urban; da Silva, Francesca Aparecida Ramos; Rodrigues, Bruno Lima; Lana, José Fabio Santos Duarte; Annichino-Bizzacchi, Joyce Maria

    2016-01-01

    Introduction: The use of PRP has been studied for different fields, with promising results in regenerative medicine. Until now, there is no study in the literature evaluating thrombin levels in serum, used as autologous thrombin preparation. Therefore, in the present study we evaluated the role played by different thrombin concentrations in PRP and the impact in the release of growth factors. Also, different activators for PRP gel formation were evaluated. Methods: Thrombin levels were measured in different autologous preparations: serum, L-PRP (PRP rich in leukocytes) and T-PRP (thrombin produced through PRP added calcium gluconate). L-PRP was prepared according to the literature, with platelets and leukocytes being quantified. The effect of autologous thrombin associated or not with calcium in PRP gel was determined by measuring the time of gel formation. The relationship between thrombin concentration and release of growth factors was determined by growth factors (PDGF-AA, VEGF and EGF) multiplex analysis. Results: A similar concentration of thrombin was observed in serum, L-PRP and T-PRP (8.13 nM, 8.63 nM and 7.56 nM, respectively) with a high variation between individuals (CV%: 35.07, 43 and 58.42, respectively). T-PRP and serum with calcium chloride showed similar results in time to promote gel formation. The increase of thrombin concentrations (2.66, 8 and 24 nM) did not promote an increase in growth factor release. Conclusions: The technique of using serum as a thrombin source proved to be the most efficient and reproducible for promoting PRP gel formation, with some advantages when compared to other activation methods, as this technique is easier and quicker with no need of consuming part of PRP. Noteworthy, PRP activation using different thrombin concentrations did not promote a higher release of growth factors, appearing not to be necessary when PRP is used as a suspension. PMID:27397996

  6. Observations on the occurrence of the fish louse Argu/us japonicus ...

    African Journals Online (AJOL)

    in various parts of the world. Infected fish include Cyprinus carpio, Israel (Reich 1949), Cyprinus carpio and Carassius carassius, Japan (Tokioka 1936; Gopalakrishnan 1968) and. Carassius aura/us, U.S.A. (Meehean 1940). More than 20 species of ArguJus, including A. japonicus, from various fish species have thus been ...

  7. Developing Face-to-Face Argumentation Skills: Does Arguing on the Computer Help?

    Science.gov (United States)

    Iordanou, Kalypso

    2013-01-01

    Arguing on the computer was used as a method to promote development of face-to-face argumentation skills in middle schoolers. In the study presented, sixth graders engaged in electronic dialogues with peers on a controversial topic and in some reflective activities based on transcriptions of the dialogues. Although participants initially exhibited…

  8. "Pay Now, Argue Later" Rule – Before and After the Tax ...

    African Journals Online (AJOL)

    In order to ensure effective and prompt collection of taxes, the payment of tax is not suspended pending an objection or an appeal, unless directed otherwise. This is also known as the "pay now, argue later" rule, and, for value-added tax purposes, is provided for in terms of section 36 of the Value-Added Tax Act 89 of 1991.

  9. Genetic variation of the prion protein gene (PRNP) in alpaca (Vicugna pacos)

    Science.gov (United States)

    Transmissible spongiform encephalopathies (TSE) are caused by accumulation of a misfolded form of the prion protein (PrP). The normal cellular isoform of PrP is produced by the prion gene (PRNP) and is highly expressed in the central nervous system. Currently, there is an absence of information rega...

  10. On the importance of Task 1 and error performance measures in PRP dual-task studies

    Directory of Open Access Journals (Sweden)

    Tilo eStrobach

    2015-04-01

    Full Text Available The Psychological Refractory Period (PRP paradigm is a dominant research tool in the literature on dual-task performance. In this paradigm a first and second component task (i.e., Task 1 and 2 are presented with variable stimulus onset asynchronies (SOAs and priority to perform Task 1. The main indicator of dual-task impairment in PRP situations is an increasing Task 2-RT with decreasing SOAs. This impairment is typically explained with some task components being processed strictly sequentially in the context of the prominent central bottleneck theory. This assumption could implicitly suggest that processes of Task 1 are unaffected by Task 2 and bottleneck processing, i.e. decreasing SOAs do not increase RTs and error rates of the first task. The aim of the present review is to assess whether PRP dual-task studies included both RT and error data presentations and statistical analyses and whether studies including both data types (i.e., RTs and error rates show data consistent with this assumption (i.e., decreasing SOAs and unaffected RTs and/ or error rates in Task 1. This review demonstrates that, in contrast to RT presentations and analyses, error data is underrepresented in a substantial number of studies. Furthermore, a substantial number of studies with RT and error data showed a statistically significant impairment of Task 1 performance with decreasing SOA. Thus, these studies produced data that is not primarily consistent with the strong assumption that processes of Task 1 are unaffected by Task 2 and bottleneck processing in the context of PRP dual-task situations; this calls for a more careful report and analysis of Task 1 performance in PRP studies and for a more careful consideration of theories proposing additions to the bottleneck assumption, which are sufficiently general to explain Task 1 and Task 2 effects.

  11. [Immunogenicity and safety of DTaP-IPV//PRP-T combined vaccine in infants in China].

    Science.gov (United States)

    Li, Yan-ping; Li, Feng-xiang; Hou, Qi-ming; Li, Chang-gui; Li, Ya-nan; Chen, Fu-sheng; Hu, Xue-zhong; Su, Wen-bin; Zhang, Shu-min; Fang, Han-hua; Ye, Qiang; Zeng, Tian-de; Liu, Tao-xuan; Li, Xiu-bi; Huang, Yun-neng; Deng, Man-ling; Li, Rong-cheng; Zhang, Yan-ping; Esteban, Ortiz

    2011-08-01

    The aim of this study was to demonstrate the immunogenicity and safety of diphtheria, tetanus, pertussis (acellular, component), poliomyelitis (inactivated) vaccine (adsorbed) and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV//PRP-T) combined vaccine compared with commercially available DTaP (diphtheria, tetanus and pertussis), Haemophilus influenzae type b (Hib), tetanus conjugate and IPV monovalent vaccine. Subjects were randomly divided into three groups, Group A and Group B were DTaP-IPV//PRP-T combined vaccine (PENTAXIM(TM)) vaccinated at 2, 3, 4 months of age or 3, 4, 5 months of age respectively; Group C was commercially available DTaP. Hib tetanus conjugate (Act-HIB(TM)) and IPV (IMOVAX PolioTM(TM)) vaccines vaccinated at 3, 4, 5 months of age. All groups received booster dose at 18 to 20 months of age, with antibody titers tested. Non-inferiority analysis was demonstrated in terms of seroprotection/seroconversion rates between Group A, Group B respectively and Group C. Safety information was collected after each vaccination to assess the safety of investigational vaccines. The non-inferiority of DTaP-IPV//PRP-T combined vaccine vaccinated at 2, 3, 4 or 3, 4, 5 months of age versus DTaP, Hib tetanus conjugate and IPV vaccine was demonstrated for all vaccine antigens in both primary and booster phases in terms of seroprotection/seroconversion rates. DTaP-IPV//PRP-T combined vaccine was well tolerated. The rate of solicited/unsolicited severe adverse reactions was very low and similar to the control vaccines. DTaP-IPV//PRP-T combined vaccine was highly immunogenic with good safety profile in Chinese infants, which was comparable to the commercially available control vaccines.

  12. On the importance of Task 1 and error performance measures in PRP dual-task studies.

    Science.gov (United States)

    Strobach, Tilo; Schütz, Anja; Schubert, Torsten

    2015-01-01

    The psychological refractory period (PRP) paradigm is a dominant research tool in the literature on dual-task performance. In this paradigm a first and second component task (i.e., Task 1 and Task 2) are presented with variable stimulus onset asynchronies (SOAs) and priority to perform Task 1. The main indicator of dual-task impairment in PRP situations is an increasing Task 2-RT with decreasing SOAs. This impairment is typically explained with some task components being processed strictly sequentially in the context of the prominent central bottleneck theory. This assumption could implicitly suggest that processes of Task 1 are unaffected by Task 2 and bottleneck processing, i.e., decreasing SOAs do not increase reaction times (RTs) and error rates of the first task. The aim of the present review is to assess whether PRP dual-task studies included both RT and error data presentations and statistical analyses and whether studies including both data types (i.e., RTs and error rates) show data consistent with this assumption (i.e., decreasing SOAs and unaffected RTs and/or error rates in Task 1). This review demonstrates that, in contrast to RT presentations and analyses, error data is underrepresented in a substantial number of studies. Furthermore, a substantial number of studies with RT and error data showed a statistically significant impairment of Task 1 performance with decreasing SOA. Thus, these studies produced data that is not primarily consistent with the strong assumption that processes of Task 1 are unaffected by Task 2 and bottleneck processing in the context of PRP dual-task situations; this calls for a more careful report and analysis of Task 1 performance in PRP studies and for a more careful consideration of theories proposing additions to the bottleneck assumption, which are sufficiently general to explain Task 1 and Task 2 effects.

  13. The R/V Discoverer cruise to Manus Island. The BNL Portable Radiometer Package (PRP) evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, R.M.; Smith, S.

    1996-05-24

    Brookhaven National Laboratory installed and operated a Portable Radiation Package (PRP) on the NOAA ship R/V DISCOVERER as part of the Combined Sensor Program cruise in the Tropical Western Pacific Ocean. The DISCOVERER transported a collection of radiation and atmospheric instrumentation to positions offshore of manus Island to compare cloud and radiation fields to like instruments measured from a station on the island. The ship sailed NW from Pago Pago, American Samoa, on 14 March 1996 to a latitude of 1{degree}S then due West until it approached manus Island (2{degree}S and 148{degree}E) on approximately 7 April. The ship then turned SW and approached Manus Island in three steps. This route was reversed during the ship`s return to Hawaii. The PRP package is a compact low-power integration of simple sensors that measure long- and short-wave irradiance from moving platforms. A rapid rotating shadowband radiometer that is designed to provide good estimates of diffuse (sky) radiation even from moving buoys or ships was being evaluated. The PRP provided the only means of making diffuse (sky) radiation measurements from the ship. The CSP cruise provided an excellent opportunity to intercompare the PRP with other like instruments in the TWP locale. The unit was located on the starboard flying bridge which was fully exposed to direct sunlight during the ship`s westward transit. When the ship was at its closest approach to manus, the PRP was moved to the island where careful intercomparison with the Manus instrumentation was conducted.

  14. Na+/K+-ATPase is present in scrapie-associated fibrils, modulates PrP misfolding in vitro and links PrP function and dysfunction.

    Directory of Open Access Journals (Sweden)

    James F Graham

    Full Text Available Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms of the prion protein. These aggregated forms are produced by misfolding of the normal prion protein, PrP(C, to the disease-associated form, PrP(Sc, through mechanisms that remain elusive but which require either direct or indirect interaction between PrP(C and PrP(Sc isoforms. A wealth of evidence implicates other non-PrP molecules as active participants in the misfolding process, to catalyse and direct the conformational conversion of PrP(C or to provide a scaffold ensuring correct alignment of PrP(C and PrP(Sc during conversion. Such molecules may be specific to different scrapie strains to facilitate differential prion protein misfolding. Since molecular cofactors may become integrated into the growing protein fibril during prion conversion, we have investigated the proteins contained in prion disease-specific deposits by shotgun proteomics of scrapie-associated fibrils (SAF from mice infected with 3 different strains of mouse-passaged scrapie. Concomitant use of negative control preparations allowed us to identify and discount proteins that are enriched non-specifically by the SAF isolation protocol. We found several proteins that co-purified specifically with SAF from infected brains but none of these were reproducibly and demonstrably specific for particular scrapie strains. The α-chain of Na(+/K(+-ATPase was common to SAF from all 3 strains and we tested the ability of this protein to modulate in vitro misfolding of recombinant PrP. Na(+/K(+-ATPase enhanced the efficiency of disease-specific conversion of recombinant PrP suggesting that it may act as a molecular cofactor. Consistent with previous results, the same protein inhibited fibrillisation kinetics of recombinant PrP. Since functional interactions between PrP(C and Na(+/K(+-ATPase have previously been reported in astrocytes, our data highlight this molecule as

  15. Is PRP useful in alveolar cleft reconstruction? Platelet-rich plasma in secondary alveoloplasty.

    Science.gov (United States)

    Luaces-Rey, Ramon; Arenaz-Búa, Jorge; Lopez-Cedrún-Cembranos, José-Luis; Herrero-Patiño, Susana; Sironvalle-Soliva, Sheyla; Iglesias-Candal, Emma; Pombo-Castro, María

    2010-07-01

    Cleft lip and palate is a congenital facial malformation with an established treatment protocol. Mixed dentition period is the best moment for correct maxillary bone defect with an alveoloplasty. The aim of this surgical procedure is to facilitate dental eruption, re-establish maxillary arch, close any oro-nasal communication, give support to nasal ala, and in some cases allow dental rehabilitation with osteointegrated implants. Twenty cleft patients who underwent secondary alveoloplasty were included. In 10 of them autogenous bone graft were used and in other 10 autogenous bone and platelet-rich plasma (PRP) obtained from autogenous blood. Bone formation was compared by digital orthopantomography made on immediate post-operatory and 3 and 6 months after the surgery. No significant differences were found between both therapeutic groups on bone regeneration. We do not find justified the use of PRP for alveoloplasty in cleft patients' treatment protocol.

  16. Tendinopathies and platelet-rich plasma (PRP): from pre-clinical experiments to therapeutic use

    Science.gov (United States)

    Kaux, Jean-François; Drion, Pierre; Croisier, Jean-Louis; Crielaard, Jean-Michel

    2015-01-01

    Objectives: The restorative properties of platelets, through the local release of growth factors, are used in various medical areas. This article reviews fundamental and clinical research relating to platelet-rich plasma applied to tendinous lesions. Materials and method: Articles in French and English, published between 1 January 2012 and 31 December 2014. dealing with PRP and tendons were searched for using the Medline and Scopus data bases. Results: Forty-seven articles were identified which addressed pre-clinical and clinical studies: 27 relating to in vitro and in vivo animal studies and 20 relating to human studies. Of these, five addressed lateral epicondylitis, two addressed rotator cuff tendinopathies, ten dealt with patellar tendinopathies and three looked at Achilles tendinopathies. Conclusions: The majority of pre-clinical studies show that PRP stimulates the tendon’s healing process. However, clinical series remain more controversial and level 1, controlled, randomised studies are still needed. PMID:26195890

  17. Tendinopathies and platelet-rich plasma (PRP: from pre-clinical experiments to therapeutic use

    Directory of Open Access Journals (Sweden)

    Kaux JF

    2015-05-01

    Full Text Available Objectives: The restorative properties of platelets, through the local release of growth factors, are used in various medical areas. This article reviews fundamental and clinical research relating to platelet-rich plasma applied to tendinous lesions. Materials and method: Articles in French and English, published between 1 January 2012 and 31 December 2014. dealing with PRP and tendons were searched for using the Medline and Scopus data bases. Results: Forty-seven articles were identified which addressed pre-clinical and clinical studies: 27 relating to in vitro and in vivo animal studies and 20 relating to human studies. Of these, five addressed lateral epicondylitis, two addressed rotator cuff tendinopathies, ten dealt with patellar tendinopathies and three looked at Achilles tendinopathies. Conclusions: The majority of pre-clinical studies show that PRP stimulates the tendon's healing process. However, clinical series remain more controversial and level 1, controlled, randomised studies are still needed.

  18. IMPACT OF NATURAL FERTILIZATION USING PRP FIX ON SOME SOIL FERTILITY INDICATORS

    Directory of Open Access Journals (Sweden)

    Ewa Możdżer

    2017-07-01

    Contents of determined macronutrients in the soil were higher in objects where slurry was applied with addition of 8 kg or 12 kg of PRP FIX per 1 m3 as compared to those with exclusively mineral fertilization or slurry. The soil after test plants harvest contained more N, Corg., P, K, Mg, Ca, S, and available forms of P, K, Mg and SO3 in relation to levels before experiment establishment. In general, more soil fertility indicators were recorded in objects treated with the slurry along with PRP FIX preparation and additional PK nutrition (series II as compared to series I. Differences in macronutrients in the soil due to the fertilization system applied were diverse, however they not always were significant.

  19. "PAY NOW, ARGUE LATER" RULE – BEFORE AND AFTER THE TAX ADMINISTRATION ACT

    Directory of Open Access Journals (Sweden)

    Carika Keulder

    2013-12-01

    Full Text Available The South African Revenue Service (SARS is entrusted with the duty of collecting tax on behalf of the South African government. In order to ensure effective and prompt collection of taxes, the payment of tax is not suspended pending an objection or an appeal, unless directed otherwise. This is also known as the "pay now, argue later" rule, and, for value-added tax purposes, is provided for in terms of section 36 of the Value-Added Tax Act 89 of 1991. The "pay now, argue later" rule in terms of section 36 of the Value-Added Tax Act prima facie infringes on a taxpayer's right of access to the courts as envisaged in section 34 of the Constitution. This is due to the fact that a taxpayer is obliged to pay tax before being afforded the opportunity to challenge the assessment in a court. In Metcash Trading Ltd v Commissioner for the South African Revenue Service, the Constitutional Court held the "pay now, argue later" rule in terms of section 36 to be constitutional. Olivier, however, does not agree with the court on several matters. Amongst the problems she indicates are that the taxpayer does not have access to the courts at the time the rule is invoked, and that the court did not consider the fact that there might be less invasive means available which would ensure that SARS's duty is balanced with the taxpayer's right of access to the courts. Guidelines were also issued which provide legal certainty regarding the factors SARS may consider in determining whether the payment of tax should be suspended or not. These guidelines also evoked some points of criticism. Since 1 October 2012, the "pay now, argue later" rule has been applied in terms of section 164 of the Tax Administration Act 28 of 2011. The question arises whether this provision addresses the problems identified in respect of section 36 of the Value-Added Tax Act and the guidelines. In comparing these sections, only slight differences emerged. The most significant difference is that

  20. Using PRP and human amniotic fluid combination for osteogenesis in rabbit socket preservation

    Directory of Open Access Journals (Sweden)

    Amir Hossein Moradi

    2015-01-01

    Full Text Available Introduction: Platelet-rich plasma (PRP is used as an adjunct treatment during periodontal grafting surgery because of its capability of enhancing healing process. Amniotic fluid is a rich source of growth factors and hyaluronic acid (HA and a good point to study its properties of wound healing and bone formation. The aim of this study was to evaluate the osteogenic properties of a combination of amniotic fluid and PRP in rabbit′s dental socket preservation. Materials and Methods: The study population consisted of 24 healthy male laboratory rabbits (average weight 3,125 ± 185 gr that were randomly allocated into four groups. PRP for the first group, human amniotic fluid (HAF for the second group, a combination of PRP and HAF (PRHA for the third group was used. In the fourth (control group, no biomaterial was used. In each group, half of the rabbits were sacrificed at 4 weeks following surgery and the rest were sacrificed after 8 weeks. Histological analysis of biopsies of the sockets was performed using hematoxylin and eosin (H&E staining. Data were analyzed using Statistical Package for the Social Sciences (SPSS software (version 16 and P-value <0.05 was considered significance. Results: All three experimental groups showed positive effect on bone formation in terms of area of trabecular bone and number of osteocytes and also vessel formation. Socket preservation using HAF and PRHA showed the highest impact on bone formation. Socket preservation using HAF also had the highest impact on vessel formation. Conclusion: PRHA and HAF appear to be useful for enhancing bone formation. Since there was no difference between HAF and PRHA, it seems beneficial to use HAF due to its simplicity of application.

  1. Efectividad del PRP en el tratamiento de la artrosis de rodilla: Estudio de casos

    OpenAIRE

    Fernández Valverde, Noelia; Fidalgo González, Verónica

    2016-01-01

    La artrosis es una enfermedad degenerativa de elevada prevalencia para la cual, en la actualidad, no hay tratamiento curativo. Una de las localizaciones más frecuentes es la rodilla. La utilización de infiltraciones de plasma rico en plaquetas constituye una alternativa en el tratamiento de esta patología. Objetivo: demostrar la efectividad y la seguridad de las infiltraciones con PRP en el tratamiento de pacientes con artrosis de rodilla. Resultado: este trabajo muestra una...

  2. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration

    National Research Council Canada - National Science Library

    Albanese, Antonino; Licata, Maria E; Polizzi, Bianca; Campisi, Giuseppina

    2013-01-01

    Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients...

  3. Efficacy of leukocyte‐ and platelet‐rich plasma gel (L‐PRP gel) in treating osteomyelitis in a rabbit model

    National Research Council Canada - National Science Library

    Li, Guang‐Yi; Yin, Ji‐Min; Ding, Hao; Jia, Wei‐Tao; Zhang, Chang‐Qing

    2013-01-01

    Leukocyte‐ and platelet‐rich plasma gel (L‐PRP gel), a new autologous product which was previously utilized in several surgical procedures to enhance tissue healing, is now increasingly used as a promising treatment method for infections...

  4. Split face comparative study of microneedling with prp versus microneedling with vitamin c in treating atrophic post acne scars: Erratum

    National Research Council Canada - National Science Library

    2015-01-01

      The article, "Split Face Comparative Study of Microneedling with PRP Versus Microneedling with Vitamin C in Treating Atrophic Post Acne Scars", which appeared in the pages 209-212 Issue 4, Vol 7...

  5. Comparing hybrid hyaluronic acid with PRP in end career athletes with degenerative cartilage lesions of the knee.

    Science.gov (United States)

    Papalia, R; Zampogna, B; Russo, F; Vasta, S; Tirindelli, M C; Nobile, C; Di Martino, A C; Vadalà, G; Denaro, V

    2016-01-01

    Cartilage lesions are very common causes of chronic knee pain in athletes. Current treatment options consist in conservative strategies, such as viscosupplementation and platelet-rich plasma injections. This randomized controlled trial aims to investigate the effect of intra-articular Hybrid Hyaluronic Acid injections compared to PRP for the treatment of cartilage lesions among athletes at the end of their career. Since March 2015, 48 professional soccer players were randomized into two groups: 24 patients received 3 injections of HHA and 23 patients received 3 intra-articular injections of PRP. All patients achieved a statistically significant clinical improvement from preoperative to postoperative time in both groups. Patients in the HHA group showed a significant superiority compared to PRP group at 3 and 6 months. Intergroup differences decrease gradually until loss of significance at 12 months follow-up. Athletes with chronic degenerative cartilage lesions of the knee responded positively both to HHA and PRP until last follow up.

  6. NMR structure of the mouse prion protein domain PrP(121-231).

    Science.gov (United States)

    Riek, R; Hornemann, S; Wider, G; Billeter, M; Glockshuber, R; Wüthrich, K

    1996-07-11

    The 'protein only' hypothesis states that a modified form of normal prion protein triggers infectious neurodegenerative diseases, such as bovine spongiform encephalopathy (BSE), or Creutzfeldt-Jakob disease (CJD) in humans. Prion proteins are thought to exist in two different conformations: the 'benign' PrPcform, and the infectious 'scrapie form', PrPsc. Knowledge of the three-dimensional structure of PrPc is essential for understanding the transition to PrPsc. The nuclear magnetic resonance (NMR) structure of the autonomously folding PrP domain comprising residues 121-231 (ref. 6) contains a two-stranded antiparallel beta-sheet and three alpha-helices. This domain contains most of the point-mutation sites that have been linked, in human PrP, to the occurrence of familial prion diseases. The NMR structure shows that these mutations occur within, or directly adjacent to, regular secondary structures. The presence of a beta-sheet in PrP(121-231) is in contrast with model predictions of an all-helical structure of PrPc (ref. 8), and may be important for the initiation of the transition from PrPc to PrPsc.

  7. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.

    Science.gov (United States)

    Albanese, Antonino; Licata, Maria E; Polizzi, Bianca; Campisi, Giuseppina

    2013-06-13

    Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

  8. In Vitro Studies on the Degradability, Bioactivity, and Cell Differentiation of PRP/AZ31B Mg Alloys Composite Scaffold

    Directory of Open Access Journals (Sweden)

    Jian Zou

    2017-01-01

    Full Text Available In recent years, more and more methods have been developed to improve the bioactivity of the biodegradable materials in bone tissue regeneration. In present study, we used rat mesenchymal stem cells (rMSCs to evaluate the outcomes of Mg alloys (AZ31B, Magnesium, and Aluminum and Platelet-rich plasma (PRP/Mg alloys on rMSCs biocompatibility and osteogenic differentiation. Water absorption experiments indicated that both bare AZ31B and PRP/AZ31B were capable of absorbing large amounts of water. But the water absorption ratio for PRP/AZ31B was significantly higher than that for bare AZ31B. The degradability experiments implied that both samples degraded at same speed. rMSCs on the surface of AZ31B distributed more and better than those on the AZ31B scaffold. In ALP activity experiment, the activity of rMSCs on the PRP/AZ31B was markedly higher than that on the AZ31B scaffolds on the 7th day and 14th day. qRT-PCR also showed that OPN and OCN were expressed in both samples. OPN and OCN expression in PRP/AZ31B sample were higher than those in bare AZ31B samples. In summary, the in vitro study implied that AZ31B combined with PRP could remarkably improve cell seeding, attachment, proliferation, and differentiation.

  9. Tratamiento de quemaduras mediante plasma rico en plaquetas (PRP: parte I

    Directory of Open Access Journals (Sweden)

    G. Rossani

    2014-06-01

    Full Text Available El objetivo del presente trabajo es determinar la eficacia clínica del plasma rico en plaquetas (PRP en las quemaduras de segundo grado. Estudiamos el tiempo requerido en la reepitelización del tejido dañado, la estancia hospitalaria asociada a la curación de las lesiones y la satisfacción del paciente. Realizamos un estudio prospectivo, observacional y longitudinal, en una muestra de 115 pacientes con quemaduras de segundo grado según la clasificación de Converse-Smith. Las lesiones fueron de menos de 48 horas de evolución, en diferentes zonas de cara y cuerpo. A todos los pacientes se les aplicó de forma ambulatoria PRP por goteo, completándose el tratamiento con la aplicación de gasas parafinadas. El estudio se realizó entre marzo de 2011 y agosto de 2013. Las quemaduras que evolucionaron mejor y de forma más rápida fueron las de cara, seguidas por las de abdomen y, por último, las de extremidades inferiores. En todas, el tiempo de epitelización fue un 30 % inferior que en quemaduras de similar extensión, profundidad y localización, en pacientes anteriormente tratados sin PRP. Los pacientes fueron atendidos ambulatoriamente cuando las lesiones lo permitieron, y si presentaban lesiones más extensas fueron hospitalizados. El tiempo de internamiento en estos casos se redujo como promedio 18 días con respecto al grupo no tratado con PRP. El tiempo de reepitelización, estancia hospitalaria y la satisfacción de los pacientes, alcanzaron significación estadística p< 0,05. En conclusión, creemos que el uso de PRP acorta el tiempo de recuperación en quemaduras de segundo grado, reduce el tiempo de hospitalización y conlleva un alto grado de satisfacción de los pacientes por los resultados obtenidos.

  10. Peroxiredoxin 6 promotes upregulation of the prion protein (PrP in neuronal cells of prion-infected mice

    Directory of Open Access Journals (Sweden)

    Wagner Wibke

    2012-12-01

    Full Text Available Abstract Background It has been widely established that the conversion of the cellular prion protein (PrPC into its abnormal isoform (PrPSc is responsible for the development of transmissible spongiform encephalopathies (TSEs. However, the knowledge of the detailed molecular mechanisms and direct functional consequences within the cell is rare. In this study, we aimed at the identification of deregulated proteins which might be involved in prion pathogenesis. Findings Apolipoprotein E and peroxiredoxin 6 (PRDX6 were identified as upregulated proteins in brains of scrapie-infected mice and cultured neuronal cell lines. Downregulation of PrP gene expression using specific siRNA did not result in a decrease of PRDX6 amounts. Interestingly, selective siRNA targeting PRDX6 or overexpression of PRDX6 controlled PrPC and PrPSc protein amounts in neuronal cells. Conclusions Besides its possible function as a novel marker protein in the diagnosis of TSEs, PDRX6 represents an attractive target molecule in putative pharmacological intervention strategies in the future.

  11. Cell Proliferation Pattern and Twist Expression in an Aplacophoran Mollusk Argue Against Segmented Ancestry of Mollusca.

    Science.gov (United States)

    Redl, Emanuel; Scherholz, Maik; Wollesen, Tim; Todt, Christiane; Wanninger, Andreas

    2016-11-01

    The study of aplacophoran mollusks (i.e., Solenogastres or Neomeniomorpha and Caudofoveata or Chaetodermomorpha) has traditionally been regarded as crucial for reconstructing the morphology of the last common ancestor of the Mollusca. Since their proposed close relatives, the Polyplacophora, show a distinct seriality in certain organ systems, the aplacophorans are also in the focus of attention with regard to the question of a potential segmented ancestry of mollusks. To contribute to this question, we investigated cell proliferation patterns and the expression of the twist ortholog during larval development in solenogasters. In advanced to late larvae, during the outgrowth of the trunk, a pair of longitudinal bands of proliferating cells is found subepithelially in a lateral to ventrolateral position. These bands elongate during subsequent development as the trunk grows longer. Likewise, expression of twist occurs in two laterally positioned, subepithelial longitudinal stripes in advanced larvae. Both, the pattern of proliferating cells and the expression domain of twist demonstrate the existence of extensive and long-lived mesodermal bands in a worm-shaped aculiferan, a situation which is similar to annelids but in stark contrast to conchiferans, where the mesodermal bands are usually rudimentary and ephemeral. Yet, in contrast to annelids, neither the bands of proliferating cells nor the twist expression domain show a separation into distinct serial subunits, which clearly argues against a segmented ancestry of mollusks. Furthermore, the lack of twist expression during the development of the ventromedian muscle argues against homology of a ventromedian longitudinal muscle in protostomes with the notochord of chordates. © 2016 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution published by Wiley Periodicals, Inc.

  12. Arguing from Nature: The Role of "Nature" in Students' Argumentations on a Socio-Scientific Issue

    Science.gov (United States)

    Nielsen, Jan Alexis

    2012-01-01

    This paper explores how students invoked different conceptions of "nature" in eight socio-scientific group discussions about human gene therapy. The paper illustrates and discusses how the students articulated nature and to what extent they elicited science factual content in the process. While the students in this study invoked nature at key…

  13. Split face comparative study of microneedling with PRP versus microneedling with vitamin C in treating atrophic post acne scars

    Directory of Open Access Journals (Sweden)

    Simran Chawla

    2014-01-01

    Full Text Available Introduction: Acne scars are largely preventable complications of acne. 95% of the scars occur over the face thus impacting the quality of life. Correction of scars is the priority for acne patients. Materials and Methods: Thirty patients with post acne atrophic facial scars attending the OPD during the period from April to October 2013 were offered four sittings of microneedling with PRP on one side and microneedling with vitamin C on other side of the face at an interval of 1 month. Results: Twenty-seven out of the total 30 patients completed the treatment schedule. Two patients were lost to follow up and one dropped out of the study due to severe PIH. Mean age of the patients was 27.5 years. Out of 30 patients, 23 achieved reduction in scarring by one or two grades. Excellent response was seen in five (18.5% patients with platelet-rich plasma (PRP as compared to two (7% patients who received treatment with vitamin C according to physician′s assessment. As far as up gradation by 1 score is considered, i.e., good response, it was similar in both cases. Vitamin C did not prove to be as efficacious as PRP since 10 (37% patients had poor response in vitamin C-treated area compared to only 6 (22.2% patients who underwent PRP therapy, but vitamin C proved to be efficacious in dealing with post inflammatory hyper-pigmentation secondary to acne. Patients were more satisfied with PRP as compared to vitamin C. The results were evaluated and statistical analysis was done using SPSS 16.0.2. Conclusions: Overall results were better with microneedling and PRP. Vitamin C combined with microneedling also showed improvement with respect to firmness and smoothness of skin; as well as post inflammatory hyper-pigmentation. Microneedling combined with PRP proved to be good in treating boxcar and rolling scars but had limited efficacy in dealing with ice pick scars.

  14. The development rubrics skill argued as alternative assessment floating and sinking materials

    Science.gov (United States)

    Viyanti; Cari; Sunarno, Widha; Prasetyo, Zuhdan Kun

    2017-11-01

    The quality of arguing to learners of floating and sinking material can be assessed by using the rubric of an argumentation assessment skill as an alternative assessment. The quality of the argument is measured by the ability of learners to express the claim in a structured manner in order to maintain the claim with supporting data. The purpose of this study was to develop an argument skill rubric based on the preliminary study results which showed a gap between demands and reality related to the students ‘floating and sinking students’ argument skills. This research was conducted in one of State Senior High School Bandar Lampung. The study population is all students of senior high scholl class XI. Research sample was taken by randomly obtained by 20 students. The research used descriptive survey method. Data were obtained through a multiple choice test both grounded and interview. The results were analyzed based on the level of students’ argumentation skills that had met the criteria which developed in the assessment rubric. The results of the data analysis found that the learners are in the range of levels 1 through 3. Based on the data the average learner is at the level of quality argument “high” for component I and the quality of “low” argument for component 2. This indicates learners experience difficulty which making alternative statement supported by reference in accordance with the initial statement submitted. This fact is supported by interviews that learners need a structured strategy to design alternative statements from shared reading sources to support the preliminary statements presented.

  15. Tratamiento de quemaduras mediante plasma rico en plaquetas (PRP): parte I

    OpenAIRE

    G. Rossani; I. Hernández; J.M. Alcolea; R. Castro-Sierra; W. Pérez-Soto; M.A. Trelles

    2014-01-01

    El objetivo del presente trabajo es determinar la eficacia clínica del plasma rico en plaquetas (PRP) en las quemaduras de segundo grado. Estudiamos el tiempo requerido en la reepitelización del tejido dañado, la estancia hospitalaria asociada a la curación de las lesiones y la satisfacción del paciente. Realizamos un estudio prospectivo, observacional y longitudinal, en una muestra de 115 pacientes con quemaduras de segundo grado según la clasificación de Converse-Smith. Las lesiones fueron ...

  16. Beneficios del adhesivo autólogo de fibrina y PRP en ritidectomía

    OpenAIRE

    I. Hernández; G. Rossani; R. Castro-Sierra

    2015-01-01

    Determinamos la eficacia clínica del adhesivo autólogo de fibrina y la fracción de sangre rica en plaquetas (PRP) en la disminución de complicaciones en ritidectomía. Se intervino con igual técnica ambas hemicaras, pero solo una, aleatoriamente, recibió tratamiento con hemoderivados. Estudiamos comparativamente la evolución postquirúrgica de una hemicara frente a otra: tiempo de recuperación a corto, medio y largo plazo; incidencia de hematomas, seromas, epidermolisis, necrosis y equimosis; y...

  17. Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure

    Energy Technology Data Exchange (ETDEWEB)

    Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

    2015-09-01

    Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

  18. The fate of PrP GPI-anchor signal peptide is modulated by P238S pathogenic mutation.

    Science.gov (United States)

    Guizzunti, Gianni; Zurzolo, Chiara

    2014-01-01

    Glycosylphosphatidylinositol (GPI)-anchored proteins are localized to the plasma membrane via a C-terminally linked GPI anchor. The GPI anchor is added concomitantly to the cleavage of the carboxy-terminal GPI-anchor signal sequence, thereby causing the release of a C-terminal hydrophobic peptide, whose fate has not yet been investigated. Here we followed the fate of the GPI-attachment signal of the prion protein (PrP), a protein implicated in various types of transmissible neurodegenerative spongiform encephalopathies (TSE). The PrP GPI-anchor signal sequence shows a remarkable and unusual degree of conservation across the species and contains two point mutations (M232R/T and P238S) that are responsible for genetic forms of prion disorders. We show that the PrP GPI-anchor signal peptide (SP), but not the one from an unrelated GPI-anchored protein (folate receptor), undergoes degradation via the proteasome. Moreover, the P238S point mutation partially protects the PrP GPI-anchor SP from degradation. Our data provide the first attempt to address the fate of a GPI-anchor SP and identify a role for the P238S mutation, suggesting the possibility that the PrP GPI-anchor SP could play a role in neurodegenerative prion diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure.

    Science.gov (United States)

    Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

    2015-01-01

    Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

  20. Should we embed randomized controlled trials within action research: arguing from a case study of telemonitoring

    Directory of Open Access Journals (Sweden)

    Karen Day

    2016-06-01

    Full Text Available Abstract Background Action research (AR and randomized controlled trials (RCTs are usually considered to be theoretically and practically incompatible. However, we argue that their respective strengths and weaknesses can be complementary. We illustrate our argument from a recent study assessing the effect of telemonitoring on health-related quality of life, self-care, hospital use, costs and the experiences of patients, informal carers and health care professionals in two urban hospital services and one remote rural primary care service in New Zealand. Methods Data came from authors’ observations and field notes of discussions with three groups: the healthcare providers and healthcare consumers who participated in the research, and a group of 17 researchers and collaborators. The consumers had heart failure (Site A, urban, airways disease (Site B, urban, and diabetes (Site C, rural. The research ran from 2008 (project inception until 2012 (project close-off. Researchers came from a wide range of disciplines. Both RCT and AR methods were recognised from early in the process but often worked in parallel rather than together. In retrospect, we have mapped our observed research processes to the AR cycle characteristics (creation of communicative space, democracy and participation, iterative learning and improvement, emergence, and accommodation of different ways of knowing. Results We describe the context, conduct and outcomes of the telemonitoring trial, framing the overall process in the language of AR. Although not fully articulated at the time, AR processes made the RCT sensitive to important context, e.g. clinical processes. They resulted in substantive changes to the design and conduct of the RCT, and to interpretation and uptake of findings, e.g. a simpler technology procurement process emerged. Creating a communicative space enabled co-design between the researcher group and collaborators from the provider participant group, and a stronger

  1. Antibody persistence after a primary series of a new DTaP-IPV-Hep B-PRP-T combined vaccine or separate DTaP-IPV//PRP-T and hepatitis B vaccines at 2, 4, and 6 months of age and the effect of a subsequent DTaP-IPV//PRP-T booster vaccination at 18 months of age in healthy Argentinean infants.

    Science.gov (United States)

    Tregnaghi, Marcelo; Zambrano, Betzana; Santos-Lima, Eduardo

    2012-01-01

    To assess antibody persistence after vaccination with a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine at 18 months of age versus licensed DTaP-IPV//PRP-T and hepatitis B (Hep B) vaccines, and to assess the immunogenicity and safety of a subsequent DTaP-IPV//PRP-T booster. A phase III, open-label, single-center study was conducted. Infants previously primed with 3 doses of DTaP-IPV-Hep B-PRP-T (Hexaxim: N = 232 [group 1]) or DTaP-IPV//PRP-T and hepatitis B vaccine (Pentaxim + Engerix B Pediatrico: N = 226 [group 2]) at 2, 4, and 6 months of age received a DTaP-IPV//PRP-T booster at 18 months of age. Antibodies were measured before and 1 month after booster vaccination. Safety was evaluated from parental reports. Analyses were descriptive. Antibody persistence was high and similar in each group for each antigen except for Hep B, for which the percentage (95% confidence interval) of participants with a titer of ≥ 10 mIU/mL was higher in group 2 (99.5% [97.5%, 100.0%]) than in group 1 (85.5% [80.3%, 89.8%]). Postbooster seroprotection (diphtheria, tetanus, inactivated poliovirus, polyribosyl-ribitol phosphate) and serconversion (pertussis toxoid, filamentous hemagglutinin) rates were high and similar in each group, and geometric mean antibody concentrations increased markedly in both groups. Safety after the booster vaccination was good and independent of the primary-series vaccine, although one serious adverse event of convulsions was considered to be vaccine related. The DTaP-IPV/PRP-T booster vaccination at 18 months of age was similarly immunogenic and well tolerated after primary-series vaccination with either the investigational hexavalent vaccine or the reference pentavalent vaccine. This confirms the suitability of a booster vaccination of DTaP-IPV//PRP-T after a primary series of the new DTaP-IPV-Hep B-PRP-T vaccine.

  2. PRP Comments for ICF Q1/Q2 FY17 Experiments 3/10/16

    Energy Technology Data Exchange (ETDEWEB)

    Kauffman, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-04-14

    The PRP generally endorsed the Program plan during the short time for discussions. We agree that the strategy to develop a hohlraum that is symmetric and has low laser-plasma instabilities and to develop an alternative method for supporting the capsule is the best path forward for making progress in understanding ignition performance. The Program is oriented toward a milestone in 2020 for “determining the efficacy of NIF for ignition and credible physics-scaling to multi-megajoule yields for all ICF approaches.” We are concerned that the time and resources are not sufficient to vet all of the various approaches that are being pursued to make an informed decision by this date. For NIF to meet this goal, a process will be needed to to select the most promising paths forward. We recommend that the Program develop this process for selecting the path forward to optimize resources. We were glad to see that the direct drive program took our comments under consideration. We think that the proposed experiments have the program headed in a better direction. The PRP had only a short time to discuss the detailed experimental proposals. The following are comments on the detailed proposals. We did not have time to discuss them as a group. They represent individual opinions and provided to you as feedback to your proposals.

  3. A modified three-term PRP conjugate gradient algorithm for optimization models.

    Science.gov (United States)

    Wu, Yanlin

    2017-01-01

    The nonlinear conjugate gradient (CG) algorithm is a very effective method for optimization, especially for large-scale problems, because of its low memory requirement and simplicity. Zhang et al. (IMA J. Numer. Anal. 26:629-649, 2006) firstly propose a three-term CG algorithm based on the well known Polak-Ribière-Polyak (PRP) formula for unconstrained optimization, where their method has the sufficient descent property without any line search technique. They proved the global convergence of the Armijo line search but this fails for the Wolfe line search technique. Inspired by their method, we will make a further study and give a modified three-term PRP CG algorithm. The presented method possesses the following features: (1) The sufficient descent property also holds without any line search technique; (2) the trust region property of the search direction is automatically satisfied; (3) the steplengh is bounded from below; (4) the global convergence will be established under the Wolfe line search. Numerical results show that the new algorithm is more effective than that of the normal method.

  4. A DTAP–IPV//PRP~T VACCINE: A REVIEW OF 16 YEARS’ CLINICAL EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Stanley A. Plotkin

    2012-01-01

    Full Text Available Owing to their low reactogenicity, confirmed efficacy and availability in combination vaccines, acellular pertussis (aP-inactivated poliovirus (IPV combined vaccines are now included in various national immunization programs worldwide. We provide an overview of 16 years of clinical experience with a diphtheria (D, tetanus (T, aP, IPV and Haemophilus influenzae type b (Hib polysaccharide conjugated to tetanus protein (PRP~T combined vaccine (DTaP–IPV//PRP~T — Pentaxim, Sanofi Pasteur, France. Good immunogenicity has been demonstrated after primary vaccination with Pentaxim, regardless of the population ethnicity and primary vaccination schedule. A booster vaccination in the second year of life also resulted in a high immune response for each antigen. Furthermore, 10 years of national surveillance in Sweden has demonstrated the effectiveness of Pentaxim in controlling pertussis. As is the case for other aP-containing combined vaccines, Pentaxim is well tolerated, with the safety profile being better than for whole-cell pertussiscontaining combination vaccines for primary and booster vaccinations.

  5. Prediction and optimization of the recovery rate in centrifugal separation of platelet-rich plasma (PRP)

    Science.gov (United States)

    Piao, Linfeng; Park, Hyungmin; Jo, Chris

    2016-11-01

    We present a theoretical model of the recovery rate of platelet and white blood cell in the process of centrifugal separation of platelet-rich plasma (PRP). For the practically used conditions in the field, the separation process is modeled as a one-dimensional particle sedimentation; a quasi-linear partial differential equation is derived based on the kinematic-wave theory. This is solved to determine the interface positions between supernatant-suspension and suspension-sediment, used to estimate the recovery rate of the plasma. While correcting the Brown's hypothesis (1989) claiming that the platelet recovery is linearly proportional to that of plasma, we propose a new correlation model for prediction of the platelet recovery, which is a function of the volume of whole blood, centrifugal acceleration and time. For a range of practical parameters, such as hematocrit, volume of whole blood and centrifugation (time and acceleration), the predicted recovery rate shows a good agreement with available clinical data. We propose that this model is further used to optimize the preparation method of PRP that satisfies the customized case. Supported by a Grant (MPSS-CG-2016-02) through the Disaster and Safety Management Institute funded by Ministry of Public Safety and Security of Korean government.

  6. CLINICAL RESULTS FROM THE TREATMENT OF CHRONIC SKIN WOUNDS WITH PLATELET RICH PLASMA (PRP

    Directory of Open Access Journals (Sweden)

    Pencho Kossev

    2015-12-01

    Full Text Available PURPOSE: To show platelet rich plasma (PRP application of chronic skin wounds and to evaluate the results from the treatment. MATERIAL AND METHODS: A total of 14 patients with problematic skin wounds had been treated at the clinic for a period of five years (from May 2009 to December 2014 with the following patient sex ratio: male patients - 5 and female patients - 9. Average age - 48,5 (30-76. Patients with Type 2 Diabetes - 4, with decubitus ulcers - 6, traumatic - 8, with infection - 5. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 - 6 months (4,5 on average. RESULTS: The results have been evaluated based on the following functional scoring systems - Total wound score, Total anatomic score and Total score (20. The baseline values at the very beginning of the follow-up period were as follows: Total wound score - 12 p.; Total anatomic score - 10 p., Total score - 17 p. By the end of the treatment period the score was 0 p., which means excellent results, i.e. complete healing of the wounds. CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of difficult to heal wounds around joints, bone, subject tendons, plantar surface of the foot, etc., as it opens new perspectives in the field of human tissue regeneration.

  7. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP versus Hyaluronic Acid (A one-year randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Seyed Ahmad Raeissadat

    2015-01-01

    Full Text Available Introduction Knee osteoarthritis (OA is the most common articular disease. Different methods are used to alleviate the symptoms of patients with knee OA, including analgesics, physical therapy, exercise prescription, and intra-articular injections (glucocorticoids, hyaluronic acid [HA], etc. New studies have focused on modern therapeutic methods that stimulate cartilage healing process and improve the damage, including the use of platelet-rich plasma (PRP as a complex of growth factors. Due to the high incidence of OA and its consequences, we decided to study the long-term effect of intraarticular injection of PRP and HA on clinical outcome and quality of life of patients with knee OA. Method This non-placebo-controlled randomized clinical trial involved 160 patients affected by knee OA, grade 1–4 of Kellgren–Lawrence scale. In the PRP group ( n = 87, two intra-articular injections at 4-week interval were applied, and in the HA group ( n = 73, three doses of intra-articular injection at 1-week interval were applied. All patients were prospectively evaluated before and at 12 months after the treatment by Western Ontario and McMaster Universities Arthritis Index (WOMAC and SF-36 questionnaires. The results were analyzed using SPSS 16.1 software (RCT code: IRCT2014012113442N5. Results At the 12-month follow-up, WOMAC pain score and bodily pain significantly improved in both groups; however, better results were determined in the PRP group compared to the HA group ( P < 0.001. Other WOMAC and SF-36 parameters improved only in the PRP group. More improvement (but not statistically significant was achieved in patients with grade 2 OA in both the groups. Conclusion This study suggests that PRP injection is more efficacious than HA injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee OA who have not responded to conventional treatment.

  8. Oxidation reduces the fibrillation but not the neurotoxicity of the prion peptide PrP106-126

    DEFF Research Database (Denmark)

    Bergstrøm, Linda Alice; Chabry, J.; Bastholm, L.

    2007-01-01

    There is increasing evidence that soluble oligomers of misfolded protein may play a role in the pathogenesis of protein misfolding diseases including the transmissible spongiform encephalopathies (TSE) where the protein involved is the prion protein, PrP. The effect of oxidation on fibrillation...... tendency and neurotoxicity of different molecular variants of the prion peptide PrP106-126 was investigated. It was found that methionine oxidation significantly reduced amyloid fibril formation and proteinase K resistance, but it did not reduce (but rather increase slightly) the neurotoxicity...

  9. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Moussa, Mayssam, E-mail: Moussa-mayssam@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Lajeunesse, Daniel, E-mail: daniel.lajeunesse@umontreal.ca [Research Centre in Osteoarthritis, Research Centre in Monteral University (Canada); Hilal, George, E-mail: George2266@gmail.com [Cancer and metabolism Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); El Atat, Oula, E-mail: oulaatat@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Haykal, Gaby, E-mail: Gaby.haykal@hdf.usj.edu.lb [Hotel Dieu de France, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Serhal, Rim, E-mail: rim.basbous@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Chalhoub, Antonio, E-mail: Mava.o@hotmail.com [Carantina Hospital, Beirut (Lebanon); Khalil, Charbel, E-mail: charbelk3@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Alaaeddine, Nada, E-mail: Nada.aladdin@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon)

    2017-03-01

    Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1–2–3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. Conclusion: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. - Highlights: • Platelet Rich Plasma is suggested as a new treatment for osteoarthritis. • The proposed therapeutic effect is

  10. Immunogenicity and safety study of a new DTaP-IPV-Hep B-PRP-T combined vaccine compared to a licensed DTaP-IPV-Hep B//PRP-T comparator, both concomitantly administered with a 7-valent pneumococcal conjugate vaccine at 2, 4, and 6 months of age in Thai infants.

    Science.gov (United States)

    Kosalaraksa, Pope; Thisyakorn, Usa; Benjaponpitak, Suwat; Chokephaibulkit, Kulkanya; Santos-Lima, Eduardo

    2011-04-01

    To assess a new, fully-liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine (diphtheria toxoid (D), tetanus toxoid (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (Hep B), and Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (PRP-T) antigens) compared to a licensed DTaP-IPV-Hep B//PRP-T vaccine following primary series co-administration with a 7-valent pneumococcal conjugate vaccine (PCV7). This was a randomized, phase III, observer-blind study in Thai infants (N=412), who received DTaP-IPV-Hep B-PRP-T or DTaP-IPV-Hep B//PRP-T at 2, 4, and 6 months of age, co-administered with PCV7. All received Hep B at birth. Non-inferiority for Hep B ≥ 10 mIU/ml and PRP ≥0.15μg/ml was analyzed (DTaP-IPV-Hep B-PRP-T relative to DTaP-IPV-Hep B//PRP-T) at 1 month post-primary. Seroprotection/seroconversion and geometric mean titers (GMTs) were analyzed descriptively for all hexavalent components. Safety was evaluated from parental reports. Anti-Hep B and anti-PRP antibody seroprotection rates were high for DTaP-IPV-Hep B-PRP-T (n=189) and DTaP-IPV-Hep B//PRP-T (n=190), and non-inferiority was demonstrated. Anti-D and anti-T ≥ 0.01 IU/ml, anti-polio types 1, 2, and 3 ≥ 8 (1/dil), and anti-PT and anti-FHA seroconversion were high and similar in each group. For DTaP-IPV-Hep B-PRP-T and DTaP-IPV-Hep B//PRP-T, anti-Hep B ≥ 100 mIU/ml was 98.4% and 99.5% (GMTs 2477 and 2442 mIU/ml), respectively; anti-PRP ≥ 1.0 μg/ml was 85.2% and 71.1% (GMTs 5.07 and 2.41 μg/ml), respectively. Safety profiles were comparable. There were no vaccine-related serious adverse events. Following co-administration with PCV7 the investigational DTaP-IPV-Hep B-PRP-T vaccine was safe and immunogenic. Non-inferiority to DTaP-IPV-Hep B//PRP-T was shown for Hep B and PRP. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. Investigation of modified platelet-rich plasma (mPRP) in promoting the proliferation and differentiation of dental pulp stem cells from deciduous teeth.

    Science.gov (United States)

    Wen, J; Li, H T; Li, S H; Li, X; Duan, J M

    2016-09-01

    Stem cells from human exfoliated deciduous teeth (SHEDs) have great potential to treat various dental-related diseases in regenerative medicine. They are usually maintained with 10% fetal bovine serum (FBS) in vitro. Modified platelet-rich plasma (mPRP) would be a safe alternative to 10% FBS during SHEDs culture. Therefore, our study aimed to compare the proliferation and differentiation of SHEDs cultured in mPRP and FBS medium to explore an optimal concentration of mPRP for SHEDs maintenance. Platelets were harvested by automatic blood cell analyzer and activated by repeated liquid nitrogen freezing and thawing. The platelet-related cytokines were examined and analyzed by ELISA. SHEDs were extracted and cultured with different concentrations of mPRP or 10% FBS medium. Alkaline phosphatase (ALP) activity was measured. Mineralization factors, RUNX2 and OCN, were measured by real-time PCR. SHEDs were characterized with mesenchymal stem cells (MSCs) markers including vimentin, CD44, and CD105. mPRP at different concentrations (2, 5, 10, and 20%) enhanced the growth of SHEDs. Moreover, mPRP significantly stimulated ALP activity and promoted expression of RUNX2 and OCN compared with 10% FBS. mPRP could efficiently facilitate proliferation and differentiation of SHEDs, and 2% mPRP would be an optimal substitute for 10% FBS during SHEDs expansion and differentiation in clinical scale manufacturing.

  12. Investigation of modified platelet-rich plasma (mPRP in promoting the proliferation and differentiation of dental pulp stem cells from deciduous teeth

    Directory of Open Access Journals (Sweden)

    J. Wen

    2016-01-01

    Full Text Available Stem cells from human exfoliated deciduous teeth (SHEDs have great potential to treat various dental-related diseases in regenerative medicine. They are usually maintained with 10% fetal bovine serum (FBS in vitro. Modified platelet-rich plasma (mPRP would be a safe alternative to 10% FBS during SHEDs culture. Therefore, our study aimed to compare the proliferation and differentiation of SHEDs cultured in mPRP and FBS medium to explore an optimal concentration of mPRP for SHEDs maintenance. Platelets were harvested by automatic blood cell analyzer and activated by repeated liquid nitrogen freezing and thawing. The platelet-related cytokines were examined and analyzed by ELISA. SHEDs were extracted and cultured with different concentrations of mPRP or 10% FBS medium. Alkaline phosphatase (ALP activity was measured. Mineralization factors, RUNX2 and OCN, were measured by real-time PCR. SHEDs were characterized with mesenchymal stem cells (MSCs markers including vimentin, CD44, and CD105. mPRP at different concentrations (2, 5, 10, and 20% enhanced the growth of SHEDs. Moreover, mPRP significantly stimulated ALP activity and promoted expression of RUNX2 and OCN compared with 10% FBS. mPRP could efficiently facilitate proliferation and differentiation of SHEDs, and 2% mPRP would be an optimal substitute for 10% FBS during SHEDs expansion and differentiation in clinical scale manufacturing.

  13. Beneficios del adhesivo autólogo de fibrina y PRP en ritidectomía

    Directory of Open Access Journals (Sweden)

    I. Hernández

    2015-09-01

    Full Text Available Determinamos la eficacia clínica del adhesivo autólogo de fibrina y la fracción de sangre rica en plaquetas (PRP en la disminución de complicaciones en ritidectomía. Se intervino con igual técnica ambas hemicaras, pero solo una, aleatoriamente, recibió tratamiento con hemoderivados. Estudiamos comparativamente la evolución postquirúrgica de una hemicara frente a otra: tiempo de recuperación a corto, medio y largo plazo; incidencia de hematomas, seromas, epidermolisis, necrosis y equimosis; y satisfacción con los resultados. Todos los datos recogidos fueron analizados estadísticamente. Realizamos un estudio clínico prospectivo en fase I, randomizado y a doble ciego, en una muestra de 19 pacientes, mayores de 50 años, sometidos a ritidectomía. A todos se les aplicó por goteo las fracciones de fibrina y PRP en la hemicara seleccionada hasta cubrir toda el área quirúrgica antes del cierre con suturas: sienes, mejillas y cuello. El tratamiento se completó en ambas hemicaras con drenaje laminar durante 24 horas y vendaje oclusivo durante 72 horas. Las hemicaras que presentaron menos complicaciones, evolucionaron mejor y de forma más rápida fueron las tratadas con la composición de hemoderivados. En todas, el tiempo de recuperación promedio fue un 48% menor respecto a las no tratadas. Las equimosis fueron más evidentes en las hemicaras no tratadas y solo en ellas se desarrollaron hematomas. La cicatrización con epidermolisis de los bordes de los colgajos se observó en 10 casos: 2 en hemicara tratadas con hemoderivados y 8 en las hemicaras control. Las hemicaras tratadas evolucionaron más rápidamente, sin secuelas cicatriciales y con notable satisfacción por parte de los pacientes. Concluimos que el efecto del adhesivo autólogo de fibrina combinado con PRP en las ritidectomías reduce la incidencia de seromas, equimosis, epidermólisis y el tiempo de recuperación, y favorece una evidente supervivencia de la cicatrizaci

  14. Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems.

    Science.gov (United States)

    Gentile, Pietro; Cole, John P; Cole, Megan A; Garcovich, Simone; Bielli, Alessandra; Scioli, Maria Giovanna; Orlandi, Augusto; Insalaco, Chiara; Cervelli, Valerio

    2017-02-14

    Platelet rich plasma (PRP) was tested as a potential therapy for androgenetic alopecia (AGA) through two different clinical protocols in which one population (18 participants) received half-head treatment with autologous non-activated PRP (A-PRP) produced by CPunT Preparation System (Biomed Device, Modena, Italy) and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group) received treatment with calcium-activated PRP (AA-PRP) produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System). For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs) and in total hair density (65±  5 hair cm2), whereas negligible improvements in hair count (1.1±  1.4 hairs) and density (1.9 ± 10.2 hair cm2) were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex). Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

  15. A Randomized, Controlled Study of DTaP-IPV-HB-PRP-T, a Fully Liquid Hexavalent Vaccine, Administered in a 3-, 5- and 11- to 12-month Schedule.

    Science.gov (United States)

    Vesikari, Timo; Silfverdal, Sven-Arne; Jordanov, Emilia; Feroldi, Emmanuel

    2017-01-01

    To assess the immunogenicity and safety of a fully liquid, ready-to-use hexavalent DTaP-IPV-HB-PRP-T vaccine when administered in a 2 + 1 schedule at 3, 5 and 11-12 months of age. Phase III, randomized, active-controlled, observer-blind, multicenter study. Infants were randomized to receive DTaP-IPV-HB-PRP-T (N = 275) or a licensed control hexavalent vaccine (DTaP-IPV-HB//PRP~T: N = 275), both given in coadministration with Prevenar 13. Serum was analyzed for immune responses to all vaccine antigens. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was tested at completion of the primary series using predefined seroprotection (SP) rate and vaccine response (VR) rates. Safety was assessed using parental reports. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was demonstrated postdose 3 for each antigen, and the SP (for D, T, poliovirus 1, 2 and 3, hepatitis B and polyribosylribitol phosphate) and VR rates (for pertussis toxin and filamentous hemagglutinin) were high in each group. SP rates for D, T, polio 1, 2, 3 and VR rates for pertussis toxin and filamentous hemagglutinin were similar in each group. For hepatitis B, SP rate was slightly higher for DTaP-IPV-HB//PRP~T (99.6%) than DTaP-IPV-HB-PRP-T (96.4%), and for PRP, SP rate was higher for DTaP-IPV-HB-PRP-T (93.5%) than DTaP-IPV-HB//PRP~T (85.2%). For Prevenar 13, the SP rate was high for each serotype and similar for both groups. All vaccines were well tolerated. These study findings confirm the safety and immunogenicity and thus the suitability of this fully liquid hexavalent vaccine for administration in a 2 + 1 schedule.

  16. Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems

    Directory of Open Access Journals (Sweden)

    Pietro Gentile

    2017-02-01

    Full Text Available Platelet rich plasma (PRP was tested as a potential therapy for androgenetic alopecia (AGA through two different clinical protocols in which one population (18 participants received half-head treatment with autologous non-activated PRP (A-PRP produced by CPunT Preparation System (Biomed Device, Modena, Italy and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group received treatment with calcium-activated PRP (AA-PRP produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System. For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs and in total hair density (65±  5 hair cm2, whereas negligible improvements in hair count (1.1±  1.4 hairs and density (1.9 ± 10.2 hair cm2 were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex. Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

  17. Microbicidal properties of Leukocyte- and Platelet-Rich Plasma/Fibrin (L-PRP/L-PRF): new perspectives.

    Science.gov (United States)

    Cieslik-Bielecka, A; Dohan Ehrenfest, D M; Lubkowska, A; Bielecki, T

    2012-01-01

    Platelets, as main actors of the first stage of the healing process, play an important role in tissue repair. Their granules contain many active substances, particularly over 30 growth factors with significant effects on the resident cells at the site of injury, such as mesenchymal stem cells, chondrocytes, fibroblasts, osteoblasts. This potential may be increased by the concentration of the platelets, using platelet-rich plasma/fibrin products. In the four families of platelet concentrates, 2 families contain also significant concentrations of leukocytes: L-PRP (Leukocyte- and Platelet-Rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). Inductive properties of platelet concentrates were widely described. However, they present also antimicrobial effects. The antibacterial effects of L-PRP were highlighted in only a few in vitro studies. Strong activity comparable to gentamicin and oxacillin for L-PRP against methicillin susceptible Staphylococcus aureus (MSSA) was already demonstrated. L-PRP also inhibited the growth of methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli. Some authors also reported clinical observations about the reduction of infections and the induction of healing processes after the use of platelet concentrates in cardiac, orthopaedic, oral and maxillofacial surgery. However, very little is yet known about the antibacterial effects of these concentrates. In this manuscript, the current data about the antimicrobial agents and cells present in the platelet-rich plasma/fibrin are highlighted and discussed, in order to introduce this new key chapter of the platelet concentrate technology history.

  18. Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies

    Directory of Open Access Journals (Sweden)

    Jorge M. Charco

    2017-12-01

    Full Text Available The misfolding of the cellular prion protein (PrPC into the disease-associated isoform (PrPSc and its accumulation as amyloid fibrils in the central nervous system is one of the central events in transmissible spongiform encephalopathies (TSEs. Due to the proteinaceous nature of the causal agent the molecular mechanisms of misfolding, interspecies transmission, neurotoxicity and strain phenomenon remain mostly ill-defined or unknown. Significant advances were made using in vivo and in cellula models, but the limitations of these, primarily due to their inherent complexity and the small amounts of PrPSc that can be obtained, gave rise to the necessity of new model systems. The production of recombinant PrP using E. coli and subsequent induction of misfolding to the aberrant isoform using different techniques paved the way for the development of cell-free systems that complement the previous models. The generation of the first infectious recombinant prion proteins with identical properties of brain-derived PrPSc increased the value of cell-free systems for research on TSEs. The versatility and ease of implementation of these models have made them invaluable for the study of the molecular mechanisms of prion formation and propagation, and have enabled improvements in diagnosis, high-throughput screening of putative anti-prion compounds and the design of novel therapeutic strategies. Here, we provide an overview of the resultant advances in the prion field due to the development of recombinant PrP and its use in cell-free systems.

  19. PLATELET-RICH PLASMA (PRP FOR THE TREATMENT OF PROBLEMATIC SKIN WOUNDS

    Directory of Open Access Journals (Sweden)

    Tsvetan Sokolov

    2016-12-01

    Full Text Available OBJECTIVE: To show platelet-rich plasma (PRP application of problematic skin wounds and to evaluate the results from the treatment. MATERIAL AND METHODS: A total of 31 patients with problematic skin wounds had been treated at the clinic for a period of five years (from May 2010 to September 2015 with the following patient sex ratio: male patients– 13 and female patients– 18. Average age– 46,5 (22-82. Patients with Type 2 Diabetes– 10, with decubitus ulcers– 2, traumatic– 29, with infection– 12, acute– 15, chronic– 16. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 – 6 months (4,5 on average. We used platelet rich plasma derived by PRGF Endoret system, applied on the wound bed on a weekly basis. RESULTS: The results have been evaluated based on the following functional scoring systems - Total wound score, Total anatomic score and Total score (20. The baseline values at the very beginning of the follow-up period were as follows: Total wound score – 10 p.; Total anatomic score – 8 p., Total score – 15 p. By the end of the treatment period the score was 0 p., which means excellent results, i.e. complete healing of the wounds. CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of difficult to heal wounds around joints, bone, subject tendons, plantar surface of the foot, etc., as it opens new perspectives in the field of human tissue regeneration.

  20. Faithful mRNA splicing depends on the Prp19 complex subunit faint sausage and is required for tracheal branching morphogenesis in Drosophila.

    Science.gov (United States)

    Sauerwald, Julia; Soneson, Charlotte; Robinson, Mark D; Luschnig, Stefan

    2017-02-15

    Morphogenesis requires the dynamic regulation of gene expression, including transcription, mRNA maturation and translation. Dysfunction of the general mRNA splicing machinery can cause surprisingly specific cellular phenotypes, but the basis for these effects is not clear. Here, we show that the Drosophila faint sausage (fas) locus, which is implicated in epithelial morphogenesis and has previously been reported to encode a secreted immunoglobulin domain protein, in fact encodes a subunit of the spliceosome-activating Prp19 complex, which is essential for efficient pre-mRNA splicing. Loss of zygotic fas function globally impairs the efficiency of splicing, and is associated with widespread retention of introns in mRNAs and dramatic changes in gene expression. Surprisingly, despite these general effects, zygotic fas mutants show specific defects in tracheal cell migration during mid-embryogenesis when maternally supplied splicing factors have declined. We propose that tracheal branching, which relies on dynamic changes in gene expression, is particularly sensitive for efficient spliceosome function. Our results reveal an entry point to study requirements of the splicing machinery during organogenesis and provide a better understanding of disease phenotypes associated with mutations in general splicing factors. © 2017. Published by The Company of Biologists Ltd.

  1. GHRH, PRP-PACAP and GHRHR Target Sequencing via an Ion Torrent Personal Genome Machine Reveals an Association with Growth in Orange-Spotted Grouper (Epinephelus coioides

    Directory of Open Access Journals (Sweden)

    Liang Guo

    2015-11-01

    Full Text Available Growth hormone-releasing hormone (GHRH and the receptor, GHRHR, constitute important components of the hypothalamus-pituitary growth axis and act on the downstream growth hormone (GH. PACAP-related peptide/pituitary adenylate cyclase activating polypeptide (PRP-PACAP is a paralog of GHRH. These genes all play key roles in development and growth patterns. To improve the quality of cultured fish strains, natural genetic variation must be examined and understood. A mixed linear model has been widely used in association mapping, taking the population structures and pairwise kinship patterns into consideration. In this study, a mass cross population of orange-spotted grouper (Epinephelus coioides was examined. These candidate genes were found to harbor low nucleotide diversity (θw from 0.00154 to 0.00388 and linkage disequilibrium levels (delay of 50% within 2 kbp. Association mapping was employed, and two single-nucleotide polymorphisms (KR269823.1:g.475A>C and KR269823.1:g.2143T>C were found to be associated with growth (false discovery rate Q < 0.05, explaining 9.0%–17.0% of the phenotypic variance. The association of KR269823.1:g.2143T>C was also found via haplotype-based association (p < 0.05. The identified associations offer new insights into gene functions, and the associated single-nucleotide polymorphisms (SNPs may be used for breeding purposes.

  2. Motif-grafted antibodies containing the replicative interface of cellular PrP are specific for PrPSc.

    Science.gov (United States)

    Moroncini, Gianluca; Kanu, Nnennaya; Solforosi, Laura; Abalos, Gil; Telling, Glenn C; Head, Mark; Ironside, James; Brockes, Jeremy P; Burton, Dennis R; Williamson, R Anthony

    2004-07-13

    Prion diseases are closely associated with the conversion of the cellular prion protein (PrPC) to an abnormal conformer (PrPSc) [Prusiner, S. B. (1998) Proc. Natl. Acad. Sci. USA 95, 13363-13383]. Monoclonal antibodies that bind epitopes comprising residues 96-104 and 133-158 of PrPC potently inhibit this process, presumably by preventing heterodimeric association of PrPC and PrPSc, and suggest that these regions of PrPC may be critical components of the PrPC-PrPSc replicative interface. We reasoned that transplanting PrP sequence corresponding to these regions into a suitable carrier molecule, such as an antibody, could impart specific recognition of disease-associated forms of PrP. To test this hypothesis, polypeptides containing PrP sequence between residues 89-112 or 136-158 were used to replace the extended heavy chain complementarity-determining region 3 of an IgG antibody specific for the envelope glycoprotein of HIV-1. Herein the resulting engineered PrP-IgGs are shown to bind specifically to infective fractions of PrP in mouse, human, and hamster prion-infected tissues, but not to PrPC, other cellular components, or the HIV-1 envelope. PrPSc reactivity was abolished when the sequence of the PrP 89-112 and 136-158 grafts was mutated, scrambled, or N-terminally truncated. Our findings suggest that residues within the 89-112 and 136-158 segments of PrPC are key components of one face of the PrPC-PrPSc complex. PrPSc-specific antibodies produced by the approach described may find widespread application in the study of prion biology and replication and in the detection of infectious prions in human and animal materials.

  3. CONTAMINATED PROBLEMATIC SKIN WOUNDS IN DIABETIC PATIENTS TREATED WITH AUTOLOGOUS PLATELET-RICH PLASMA (PRP: A case series study

    Directory of Open Access Journals (Sweden)

    Tsvetan Sokolov

    2016-03-01

    Full Text Available OBJECTIVE: To study the effect of platelet-rich plasma (PRP on contaminated problematic skin ulcers in patients with diabetes. MATERIAL AND METHODS: A total of 6 patients had been treated within the period from 2012 to 2014; they had various types of problematic wounds and diabetes type 2. Patients’ distribution by sex was as follows: 1 man and 5 women; mean age- 68 years. Ulcer types: acute (2 patients, hard-to-heal (2 patients and chronic (2 patients ulcers. The mean size of the skin and soft tissue defect was 9,5 cm2. Pathogenic microflora was isolated in 4 patients - S. aureus in three and Е. Coli in one. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 – 6 months (4,5 on average. We used platelet rich plasma derived by PRGF Endoret system, applied on the wound bed on a weekly basis. RESULTS: Application of PRP allowed successful closure of all wounds. There were no complications associated with treatment of PRP. Epithelialization of the wound took 15 weeks on average for all patients. One patient presented with hyperkeratosis. Initial score of followed wounds, based on the scales are as follows: Total wound score – 10 p. Total anatomic score – 8 p. Total score – 15 p. at the initial stage. At the end of the treatment period scores were as follows - 0 p., which means excellent results CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of contaminated problematic wounds in diabetic patients. PRP not only stimulates wound healing, but also has antimicrobial properties, which may contribute to the prevention of infections.

  4. Arguing to motivate decisions

    NARCIS (Netherlands)

    van der Weide, T.L.

    2011-01-01

    Decision makers often have to make difficult trade-offs in situations where multiple aspects matter that are different by nature. For example, in a crisis scenario with a big fire in a factory, trade-offs may have to be made between the safety of the victims and personnel, and the effects on the

  5. When Parents Argue

    Science.gov (United States)

    ... They might disagree about important things like finances, careers, or major family decisions. Or they might disagree about little things ... are until you tell them how their arguments affect you. If this doesn't work, you could try talking to another family member to help you figure out what to ...

  6. The rules of arguing

    African Journals Online (AJOL)

    narcissistic antisocial partner. I take a few deep breaths, and try not to react or take sides, but just repeat the concerns, almost verbatim, in a Rogerian way, while I furiously think of ways of defusing the impasse. You otherwise find that the two of you want to kill the other party. One often feels that nothing is being achieved in ...

  7. Small kinetochore associated protein (SKAP promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19.

    Directory of Open Access Journals (Sweden)

    Shan Lu

    Full Text Available Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19. We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19.

  8. A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers

    Science.gov (United States)

    Ceyhan, Mehmet; Yıldırım, İnci; Tezer, Hasan; Devrim, İlker; Feroldi, Emmanuel

    2017-08-23

    Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

  9. Investigation of modified platelet-rich plasma (mPRP) in promoting the proliferation and differentiation of dental pulp stem cells from deciduous teeth

    OpenAIRE

    Wen, J.; Li, H T; Li, S H; LI, X.; Duan, J. M.

    2016-01-01

    Stem cells from human exfoliated deciduous teeth (SHEDs) have great potential to treat various dental-related diseases in regenerative medicine. They are usually maintained with 10% fetal bovine serum (FBS) in vitro. Modified platelet-rich plasma (mPRP) would be a safe alternative to 10% FBS during SHEDs culture. Therefore, our study aimed to compare the proliferation and differentiation of SHEDs cultured in mPRP and FBS medium to explore an optimal concentration of mPRP for SHEDs maintenance...

  10. Amidation and structure relaxation abolish the neurotoxicity of the prion peptide PrP106-126 in vivo and in vitro

    DEFF Research Database (Denmark)

    Bergstrøm, Linda Alice; Hvass, Henriette Cordes; Zsurger, N.

    2005-01-01

    One of the major pathological hallmarks of transmissible spongiform encephalopathies (TSEs) is the accumulation of a pathogenic (scrapie) isoform (PrPSc) of the cellular prion protein (PrPC) primarily in the central nervous system. The synthetic prion peptide PrP106-126 shares many characteristics...... with PrPSc in that it shows PrPC-dependent neurotoxicity both in vivo and in vitro. Moreover, PrP106-126 in vitro neurotoxicity has been closely associated with the ability to form fibrils. Here, we studied the in vivo neurotoxicity of molecular variants of PrP106-126 toward retinal neurons using...

  11. Rôle du domaine N-terminal de la PrP dans la pathogenèse des maladies à prions

    OpenAIRE

    Erlich, Paul

    2009-01-01

    The role of the N-terminal (N-ter) domain of PrP protein in the conversion of PrPc into an infectious isoform PrPSc is poorly understood. The objective of my thesis was to create a synthetic prion composed of the N-ter domain of PrP and the Doppel protein to get an insight in the involvement of this PrP domain in the aggregation mechanisms and the pathogenesis of prion diseases. Three PrP/Dpl chimeric recombinant proteins were expressed, purified and aggregated in vitro into oligomers. These ...

  12. Effect of Platelet-Rich Plasma (PRP) versus Autologous Whole Blood on Pain and Function Improvement in Tennis Elbow: A Randomized Clinical Trial

    OpenAIRE

    Raeissadat, Seyed Ahmad; Sedighipour, Leyla; Rayegani, Seyed Mansoor; Bahrami, Mohammad Hasan; Bayat, Masume; Rahimi, Rosa

    2014-01-01

    Background. Autologous whole blood and platelet-rich plasma (PRP) have been both suggested to treat chronic tennis elbow. The aim of the present study was to compare the effects of PRP versus autologous whole blood local injection in chronic tennis elbow. Methods. Forty patients with tennis elbow were randomly divided into 2 groups. Group 1 was treated with a single injection of 2 mL of autologous PRP and group 2 with 2 mL of autologous blood. Tennis elbow strap, stretching, and strengthening...

  13. Arguing as an Academic Purpose: The Role of Asynchronous Conferencing in Supporting Argumentative Dialogue in School and University

    Science.gov (United States)

    Coffin, Caroline; Hewings, Ann; North, Sarah

    2012-01-01

    Learning to argue is a key academic purpose for both first and second language students. It has been claimed that computer mediated asynchronous text-based conferencing is a useful medium for developing argumentation skills (Andriessen, Baker, & Suthers, 2003). This paper reports on two research studies which explore this claim. One study focused…

  14. Dynamic Contacts of U2, RES, Cwc25, Prp8 and Prp45 Proteins with the Pre-mRNA Branch-Site and 3' Splice Site during Catalytic Activation and Step 1 Catalysis in Yeast Spliceosomes.

    Directory of Open Access Journals (Sweden)

    Cornelius Schneider

    Full Text Available Little is known about contacts in the spliceosome between proteins and intron nucleotides surrounding the pre-mRNA branch-site and their dynamics during splicing. We investigated protein-pre-mRNA interactions by UV-induced crosslinking of purified yeast B(act spliceosomes formed on site-specifically labeled pre-mRNA, and analyzed their changes after conversion to catalytically-activated B* and step 1 C complexes, using a purified splicing system. Contacts between nucleotides upstream and downstream of the branch-site and the U2 SF3a/b proteins Prp9, Prp11, Hsh49, Cus1 and Hsh155 were detected, demonstrating that these interactions are evolutionarily conserved. The RES proteins Pml1 and Bud13 were shown to contact the intron downstream of the branch-site. A comparison of the B(act crosslinking pattern versus that of B* and C complexes revealed that U2 and RES protein interactions with the intron are dynamic. Upon step 1 catalysis, Cwc25 contacts with the branch-site region, and enhanced crosslinks of Prp8 and Prp45 with nucleotides surrounding the branch-site were observed. Cwc25's step 1 promoting activity was not dependent on its interaction with pre-mRNA, indicating it acts via protein-protein interactions. These studies provide important insights into the spliceosome's protein-pre-mRNA network and reveal novel RNP remodeling events during the catalytic activation of the spliceosome and step 1 of splicing.

  15. Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Sabina Eigenbrod

    Full Text Available Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC at octapeptide repeat (OR and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1-4, H60G, H68G, H76G, H84G, "TetraH>G" allele or at site 5 (composed of residues His-95 and His-110; "H95G" allele and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G at levels comparable to wild-type (wt controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G mice and diffuse PrPSc deposition in (TgPrP(H95G mice, were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain.

  16. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).

    Science.gov (United States)

    Dohan Ehrenfest, David M; Rasmusson, Lars; Albrektsson, Tomas

    2009-03-01

    The topical use of platelet concentrates is recent and its efficiency remains controversial. Several techniques for platelet concentrates are available; however, their applications have been confusing because each method leads to a different product with different biology and potential uses. Here, we present classification of the different platelet concentrates into four categories, depending on their leucocyte and fibrin content: pure platelet-rich plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; leucocyte- and platelet-rich plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan or GPS PRP; pure plaletet-rich fibrin (P-PRF), such as Fibrinet; and leucocyte- and platelet-rich fibrin (L-PRF), such as Choukroun's PRF. This classification should help to elucidate successes and failures that have occurred so far, as well as providing an objective approach for the further development of these techniques.

  17. In vitro immunological and biological evaluations of the angiogenic potential of platelet-rich fibrin preparations: a standardized comparison with PRP preparations

    National Research Council Canada - National Science Library

    Kobayashi, Mito; Kawase, Tomoyuki; Okuda, Kazuhiro; Wolff, Larry F; Yoshie, Hiromasa

    2015-01-01

    Platelet-rich fibrin (PRF), a platelet-rich plasma (PRP) derivative mainly composed of fibrin networks, has been increasingly demonstrated to be effective in wound healing in clinical and pre-clinical animal studies...

  18. The Effect of Autologous Activated Platelet Rich Plasma (AA-PRP Injection on Pattern Hair Loss: Clinical and Histomorphometric Evaluation

    Directory of Open Access Journals (Sweden)

    V. Cervelli

    2014-01-01

    Full Text Available To investigate the safety and clinical efficacy of AA-PRP injections for pattern hair loss. AA-PRP, prepared from a small volume of blood, was injected on half of the selected patients’ scalps with pattern hair loss. The other half was treated with placebo. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair re-growth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. At the end of the 3 cycles of treatment, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 18.0 hairs in the target area, and a mean increase in total hair density of 27.7 ( number of hairs/cm2 compared with baseline values. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles two weeks after the last AA-PRP treatment compared to baseline value (P<0.05. We also observed an increase of Ki67+ keratinocytes of epidermis and of hair follicular bulge cells and a slight increase of small blood vessels around hair follicles in the treated skin compared to baseline (P<0.05.

  19. Behavior of Gingival Fibroblasts on Titanium Implant Surfaces in Combination with either Injectable-PRF or PRP

    Directory of Open Access Journals (Sweden)

    Xuzhu Wang

    2017-02-01

    Full Text Available Various strategies have been employed to speed tissue regeneration using bioactive molecules. Interestingly, platelet concentrates derived from a patient’s own blood have been utilized as a regenerative strategy in recent years. In the present study, a novel liquid platelet formulation prepared without the use of anti-coagulants (injectable-platelet-rich fibrin, i-PRF was compared to standard platelet-rich plasma (PRP with gingival fibroblasts cultured on smooth and roughened titanium implant surfaces. Standard PRP and i-PRF (centrifuged at 700 rpm (60× g for 3 min were compared by assays for fibroblast biocompatibility, migration, adhesion, proliferation, as well as expression of platelet-derived growth factor (PDGF, transforming growth factor-β (TGF-β, collagen1 (COL1 and fibronectin (FN. The results demonstrate that i-PRF induced significantly higher cell migration, as well as higher messenger RNA (mRNA levels of PDGF, TGF-β, collagen1 and fibronectin when compared to PRP. Furthermore, collagen1 synthesis was highest in the i-PRF group. These findings demonstrate that liquid platelet concentrates can be formulated without the use of anticoagulants and present much translational potential for future research. Future animal and clinical trials are now necessary to further investigate the potential of utilizing i-PRF for soft tissue regenerative protocols in combination with various biomaterials.

  20. A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children.

    Science.gov (United States)

    Aquino, Amalia Guadalupe Becerra; Brito, Maricruz Gutiérrez; Doniz, Carlos E Aranza; Herrera, Juan Francisco Galán; Macias, Mercedes; Zambrano, Betzana; Plennevaux, Eric; Santos-Lima, Eduardo

    2012-10-05

    To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim™) vaccine for primary and booster vaccination of healthy children in Mexico. Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix™ hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. Post-primary vaccination, ≥95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Effect of Platelet-Rich Plasma (PRP versus Autologous Whole Blood on Pain and Function Improvement in Tennis Elbow: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Seyed Ahmad Raeissadat

    2014-01-01

    Full Text Available Background. Autologous whole blood and platelet-rich plasma (PRP have been both suggested to treat chronic tennis elbow. The aim of the present study was to compare the effects of PRP versus autologous whole blood local injection in chronic tennis elbow. Methods. Forty patients with tennis elbow were randomly divided into 2 groups. Group 1 was treated with a single injection of 2 mL of autologous PRP and group 2 with 2 mL of autologous blood. Tennis elbow strap, stretching, and strengthening exercises were administered for both groups during a 2-month followup. Pain and functional improvements were assessed using visual analog scale (VAS, modified Mayo Clinic performance index for the elbow, and pressure pain threshold (PPT at 0, 4, and 8 weeks. Results. All pain and functional variables including VAS, PPT, and Mayo scores improved significantly in both groups 4 weeks after injection. No statistically significant difference was noted between groups regarding pain scores in 4-week follow-up examination (P>0.05. At 8-week reevaluations, VAS and Mayo scores improved only in PRP group (P<0.05. Conclusion. PRP and autologous whole blood injections are both effective to treat chronic lateral epicondylitis. PRP might be slightly superior in 8-week followup. However, further studies are suggested to get definite conclusion.

  2. Effect of Platelet-Rich Plasma (PRP) versus Autologous Whole Blood on Pain and Function Improvement in Tennis Elbow: A Randomized Clinical Trial.

    Science.gov (United States)

    Raeissadat, Seyed Ahmad; Sedighipour, Leyla; Rayegani, Seyed Mansoor; Bahrami, Mohammad Hasan; Bayat, Masume; Rahimi, Rosa

    2014-01-01

    Background. Autologous whole blood and platelet-rich plasma (PRP) have been both suggested to treat chronic tennis elbow. The aim of the present study was to compare the effects of PRP versus autologous whole blood local injection in chronic tennis elbow. Methods. Forty patients with tennis elbow were randomly divided into 2 groups. Group 1 was treated with a single injection of 2 mL of autologous PRP and group 2 with 2 mL of autologous blood. Tennis elbow strap, stretching, and strengthening exercises were administered for both groups during a 2-month followup. Pain and functional improvements were assessed using visual analog scale (VAS), modified Mayo Clinic performance index for the elbow, and pressure pain threshold (PPT) at 0, 4, and 8 weeks. Results. All pain and functional variables including VAS, PPT, and Mayo scores improved significantly in both groups 4 weeks after injection. No statistically significant difference was noted between groups regarding pain scores in 4-week follow-up examination (P > 0.05). At 8-week reevaluations, VAS and Mayo scores improved only in PRP group (P PRP and autologous whole blood injections are both effective to treat chronic lateral epicondylitis. PRP might be slightly superior in 8-week followup. However, further studies are suggested to get definite conclusion.

  3. Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.

    Science.gov (United States)

    Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

    2016-08-31

    Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (pvaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846. Copyright © 2016 The Authors

  4. Arguing for an immersive method: Reflexive meaning-making, the visible researcher, and moral responses to gameplay

    Directory of Open Access Journals (Sweden)

    Joanna Cuttell

    2015-06-01

    Full Text Available This article argues for the adoption of an immersive-participatory method when analysing interactive media. It builds upon and extends existing theorisations of immersion and applies them to the development of new methods of analysis. This paper theorises immersion during gameplay as an affective, embodied state, which is both active and passive and achieved via both visual and imaginative engagement with the game world and haptic communication with the player character. This article’s argument is fourfold: firstly, it situates and negotiates the tensions surrounding the major debates, discussions and analyses in the study of immersion, both within gaming and in wider contexts; secondly, it argues for the inclusion of a participatory immersive method to be undertaken by the researcher when analysing media (especially interactive media such as video games; thirdly, it outlines the ways in which this method could be implemented by researchers, and finally, it draws on examples from my own research journal and discusses the possibility of a moral habitus which allows the player to engage in violent gameplay without experiencing the moral dissonance that can disrupt immersive states. Ultimately, this article aims to render the position of the researcher visible in order that we might gain critical purchase on the immersive praxis of gaming and the ethical/political responses of the player. In so doing, it is hoped that this article will aid theoretical and methodological innovation in this field and provoke discussion in a wider media studies context.

  5. Autologous platelet-rich plasma (PRP) in chronic penile lichen sclerosus: the impact on tissue repair and patient quality of life.

    Science.gov (United States)

    Casabona, Francesco; Gambelli, Ilaria; Casabona, Federica; Santi, Pierluigi; Santori, Gregorio; Baldelli, Ilaria

    2017-04-01

    Lichen sclerosus (LS) is a chronic inflammatory skin condition that frequently involves the anogenital region. Ongoing research is focused on finding more effective treatments for tissue repair and reducing symptoms. The aim of this study is to evaluate the effectiveness of platelet-rich plasma (PRP) local injections in penile LS. Forty-five male patients affected by penile LS underwent injections of autologous PRP in the affected skin areas. Age at diagnosis and at first treatment, number of treatments, clinical conditions (phimosis, splitting, inflammation, synechiae, meatus stenosis), symptoms (pain, burning, itching), and functional impairment were considered. Treatment efficacy was also evaluated through the Investigator's Global Assessment (IGA) on a six-point Likert scale and the Dermatology Life Quality Index (DLQI). The patient age at LS diagnosis was 36.20 ± 9.19 years, while the mean age at the first PRP treatment was 42.96 ± 11.32 years (p < 0.001). The number of treatments/patient ranged from 2 to 10. The follow-up was 17.60 ± 5.63 months. After PRP injections, it was observed in all patients a significant improvement in clinical conditions, with reduction/disappearance of symptoms. Topical steroid therapy, interrupted before PRP treatment, was not restarted by any patient. Only one patient underwent a later circumcision procedure. Both IGA scale and DLQI score showed a significant difference (p < 0.001) before and after PRP treatment. PRP treatment in penile LS seems to be helpful to regenerate scarring, reduce symptoms, and improve patient quality of life. Further studies are necessary to evaluate long-term results.

  6. A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers.

    Directory of Open Access Journals (Sweden)

    Geoffrey P Noble

    2015-06-01

    Full Text Available Infectious prions contain a self-propagating, misfolded conformer of the prion protein termed PrPSc. A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious. However, some autocatalytic recombinant PrPSc molecules have low or undetectable levels of specific infectivity in bioassays, and the essential determinants of recombinant prion infectivity remain obscure. To identify structural and functional features specifically associated with infectivity, we compared the properties of two autocatalytic recombinant PrP conformers derived from the same original template, which differ by >105-fold in specific infectivity for wild-type mice. Structurally, hydrogen/deuterium exchange mass spectrometry (DXMS studies revealed that solvent accessibility profiles of infectious and non-infectious autocatalytic recombinant PrP conformers are remarkably similar throughout their protease-resistant cores, except for two domains encompassing residues 91-115 and 144-163. Raman spectroscopy and immunoprecipitation studies confirm that these domains adopt distinct conformations within infectious versus non-infectious autocatalytic recombinant PrP conformers. Functionally, in vitro prion propagation experiments show that the non-infectious conformer is unable to seed mouse PrPC substrates containing a glycosylphosphatidylinositol (GPI anchor, including native PrPC. Taken together, these results indicate that having a conformation that can be specifically adopted by post-translationally modified PrPC molecules is an essential determinant of biological infectivity for recombinant prions, and suggest that this ability is associated with discrete features of PrPSc structure.

  7. A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers

    Science.gov (United States)

    Noble, Geoffrey P.; Wang, Daphne W.; Walsh, Daniel J.; Barone, Justin R.; Miller, Michael B.; Nishina, Koren A.; Li, Sheng; Supattapone, Surachai

    2015-01-01

    Infectious prions contain a self-propagating, misfolded conformer of the prion protein termed PrPSc. A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious. However, some autocatalytic recombinant PrPSc molecules have low or undetectable levels of specific infectivity in bioassays, and the essential determinants of recombinant prion infectivity remain obscure. To identify structural and functional features specifically associated with infectivity, we compared the properties of two autocatalytic recombinant PrP conformers derived from the same original template, which differ by >105-fold in specific infectivity for wild-type mice. Structurally, hydrogen/deuterium exchange mass spectrometry (DXMS) studies revealed that solvent accessibility profiles of infectious and non-infectious autocatalytic recombinant PrP conformers are remarkably similar throughout their protease-resistant cores, except for two domains encompassing residues 91-115 and 144-163. Raman spectroscopy and immunoprecipitation studies confirm that these domains adopt distinct conformations within infectious versus non-infectious autocatalytic recombinant PrP conformers. Functionally, in vitro prion propagation experiments show that the non-infectious conformer is unable to seed mouse PrPC substrates containing a glycosylphosphatidylinositol (GPI) anchor, including native PrPC. Taken together, these results indicate that having a conformation that can be specifically adopted by post-translationally modified PrPC molecules is an essential determinant of biological infectivity for recombinant prions, and suggest that this ability is associated with discrete features of PrPSc structure. PMID:26125623

  8. PLATELET-RICH PLASMA (PRP AND ITS APPLICATION IN THE TREATMENT OF CHRONIC AND HARD-TO-HEAL SKIN WOUNDS. A Review.

    Directory of Open Access Journals (Sweden)

    Tsvetan Sokolov

    2015-12-01

    Full Text Available In the last few years various methods are being applied in the use of platelet-rich plasma (PRP during treatment in different orthopedic disease. They allow improvement of local biological condition and regeneration of different types of tissues. PRP is a modern treatment strategy with worldwide recognition. There is a high concentration of platelet growth factors in small amounts of plasma. PRP and its various forms have become one of the best methods to support the healing process of various tissues. PRP is used in regenerative medicine, because it provides two of three components (growth factors and scaffolds necessary for complete tissue regeneration. The particular reason for the appearance of lesions is important in order to select an appropriate treatment method and technical application. PRP may be used for treatment of various chronic and hard-to-heal cutaneous wounds, especially when standard conventional therapy is not good enough and surgical treatment is not possible. It reduces the duration, cost of treatment and the hospital stay. There is reduction of wound pain after starting the treatment, reduced risk of blood-borne disease transmission, wound healing is restored, and local immunity is activated.

  9. PrP glycoforms are associated in a strain-specific ratio in native PrPSc.

    Science.gov (United States)

    Khalili-Shirazi, Azadeh; Summers, Linda; Linehan, Jacqueline; Mallinson, Gary; Anstee, David; Hawke, Simon; Jackson, Graham S; Collinge, John

    2005-09-01

    Prion diseases involve conversion of host-encoded cellular prion protein (PrPC) to a disease-related isoform (PrPSc). Using recombinant human beta-PrP, a panel of monoclonal antibodies was produced that efficiently immunoprecipitated native PrPSc and recognized epitopes between residues 93-105, indicating for the first time that this region is exposed in both human vCJD and mouse RML prions. In contrast, monoclonal antibodies raised to human alpha-PrP were more efficient in immunoprecipitating PrPC than PrPSc, and some of them could also distinguish between different PrP glycoforms. Using these monoclonal antibodies, the physical association of PrP glycoforms was studied in normal brain and in the brains of humans and mice with prion disease. It was shown that while PrPC glycoforms can be selectively immunoprecipitated, the differentially glycosylated molecules of native PrPSc are closely associated and always immunoprecipitate together. Furthermore, the ratio of glycoforms comprising immunoprecipitated native PrPSc from diverse prion strains was similar to those observed on denaturing Western blots. These studies are consistent with the view that the proportion of each glycoform incorporated into PrPSc is probably controlled in a strain-specific manner and that each PrPSc particle contains a mixture of glycoforms.

  10. L-PRP/L-PRF in esthetic plastic surgery, regenerative medicine of the skin and chronic wounds.

    Science.gov (United States)

    Cieslik-Bielecka, Agata; Choukroun, Joseph; Odin, Guillaume; Dohan Ehrenfest, David M

    2012-06-01

    The use of platelet concentrates for topical use is of particular interest for the promotion of skin wound healing. Fibrin-based surgical adjuvants are indeed widely used in plastic surgery since many years in order to improve scar healing and wound closure. However, the addition of platelets and their associated growth factors opened a new range of possibilities, particularly for the treatment of chronic skin ulcers and other applications of regenerative medicine on the covering tissues. In the 4 families of platelet concentrates available, 2 families were particularly used and tested in this clinical field: L-PRP (Leukocyte- and Platelet-rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). These 2 families have in common the presence of significant concentrations of leukocytes, and these cells are important in the local cleaning and immune regulation of the wound healing process. The main difference between them is the fibrin architecture, and this parameter considerably influences the healing potential and the therapeutical protocol associated to each platelet concentrate technology. In this article, we describe the historical evolutions of these techniques from the fibrin glues to the current L-PRP and L-PRF, and discuss the important functions of the platelet growth factors, the leukocyte content and the fibrin architecture in order to optimize the numerous potential applications of these products in regenerative medicine of the skin. Many outstanding perspectives are appearing in this field and require further research.

  11. Assessment of efficacy of platelet-rich plasma (PRP) on infraorbital dark circles and crow's feet wrinkles.

    Science.gov (United States)

    Mehryan, Pedram; Zartab, Hamed; Rajabi, Ali; Pazhoohi, Neda; Firooz, Alireza

    2014-03-01

    Infraorbital skin hyperpigmentation, commonly called dark circles, and crow's feet wrinkles are common cosmetic concerns. Various methods of treatment have been evaluated with variable outcomes. This study was performed to assess the efficacy of platelet-rich plasma (PRP) injection for treating periorbital dark circles and crow's feet. Ten participants with a mean age of 41.2 years were treated in a single session with intradermal injections of 1.5 mL PRP into tear trough area and crow's feet wrinkles on each side. The effects on melanin content, color homogeneity of the treated area, epidermal stratum corneum hydration, and wrinkle volume and visibility index were compared 3 months after treatment with baseline. Physician's global assessment and participants' satisfaction and any potential side effects were also assessed. The improvement in infraorbital color homogeneity was statistically significant (P = 0.010), but no statistically significant changes were observed in melanin content, stratum corneum hydration, wrinkle volume, and visibility index. Participant's satisfaction score and physician's global assessment score were 2.2 and 1.7, respectively, on a 0-3 scale. Platelet-rich plasma may have the potential to improve infraorbital dark circle in terms of color homogeneity of the region, though this remains to be proven using larger, controlled studies using multiple injections. © 2014 Wiley Periodicals, Inc.

  12. PrP(ST, a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

    Directory of Open Access Journals (Sweden)

    Yael Friedman-Levi

    Full Text Available While the conversion of PrP(C into PrP(Sc in the transmissible form of prion disease requires a preexisting PrP(Sc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST, a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST as in TgMHu2ME199K mice, and "classical" PrP(Sc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

  13. Gene

    Data.gov (United States)

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

  14. Assessing Current Instructional Practices in General Biology One (BIO1010) and Arguing for a Model-Centered Curriculum

    Science.gov (United States)

    Manthey, Seth

    This collected papers dissertation focused on the argument for the need to adapt and develop a model-centered General Biology I course through the analyses of current instructional practices at a large, public, Hispanic-serving university. This dissertation included a comparison of General Biology I course sections taught in two differing formats, one is a traditional lecture with face-to-face meetings and the other is an online instruction setting. The comparison of these sections was accomplished through the use of a conceptual inventory, student attitude survey, drop-fail-withdraw (DFW) rates, and Social Network Analysis. This comparison found that there was no detectible significant difference between course type for both the conceptual understanding and formation of student-to-student networks. It was also found that there was a significant difference between course type when looking at students' attitudes towards Biology and success in the two course types. Additionally in a second study the project used a phenomoenographic analysis of student interviews that explored the students' use of scientific models when asked about plant cells and animal cells. It was found that during the analysis of students' ideas that students predominantly used a single model function. The cell types of focus in the second study were two models that were identified, in a third study, through a coded analysis of faculty interviews and textbook analysis. These models are viewed as essential for students to possess an understanding of upon completion of General Biology I. The model-based course that this study argued for is based on a curricular framework initially developed for use in introductory physics courses. University Modeling Instruction courses in physics (UMI-P) have been linked to improved student conceptual understanding positive attitudinal shifts, and decreased DFW rates. UMI, however, has not been expanded for implementation within the other science disciplines

  15. Temporal growth factor release from platelet-rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression.

    Science.gov (United States)

    McCarrel, Taralyn; Fortier, Lisa

    2009-08-01

    Platelet-rich plasma (PRP) has generated substantial interest for tendon and ligament regeneration because of the high concentrations of growth factors in platelet alpha-granules. This study compared the temporal release of growth factors from bone marrow aspirate (BMA), PRP, and lyophilized platelet product (PP), and measured their effects on tendon and ligament gene expression. Blood and BMA were collected and processed to yield PRP and plasma. Flexor digitorum superficialis tendon (FDS) and suspensory ligament (SL) explants were cultured in 10% plasma in DMEM (control), BMA, PRP, or PP. TGF-beta1 and PDGF-BB concentrations were determined at 0, 24, and 96 h of culture using ELISA. Quantitative RT-PCR for collagen types I and III (COL1A1, COL3A1), cartilage oligomeric matrix protein (COMP), decorin, and matrix metalloproteinases-3 and 13 (MMP-3, MMP-13) was performed. TGF-beta1 and PDGF-BB concentrations were highest in PRP and PP. Growth factor quantity was unchanged in BMA, increased in PRP, and decreased in PP over 4 days. TGF-beta1 and platelet concentrations were positively correlated. Lyophilized PP and PRP resulted in increased COL1A1:COL3A1 ratio, increased COMP, and decreased MMP-13 expression. BMA resulted in decreased COMP and increased MMP-3 and MMP-13 gene expression. Platelet concentration was positively correlated with COL1A1, ratio of COL1A1:COL3A1, and COMP, and negatively correlated with COL3A1, MMP-13, and MMP-3. White blood cell concentration was positively correlated with COL3A1, MMP3, and MMP13, and negatively correlated with a ratio of COL1A1:COL3A1, COMP, and decorin. These findings support further in vivo investigation of PRP and PP for treatment of tendonitis and desmitis. Copyright 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  16. Phylogenetic analysis of cystic fibrosis transmembrane conductance regulator gene in mammalian species argues for the development of a rabbit model for cystic fibrosis

    National Research Council Canada - National Science Library

    Vuillaumier, S; Kaltenboeck, B; Lecointre, G; Lehn, P; Denamur, E

    1997-01-01

    ... (Primates, Artiodactyla, Lagomorpha and Rodentia) were analyzed. Distance matrices and unrooted trees of the CFTR promoter region sequences yielded two deeply separated groups, one including man (Homo sapiens...

  17. Kuru: genes, cannibals and neuropathology.

    Science.gov (United States)

    Liberski, Pawel P; Sikorska, Beata; Lindenbaum, Shirley; Goldfarb, Lev G; McLean, Catriona; Hainfellner, Johannes A; Brown, Paul

    2012-02-01

    Kuru was the first human transmissible spongiform encephalopathy (TSE) or prion disease identified, occurring in the Fore linguistic group of Papua New Guinea. Kuru was a uniformly fatal cerebellar ataxic syndrome, usually followed by choreiform and athetoid movements. Kuru imposed a strong balancing selection on the Fore population, with individuals homozygous for the 129 Met allele of the gene (PRNP) encoding for prion protein (PrP) being the most susceptible. The decline in the incidence of kuru in the Fore has been attributed to the exhaustion of the susceptible genotype and ultimately by discontinuation of exposure via cannibalism. Neuropathologically, kuru-affected brains were characterized by widespread degeneration of neurons, astroglial and microglial proliferation, and the presence of amyloid plaques. These early findings have been confirmed and extended by recent immunohistochemical studies for the detection of the TSE-specific PrP (PrP). Confocal laser microscopy also showed the concentration of glial fibrillary acidic protein-positive astrocytic processes at the plaque periphery. The fine structure of plaques corresponds to that described earlier by light microscopy. The successful experimental transmission of kuru led to the awareness of its similarity to Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease and formed a background against which the recent epidemics of iatrogenic and variant Creutzfeldt-Jakob disease could be studied.

  18. The Healing Effects of Aquatic Activities and Allogenic Injection of Platelet-Rich Plasma (PRP) on Injuries of Achilles Tendon in Experimental Rat.

    Science.gov (United States)

    Rajabi, Hamid; Sheikhani Shahin, Homa; Norouzian, Manijeh; Mehrabani, Davood; Dehghani Nazhvani, Seifollah

    2015-01-01

    Clinical tendon injuries represent serious and unresolved issues of the case on how the injured tendons could be improved based on natural structure and mechanical strength. The aim of this studies the effect of aquatic activities and alogenic platelet rich plasma (PRP) injection in healing Achilles tendons of rats. Forty rats were randomly divided into 5 equal groups. Seventy two hours after a crush lesion on Achilles tendon, group 1 underwent aquatic activity for 8 weeks (five sessions per week), group 2 received intra-articular PRP (1 ml), group 3 had aquatic activity together with injection PRP injection after an experimental tendon injury, group 4 did not receive any treatment after tendon injury and the control group with no tendon injuries. of 32 rats. After 8 weeks, the animals were sacrificed and the tendons were transferred in 10% formalin for histological evaluation. There was a significant increase in number of fibroblast and cellular density, and collagen deposition in group 3 comparing to other groups denoting to an effective healing in injured tendons. However, there was no significant difference among the studied groups based on their tendons diameter. Based on our findings on the number of fibroblast, cellular density, collagen deposition, and tendon diameter, it was shown that aquatic activity together with PRP injection was the therapeutic measure of choice enhance healing in tendon injuries that can open a window in treatment of damages to tendons.

  19. Multi-center study on the simultaneous administration of DPT-IPV and Hib PRP-T vaccines. Part 1. Immunogenicity

    NARCIS (Netherlands)

    Labadie J; Sundermann LC; Rumke HC; the DPT-IPV Hib vaccine study group; LVO; LVM; LCB; LBA; LPO

    1996-01-01

    Results are presented of a multi-center clinical study into the antibody formation following two vaccination regimens with simultaneous and combined administration of DPT-IPV and Hib PRP-T vaccines. 543 infants were recruited from 42 baby clinics in Apeldoorn, Capelle and Rotterdam. The antibody

  20. Arcabouço de PRP-gel associado a células tronco mesenquimais: uso em lesões condrais em modelo experimental equino

    Directory of Open Access Journals (Sweden)

    Ana Lúcia M. Yamada

    2016-06-01

    Full Text Available Resumo: O plasma rico em plaquetas (PRP é conhecido por apresentar propriedades anabólicas, anti-inflamatórias e capacidade de gelificação. Atualmente o PRP é considerado eficaz na reparação da cartilagem, sendo sua capacidade de formação de gel indicada para o preenchimento de defeitos condrais. O objetivo desse estudo foi analisar o uso do PRP ativado, no formato de arcabouço, como suporte para o implante de células tronco mesenquimais (CTM, no preenchimento e tratamento de lesões condrais induzidas em equinos. Doze equinos foram submetidos a uma cirurgia artroscópica no tempo zero do experimento (T0, onde foi induzida uma lesão condral de 15 mm de diâmetro na tróclea medial femoral dos membros pélvicos direito. As 12 articulações foram divididas em dois grupos distintos com seis articulações cada (GA e GB. As articulações do GA foram submetidas ao tratamento com o implante de CTM em gel de PRP. As articulações de GB foram o grupo controle do experimento. As CTMs foram extraídas do tecido adiposo e o PRP em gel foi obtido por protocolo de dupla centrifugação seguido da adição de trombina liofilizada. Após cinco meses (T150 foi realizada nova artroscopia para avaliação macroscópica do local, coleta de amostras do tecido de reparação para análises de microscopia eletrônica, sendo realizadas imagens ressonância magnética e tomografia computadorizada no local do implante no GA. Observamos que o gel de PRP associado às CTM demonstrou ser adequado no tratamento de defeitos condrais experimentais dos equinos. GA evidenciou um melhor aspecto macroscópico e microscópico do tecido de reparação, sendo que GB mostrou maior desorganização das fibras colágenas. Nas imagens de ressonância magnética e tomografia computadorizada apenas foi relevante o local da lesão condral. O arcabouço de gel de PRP demonstrou ser apropriado no suporte do tratamento com as CTMs, sendo de fácil aplicação e efetivo

  1. Comparative Analysis of the Index of Success of Implantations with Osteointegrations with and without the Use of PRP, in the Protocol of Setting Análise Comparativa do Índice de Sucesso dos Implantes Osteointegrados com e sem a Utilização de PRP, no Protocolo de Fixação

    Directory of Open Access Journals (Sweden)

    Adriana Passanezi

    2004-10-01

    Full Text Available This work deals with the data gathering of 1267 dental records from CID – Center of Dental Implants in Londrina, evaluating the success and loss results of osteo-integrated implants and separating them by trademark of the implant FOB – USP and ACTIVE (this one with two types of surface: smooth and sandblasted and whether the PRP was used or not in the protocol of setting. One thousand five hundred and seventy-two implants were analyzed. In 642 of them the PRP was used in the protocol of setting and there were 16 losses which represent a success percentage of 97,51%. In 930 implants the PRP was not used and there were 66 losses, showing a success index of 92,90%. The results were discussed based on the current literature, and it was concluded that the PRP used in the protocol of implant setting leads to a loss reduction of the osteo-integrated implants, increasing the success index; the influence of the PRP in the success index of osteo-integrated implants is more significant in the maxilla than in the mandible; the PRP represents a promising material in the processes of bone reconstruction in a general sense, being its use recommended in certain situations of implant settings.   O presente trabalho refere-se ao levantamento de dados de 1267 prontuários do CID – Centro de Implantes Dentários de Londrina. Os resultados de sucessos e perdas de implantes ósseo-integrados foram anotados e, a seguir, separados por marca do implante FOB-USP e ACTIVE, este com dois tipos de superfície (lisa ou jateada. Também se verificou se houve ou não utilização de PRP no protocolo de fixação.Foi analisado o total de 1572 implantes, em 642 dos quais foi utilizado o PRP no protocolo de fixação. Ocorreram 16 perdas,representando um percentual de sucesso de 97,51%. Em 930 implantes, não foi utilizado o PRP e houve 66 perdas, demonstrando um índice de sucesso de 92,90%. Os resultados foram discutidos à luz da literatura atual, e pode-se concluir que

  2. Learning to argue via apprenticeship.

    Science.gov (United States)

    Papathomas, Lia; Kuhn, Deanna

    2017-07-01

    We examined apprenticeship, in the form of interaction with a more capable other, as a mechanism of development of higher-order reasoning skills, specifically argumentation. Over a 1-year period, middle school students engaged in twice-weekly electronic dialogs with a sequence of different peers on a series of social issues. In one group, unbeknownst to participants, a highly capable adult substituted for peers in half of their dialogs. Beginning immediately, increasing with time, and extending to peer-only dialogs on a new topic, the quality of argumentation shown by the experimental group exceeded that of a comparison peer-only group, highlighting the power of apprenticeship as a mechanism in the development of reasoning, a demonstration of both theoretical and applied significance. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Immunohistochemistry for PrPSc in natural scrapie reveals patterns which are associated with the PrP genotype.

    Science.gov (United States)

    Spiropoulos, J; Casalone, C; Caramelli, M; Simmons, M M

    2007-08-01

    Immunohistochemistry for PrPSc is used widely in scrapie diagnosis. In natural scrapie cases the use of immunohistochemistry (IHC) has revealed the existence of up to 12 different morphological types of immunostained deposits. The significance of this pattern variability in relation to genotype has not been studied extensively in natural disease. In this study we recorded in detail PrPSc patterns at the obex level of the medulla oblongata from 163 animals derived from 55 flocks which presented through passive surveillance in the UK and Italy. A strong association was seen between PrPSc patterns and PrP genotype, particularly in relation to codon 136. In a blind assessment of this association we were able to predict, with over 80% accuracy, the genotype of 151 scrapie cases which were presented through passive surveillance from 13 farms. The genotype of these cases was ARQ/ARQ or VRQ/VRQ. The association of PrPsc patterns with genotype was generally stronger in those farms where all the affected animals belonged to a single genotype compared with farms where both genotypes were identified, with the exception of one farm in which the genotype of all affected sheep was ARQ/ARQ and the PrPSc patterns were of the VRQ/VRQ type. Our observations support the hypothesis that the observed association between specific IHC patterns and genotypes may in fact be strain driven but in natural disease individual scrapie strains may demonstrate a genotypic tropism.

  4. Immediately loaded dental implants bioactivated with platelet-rich plasma (PRP) placed in maxillary and mandibular region.

    Science.gov (United States)

    Inchingolo, F; Ballini, A; Cagiano, R; Inchingolo, A D; Serafini, M; De Benedittis, M; Cortelazzi, R; Tatullo, M; Marrelli, M; Inchingolo, A M; Vermesan, D; Del Corso, M; Malcangi, G; Diteodoro, S; Mura, S A; Cantore, S; Cortelazzi, A; Paduanelli, G; Resta, G; Muollo, F; Cirulli, N; Pettini, F; Farronato, D; De Vito, D; Caprio, M; Haragus, H; Dipalma, G

    2015-01-01

    Dental implants have today deeply changed the dental field. In fact, after almost 50 years, the permanent placement of a titanium screw with an attached tooth have, step by step, changed the society's standard toward a permanently replacement of missed or severely damaged teeth. In fact, the host of benefits born from dental implants have affected both patients and dental professionals. The aim of the present study is to report the outcomes of an implant therapy protocol supporting fixed prostheses implanted soon after extractions and loaded with flapless guided surgery by a 3D software planning. 37 patients, requiring rehabilitation of booth dental arches with a one-to-one technique, were enrolled in a follow-up study plan which established clinical and radiological examinations on the day after surgery, seven months and one year later. Platelet Rich Plasma (PRP), in combination with autogenous bone, organic bone material and organic bone substitutes, was used before implant-prosthetic rehabilitation with an its prompt loading just before the implant insertion phase. Definitive restorations were delivered at 6-12 months after surgical procedure. One year after loading there were no dropouts and no failure of the definitive prosthesis. Furthermore, the feedback from patients resulted positive. Patients resulted satisfied both aesthetically and functionally regarding these types of prosthetic reconstructions made at the time.

  5. The AGAAAAGA palindrome in PrP is required to generate a productive PrPSc-PrPC complex that leads to prion propagation.

    Science.gov (United States)

    Norstrom, Eric M; Mastrianni, James A

    2005-07-22

    The molecular hallmark of prion disease is the conversion of normal prion protein (PrPC) to an insoluble, proteinase K-resistant, pathogenic isoform (PrPSc). Once generated, PrPSc propagates by complexing with, and transferring its pathogenic conformation onto, PrPC. Defining the specific nature of this PrPSc-PrPC interaction is critical to understanding prion genesis. To begin to approach this question, we employed a prion-infected neuroblastoma cell line (ScN2a) combined with a heterologous yeast expression system to independently model PrPSc generation and propagation. We additionally applied fluorescence resonance energy transfer analysis to the latter to specifically study PrP-PrP interactions. In this report we focus on an N-terminal hydrophobic palindrome of PrP (112-AGAAAAGA-119) thought to feature intimately in prion generation via an unclear mechanism. We found that, in contrast to wild type (wt) PrP, PrP lacking the palindrome (PrPDelta112-119) neither converted to PrPSc when expressed in ScN2a cells nor generated proteinase K-resistant PrP when expressed in yeast. Furthermore, PrPDelta112-119 was a dominant-negative inhibitor of wtPrP in ScN2a cells. Both wtPrP and PrPDelta112-119 were highly insoluble when expressed in yeast and produced distinct cytosolic aggregates when expressed as fluorescent fusion proteins (PrP::YFP). Although self-aggregation was evident, fluorescence resonance energy transfer studies in live yeast co-expressing PrPSc-like protein and PrPDelta112-119 indicated altered interaction properties. These results suggest that the palindrome is required, not only for the attainment of the PrPSc conformation but also to facilitate the proper association of PrPSc with PrPC to effect prion propagation.

  6. THE EFFECT OF ORGANIC FERTILISATION OF LIQUID MANURE AND THE PRP FIX PREPARATION ON THE YIELD AND CHEMICAL COMPOSITION OF WINTER RAPE SEEDS AND SPRING WHEAT GRAIN

    Directory of Open Access Journals (Sweden)

    Ewa Możdżer

    2017-01-01

    Full Text Available In 2011–2013, a field experiment was carried out at the Experimental Station of Cultivar Evaluation in Szczecin-Dąbie. The experiment aimed at determining the effect of slurry without and with addition of increasing PRP Fix preparation doses on the crop yields and some of their qualitative traits. The soil where the experiment was set up was slightly acidic (pHKCL 5.95; nitrogen, phosphorus and potassium contents were 0.86, 1.55 and 2.70 g·kg-1 d.m., respectively. The total content of macro-elements for this type of soil was average. The content of bioavailable forms of phosphorus, magnesium and sulphur was average, while that of potassium was high. The content of organic carbon in soil was low, while the C:N ratio was 10.2:1 and was average for that type of soils. The obtained results show that the applied fertilisation with slurry combined with PRP Fix preparation and PK fertilisation increased the yield of winter rape seeds and spring wheat grain and the content of macro-elements being examined in them. The yields of the test plants were larger in the fertilisation objects where fertilisation with slurry with addition of 8 kg PRP Fix preparation per 1 m3 slurry was applied, when compared to those where only mineral fertilisation or slurry was used. Winter rape seeds and spring wheat grain usually contained more nitrogen, phosphorus, potassium, magnesium, calcium and sulphur in the fertilisation objects being fertilised with slurry with PRP Fix preparation in the amount of 8 or 12 kg per 1 m3 slurry with additional PK fertilisation (experimental series II compared to experimental series I without additional PK fertilisation. Differences in the content of macro-elements in test plants after application of the fertilisation scheme being used varied. These differences were not always significant.

  7. Intraoperative application Platelet rich fibrin, postoperative injections OF PRP or microfracture only for osteochondral lesions of the knee: a five-year retrospective evaluation.

    Science.gov (United States)

    Papalia, R; Diaz Balzani, L; Torre, G; Tirindelli, M C; Nobile, C; Maffulli, N; Denaro, V

    2016-01-01

    Cartilage lesions are the most common cause of chronic knee pain. Micro-fracturing is reliable, effective, easy to perform and inexpensive. We propose a novel approach to cartilage lesions where microfractures are performed contextually to intra-operative or post-operative administration of platelet concentrates. We retrospectively evaluate 48 patients divided in 3 groups. Group 1: 15 patients underwent microfractures and intraoperative administration of PRF (PRF group); group 2: 16 microfractures and postoperative injections of PRP (PRP group); group 3: 17 patients with isolated microfractures (Microfractures group). Clinical scores (IKDC, VAS pain) were administered at 2 and 5 years postoperative and MRI was performed to evaluate the lesions of patients according to the MOCART criteria (2006). Patients treated with platelet concentrates achieved better clinical results compared to patients treated with microfracture only. The PRF group showed better results than the PRP group at 2 years, with loss of significance at 5 years. At MOCART score, PRF group obtained better results earlier than the other two groups.

  8. A Randomized Controlled Study of a Fully Liquid DTaP-IPV-HB-PRP-T Hexavalent Vaccine for Primary and Booster Vaccinations of Healthy Infants and Toddlers in Latin America.

    Science.gov (United States)

    López, Pío; Arguedas Mohs, Adriano; Abdelnour Vásquez, Arturo; Consuelo-Miranda, Maria; Feroldi, Emmanuel; Noriega, Fernando; Jordanov, Emilia; B Chir, Siham; Zambrano, Betzana

    2017-11-01

    Hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-HB-PRP-T)-containing vaccines are increasingly the standard of care. This study evaluated the primary series (NCT01177722) and booster (NCT01444781) of a fully liquid DTaP-IPV-HB-PRP-T vaccine in Latin America. Infants (N = 1375) received hepatitis B vaccine at birth and were randomized to one of 3 batches of the investigational DTaP-IPV-HB-PRP-T or licensed control vaccine (DTaP-HB-IPV//PRP-T) at 2-4 to 6 months of age, coadministered with 7-valent pneumococcal conjugate vaccine (PCV7) (2-4-6 months) and rotavirus vaccine (2-4 months). A booster of either DTaP-IPV-HB-PRP-T or control was given at 12-24 months, coadministered with PCV7. Immunogenicity was assessed by validated assays and safety from parental reports. Primary series seroprotection and vaccine response rates were equivalent for DTaP-IPV-HB-PRP-T batches. For pooled batches, noninferiority to the control vaccine was demonstrated for each antigen. There were no descriptive differences in antibody persistence or booster response between DTaP-IPV-HB-PRP-T and the control. The booster responses to either vaccine following DTaP-IPV-HB-PRP-T primary series or to DTaP-IPV-HB-PRP-T following a control vaccine primary series were similar. The anti-aP component (filamentous hemagglutinin [FHA] and pertussis toxin [PT]) vaccine response and anti-Haemophilus influenzae type b (PRP) series seroprotection (≥0.15 µg/mL) rates were ≥73.0% after 2 primary series doses. Antipyretics had no effect on the immune response, and an extra (oral) polio vaccination had no effect on the antipolio booster response. Responses to PCV7 and rotavirus vaccine were similar for each coadministration. There were no safety concerns observed with any vaccine. These results confirm the suitability of the fully liquid DTaP-IPV-HB-PRP-T vaccine for primary and booster vaccination of infants.

  9. Emergence of two prion subtypes in ovine PrP transgenic mice infected with human MM2-cortical Creutzfeldt-Jakob disease prions.

    Science.gov (United States)

    Chapuis, Jérôme; Moudjou, Mohammed; Reine, Fabienne; Herzog, Laetitia; Jaumain, Emilie; Chapuis, Céline; Quadrio, Isabelle; Boulliat, Jacques; Perret-Liaudet, Armand; Dron, Michel; Laude, Hubert; Rezaei, Human; Béringue, Vincent

    2016-02-05

    Mammalian prions are proteinaceous pathogens responsible for a broad range of fatal neurodegenerative diseases in humans and animals. These diseases can occur spontaneously, such as Creutzfeldt-Jakob disease (CJD) in humans, or be acquired or inherited. Prions are primarily formed of macromolecular assemblies of the disease-associated prion protein PrP(Sc), a misfolded isoform of the host-encoded prion protein PrP(C). Within defined host-species, prions can exist as conformational variants or strains. Based on both the M/V polymorphism at codon 129 of PrP and the electrophoretic signature of PrP(Sc) in the brain, sporadic CJD is classified in different subtypes, which may encode different strains. A transmission barrier, the mechanism of which remains unknown, limits prion cross-species propagation. To adapt to the new host, prions have the capacity to 'mutate' conformationally, leading to the emergence of a variant with new biological properties. Here, we transmitted experimentally one rare subtype of human CJD, designated cortical MM2 (129 MM with type 2 PrP(Sc)), to transgenic mice overexpressing either human or the VRQ allele of ovine PrP(C). In marked contrast with the reported absence of transmission to knock-in mice expressing physiological levels of human PrP, this subtype transmitted faithfully to mice overexpressing human PrP, and exhibited unique strain features. Onto the ovine PrP sequence, the cortical MM2 subtype abruptly evolved on second passage, thereby allowing emergence of a pair of strain variants with distinct PrP(Sc) biochemical characteristics and differing tropism for the central and lymphoid tissues. These two strain components exhibited remarkably distinct replicative properties in cell-free amplification assay, allowing the 'physical' cloning of the minor, lymphotropic component, and subsequent isolation in ovine PrP mice and RK13 cells. Here, we provide in-depth assessment of the transmissibility and evolution of one rare subtype of

  10. Use of autologous platelet rich plasma (PRP) in stopping massive hemoptysis at the Lung Center of the Philippines: a pilot study.

    Science.gov (United States)

    Sarmiento, Armand Gregorio C; Danguilan, Jose Luis J; Mariano, Zenaida M; Barzaga, Maria Teresa A

    2017-01-01

    The purpose of this study is to determine the effect of using autologous platelet rich plasma (PRP) in patients having massive hemoptysis within a period of one week. This is a prospective cohort study involving 20 consecutive patients admitted who met the criteria for massive hemoptysis from July to October 2011. After stabilizing the patient, fiberoptic bronchoscopy (FOB) was performed for localization of bleeding within 6 hours from diagnosis. A 50mL of blood was extracted from the patient whom was to be used for autologous PRP concentrate. After identifying the anatomic site of bleeding, autologous PRP concentrate was instilled on the affected bronchus and was allowed to stay for 5 minutes after instillation. Patients were then monitored from the time the bleeding stopped in the first 24 hours, 2 days and 7 days respectively. Mean age of the study population with massive hemoptysis was 47 years old (SD 17.3). Majority of cases were male 18 out of 20 (90%) and smokers 14 (70%) with a normal BMI (75%). Identification of bleeding site was more commonly seen on the right upper lobe 9 out of 20 (45%). Overall, 14 out of 20 patients (70%) were reported to have stopped bleeding immediately. Subsequent hospital days showed that 8 out of 20 patients (40%) had no hemoptysis. However, one [1] post-tuberculosis (TB) bronchiectatic patient had recurrence of massive hemoptysis, approximately 250 mL per expectorate, expired within the 7 days observation and one patient had lobectomy on the 2nd day. The rest had non-massive hemoptysis wherein their expectorations were only streaks of blood. Moreover, there was one [1] patient who had recurrence of massive hemoptysis 1 week after autologous PRP infusion and was eventually intubated. Majority of the subjects, eleven [11] were diagnosed to have post-TB bronchiectasis. The rest of the patients were worked-up prior to operation. Overall, it was observed that the use of autologous PRP was able to stop bleeding in 40% of the study

  11. Cells exposed to a huntingtin fragment containing an expanded polyglutamine tract show no sign of ion channel formation: results arguing against the ion channel hypothesis

    DEFF Research Database (Denmark)

    Nørremølle, Anne; Grunnet, Morten; Hasholt, Lis

    2003-01-01

    Ion channels formed by expanded polyglutamine tracts have been proposed to play an important role in the pathological processes leading to neurodegeneration in Huntington's disease and other CAG repeat diseases. We tested the capacity of a huntingtin fragment containing an expanded polyglutamine ...... in the currents recorded in any of the two expression systems, indicating no changes in ion channel activity. The results therefore argue against the proposed hypothesis of expanded polyglutamines forming ion channels....

  12. Autologous US-guided PRP injection versus US-guided focal extracorporeal shock wave therapy for chronic lateral epicondylitis: A minimum of 2-year follow-up retrospective comparative study.

    Science.gov (United States)

    Alessio-Mazzola, Mattia; Repetto, Ilaria; Biti, Besmir; Trentini, Roberto; Formica, Matteo; Felli, Lamberto

    2018-01-01

    To compare the efficacy of two independent groups of patients treated with ultrasound (US)-guided extracorporeal shock wave (ESW) therapy and with US-guided injection of platelet-rich plasma (PRP) for chronic lateral epicondylitis (LE) with a minimum of 2-year follow-up. We retrospectively evaluated 63 patients treated for chronic LE (31 patients with autologous US-guided PRP injection and 32 patients with US-guided focal ESW therapy) from 2009 to 2014. All the patients were evaluated by means of Roles-Maudsley (RM) score, quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, visual analogic scale (VAS) and patient-rated tennis elbow evaluation (PRTEE) to retrospectively assess the pain relief, level of activity, the self-reported function and subjective satisfaction at minimum of 2-year follow-up. Both US-guided autologous PRP injection and US-guided focal ESW administration proved effective in chronic LE with significant improvement in the QuickDASH, VAS, RM and PRTEE scores ( p 0.05). The mean time between treatment and symptom resolution was significantly shorter for the PRP treatment ( p = 0.0212); furthermore, the mean time to return to the normal activities was quicker for PRP group ( p = 0.0119). Both PRP injection and ESW therapy are feasible and safe options for the treatment of chronic LE with low risk of complications and with good long-term follow-up results. US-guided PRP injection has quick efficacy when compared with US-guided focal ESW therapy.

  13. Selection Role on Configuration of Resistance / Susceptibility Degree to Scrapie and on Genetic Diversity at PrP Locus in the Botosani Karakul Sheep Breed

    Directory of Open Access Journals (Sweden)

    Gheorghe Hrinca

    2017-05-01

    Full Text Available The molecular-genetic profiles from the determinant locus of scrapie have been described in the Botosani Karakul breed. Sheep belonged to two farm types: elite farm from Research and Development Station for Sheep and Goat Breeding, Popauti-Botosani and several production farms of some private farmers. The two farm types differ between them by selective specificities; in the farm elite the selection pressure is stronger and the selection criteria applied to sheep have been more accuracy than in the production farms. Sheep genotyping at the PrP locus was achieved by the Real-Time PCR method. By framing the individuals in risk classes concerning the prion disease, there were identified significant differences between the two farm types in terms of resistance / susceptibility to scrapie of sheep. The elite farm population is significantly advantaged as regards the molecular-genetic endowment at the PrP locus and low probability converting of the PrPc normal protein in the PrPSc pathogenic isomorph compared to the population of production farms. The reasons for the different associations of prion genotypes with morbid phenomenon intensity in the two farm types must be sought exclusively in the characteristics of selection systems applied to the animals in each farm type. From the standpoint of informational statistics, there is a high degree of genetic similarity at the PrP locus between the two populations. Contrary to expectations, the genetic diversity of prion structures is more developed in the elite farm than in the production farms. The knowing importance of prion profiles was revealed  in pursuit of genetic and veterinary prophylaxis of the sheep populations.

  14. Association of laser phototherapy with PRP improves healing of bisphosphonate-related osteonecrosis of the jaws in cancer patients: a preliminary study.

    Science.gov (United States)

    Martins, Marco Antonio T; Martins, Manoela D; Lascala, Cesar A; Curi, Marcos M; Migliorati, César A; Tenis, Carlos A; Marques, Márcia M

    2012-01-01

    The aim of this study was to compare retrospectively the effect of three different treatments on the healing outcome of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in cancer patients. Twenty-two cancer patients were treated for BRONJ with one of the following protocols: clinical (pharmacological therapy), surgical (pharmacological plus surgical therapy), or PRP plus LPT (pharmacological plus surgical plus platelet rich plasma (PRP) plus laser phototherapy (LPT). The laser treatment was applied with a continuous diode laser (InGaAlP, 660 nm) using punctual and contact mode, 40 mW, spot size 0.042 cm(2), 6 J/cm(2) (6 s) and total energy of 0.24 J per point. The irradiations were performed on the exposed bone and surrounding soft tissue. The analysis of demographic data and risk factors was performed by gathering the following information: age, gender, primary tumor, bisphosphonate (BP) used, duration of BP intake, history of chemotherapy, use of steroids, and medical history of diabetes. The association between the current state of BRONJ (with or without bone exposure) and other qualitative variables was determined using the chi-square or Fisher's exact test. In all tests, the significance level adopted was 5%. Most BRONJ lesions occurred in the mandible (77%) after tooth extraction (55%) and in women (72%). A significantly higher percentage of patients reached the current state of BRONJ without bone exposure (86%) in the PPR plus LPT group than in the pharmacological (0%) and surgical (40%) groups after 1-month follow-up assessment. These results suggest that the association of pharmacological therapy and surgical therapy with PRP plus LPT significantly improves BRONJ healing in oncologic patients. Although prospective studies with larger sample sizes are still needed, this preliminary study may be used to inform a better-designed future study. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Regenerative endodontic treatment of an immature tooth with a necrotic pulp and apical periodontitis using platelet-rich plasma (PRP) and mineral trioxide aggregate (MTA): a case report.

    Science.gov (United States)

    Sachdeva, G S; Sachdeva, L T; Goel, M; Bala, S

    2015-09-01

    To report the successful clinical and radiographic outcome of a regenerative endodontic treatment. A 16-year-old male patient presented with a discoloured, maxillary left lateral incisor with a necrotic pulp. Radiographic examination revealed an incompletely developed root with an open apex. Under local anaesthesia and rubber dam isolation, an access cavity was prepared and the necrotic pulpal remnants were removed. The canal was disinfected without mechanical instrumentation with 5.25% NaOCl solution and dried with sterile paper points. A triple antibiotic (metronidazole, ciprofloxacin and minocycline) mixed with distilled water was packed in the canal and left for 28 days. Ten millimetres of whole blood was drawn by venipuncture from the patients antecubital vein for preparation of platelet-rich plasma (PRP). After removal of the antibiotic mixture, the PRP was injected into the canal space up to the cementoenamel junction level. Three millimetres of white MTA was placed directly over the PRP clot. Two days later, the tooth was restored with permanent filling materials. The patient was recalled for 3, 6, 12, 24 and 36 months clinical/radiographic follow-up. A 3-year follow-up radiograph revealed resolution of the periapical lesion, increased thickening of the root walls, further root development and continued apical closure of the root apex. The tooth was not responsive to cold tests; however, sensitivity tests with an electric pulp tester (EPT) elicited a delayed positive response. Regeneration is a viable treatment modality that allows continued root development of immature teeth with open apices and necrotic pulps. Platelet-rich plasma appears to be a suitable scaffold for regeneration of vital tissues in teeth with a necrotic pulps and an associated periapical lesion. Regenerative endodontic procedures may offer an effective treatment option to save teeth with compromised structural integrity. © 2014 International Endodontic Journal. Published by John Wiley

  16. Inside-out and standard vein grafts associated with platelet-rich plasma (PRP) in sciatic nerve repair. A histomorphometric study.

    Science.gov (United States)

    Roque, José Sidney; Pomini, Karina Torres; Buchaim, Rogério Leone; Buchaim, Daniela Vieira; Andreo, Jesus Carlos; Roque, Domingos Donizeti; Rodrigues, Antonio de Castro; Rosa, Geraldo Marco; Moraes, Luis Henrique Rapucci; Viterbo, Fausto

    2017-08-01

    To evaluated the tubulization technique with standard and inside-out vein, filled or not with platelet-rich plasma (PRP), in sciatic nerve repair. Seventy male Wistar rats were randomly divided into five groups: IOVNF (Inside-Out Vein with No Filling); IOVPRP (Inside-Out Vein filled with PRP); SVNF (Standard Vein with No Filling); SVPRP (Standard Vein filled with PRP); Sham (Control). The left external jugular vein was used as graft in a 10 mm nervous gap. In the morphological analysis of all groups, myelinated nerve fibers with evident myelin sheath, neoformation of the epineurium and perineurium, organization of intraneural fascicles and blood vessels were observed. In the morphometry of the distal stump fibers, SVPRP group had the highest means regarding fiber diameter (3.63±0.42 μm), axon diameter (2.37±0.31 μm) and myelin sheath area (11.70±0.84 μm2). IOVPRP group had the highest means regarding axon area (4.39±1.16 μm2) and myelin sheath thickness (0.80±0.19 μm). As for values of the fiber area, IOVNF group shows highest means (15.54±0.67 μm2), but are still lower than the values of the Sham group. The graft filled with platelet-rich plasma, with use standard (SVPRP) or inside-out vein (IOVPRP), promoted the improvement in axonal regeneration on sciatic nerve injury.

  17. Efficacy of Platelet-Rich-Plasma (PRP and Highly Purified Bovine Xenograft (Laddec® Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

    Directory of Open Access Journals (Sweden)

    Sabrina Pappalardo

    2013-10-01

    Full Text Available Objectives: The purpose of the present study was to evaluate the efficacy of adding platelet-rich plasma (PRP to a new highly purified bovine allograft (Laddec® in the bone regeneration of cystic bony defects augmented following cystectomy.Material and Methods: Study sample included 20 patients undergoing cystectomy in which the bone defect was filled with PRP and Laddec®. All patients were examined with periapical radiographs before operation and at follow-up. After 3 months, at re-entry surgery for implant placement, bone core was taken for histological and histomorphometric analysis.Results: The postoperative successive radiographs showed a good regeneration of bone in the height of bony defects with application of PRP to bone graft. By the first postoperative month, about 48% of the defect was filled, which gradually increased in each month and showed about 90% of defect-fill by 6 months. Histological and histomorphometric analysis, showed a significant presence of bone tissue and vessels, with newly formed bone in contact with anorganic bone particles. The mean volume of vital bone was 68 ± 1.6% and the mean percentage of vital bone was 48 ± 2.4%. The mean percentage of inorganic particles in tissues was 20 ± 1.2% of the total volume. All the samples analyzed did not evidence the presence of inflammatory cells.Conclusions: The results of this study showed how the use of Laddec® in association with platelet-rich plasma allows bone regeneration and has a potential for routine clinical use for regeneration of cystic bony defects.

  18. ANALYSIS OF THE RESULTS OF APPLYING THE METHOD PLATELET-RICH PLASMA (PRP FOR THE TREATMENT OF PROBLEMATIC SKIN WOUNDS

    Directory of Open Access Journals (Sweden)

    Tsvetan Sokolov

    2017-02-01

    Full Text Available OBJECTIVE: To show analysis of the results of applying the method platelet-rich plasma (PRP for the treatment of problematic skin wounds. The paper’s objective is to prove its reliability and relevance, to evaluate its efficiency and applicability to Bulgarian patients. MATERIAL AND METHODS: Out of a total of 154 hospitalized patients with problematic skin wounds 83 have been treated with platelet-rich plasma, comprising the Experimental group (EG, and 71 patients with similar wounds have been treated by using traditional methods for the respective pathology at the Department of Orthopedics and Traumatology, Vessel and Plastic Surgery Department, comprising the Control Group (CG. Data on the condition of monitored symptoms of researched cases was collected for the research. A variable is defined for every symptom and its value and weight is correspondingly introduced. Scores introduced by Cancela AM are used for the assessment of the respective wound. Each of these scores is used for assessing specific wound parameters: Total Wound Score (TWS; total anatomic score (TAS of wound and Total Score of Wound data (TSWD. RESULTS: Analysis of variance was performed to achieve the objectives and solve the research tasks; variables containing information on initial and final data from each series of experiments have been analyzed in order to determine basic numerical characteristics of variables, and by comparative analysis to check how they tend to vary in experimental (EG and control (CG group. Statistical survey shows that the platelet-rich plasma method gives significant results when treating problematic skin wounds leading to full recovery as compared to traditional methods typical for the pathology. The graphical interpretation allows to identify forecast relations between assessed aspects of problematic wounds and weeks of treatment. CONCLUSION: By analyzing the results of our study we can conclude that the use of platelet-rich plasma to treat

  19. Mouse Prion Protein (PrP) Segment 100 to 104 Regulates Conversion of PrPC to PrPSc in Prion-Infected Neuroblastoma Cells

    Science.gov (United States)

    Hara, Hideyuki; Okemoto-Nakamura, Yuko; Shinkai-Ouchi, Fumiko; Hanada, Kentaro; Yamakawa, Yoshio

    2012-01-01

    Prion diseases are characterized by the replicative propagation of disease-associated forms of prion protein (PrPSc; PrP refers to prion protein). The propagation is believed to proceed via two steps; the initial binding of the normal form of PrP (PrPC) to PrPSc and the subsequent conversion of PrPC to PrPSc. We have explored the two-step model in prion-infected mouse neuroblastoma (ScN2a) cells by focusing on the mouse PrP (MoPrP) segment 92-GGTHNQWNKPSKPKTN-107, which is within a region previously suggested to be part of the binding interface or shown to differ in its accessibility to anti-PrP antibodies between PrPC and PrPSc. Exchanging the MoPrP segment with the corresponding chicken PrP segment (106-GGSYHNQKPWKPPKTN-121) revealed the necessity of MoPrP residues 99 to 104 for the chimeras to achieve the PrPSc state, while segment 95 to 98 was replaceable with the chicken sequence. An alanine substitution at position 100, 102, 103, or 104 of MoPrP gave rise to nonconvertible mutants that associated with MoPrPSc and interfered with the conversion of endogenous MoPrPC. The interference was not evoked by a chimera (designated MCM2) in which MoPrP segment 95 to 104 was changed to the chicken sequence, though MCM2 associated with MoPrPSc. Incubation of the cells with a synthetic peptide composed of MoPrP residues 93 to 107 or alanine-substituted cognates did not inhibit the conversion, whereas an anti-P8 antibody recognizing the above sequence in PrPC reduced the accumulation of PrPSc after 10 days of incubation of the cells. These results suggest the segment 100 to 104 of MoPrPC plays a key role in conversion after binding to MoPrPSc. PMID:22398286

  20. Uso de matrices biodegradables enriquecidas con PRP, para restitución inmediata de volumen y regeneración tisular

    OpenAIRE

    Peluffo, Eugenio José

    2012-01-01

    Se plantea un ensayo clínico a fin de determinar la utilidad de una matriz estructural biodegradable (ME, en trámite de licencia de patente) enriquecida con fibrina y/o plasma rico en plaquetas (PRP) para restitución de volumen y regeneración tisular. Consta de dos fases. La primera in vitro, donde se definen las características físicas y químicas de la matriz estructural. La segunda, in vivo, que consiste en el análisis de la matriz enriquecida implantada en el tejido subcutáneo abdominal de...

  1. Effectiveness of Polyene Antibiotics in Treatment of Transmissible Spongiform Encephalopathy in Transgenic Mice Expressing Syrian Hamster PrP Only in Neurons

    OpenAIRE

    Demaimay, Remi; Race, Richard; Chesebro, Bruce

    1999-01-01

    To date very few drugs have favorably influenced the course of transmissible spongiform encephalopathies. In previous studies, the polyene antibiotics amphotericin B (AmB) and MS-8209 prolonged the incubation time in Syrian hamsters of the 263K strain of scrapie, but AmB had no effect against other scrapie strains in Syrian hamsters. In the present experiments using transgenic mice expressing Syrian hamster PrP in neurons only, MS-8209 extended the life spans of animals infected with the 263K...

  2. Genomic assessment of the evolution of the prion protein gene family in vertebrates.

    Science.gov (United States)

    Harrison, Paul M; Khachane, Amit; Kumar, Manish

    2010-05-01

    Prion diseases are devastating neurological disorders caused by the propagation of particles containing an alternative beta-sheet-rich form of the prion protein (PrP). Genes paralogous to PrP, called Doppel and Shadoo, have been identified, that also have neuropathological relevance. To aid in the further functional characterization of PrP and its relatives, we annotated completely the PrP gene family (PrP-GF), in the genomes of 42 vertebrates, through combined strategic application of gene prediction programs and advanced remote homology detection techniques (such as HMMs, PSI-TBLASTN and pGenThreader). We have uncovered several previously undescribed paralogous genes and pseudogenes. We find that current high-quality genomic evidence indicates that the PrP relative Doppel, was likely present in the last common ancestor of present-day Tetrapoda, but was lost in the bird lineage, since its divergence from reptiles. Using the new gene annotations, we have defined the consensus of structural features that are characteristic of the PrP and Doppel structures, across diverse Tetrapoda clades. Furthermore, we describe in detail a transcribed pseudogene derived from Shadoo that is conserved across primates, and that overlaps the meiosis gene, SYCE1, thus possibly regulating its expression. In addition, we analysed the locus of PRNP/PRND for significant conservation across the genomic DNA of eleven mammals, and determined the phylogenetic penetration of non-coding exons. The genomic evidence indicates that the second PRNP non-coding exon found in even-toed ungulates and rodents, is conserved in all high-coverage genome assemblies of primates (human, chimp, orang utan and macaque), and is, at least, likely to have fallen out of use during primate speciation. Furthermore, we have demonstrated that the PRNT gene (at the PRNP human locus) is conserved across at least sixteen mammals, and evolves like a long non-coding RNA, fashioned from fragments of ancient, long

  3. Low frequency of the scrapile resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed

    NARCIS (Netherlands)

    Acutis, P.L.; Sbaiz, L.; Verburg, F.J.; Riina, M.V.; Ru, G.; Moda, G.; Caramelli, M.; Bossers, A.

    2004-01-01

    Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele

  4. Manipulating the Prion Protein Gene Sequence and Expression Levels with CRISPR/Cas9.

    Directory of Open Access Journals (Sweden)

    Lech Kaczmarczyk

    Full Text Available The mammalian prion protein (PrP, encoded by Prnp is most infamous for its central role in prion diseases, invariably fatal neurodegenerative diseases affecting humans, food animals, and animals in the wild. However, PrP is also hypothesized to be an important receptor for toxic protein conformers in Alzheimer's disease, and is associated with other clinically relevant processes such as cancer and stroke. Thus, key insights into important clinical areas, as well as into understanding PrP functions in normal physiology, can be obtained from studying transgenic mouse models and cell culture systems. However, the Prnp locus is difficult to manipulate by homologous recombination, making modifications of the endogenous locus rarely attempted. Fortunately in recent years genome engineering technologies, like TALENs or CRISPR/Cas9 (CC9, have brought exceptional new possibilities for manipulating Prnp. Herein, we present our observations made during systematic experiments with the CC9 system targeting the endogenous mouse Prnp locus, to either modify sequences or to boost PrP expression using CC9-based synergistic activation mediators (SAMs. It is our hope that this information will aid and encourage researchers to implement gene-targeting techniques into their research program.

  5. A naturally occurring C-terminal fragment of the prion protein (PrP) delays disease and acts as a dominant-negative inhibitor of PrPSc formation.

    Science.gov (United States)

    Westergard, Laura; Turnbaugh, Jessie A; Harris, David A

    2011-12-23

    The cellular prion protein (PrPC) undergoes constitutive proteolytic cleavage between residues 111/112 to yield a soluble N-terminal fragment (N1) and a membrane-anchored C-terminal fragment (C1). The C1 fragment represents the major proteolytic fragment of PrPC in brain and several cell types. To explore the role of C1 in prion disease, we generated Tg(C1) transgenic mice expressing this fragment (PrP(Δ23-111)) in the presence and absence of endogenous PrP. In contrast to several other N-terminally deleted forms of PrP, the C1 fragment does not cause a spontaneous neurological disease in the absence of endogenous PrP. Tg(C1) mice inoculated with scrapie prions remain healthy and do not accumulate protease-resistant PrP, demonstrating that C1 is not a substrate for conversion to PrPSc (the disease-associated isoform). Interestingly, Tg(C1) mice co-expressing C1 along with wild-type PrP (either endogenous or encoded by a second transgene) become ill after scrapie inoculation, but with a dramatically delayed time course compared with mice lacking C1. In addition, accumulation of PrPSc was markedly slowed in these animals. Similar effects were produced by a shorter C-terminal fragment of PrP(Δ23-134). These results demonstrate that C1 acts as dominant-negative inhibitor of PrPSc formation and accumulation of neurotoxic forms of PrP. Thus, C1, a naturally occurring fragment of PrPC, might play a modulatory role during the course of prion diseases. In addition, enhancing production of C1, or exogenously administering this fragment, represents a potential therapeutic strategy for the treatment of prion diseases.

  6. Tobacco industry argues domestic trademark laws and international treaties preclude cigarette health warning labels, despite consistent legal advice that the argument is invalid.

    Science.gov (United States)

    Crosbie, Eric; Glantz, Stanton A

    2014-05-01

    To analyse the tobacco industry's use of international trade agreements to oppose policies to strengthen health warning labels (HWLs). A review of tobacco industry documents, tobacco control legislation and international treaties. During the early 1990s, the tobacco industry became increasingly alarmed about the advancement of HWLs on cigarettes packages. In response, it requested legal opinions from British American Tobacco's law firms in Australia and England, Britain's Department of Trade and Industry and the World Intellectual Property Organisation on the legality of restricting and prohibiting the use of their trademarks, as embodied in cigarette packages. The consistent legal advice, privately submitted to the companies, was that international treaties do not shield trademark owners from government limitations (including prohibition) on the use of their trademarks. Despite receiving this legal advice, the companies publicly argued that requiring large HWLs compromised their trademark rights under international treaties. The companies successfully used these arguments as part of their successful effort to deter Canadian and Australian governments from enacting laws requiring the plan packaging of cigarettes, which helped delay large graphic HWLs, including 'plain' packaging, for over a decade. Governments should not be intimidated by tobacco company threats and unsubstantiated claims, and carefully craft HWL laws to withstand the inevitable tobacco industry lawsuits with the knowledge that the companies' own lawyers as well as authoritative bodies have told the companies that the rights they claim do not exist.

  7. Dodecylphosphocholine Micelles Induce Amyloid Formation of the PrP(110-136 Peptide via an α-Helical Metastable Conformation.

    Directory of Open Access Journals (Sweden)

    Simon Sauvé

    Full Text Available A peptide encompassing the conserved hydrophobic region and the first β-strand of the prion protein (PrP(110-136 shown to interact with the surface of dodecylphosphocholine micelles adopts an α-helical conformation that is localized below the head-group layer. This surface-bound peptide has a half-life of one day, and readily initiates the formation of amyloid fibrils. The presence of the latter was confirmed using birefringence microscopy upon Congo red binding and thioflavin T-binding induced fluorescence. The observation of this metastable α-helical conformer provides a unique snapshot of the early steps of the inter-conversion pathway. These findings together with the body of evidence from the prion literature allowed us to propose a mechanism for the conversion of PrPC to amyloid material.

  8. Comparison of the Effect of PRP, PRF and Induced Bleeding in the Revascularization of Teeth with Necrotic Pulp and Open Apex: A Triple Blind Randomized Clinical Trial.

    Science.gov (United States)

    Shivashankar, Vasundara Yayathi; Johns, Dexton Antony; Maroli, Ramesh Kumar; Sekar, Mahalaxmi; Chandrasekaran, Rathinavel; Karthikeyan, Shanmugavel; Renganathan, Senthil Kumar

    2017-06-01

    Treatment of a tooth with necrotic pulp and open apex is a special challenge to the clinicians. Apexification with calcium hydroxide and MTA barrier technique fails to induce continued root maturation which makes the tooth susceptible to root fracture. Hence, an ideal outcome for such a tooth should be regeneration of pulp like tissue into the root canal capable of continuing normal root maturation. This study aims to compare the effect of Platelet Rich Fibrin (PRF), induced bleeding technique and Platelet Rich Plasma (PRP) in the revascularization of tooth with necrotic pulp and open apex. The main objectives of the study were to: (a) Radiographically evaluate the continuation of root development, increase in the dentin wall thickness and narrowing of canal space, apical closure and resolution of the periapical lesion; and to (b) To clinically evaluate the response to pulp sensibility testing and response to percussion and palpation tests. Sixty patients (6 to 28 years) with necrotic immature permanent tooth were randomly categorised into three groups after the root canal disinfection procedure. PRF as scaffolding material (Group A: n=20), revascularization with conventional induced bleeding technique (Group B: n=20), and PRP as the biomaterial (Group C: n=20). The primary outcome variable was measured using Periapical Index (PAI) (for periapical healing), Chen and Chen index (for apical responses), Schei's ruler (for root lengthening and root thickening) and other clinical parameters. The Chi-square test was used to interpret the data among the three groups at the end of 12 months for the variables root lengthening and lateral wall thickness. ANOVA test was performed to compare the mean of the PAI scores of the three groups at preoperative stage and 12 months. If statistically significant, Bonferroni test was done to compare the outcome among the three groups. The significant level was set at prevascularization of a non vital immature permanent tooth.

  9. Nuestra experiencia en el tratamiento de úlceras crónicas mediante PRF-Vivostat®: Serie de 10 casos Our experience in the treatment of chronic ulcers by PRP-Vivostat®: Series of 10 cases

    Directory of Open Access Journals (Sweden)

    E. Monclús Fuertes

    2009-06-01

    Full Text Available Pretendemos mostrar nuestra experiencia clínica en el manejo de úlceras crónicas de distinta etiología, mediante tratamiento conservador con gel rico en fibrina autóloga más factores de crecimiento plaquetarios o PRP, experiencia que reafirma los buenos resultados obtenidos en estudios anteriores referentes a Cirugía Plástica, Estética y Reparadora El hecho diferencial de nuestro estudio es el trato de las lesiones única y exclusivamente con PRP, sin otros tratamientos adyuvantes como es habitual en otros estudios acerca de este tema Entre los años 2002 y 2007 tratamos con PRP 10 pacientes con historia de fallo en los tratamientos convencionales, con una edad media de 65.6 años. Se realizaron entre 3 y 5 sesiones por paciente, espaciadas por una semana. El método de obtención elegido fue el sistema VIVOSTAT® (MBA Group. Se realizó un control fotográfico en cada sesión. Realizamos un seguimiento visual de las lesiones (pretratamiento- postratamiento, valorándolas según una modificación de la escala de Valbonesi et al a la que llamamos "Escala de Zaragoza", siendo el resultado pobre en 1 paciente, regular en 2, bueno en 5 y excelente en 2. El uso de PRP para úlceras crónicas en pacientes refractarios a otro tipo de tratamientos, tanto conservadores como quirúrgicos, es actualmente una alternativa real para conseguir una mejoría evidente e incluso la curación completa de las lesiones.The aim of this study is to evaluate our clinical experience in the management of chronic ulcers by conservative treatment with autologous fibrin-rich gel further platelet growth factors or PRP. This experience reaffirms the good results obtained in earlier studies relating to Plastic, Reconstructive and Aesthetic Surgery; moreover, the strength of our study is the use of PRP as the only treatment of such injuries, without other adjuvant treatments as usual in other works on this topic. From 2002 to 2007, we treated with PRP 10 patients with a

  10. The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants.

    Science.gov (United States)

    Kang, Jin Han; Lee, Hoan Jong; Kim, Kyung Hyo; Oh, Sung Hee; Cha, Sung Ho; Lee, Jin; Kim, Nam Hee; Eun, Byung Wook; Kim, Chang Hwi; Hong, Young Jin; Kim, Hyun Hee; Lee, Kyung Yil; Kim, Yae Jean; Cho, Eun Young; Kim, Hee Soo; Guitton, Fabrice; Ortiz, Esteban

    2016-09-01

    Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 μg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 μg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

  11. Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 1: Periodontal and dentoalveolar surgery.

    Science.gov (United States)

    Del Corso, Marco; Vervelle, Alain; Simonpieri, Alain; Jimbo, Ryo; Inchingolo, Francesco; Sammartino, Gilberto; Dohan Ehrenfest, David M

    2012-06-01

    Platelet concentrates for surgical use are innovative tools of regenerative medicine, and were widely tested in oral and maxillofacial surgery. Unfortunately, the literature on the topic is contradictory and the published data are difficult to sort and interpret. In periodontology and dentoalveolar surgery, the literature is particularly dense about the use of the various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte- and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In this first article, we describe and discuss the current published knowledge about the use of PRP and PRF during tooth avulsion or extraction, mucogingival surgery, Guided Tissue Regeneration (GTR) or bone filling of periodontal intrabony defects, and regeneration of alveolar ridges using Guided Bone Regeneration (GBR), in a comprehensive way and in order to avoid the traps of a confusing literature and to highlight the underlying universal mechanisms of these products. Finally, we particularly insist on the perspectives in this field, through the description and illustration of the systematic use of L-PRF (Leukocyte- and Platelet- Rich Fibrin) clots and membranes during tooth avulsion, cyst exeresis or the treatment of gingival recessions by root coverage. The use of L-PRF also allowed to define new therapeutic principles: NTR (Natural Tissue Regeneration) for the treatment of periodontal intrabony lesions and Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges. In periodontology, this field of research will soon find his golden age by the development of user-friendly platelet concentrate procedures, and the definition of new efficient concepts and clinical protocols.

  12. Effects of in vivo applications of peripheral blood-derived mesenchymal stromal cells (PB-MSCs) and platlet-rich plasma (PRP) on experimentally injured deep digital flexor tendons of sheep.

    Science.gov (United States)

    Martinello, Tiziana; Bronzini, Ilaria; Perazzi, Anna; Testoni, Stefania; De Benedictis, Gulia Maria; Negro, Alessandro; Caporale, Giovanni; Mascarello, Francesco; Iacopetti, Ilaria; Patruno, Marco

    2013-02-01

    Tendon injuries, degenerative tendinopathies, and overuse tendinitis are common in races horses. Novel therapies aim to restore tendon functionality by means of cell-based therapy, growth factor delivery, and tissue engineering approaches. This study examined the use of autologous mesenchymal stromal cells derived from peripheral blood (PB-MSCs), platelet-rich plasma (PRP) and a combination of both for ameliorating experimental lesions on deep digital flexor tendons (DDFT) of Bergamasca sheep. In particular, testing the combination of blood-derived MSCs and PRP in an experimental animal model represents one of the few studies exploring a putative synergistic action of these treatments. Effectiveness of treatments was evaluated at 30 and 120 days comparing clinical, ultrasonographic, and histological features together with immunohistochemical expression of collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP). Significant differences were found between treated groups and their corresponding controls (placebo) regarding tendon morphology and extracellular matrix (ECM) composition. However, our results indicate that the combined use of PRP and MSCs did not produce an additive or synergistic regenerative response and highlighted the predominant effect of MSCs on tendon healing, enhanced tissue remodeling and improved structural organization. Copyright © 2012 Orthopaedic Research Society.

  13. Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.

    Directory of Open Access Journals (Sweden)

    Martine Bruley Rosset

    Full Text Available In prion diseases, PrP(c, a widely expressed protein, is transformed into a pathogenic form called PrP(Sc, which is in itself infectious. Antibodies directed against PrP(c have been shown to inhibit PrP(c to PrP(Sc conversion in vitro and protect in vivo from disease. Other effectors with potential to eliminate PrPSc-producing cells are cytotoxic T cells directed against PrP-derived peptides but their ability to protect or to induce deleterious autoimmune reactions is not known. The natural tolerance to PrP(c makes difficult to raise efficient adaptive responses. To break tolerance, adenovirus (Ad encoding human PrP (hPrP or control Ad were administered to wild-type mice by direct injection or by transfer of Ad-transduced dendritic cells (DCs. Control Ad-transduced DCs from Tg650 mice overexpressing hPrP were also used for immunization. DC-mediated but not direct administration of AdhPrP elicited antibodies that bound to murine native PrP(c. Frequencies of PrP-specific IFNgamma-secreting T cells were low and in vivo lytic activity only targeted cells strongly expressing hPrP. Immunohistochemical analysis revealed that CD3(+ T cell infiltration was similar in the brain of vaccinated and unvaccinated 139A-infected mice suggesting the absence of autoimmune reactions. Early splenic PrP(Sc replication was strongly inhibited ten weeks post infection and mean survival time prolonged from 209 days in untreated 139A-infected mice to 246 days in mice vaccinated with DCs expressing the hPrP. The efficacy appeared to be associated with antibody but not with cytotoxic cell-mediated PrP-specific responses.

  14. Platelet-rich plasma (PRP) and Platelet-Rich Fibrin (PRF): surgical adjuvants, preparations for in situ regenerative medicine and tools for tissue engineering.

    Science.gov (United States)

    Bielecki, Tomasz; Dohan Ehrenfest, David M

    2012-06-01

    The recent developement of platelet concentrate for surgical use is an evolution of the fibrin glue technologies used since many years. The initial concept of these autologous preparations was to concentrate platelets and their growth factors in a plasma solution, and to activate it into a fibrin gel on a surgical site, in order to improve local healing. These platelet suspensions were often called Platelet-Rich Plasma (PRP) like the platelet concentrate used in transfusion medicine, but many different technologies have in fact been developed; some of them are even no more platelet suspensions, but solid fibrin-based biomaterials called Platelet-Rich Fibrin (PRF). These various technologies were tested in many different clinical fields, particularly oral and maxillofacial surgery, Ear-Nose-Throat surgery, plastic surgery, orthopaedic surgery, sports medicine, gynecologic and cardiovascular surgery and ophthalmology. This field of research unfortunately suffers from the lack of a proper accurate terminology and the associated misunderstandings, and the literature on the topic is quite contradictory. Indeed, the effects of these preparations cannot be limited to their growth factor content: these products associate many actors of healing in synergy, such as leukocytes, fibrin matrix, and circulating progenitor cells, and are in fact as complex as blood itself. If platelet concentrates were first used as surgical adjuvants for the stimulation of healing (as fibrin glues enriched with growth factors), many applications for in situ regenerative medicine and tissue engineering were developed and offer a great potential. However, the future of this field is first dependent on his coherence and scientific clarity. The objectives of this article is to introduce the main definitions, problematics and perspectives that are described in this special issue of Current Pharmaceutical Biotechnology about platelet concentrates.

  15. How not to argue about immigration

    Directory of Open Access Journals (Sweden)

    Corlett Angelo J.

    2013-01-01

    Full Text Available This paper describes and assesses the arguments offered both against closed borders and in favor of a more open borders approach to U.S. immigration reform as those arguments are set forth in R. Pevnick’s book, Immigration and the Constraints of Justice. We find numerous problems with Pevnick’s reasoning on both counts.

  16. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  17. Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery part 2: Bone graft, implant and reconstructive surgery.

    Science.gov (United States)

    Simonpieri, Alain; Del Corso, Marco; Vervelle, Alain; Jimbo, Ryo; Inchingolo, Francesco; Sammartino, Gilberto; Dohan Ehrenfest, David M

    2012-06-01

    Platelet concentrates for surgical use are innovative tools of regenerative medicine, and were widely tested in oral and maxillofacial surgery. Unfortunately, the literature on the topic is contradictory and the published data are difficult to sort and interpret. In bone graft, implant and reconstructive surgery, the literature is particularly dense about the use of the various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte- and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In this second article, we describe and discuss the current published knowledge about the use of PRP and PRF during implant placement (particularly as surface treatment for the stimulation of osseointegration), the treatment of peri-implant bone defects (after peri-implantitis, during implantation in an insufficient bone volume or during immediate post-extraction or post-avulsion implantation), the sinuslift procedures and various complex implant-supported treatments. Other potential applications of the platelet concentrates are also highlighted in maxillofacial reconstructive surgery, for the treatment of patients using bisphosphonates, anticoagulants or with post-tumoral irradiated maxilla. Finally, we particularly insist on the perspectives in this field, through the description and illustration of the use of L-PRF (Leukocyte- and Platelet-Rich Fibrin) clots and membranes during the regeneration of peri-implant bone defects, during the sinus-lift procedure and during complex implant-supported rehabilitations. The use of L-PRF allowed to define a new therapeutic concept called the Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges at the gingival and bone levels. As it is illustrated in this article, the NBR principles allow to push away some technical limits of global implant-supported rehabilitations, particularly when combined with other powerful biotechnological tools

  18. Interaction of the human prion PrP(106-126) sequence with copper(II), manganese(II), and zinc(II): NMR and EPR studies.

    Science.gov (United States)

    Gaggelli, Elena; Bernardi, Francesca; Molteni, Elena; Pogni, Rebecca; Valensin, Daniela; Valensin, Gianni; Remelli, Maurizio; Luczkowski, Marek; Kozlowski, Henryk

    2005-01-26

    The synthetic peptide encompassing residues 106-126 (PrP106-126, KTNMKHMAGAAAAGAVVGGLG) of the human prion protein was considered for its binding properties toward copper(II), manganese(II) and zinc(II) at pH 5.7. 1H and 13C 1D spectra, 1H spin-lattice relaxation rates, and 1H-15N and 1H-13C HSQC 2D experiments were obtained in the absence and in the presence of metal ions. While Zn(II) was found to yield negligible effects upon any NMR parameter, metal-peptide association was demonstrated by the paramagnetic effects of Cu(II) and Mn(II) upon 1D and 2D spectra. Delineation of structures of metal complexes was sought by interpreting the paramagnetic effect on 1H spin-lattice relaxation rates. Exchange of peptide molecules from the metal coordination sphere was shown to provide sizable contribution to the observed relaxation rates. Such contribution was calculated in the case of Cu(II); whereas the faster paramagnetic rates of peptide molecules bound to Mn(II) were determining spin-lattice relaxation rates almost exclusively dominated by exchange. Proton-metal distances were therefore evaluated in the case of the Cu(II) complex only and used as restraints in molecular dynamics calculations where from the structure of the complex was obtained. The peptide was shown to bind copper through the imidazole nitrogen and the ionized amide nitrogen of His-111 and the amino-terminal group with the terminal carboxyl stabilizing the coordination sphere through ionic interactions. The data were interpreted as to demonstrate that the hydrophobic C-terminal region was not affecting the copper-binding properties of the peptide and that this hydrophobic tail is left free to interact with other target molecules. As for the complex with Mn(II), qualitative information was obtained on carbonyl oxygens of Gly-124 and Leu-125, beyond the terminal Gly-126 carboxyl, being at close distance from the metal ion, that also interacts, most likely, through a hydrogen bond of metal-bound water

  19. Epitope tagging of proteins at the native chromosomal loci of genes in mice and in cultured vertebrate cells.

    Science.gov (United States)

    Chen, Yen-I G; Maika, Shanna D; Stevens, Scott W

    2006-08-18

    Adding epitope tags to proteins is an important method for biochemical analyses and is generally accomplished in metazoan cells using ectopically expressed, tagged trans-genes. In Saccharomyces cerevisiae, the addition of epitope tags to proteins is easily achieved at the genomic locus of a gene of interest due to the high efficiency of homologous recombination in that organism. Most metazoan cells do not exhibit this high homologous recombination efficiency, and therefore trans-genes with in-frame epitope tags are used. Although epitope tagged trans-genes have proven useful, replacing the native promoter with a heterologous promoter introduces numerous artifactual possibilities. These include overexpression, which can lead to promiscuous interactions, and the loss of native transcriptional control, which in live animals often leads to developmental defects and embryonic lethality. We describe an efficient method that overcomes the problems encountered using epitope tagged trans-genes by introducing the epitope tag into the native chromosomal gene locus in vertebrate cells, embryonic stem cells and live mice. These tagged proteins are physically associated with the expected relevant particles, and highly sensitive as shown by co-purification of homologues of the yeast pre-mRNA splicing factors Prp38p and Prp39p, not previously shown to be associated with metazoan snRNPs. These techniques will enhance the validity of conclusions made regarding epitope-tagged proteins and improve our understanding of proteomic dynamics in cultured vertebrate cells and live animals.

  20. The effect of a gelatin β-tricalcium phosphate sponge loaded with mesenchymal stem cells (MSC), bone morphogenic protein-2, and platelet-rich plasma (PRP) on equine articular cartilage defect

    Science.gov (United States)

    Tsuzuki, Nao; Seo, Jong-pil; Yamada, Kazutaka; Haneda, Shingo; Furuoka, Hidefumi; Tabata, Yasuhiko; Sasaki, Naoki

    2013-01-01

    We evaluated the curative efficacy of a gelatin β-tricalcium phosphate (β-TCP) sponge loaded with mesenchymal stem cells (MSC), bone morphogenic protein-2 (BMP-2), and platelet-rich plasma (PRP) by insertion into an experimentally induced osteochondral defect. A hole of 10 mm diameter and depth was drilled in the bilateral medial femoral condyles of 7 thoroughbred horses, and into each either a loaded sponge (treatment) or a saline-infused β-TCP sponge (control) was inserted. After 16 weeks, defects were examined by computed tomography, macroscopic analyses, and histological analyses. The median subchondral bone density and macroscopic subscores for joint healing were significantly higher in the treatment legs (P < 0.05). Although there was no significant difference in total histological scores between groups, hyaline cartilaginous tissue was observed across a wider area in the treatment group. Equine joint healing can be enhanced by inserting a BMP-2-, MSC-, and PRP-impregnated β-TCP sponge at the lesion site. PMID:24155448

  1. Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives.

    Science.gov (United States)

    Dohan Ehrenfest, David M; Andia, Isabel; Zumstein, Matthias A; Zhang, Chang-Qing; Pinto, Nelson R; Bielecki, Tomasz

    2014-01-01

    Platelet concentrates for topical and infiltrative use - commonly termed Platetet-Rich Plasma (PRP) or Platelet-Rich Fibrin (PRF) - are used or tested as surgical adjuvants or regenerative medicine preparations in most medical fields, particularly in sports medicine and orthopaedic surgery. Even if these products offer interesting therapeutic perspectives, their clinical relevance is largely debated, as the literature on the topic is often confused and contradictory. The long history of these products was always associated with confusions, mostly related to the lack of consensual terminology, characterization and classification of the many products that were tested in the last 40 years. The current consensus is based on a simple classification system dividing the many products in 4 main families, based on their fibrin architecture and cell content: Pure Platelet-Rich Plasma (P-PRP), such as the PRGF-Endoret technique; Leukocyte- and Platelet-Rich Plasma (LPRP), such as Biomet GPS system; Pure Platelet-Rich Fibrin (P-PRF), such as Fibrinet; Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Intra-Spin L-PRF. The 4 main families of products present different biological signatures and mechanisms, and obvious differences for clinical applications. This classification serves as a basis for further investigations of the effects of these products. Perspectives of evolutions of this classification and terminology are also discussed, particularly concerning the impact of the cell content, preservation and activation on these products in sports medicine and orthopaedics.

  2. Combined immunogenicity data for a new DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) following primary series administration at 2, 4, 6 months of age in Latin America.

    Science.gov (United States)

    Santos-Lima, Eduardo; B'Chir, Siham; Lane, Andrew

    2013-02-18

    The immunogenicity of a primary series of a new, fully liquid DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim), administered at 2, 4, 6 months of age in four clinical studies is reviewed. Immunogenicity data at 1 month after the third vaccination were assessed and pooled from a total of 1270 participants (per-protocol population) in four randomized clinical trials in Argentina, Mexico, and Peru. Hepatitis B vaccine was not administered at birth. All seroprotection (D, T, polio-1, -2, -3, Hep B, PRP-T [Hib]), seroconversion (PT and FHA), and vaccine response (PT and FHA) data were high, and were similar to licensed comparators (pooled SP, SC, and VR rates were 97.1-100%, 96.0-97.0%, and 99.7-99.9%, respectively). These data show the good immunogenicity of this new hexavalent vaccine that can provide the opportunity to increase global compliance to complex pediatric vaccination schedules. Copyright © 2013. Published by Elsevier Ltd.

  3. Effects of pharmaceuticals on the expression of genes involved in detoxification in a carp primary hepatocyte model.

    Science.gov (United States)

    Corcoran, Jenna; Lange, Anke; Winter, Matthew J; Tyler, Charles R

    2012-06-05

    Fish in many surface freshwaters are exposed to a range of pharmaceuticals via wastewater treatment works effluent discharges. In mammals the pregnane X receptor (PXR) plays a key role in the regulation of a suite of genes involved in drug biotransformation, but information on the role of this response pathway in fish is limited. Here we investigated the effects of exposure of carp (Cyprinus carpio) primary hepatocytes to the human PXR agonist rifampicin (RIF) on expression of target genes involved in phase I (cyp2k, cyp3a) and phase II (gstα, gstπ) drug metabolism and drug transporters mdr1 and mrp2. RIF induced expression of all target genes measured and the PXR antagonist ketoconazole (KET) inhibited responses of cyp2k and cyp3a. Exposure of the primary carp hepatocytes to the pharmaceuticals ibuprofen (IBU), clotrimazole (CTZ), clofibric acid (CFA) and propranolol (PRP), found responses to IBU and CFA, but not CTZ or PRP. This is in contrast with mammals, where CTZ is a potent PXR-agonist. Collectively our data indicate potential PXR involvement in regulating selected genes involved in drug metabolism in fish, but suggest some divergence in the regulation pathways with those in mammals. The carp primary hepatocyte model serves as a useful system for screening for responses in these target genes involved in drug metabolism.

  4. Variation in Chst8 gene expression level affects PrPC to PrPSc conversion efficiency in prion-infected Mov cells.

    Science.gov (United States)

    Martin, Renaud; Chantepie, Sandrine; Chapuis, Jérôme; Le-Duc, Aurélien; Maftah, Abderrahman; Papy-Garcia, Dulcé; Laude, Hubert; Petit, Jean-Michel; Gallet, Paul-François

    2011-10-28

    The conversion of the endogenous cellular prion protein to an abnormally folded isoform is a hallmark of transmissible spongiform encephalopathies. It occurs when a misfolded prion protein contacts the cellular PrP. Among the molecular partners suggested to be involved in the misfolding process, the glycosaminoglycans seem to be good candidates. The present study was aimed to examine a possible link between PrP conversion efficiency and transcript level of Chst8 gene that encodes the carbohydrate N-acetylgalactosamine 4-O-sulfotransferase 8. Mov cells expressing ovine PrP were transfected with shRNA directed against Chst8 transcripts. Resulting clones were characterized for their Chst8 and Prnp transcript levels, and for their content in sulfated glycosaminoglycans, more particularly sulfated chondroitins. Unexpectedly, the decreased amount of Chst8 transcript induced an increase of the chondroitin sulfate percentage among total GAGs, with an increased amount of 4-O-sulfation of GalNAc residues. Upon to infection by a sheep prion, a slight amount of PrP(Sc) was observed, which rapidly disappeared upon subpassaging. Together, these findings indicate that the Chst8 transcript level affects the glycosaminoglycan environment of the cellular prion protein, and as a consequence its ability for conversion into PrP(Sc). Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Leukocyte and Platelet Rich Plasma (L-PRP) Versus Leukocyte and Platelet Rich Fibrin (L-PRF) For Articular Cartilage Repair of the Knee: A Comparative Evaluation in an Animal Model.

    Science.gov (United States)

    Kazemi, Davoud; Fakhrjou, Ashraf

    2015-10-01

    Articular cartilage injuries of the knee are among the most debilitating injuries leading to osteoarthritis due to limited regenerative capability of cartilaginous tissue. The use of platelet concentrates containing necessary growth factors for cartilage healing has recently emerged as a new treatment method. The efficacy of two types of different platelet concentrates were compared in the treatment of acute articular cartilage injuries of the knee in an animal model. Eighteen adult Iranian mixed breed male dogs were used to conduct this experimental study. Full thickness articular cartilage defects (diameter 6 mm, depth 5 mm) were created in the weight bearing area of femoral condyles of both hind limbs in all dogs (n = 72). Twelve dogs were randomly selected to receive treatment and their right and left hind limb defects were treated by L-PRP and L-PRF implantation respectively, while no treatment was undertaken in six other dogs as controls. The animals were euthanized at 4, 16 and 24 weeks following surgery and the resultant repair tissue was investigated macroscopically and microscopically. At each sampling time, 4 treated dogs and 2 control dogs were euthanized, therefore 8 defects per group were evaluated. Mean macroscopic scores of the treated defects were higher than the controls at all sampling times with significant differences (P L-PRF treated and control defects (10.13 vs. 8.37) and L-PRP treated and control defects (10 vs. 8.5) at 4 and 16 weeks, respectively. A similar trend in mean total microscopic scores was observed with a significant difference (P L-PRF could be used to effectively promote the healing of articular cartilage defects of the knee.

  6. Safety and immunogenicity of an investigational fully liquid hexavalent DTaP-IPV-Hep B-PRP-T vaccine at two, four and six months of age compared with licensed vaccines in Latin America.

    Science.gov (United States)

    Macías, Mercedes; Lanata, Claudio F; Zambrano, Betzana; Gil, Ana I; Amemiya, Isabel; Mispireta, Monica; Ecker, Lucie; Santos-Lima, Eduardo

    2012-08-01

    This trial assessed the safety of a fully liquid investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine containing 10 μg Hansenula polymorpha-derived recombinant hepatitis B (hep B) antigen for primary vaccination of infants at 2, 4 and 6 months of age compared with licensed comparators. Participants received the DTaP-IPV-Hep B-PRP-T vaccine (group 1, N = 1422) or licensed DTwP-Hep B//Hib (Tritanrix-Hep B/Hib) and oral poliovirus vaccines (group 2, N = 711). The incidence of severe fever (≥ 39.6°C rectal equivalent) in the 2 groups was compared statistically; reactogenicity was evaluated from parental reports. Anti-Hep B antibody titers were measured in a subset of participants (no hepatitis B vaccination at birth) 1 month after dose 3. The investigational vaccine was well tolerated. After any dose, fever (rectal equivalent temperature ≥ 38°C) was observed in 74.8% and 92.7% of participants in groups 1 and 2; severe fever was observed in 4.0% and 5.5% of participants. Solicited injection site and systemic reactions were numerically less frequent in group 1 than group 2, although this difference was not assessed statistically. In both groups, all participants included in the immunogenicity analysis achieved anti-Hep B ≥ 10 mIU/mL and ≥ 96.2% of participants achieved anti-Hep B ≥ 100 mIU/mL, although geometric mean titer was approximately 3-fold lower for the investigational vaccine. This new, fully liquid acellular pertussis hexavalent vaccine demonstrated less reactogenicity than the licensed comparator whole cell pertussis vaccine and was highly immunogenic for the new Hep B valence.

  7. Model-driven discovery of synergistic inhibitors against E. coli and S. enterica serovar Typhimurium targeting a novel synthetic lethal pair, aldA and prpC

    DEFF Research Database (Denmark)

    Aziz, Ramy K.; Khaw, Valerie L.; Monk, Jonathan M.

    2015-01-01

    Mathematical models of biochemical networks form a cornerstone of bacterial systems biology. Inconsistencies between simulation output and experimental data point to gaps in knowledge about the fundamental biology of the organism. One such inconsistency centers on the gene aldA in Escherichia col...... discovery and their potential use to discover new combination antibiotics....

  8. Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse

    Directory of Open Access Journals (Sweden)

    Béringue Vincent

    2010-07-01

    Full Text Available Abstract Background The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages. Results Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal Prnp disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences. Conclusions These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.

  9. From variable to constant cell numbers: cellular characteristics of the arthropod nervous system argue against a sister-group relationship of Chelicerata and "Myriapoda" but favour the Mandibulata concept.

    Science.gov (United States)

    Harzsch, Steffen; Müller, Carsten H G; Wolf, Harald

    2005-02-01

    In the new debate on arthropod phylogeny, structure and development of the nervous system provide important arguments. The architecture of the brain of Hexapoda, Crustacea and Chelicerata in recent years has been thoroughly compared against an evolutionary background. However, comparative aspects of the nervous systems in these taxa at the cellular level have been examined in only a few studies. This review sets out to summarize these aspects and to analyse the existing data with respect to the concept of individually identifiable neurons. In particular, mechanisms of neurogenesis, the morphology of serotonergic interneurons, the number of motoneurons, and cellular features and development of the lateral eyes are discussed. We conclude that in comparison to the Mandibulata, in Chelicerata the numbers of neurons in the different classes examined are much higher and in many cases are not fixed but variable. The cell numbers in Mandibulata are lower and the majority of neurons are individually identifiable. The characters explored in this review are mapped onto an existing phylogram, as derived from brain architecture in which the Hexapoda are an in-group of the Crustacea, and there is not any conflict of the current data with such a phylogenetic position of the Hexapoda. Nevertheless, these characters argue against a sister-group relationship of "Myriapoda" and Chelicerata as has been recently suggested in several molecular studies, but instead provide strong evidence in favour of the Mandibulata concept.

  10. An evidence-based approach to the creation of normative data: base rates of impaired scores within a brief neuropsychological battery argue for age corrections, but against corrections for medical conditions.

    Science.gov (United States)

    O'Connell, Megan E; Tuokko, Holly; Voll, Stacey; Simard, Martine; Griffith, Lauren E; Taler, Vanessa; Wolfson, Christina; Kirkland, Susan; Raina, Parminder

    We detail a new approach to the creation of normative data for neuropsychological tests. The traditional approach to normative data creation is to make demographic adjustments based on observations of correlations between single neuropsychological tests and selected demographic variables. We argue, however, that this does not describe the implications for clinical practice, such as increased likelihood of misclassification of cognitive impairment, nor does it elucidate the impact on decision-making with a neuropsychological battery. We propose base rate analyses; specifically, differential base rates of impaired scores between theoretical and actual base rates as the basis for decisions to create demographic adjustments within normative data. Differential base rates empirically describe the potential clinical implications of failing to create an appropriate normative group. We demonstrate this approach with data from a short telephone-administered neuropsychological battery given to a large, neurologically healthy sample aged 45-85 years old. We explored whether adjustments for age and medical conditions were warranted based on differential base rates of spuriously impaired scores. Theoretical base rates underestimated the frequency of impaired scores in older adults and overestimated the frequency of impaired scores in younger adults, providing an evidence base for the creation of age-corrected normative data. In contrast, the number of medical conditions (numerous cardiovascular, hormonal, and metabolic conditions) was not related to differential base rates of impaired scores. Despite a small correlation between number of medical conditions and each neuropsychological variable, normative adjustments for number of medical conditions does not appear warranted. Implications for creation of normative data are discussed.

  11. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  12. Sequence Classification: 890604 [

    Lifescience Database Archive (English)

    Full Text Available scriptional coactivator SKIP, can activate transcription of a reporter gene; interacts with splicing factors Prp22p and Prp46p; Prp45p || http://www.ncbi.nlm.nih.gov/protein/6319287 ...

  13. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N. [University College London, Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom); Imperial College of Science, Technology and Medicine, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, London (United Kingdom); MacManus, D.G. [University College London, NMR Research Unit, Department of Clinical Neurology, Institute of Neurology, London (United Kingdom); Collinge, J. [University College London, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom)

    2006-06-15

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  14. How genes make up your mind

    DEFF Research Database (Denmark)

    Ramsøy, Thomas; Skov, Martin

    2010-01-01

    of drug-induced and genetically driven changes in neurotransmitter levels, and their effects on value-based decision-making. Following this, we argue that in healthy subjects, individual variance in decision behavior can be explained by such genetic factors, and gene-environment interactions. We suggest...

  15. Biological Implications of Gene-Environment Interaction

    Science.gov (United States)

    Rutter, Michael

    2008-01-01

    Gene-environment interaction (G x E) has been treated as both a statistical phenomenon and a biological reality. It is argued that, although there are important statistical issues that need to be considered, the focus has to be on the biological implications of G x E. Four reports of G x E deriving from the Dunedin longitudinal study are used as…

  16. Temporal and tissue specific regulation of RP-associated splicing factor genes PRPF3, PRPF31 and PRPC8--implications in the pathogenesis of RP.

    Directory of Open Access Journals (Sweden)

    Huibi Cao

    2011-01-01

    Full Text Available Genetic mutations in several ubiquitously expressed RNA splicing genes such as PRPF3, PRP31 and PRPC8, have been found to cause retina-specific diseases in humans. To understand this intriguing phenomenon, most studies have been focused on testing two major hypotheses. One hypothesis assumes that these mutations interrupt retina-specific interactions that are important for RNA splicing, implying that there are specific components in the retina interacting with these splicing factors. The second hypothesis suggests that these mutations have only a mild effect on the protein function and thus affect only the metabolically highly active cells such as retinal photoreceptors.We examined the second hypothesis using the PRPF3 gene as an example. We analyzed the spatial and temporal expression of the PRPF3 gene in mice and found that it is highly expressed in retinal cells relative to other tissues and its expression is developmentally regulated. In addition, we also found that PRP31 and PRPC8 as well as snRNAs are highly expressed in retinal cells.Our data suggest that the retina requires a relatively high level of RNA splicing activity for optimal tissue-specific physiological function. Because the RP18 mutation has neither a debilitating nor acute effect on protein function, we suggest that retinal degeneration is the accumulative effect of decades of suboptimal RNA splicing due to the mildly impaired protein.

  17. Evolutionary and Topological Properties of Genes and Community Structures in Human Gene Regulatory Networks.

    Science.gov (United States)

    Szedlak, Anthony; Smith, Nicholas; Liu, Li; Paternostro, Giovanni; Piermarocchi, Carlo

    2016-06-01

    The diverse, specialized genes present in today's lifeforms evolved from a common core of ancient, elementary genes. However, these genes did not evolve individually: gene expression is controlled by a complex network of interactions, and alterations in one gene may drive reciprocal changes in its proteins' binding partners. Like many complex networks, these gene regulatory networks (GRNs) are composed of communities, or clusters of genes with relatively high connectivity. A deep understanding of the relationship between the evolutionary history of single genes and the topological properties of the underlying GRN is integral to evolutionary genetics. Here, we show that the topological properties of an acute myeloid leukemia GRN and a general human GRN are strongly coupled with its genes' evolutionary properties. Slowly evolving ("cold"), old genes tend to interact with each other, as do rapidly evolving ("hot"), young genes. This naturally causes genes to segregate into community structures with relatively homogeneous evolutionary histories. We argue that gene duplication placed old, cold genes and communities at the center of the networks, and young, hot genes and communities at the periphery. We demonstrate this with single-node centrality measures and two new measures of efficiency, the set efficiency and the interset efficiency. We conclude that these methods for studying the relationships between a GRN's community structures and its genes' evolutionary properties provide new perspectives for understanding evolutionary genetics.

  18. gene structure, gene expression

    Indian Academy of Sciences (India)

    Primer 5.0 software. To adjust for RNA quality and diffe- rences in cDNA concentration, we amplified actin as an internal control with the following primers: PtActin-F (5′-TG. AAGGAGAAACTTGCGTAT-3′) and PtActin-R (5′-GCA. CAATGTTACCGTACAGAT-3′). These genes were ampli- fied from first-strand cDNA using ...

  19. Risk of ovarian cancer and inherited variants in relapse-associated genes.

    Directory of Open Access Journals (Sweden)

    Abraham Peedicayil

    Full Text Available BACKGROUND: We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk. METHODS AND FINDINGS: Women with and without invasive ovarian cancer (749 cases, 1,041 controls were genotyped at 136 single nucleotide polymorphisms (SNPs within 13 candidate genes. Risk was estimated for each SNP and for overall variation within each gene. At the gene-level, variation within MSL1 (male-specific lethal-1 homolog was associated with risk of serous cancer (p = 0.03; haplotypes within PRPF31 (PRP31 pre-mRNA processing factor 31 homolog were associated with risk of invasive disease (p = 0.03. MSL1 rs7211770 was associated with decreased risk of serous disease (OR 0.81, 95% CI 0.66-0.98; p = 0.03. SNPs in MFSD7, BTN3A3, ZNF200, PTPRS, and CCND1A were inversely associated with risk (p<0.05, and there was increased risk at HEXIM1 rs1053578 (p = 0.04, OR 1.40, 95% CI 1.02-1.91. CONCLUSIONS: Tumor studies can reveal novel genes worthy of follow-up for cancer susceptibility. Here, we found that inherited markers in the gene encoding MSL1, part of a complex that modifies the histone H4, may decrease risk of invasive serous ovarian cancer.

  20. Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age Estudo de viabilidade de imunogenicidade e segurança de uma nova vacina brasileira combinada DTPw/Hib (PRP-T, comparada com uma vacina registrada, em crianças de 2, 4 e 6 meses de idade

    Directory of Open Access Journals (Sweden)

    SueAnn Costa Clemens

    2003-06-01

    Full Text Available Vaccination of infants with conjugated Haemophilus influenzae type b (Hib vaccines has been proven to reduce Hib meningitis by 95% and pneumoniae by 20%. The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI (Expanded Plan of Immunization. The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib (diphtheria-tetanus-whole cell pertussis combination, using the technology of two Brazilian manufacturers, against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2, 4 and 6 months according to the local national schedule. The Brazilian combination was highly immunogenic with Hib seroprotection rates (anti-PRP > 0.15 mg /ml of 98% after 2 doses and 100% after 3. Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart, except the diphtheria seroprotection rates and titers were lower. There was also no clinically relevant difference in reactogenicity. If these feasibility results are confirmed, the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil.A vacinação contra (Haemophilus influenzae tipo b (Hib, utilizando vacinas conjugadas, provou reduzir em 95% os casos de meningite e em 20% as pneumonias por Hib. O uso rotineiro da vacina Hib foi facilitado pela introdução das vacinas combinadas no Programa Ampliado de Imunização (PAI. O objetivo deste estudo foi comparar a imunogenicidade e reatogenicidade da mistura extemporânea da vacina combinada contra difteria-tétano-pertussis de células inteiras/Haemophilus influenzae (DTPw/Hib, de tecnologia e produção de 2 fabricantes brasileiros, à vacina européia registrada DTPw/Hib. Estudo realizado em 108 crianças em idade de 2, 4 e 6 meses, seguindo o esquema nacional de imunização. A vacina combinada brasileira foi altamente imunogênica, apresentando taxas de soroprote

  1. PRP and Articular Cartilage: A Clinical Update

    National Research Council Canada - National Science Library

    Marmotti, Antonio; Rossi, Roberto; Castoldi, Filippo; Roveda, Eliana; Michielon, Gianni; Peretti, Giuseppe M

    2015-01-01

      The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis...

  2. Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.

    Science.gov (United States)

    Uchiyama, Keiji; Miyata, Hironori; Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

    2014-01-01

    Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc.

  3. Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF).

    Science.gov (United States)

    Dohan Ehrenfest, David M; Bielecki, Tomasz; Jimbo, Ryo; Barbé, Giovanni; Del Corso, Marco; Inchingolo, Francesco; Sammartino, Gilberto

    2012-06-01

    Platelet concentrates for surgical use are tools of regenerative medicine designed for the local release of platelet growth factors into a surgical or wounded site, in order to stimulate tissue healing or regeneration. Leukocyte content and fibrin architecture are 2 key characteristics of all platelet concentrates and allow to classify these technologies in 4 families, but very little is known about the impact of these 2 parameters on the intrinsic biology of these products. In this demonstration, we highlight some outstanding differences in the growth factor and matrix protein release between 2 families of platelet concentrate: Pure Platelet-Rich Plasma (P-PRP, here the Anitua's PRGF - Preparation Rich in Growth Factors - technique) and Leukocyte- and Platelet-Rich Fibrin (L-PRF, here the Choukroun's method). These 2 families are the extreme opposites in terms of fibrin architecture and leukocyte content. The slow release of 3 key growth factors (Transforming Growth Factor β1 (TGFβ1), Platelet-Derived Growth Factor AB (PDGF-AB) and Vascular Endothelial Growth Factor (VEGF)) and matrix proteins (fibronectin, vitronectin and thrombospondin-1) from the L-PRF and P-PRP gel membranes in culture medium is described and discussed. During 7 days, the L-PRF membranes slowly release significantly larger amounts of all these molecules than the P-PRP gel membranes, and the 2 products display different release patterns. In both platelet concentrates, vitronectin is the sole molecule to be released almost completely after only 4 hours, suggesting that this molecule is not trapped in the fibrin matrix and not produced by the leukocytes. Moreover the P-PRP gel membranes completely dissolve in the culture medium after less than 5 days only, while the L-PRF membranes are still intact after 7 days. This simple demonstration shows that the polymerization and final architecture of the fibrin matrix considerably influence the strength and the growth factor trapping/release potential

  4. Gene Locater

    DEFF Research Database (Denmark)

    Anwar, Muhammad Zohaib; Sehar, Anoosha; Rehman, Inayat-Ur

    2012-01-01

    UNLABELLED: Locating genes on a chromosome is important for understanding the gene function and its linkage and recombination. Knowledge of gene positions on chromosomes is necessary for annotation. The study is essential for disease genetics and genomics, among other aspects. Currently available...... software's for calculating recombination frequency is mostly limited to the range and flexibility of this type of analysis. GENE LOCATER is a fully customizable program for calculating recombination frequency, written in JAVA. Through an easy-to-use interface, GENE LOCATOR allows users a high degree...

  5. Autobiographical reasoning: arguing and narrating from a biographical perspective.

    Science.gov (United States)

    Habermas, Tilmann

    2011-01-01

    Autobiographical reasoning is the activity of creating relations between different parts of one's past, present, and future life and one's personality and development. It embeds personal memories in a culturally, temporally, causally, and thematically coherent life story. Prototypical autobiographical arguments are presented. Culture and socializing interactions shape the development of autobiographical reasoning especially in late childhood and adolescence. Situated at the intersection of cognitive and narrative development and autobiographical memory, autobiographical reasoning contributes to the development of personality and identity, is instrumental in efforts to cope with life events, and helps to create a shared history. Copyright © 2011 Wiley Periodicals, Inc., A Wiley Company.

  6. Eliminative Argumentation: A Basis for Arguing Confidence in System Properties

    Science.gov (United States)

    2015-02-01

    Walton, D. “The Carneades Argumentation Framework,” 195–207. Proceedings from COMMA 󈧊: Computational Models of Argument. Edited by P. E. Dunne & T. J...1997] Groarke, L. A., Tindale, C. W., & Fisher, L. Good Reasoning Matters! A Constructive Approach to Critical Thinking. Oxford University Press

  7. ArgueSecure: Out-of-the-box Risk Assessment

    NARCIS (Netherlands)

    Ionita, Dan; Kegel, Roeland Hendrik,Pieter; Wieringa, Roelf J.; Baltuta, Andrei

    Most established security risk assessment methodologies aim to produce ranked lists of risks. But ranking requires quantification of risks, which in turn relies on data which may not be available or estimations which might not be accurate. As an alternative, we have previously proposed

  8. Arguing for a Contextual Approach to European Media Education Research

    Directory of Open Access Journals (Sweden)

    Hans Martens

    2012-12-01

    Full Text Available In this article, we focus on how various historical, contextual, and idiosyncratic factors shape the aims and methods of current European media educational practice. We start by briefly situating the history of European media education research and policymaking. We then discuss in more detail three important strands of media literacy initiatives within the Flemish Community (Belgium. While each of these diverging types of media education partly mirrors broader trends in European media research and policymaking, their aims and instructional methods also reveal the specificity of the Flemish media literacy context. In our discussion, we draw upon these findings to pinpoint a number of key determinants which may help to better understand similarities and differences within the European Union.

  9. Leo Szilard Lectureship Award: Arguing from the Periphery

    Science.gov (United States)

    Ramana, M. V.

    2014-03-01

    In today's societies, where the use of sophisticated and potentially dangerous technologies has become routine and where economic and political power require the constant invention and deployment of new technologies, meaningful democratization necessarily requires that people with expertise on these subjects intervene actively in the public interest, speaking truth to power as it were. There is a long history of such intervention by scientists, physicists in particular, in debates over nuclear policies in many countries around the world. This talk will explore different roles scientists have played in this contentious and disputed arena, with some recent examples from India.

  10. Taking religious pluralism seriously: arguing for an institutional turn: introduction

    NARCIS (Netherlands)

    Bader, V.M.

    2003-01-01

    Discussions of the relations between religions, society, politics, and the state in recent political philosophy are characterized, firstly, by a strong US American bias focusing on limitations of religious arguments in public debate. Even if the restriction or radical exclusion of religious reasons

  11. Arguing for Computer Science in the school curriculum

    NARCIS (Netherlands)

    Fluck, A.; Webb, M.; Cox, M.; Angeli, C.; Malyn-Smith, J.; Voogt, J.; Zagami, J.

    2016-01-01

    Computer science has been a discipline for some years, and its position in the school curriculum has been contested differently in several countries. This paper looks at its role in three countries to illustrate these differences. A reconsideration of computer science as a separate subject both in

  12. Arguing about desirable consequences: what constitutes a convincing argument?

    NARCIS (Netherlands)

    Hoeken, Hans; Timmers, R.H.M.; Schellens, P.J.

    2012-01-01

    Argument quality has consistently been shown to have strong and lasting persuasive effects. The question is what criteria people use to distinguish strong from weak arguments and how these criteria relate to the ones proposed in normative argumentation theory. In an experiment 235 participants

  13. Arguing for Computer Science in the School Curriculum

    Science.gov (United States)

    Fluck, Andrew; Webb, Mary; Cox, Margaret; Angeli, Charoula; Malyn-Smith, Joyce; Voogt, Joke; Zagami, Jason

    2016-01-01

    Computer science has been a discipline for some years, and its position in the school curriculum has been contested differently in several countries. This paper looks at its role in three countries to illustrate these differences. A reconsideration of computer science as a separate subject both in primary and secondary education is suggested. At…

  14. OpenArgue: Supporting Argumentation to Evolve Secure Software Systems

    NARCIS (Netherlands)

    Yu, Yijun; Tun, Thein Tan; Tedeschi, Alessandra; Nunes Leal Franqueira, V.; Nuseibeh, Bashar

    When software systems are verified against security requirements, formal and informal arguments provide a structure for organizing the software artifacts. Our recent work on the evolution of security-critical software systems demonstrates that our argumentation technique is useful in limiting the

  15. Patents to "treat me", no patents to "test me": an analysis of the 2009 Senate inquiry into gene patents.

    Science.gov (United States)

    Triffett, Damian

    2010-05-01

    This article critically analyses the submissions to the Senate Community Affairs Committee Inquiry into Gene Patents. It argues that gene patents are essential for attracting the investment required to ensure therapeutics based on gene technology reach the patient (patents to "treat me"). However, due to the lower costs of development, it argues that gene patent incentive is not required to ensure patient access to genetic testing services (no patents to "test me"). The article recommends that gene patents should not be prohibited by an amendment of the Patents Act 1990 (Cth), rather that regulation should occur post-grant to ensure patented technology is broadly licensed.

  16. Queer Genes: Realism, Sexuality and Science.

    Science.gov (United States)

    Griffiths, David Andrew

    2016-10-19

    What are 'gay genes' and are they real? This article looks at key research into these hypothesized gay genes, made possible, in part, by the Human Genome Project. I argue that the complexity of both genetics and human sexuality demands a truly critical approach: one that takes into account feminist epistemologies of science and queer approaches to the body, while putting into conversation resources from agential realism and critical realism. This approach is able to maintain the agential complexity of genetic materiality, while also critically challenging the seemingly stable relationships between sex, gender and sexuality.

  17. Trichoderma genes

    Science.gov (United States)

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  18. Observations Suggesting Allelism of the Achondroplasia and Hypochondroplasia Genes

    Science.gov (United States)

    McKusick, Victor A.; Kelly, Thaddeus E.; Dorst, John P.

    1973-01-01

    It is argued that there are at least two alleles at the achondroplasia locus: one responsible for classic achondroplasia and one responsible for hypochondroplasia. Homozygosity for the achondroplasia gene produces a lethal skeletal dysplasia; homozygosity for hypochondroplasia has not been described. We report here a child considered to be a genetic compound for the achondroplasia and hypochondroplasia alleles. Images PMID:4697848

  19. Gene Therapy

    Science.gov (United States)

    ... or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Researchers are still studying how and ...

  20. Implicit hype? Representations of platelet rich plasma in the news media

    Science.gov (United States)

    2017-01-01

    Platelet Rich Plasma (PRP) has gained popularity in recent years for treating sports-related injuries and the news media frequently reports on elite athletes’ and celebrities’ use of PRP. We conducted a content analysis of newspaper coverage of PRP in Australia, Canada, Ireland, New Zealand, United Kingdom, and the United States. Findings show that news media coverage of PRP appears most frequently in sports-related stories, and in relation to elite athletes use of PRP. PRP injections are largely portrayed as a routine treatment for sports-related injuries and newspaper articles rarely discuss the limitations or efficacy of PRP. We argue that while news media coverage of PRP exhibits very few common hallmarks of hype, its portrayal as a routine treatment used by elite athletes and celebrities creates an implicit hype. This implicit hype can contribute to public misunderstandings of the efficacy of PRP. PMID:28792974

  1. Implicit hype? Representations of platelet rich plasma in the news media.

    Directory of Open Access Journals (Sweden)

    Christen Rachul

    Full Text Available Platelet Rich Plasma (PRP has gained popularity in recent years for treating sports-related injuries and the news media frequently reports on elite athletes' and celebrities' use of PRP. We conducted a content analysis of newspaper coverage of PRP in Australia, Canada, Ireland, New Zealand, United Kingdom, and the United States. Findings show that news media coverage of PRP appears most frequently in sports-related stories, and in relation to elite athletes use of PRP. PRP injections are largely portrayed as a routine treatment for sports-related injuries and newspaper articles rarely discuss the limitations or efficacy of PRP. We argue that while news media coverage of PRP exhibits very few common hallmarks of hype, its portrayal as a routine treatment used by elite athletes and celebrities creates an implicit hype. This implicit hype can contribute to public misunderstandings of the efficacy of PRP.

  2. Implicit hype? Representations of platelet rich plasma in the news media.

    Science.gov (United States)

    Rachul, Christen; Rasko, John E J; Caulfield, Timothy

    2017-01-01

    Platelet Rich Plasma (PRP) has gained popularity in recent years for treating sports-related injuries and the news media frequently reports on elite athletes' and celebrities' use of PRP. We conducted a content analysis of newspaper coverage of PRP in Australia, Canada, Ireland, New Zealand, United Kingdom, and the United States. Findings show that news media coverage of PRP appears most frequently in sports-related stories, and in relation to elite athletes use of PRP. PRP injections are largely portrayed as a routine treatment for sports-related injuries and newspaper articles rarely discuss the limitations or efficacy of PRP. We argue that while news media coverage of PRP exhibits very few common hallmarks of hype, its portrayal as a routine treatment used by elite athletes and celebrities creates an implicit hype. This implicit hype can contribute to public misunderstandings of the efficacy of PRP.

  3. Medea genes, handedness and other traits

    Science.gov (United States)

    Hatfield, Jeffrey

    2015-01-01

    Medea factors or genes are maternal-effects mechanisms, found in many species, in which the mother's body selectively kills embryos of a certain genotype.Humans have a similar genetic mechanism, the gene RHD which produces Rh-factor involved in blood type.Recently I proposed that RHD acts as a maternal-effects gene that determines handedness (i.e., right handed or non-right handed) in individuals of our species. Here, I argue that RHD functions as a Medea gene as well.The handedness gene (and also RHD itself in some cases) has been implicated in autism spectrum disorders (ASD), bipolar disorder, cerebral laterality (i.e., right-brained or left-brained speech laterality), hair-whorl rotation, schizophrenia, sexual orientation, and speech dyslexia.Identifying the gene or genes that determine handedness or cerebral laterality may help uncover the mechanisms underlying these behavioral phenotypes in our species.A relatively simple test of the handedness hypothesis has been proposed:In a sample of humans for whom handedness has been evaluated, we would need to genotype for RHD by determining whether Rh+ individuals have one or two copies of the dominant allele. If RHD and perhaps also an interaction with RHCE are involved in sexual orientation, it explains how selection could favor a gene or genes which cause some people to become non-heterosexual.The literature on Medea genes provides the explanation:A Medea allele must increase in frequency, sometimes to fixation (i.e., 100% frequency) even if it reduces fecundity (e.g., birth rate).In addition, treatment for RHD maternal-fetal genotype incompatibility, which allows more fetuses to survive to term now, may be one explanation for why ASD appears to be increasing in frequency in some populations, if RHD is indeed the handedness gene, although many other mechanisms have also been suggested. One wonders if bipolar disorder and the other alternative phenotypes are also increasing in frequency.

  4. The use of genes for performance enhancement: doping or therapy?

    Directory of Open Access Journals (Sweden)

    R.S. Oliveira

    2011-12-01

    Full Text Available Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM to enhance athletic performance. In such ‘gene doping’, exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO, vascular endothelial growth factor (VEGF, insulin-like growth factor type 1 (IGF-1, myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping.

  5. Genetic predictions of prion disease susceptibility in carnivore species based on variability of the prion gene coding region.

    Directory of Open Access Journals (Sweden)

    Paula Stewart

    Full Text Available Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE during the bovine spongiform encephalopathy (BSE epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD remains an open question. Variation in the host-encoded prion protein (PrP(C largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrP(C protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo and pine marten (Martes martes were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus and mountain lion (Puma concolor from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter.

  6. Genetic predictions of prion disease susceptibility in carnivore species based on variability of the prion gene coding region.

    Science.gov (United States)

    Stewart, Paula; Campbell, Lauren; Skogtvedt, Susan; Griffin, Karen A; Arnemo, Jon M; Tryland, Morten; Girling, Simon; Miller, Michael W; Tranulis, Michael A; Goldmann, Wilfred

    2012-01-01

    Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE) during the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD) remains an open question. Variation in the host-encoded prion protein (PrP(C)) largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrP(C) protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo) and pine marten (Martes martes) were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus) and mountain lion (Puma concolor) from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter.

  7. Gene Ontology

    Directory of Open Access Journals (Sweden)

    Gaston K. Mazandu

    2012-01-01

    Full Text Available The wide coverage and biological relevance of the Gene Ontology (GO, confirmed through its successful use in protein function prediction, have led to the growth in its popularity. In order to exploit the extent of biological knowledge that GO offers in describing genes or groups of genes, there is a need for an efficient, scalable similarity measure for GO terms and GO-annotated proteins. While several GO similarity measures exist, none adequately addresses all issues surrounding the design and usage of the ontology. We introduce a new metric for measuring the distance between two GO terms using the intrinsic topology of the GO-DAG, thus enabling the measurement of functional similarities between proteins based on their GO annotations. We assess the performance of this metric using a ROC analysis on human protein-protein interaction datasets and correlation coefficient analysis on the selected set of protein pairs from the CESSM online tool. This metric achieves good performance compared to the existing annotation-based GO measures. We used this new metric to assess functional similarity between orthologues, and show that it is effective at determining whether orthologues are annotated with similar functions and identifying cases where annotation is inconsistent between orthologues.

  8. Communicative genes in the evolution of empathy and altruism.

    Science.gov (United States)

    Buck, Ross

    2011-11-01

    This paper discusses spontaneous communication and its implications for understanding empathy and altruism. The question of the possibility of "true" altruism-giving up one's genetic potential in favor of the genetic potential of another-is a fundamental issue common to the biological, behavioral, and social sciences. Darwin regarded "social instincts and sympathies" to be critical to the social order, but the possibility of biologically-based prosocial motives and emotions was questioned when selection was interpreted as operating at the level of the gene. In the selfish gene hypothesis, Dawkins argued that the unit of evolutionary selection must be an active, germ-line replicator: a unit whose activities determine whether copies of it are made across evolutionary timescales. He argued that the only active replicator existing across evolutionary timescales is the gene, so that the "selfish gene" is a replicator motivated only to make copies of itself. The communicative gene hypothesis notes that genes function by communicating, and the phenotype communication involves not only the individual sending and receiving abilities of the individual genes involved, but also the relationship between them relative to other genes. Therefore the selection of communication as phenotype involves the selection of individual genes and also their relationship. Relationships become replicators, and are selected across evolutionary timescales including social relationships (e.g., sex, nurturance, dominance-submission). An interesting implication of this view: apparent altruism has been interpreted by selfish gene theorists as due to kin selection and reciprocity, in which the survival of kin and comrade indirectly favor the genetic potential of the altruist. From the viewpoint of the communicative gene hypothesis, rather than underlying altruism, kin selection and reciprocity are ways of restricting altruism to kin and comrade: they are mechanisms not of altruism but of xenophobia.

  9. How Genes Make up Your Mind

    DEFF Research Database (Denmark)

    Ramsøy, Thomas Z.; Skov, Martin

    2010-01-01

    , a recent approach in cognitive neuroscience, often referred to as "imaging genetics", promises to make significant contributions to our understanding of both behavioral and neural aspects of value-based decision-making. Recent work has demonstrated the role of neurotransmitter alterations in clinical...... of drug-induced and genetically driven changes in neurotransmitter levels, and their effects on value-based decision-making. Following this, we argue that in healthy subjects, individual variance in decision behavior can be explained by such genetic factors, and gene-environment interactions. We suggest...

  10. Kinetic proofreading of chromatin remodeling: from gene activation to gene repression and back

    Directory of Open Access Journals (Sweden)

    Raghvendra P Singh

    2015-08-01

    Full Text Available ATP-dependent chromatin remodeling is the active displacement of nucleosomes along or off DNA induced by chromatin remodeling complexes. This key process of gene regulation in eukaryote organisms has recently been argued to be controlled by a kinetic proofreading mechanism. In this paper we present a discussion of the current understanding of this process. We review the case of gene repression via heterochromatin formation by remodelers from the ISWI family and then discuss the activation of the IFN-β gene, where the displacement of the nucleosome is initiated by histone tail acetylations by the enzyme GCN5 which are required for the recruitment of SWI-SNF remodelers. We quantify the speci city of the acetylation step in the remodeling process by peptide docking simulations.

  11. Possible Links among Mirror Neurons and Genes Related to Autism

    OpenAIRE

    Mochizuki, Mai; 望月,麻衣

    2016-01-01

    Autism includes many neurodevelopmental disorders and defi cits in communication. Althoughresearchers have considered various origins, the onset mechanism is still not clear. The aim ofthis article is to provide some clues for interaction of autism with mirror neuronal and geneticfactors. First, the impact of neural brain cells considered to infl uence autism will be discussedwith reference to mirror neurons. Then, the discussion will move to genes related to autism.Consequently, it is argued...

  12. Different Type 1 Fimbrial Genes and Tropisms of Commensal and Potentially Pathogenic Actinomyces spp. with Different Salivary Acidic Proline-Rich Protein and Statherin Ligand Specificities

    Science.gov (United States)

    Li, Tong; Khah, Massoud Kheir; Slavnic, Snjezana; Johansson, Ingegerd; Strömberg, Nicklas

    2001-01-01

    Actinomyces spp. exhibit type 1 fimbria-mediated adhesion to salivary acidic proline-rich proteins (PRPs) and statherin ligands. Actinomyces spp. with different animal and tissue origins belong to three major adhesion types as relates to ligand specificity and type 1 fimbria genes. (i) In preferential acidic-PRP binding, strains of Actinomyces naeslundii genospecies 1 and 2 from human and monkey mouths displayed at least three ligand specificities characterized by preferential acidic-PRP binding. Slot blot DNA hybridization showed seven highly conserved type 1 fimbria genes (orf1- to -6 and fimP) in genospecies 1 and 2 strains, except that orf5 and orf3 were divergent in genospecies 1. (ii) In preferential statherin binding, oral Actinomyces viscosus strains of rat and hamster origin (and strain 19246 from a human case of actinomycosis) bound statherin preferentially. DNA hybridization and characterization of the type 1 fimbria genes from strain 19246 revealed a homologous gene cluster of four open reading frames (orfA to -C and fimP). Bioinformatics suggested sortase (orfB, orf4, and part of orf5), prepilin peptidase (orfC and orf6), fimbria subunit (fimP), and usher- and autotransporter-like (orfA and orf1 to -3) functions. Those gene regions corresponding to orf3 and orf5 were divergent, those corresponding to orf2, orf1, and fimP were moderately conserved, and those corresponding to orf4 and orf6 were highly conserved. Restriction fragment length polymorphism analyses using a fimP probe separated human and monkey and rat and hamster strains into phylogenetically different groups. (iii) In statherin-specific binding, strains of A. naeslundii genospecies 1 from septic and other human infections displayed a low-avidity binding to statherin. Only the orf4 and orf6 gene regions were highly conserved. Finally, rat saliva devoid of statherin bound bacterial strains avidly irrespective of ligand specificity, and specific antisera detected either type 1, type 2, or both

  13. Evolution and differential expression of a vertebrate vitellogenin gene cluster

    Directory of Open Access Journals (Sweden)

    Kongshaug Heidi

    2009-01-01

    Full Text Available Abstract Background The multiplicity or loss of the vitellogenin (vtg gene family in vertebrates has been argued to have broad implications for the mode of reproduction (placental or non-placental, cleavage pattern (meroblastic or holoblastic and character of the egg (pelagic or benthic. Earlier proposals for the existence of three forms of vertebrate vtgs present conflicting models for their origin and subsequent duplication. Results By integrating phylogenetics of novel vtg transcripts from old and modern teleosts with syntenic analyses of all available genomic variants of non-metatherian vertebrates we identify the gene orthologies between the Sarcopterygii (tetrapod branch and Actinopterygii (fish branch. We argue that the vertebrate vtg gene cluster originated in proto-chromosome m, but that vtg genes have subsequently duplicated and rearranged following whole genome duplications. Sequencing of a novel fourth vtg transcript in labrid species, and the presence of duplicated paralogs in certain model organisms supports the notion that lineage-specific gene duplications frequently occur in teleosts. The data show that the vtg gene cluster is more conserved between acanthomorph teleosts and tetrapods, than in ostariophysan teleosts such as the zebrafish. The differential expression of the labrid vtg genes are further consistent with the notion that neofunctionalized Aa-type vtgs are important determinants of the pelagic or benthic character of the eggs in acanthomorph teleosts. Conclusion The vertebrate vtg gene cluster existed prior to the separation of Sarcopterygii from Actinopterygii >450 million years ago, a period associated with the second round of whole genome duplication. The presence of higher copy numbers in a more highly expressed subcluster is particularly prevalent in teleosts. The differential expression and latent neofunctionalization of vtg genes in acanthomorph teleosts is an adaptive feature associated with oocyte hydration

  14. Diversity and population-genetic properties of copy number variations and multicopy genes in cattle.

    Science.gov (United States)

    Bickhart, Derek M; Xu, Lingyang; Hutchison, Jana L; Cole, John B; Null, Daniel J; Schroeder, Steven G; Song, Jiuzhou; Garcia, Jose Fernando; Sonstegard, Tad S; Van Tassell, Curtis P; Schnabel, Robert D; Taylor, Jeremy F; Lewin, Harris A; Liu, George E

    2016-06-01

    The diversity and population genetics of copy number variation (CNV) in domesticated animals are not well understood. In this study, we analysed 75 genomes of major taurine and indicine cattle breeds (including Angus, Brahman, Gir, Holstein, Jersey, Limousin, Nelore, and Romagnola), sequenced to 11-fold coverage to identify 1,853 non-redundant CNV regions. Supported by high validation rates in array comparative genomic hybridization (CGH) and qPCR experiments, these CNV regions accounted for 3.1% (87.5 Mb) of the cattle reference genome, representing a significant increase over previous estimates of the area of the genome that is copy number variable (∼2%). Further population genetics and evolutionary genomics analyses based on these CNVs revealed the population structures of the cattle taurine and indicine breeds and uncovered potential diversely selected CNVs near important functional genes, including AOX1, ASZ1, GAT, GLYAT, and KRTAP9-1 Additionally, 121 CNV gene regions were found to be either breed specific or differentially variable across breeds, such as RICTOR in dairy breeds and PNPLA3 in beef breeds. In contrast, clusters of the PRP and PAG genes were found to be duplicated in all sequenced animals, suggesting that subfunctionalization, neofunctionalization, or overdominance play roles in diversifying those fertility-related genes. These CNV results provide a new glimpse into the diverse selection histories of cattle breeds and a basis for correlating structural variation with complex traits in the future. Published by Oxford University Press on behalf of Kazusa DNA Research Institute 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. Manipulating the Prion Protein Gene Sequence and Expression Levels with CRISPR/Cas9

    National Research Council Canada - National Science Library

    Kaczmarczyk, Lech; Mende, Ylva; Zevnik, Branko; Jackson, Walker S

    2016-01-01

    The mammalian prion protein (PrP, encoded by Prnp) is most infamous for its central role in prion diseases, invariably fatal neurodegenerative diseases affecting humans, food animals, and animals in the wild...

  16. Single-cell epigenomics: powerful new methods for understanding gene regulation and cell identity.

    Science.gov (United States)

    Clark, Stephen J; Lee, Heather J; Smallwood, Sébastien A; Kelsey, Gavin; Reik, Wolf

    2016-04-18

    Emerging single-cell epigenomic methods are being developed with the exciting potential to transform our knowledge of gene regulation. Here we review available techniques and future possibilities, arguing that the full potential of single-cell epigenetic studies will be realized through parallel profiling of genomic, transcriptional, and epigenetic information.

  17. REGULATION OF GENE EXPRESSION IN THE GENOMIC CONTEXT

    Directory of Open Access Journals (Sweden)

    Taylor J Atkinson

    2014-01-01

    Full Text Available Metazoan life is dependent on the proper temporal and spatial control of gene expression within the many cells—essentially all with the identical genome—that make up the organism. While much is understood about how individual gene regulatory elements function, many questions remain about how they interact to maintain correct regulation globally throughout the genome. In this review we summarize the basic features and functions of the crucial regulatory elements promoters, enhancers, and insulators and discuss some of the ways in which proper interactions between these elements is realized. We focus in particular on the role of core promoter sequences and propose explanations for some of the contradictory results seen in experiments aimed at understanding insulator function. We suggest that gene regulation depends on local genomic context and argue that more holistic in vivo investigations that take into account multiple local features will be necessary to understand how genome-wide gene regulation is maintained.

  18. Special Issue: Gene Conversion in Duplicated Genes

    Directory of Open Access Journals (Sweden)

    Hideki Innan

    2011-06-01

    Full Text Available Gene conversion is an outcome of recombination, causing non-reciprocal transfer of a DNA fragment. Several decades later than the discovery of crossing over, gene conversion was first recognized in fungi when non-Mendelian allelic distortion was observed. Gene conversion occurs when a double-strand break is repaired by using homologous sequences in the genome. In meiosis, there is a strong preference to use the orthologous region (allelic gene conversion, which causes non-Mendelian allelic distortion, but paralogous or duplicated regions can also be used for the repair (inter-locus gene conversion, also referred to as non-allelic and ectopic gene conversion. The focus of this special issue is the latter, interlocus gene conversion; the rate is lower than allelic gene conversion but it has more impact on phenotype because more drastic changes in DNA sequence are involved.

  19. Proinflammatory and Anabolic Gene Expression Effects of Platelet-Rich Gel Supernatants on Equine Synovial Membrane Explants Challenged with Lipopolysaccharide.

    Science.gov (United States)

    Carmona, Jorge U; Ríos, Diana L; López, Catalina; Álvarez, María E; Pérez, Jorge E

    2017-01-01

    Platelet-rich plasma (PRP) preparations are used in horses with osteoarthritis (OA). However, some controversies remain regarding the ideal concentration of platelets and leukocytes to produce an adequate anti-inflammatory and anabolic response in the synovial membrane. The aims of this study were to study the influence of leukoconcentrated platelet-rich gel (Lc-PRG) and leukoreduced platelet-rich gel (Lr-PRG) supernatants on the quantitative expression of some proinflammatory and anabolic genes in equine synovial membrane explants (SMEs) challenged with lipopolysaccharide (LPS). SMEs from six horses were cultured over 96 h. Then, SMEs were harvested for RNA extraction and quantitative gene expression analysis by RT-qPCR for nuclear factor kappa B (NFκB), matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), collagen type I alpha 1 (COL1A1), collagen type II alpha 1 (COL2A1), and cartilage oligomeric matrix protein (COMP). The 25% and 50% Lc-PRG supernatants led to downregulation of NFκB, MMP-13, ADAMTS-4, COL1A1, COL2A1, and COMP in SMEs. Lr-PRG supernatants (particularly at the 50% concentration) induced downregulation of NFκB, MMP-13, ADAMTS-4, and COL1A1 and upregulation of COL2A1 and COMP. Lr-PRG supernatants should be used for the treatment of inflammatory arthropathies in horses because they have anti-inflammatory and anabolic effects in the synovial membrane.

  20. Simultaneous expression of regulatory genes associated with specific drought-adaptive traits improves drought adaptation in peanut.

    Science.gov (United States)

    Ramu, Vemanna S; Swetha, Thavarekere N; Sheela, Shekarappa H; Babitha, Chandrashekar K; Rohini, Sreevathsa; Reddy, Malireddy K; Tuteja, Narendra; Reddy, Chandrashekar P; Prasad, Trichi Ganesh; Udayakumar, Makarla

    2016-03-01

    Adaptation of crops to drought-prone rain-fed conditions can be achieved by improving plant traits such as efficient water mining (by superior root characters) and cellular-level tolerance mechanisms. Pyramiding these drought-adaptive traits by simultaneous expression of genes regulating drought-adaptive mechanisms has phenomenal relevance in improving stress tolerance. In this study, we provide evidence that peanut transgenic plants expressing Alfalfa zinc finger 1 (Alfin1), a root growth-associated transcription factor gene, Pennisetum glaucum heat-shock factor (PgHSF4) and Pea DNA helicase (PDH45) involved in protein turnover and protection showed improved tolerance, higher growth and productivity under drought stress conditions. Stable integration of all the transgenes was noticed in transgenic lines. The transgenic lines showed higher root growth, cooler crop canopy air temperature difference (less CCATD) and higher relative water content (RWC) under drought stress. Low proline levels in transgenic lines substantiate the maintenance of higher water status. The survival and recovery of transgenic lines was significantly higher under gradual moisture stress conditions with higher biomass. Transgenic lines also showed significant tolerance to ethrel-induced senescence and methyl viologen-induced oxidative stress. Several stress-responsive genes such as heat-shock proteins (HSPs), RING box protein-1 (RBX1), Aldose reductase, late embryogenesis abundant-5 (LEA5) and proline-rich protein-2 (PRP2), a gene involved in root growth, showed enhanced expression under stress in transgenic lines. Thus, the simultaneous expression of regulatory genes contributing for drought-adaptive traits can improve crop adaptation and productivity under water-limited conditions. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  1. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.

    2003-01-01

    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...

  2. Intratendon Delivery of Leukocyte-Poor Platelet-Rich Plasma Improves Healing Compared With Leukocyte-Rich Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model.

    Science.gov (United States)

    Yan, Ruijian; Gu, Yanjia; Ran, Jisheng; Hu, Yejun; Zheng, Zefeng; Zeng, Mengfeng; Heng, Boon Chin; Chen, Xiao; Yin, Zi; Chen, Weishan; Shen, Weiliang; Ouyang, Hongwei

    2017-07-01

    Chronic tendinopathy is a commonly occurring clinical problem that affects both athletes and inactive middle-aged patients. Although some studies have shown that different platelet-rich plasma (PRP) preparations could exert various therapeutic effects in vitro, the role of leukocytes in PRP has not yet been defined under tendinopathy conditions in vivo. This study compared the effects of the intratendon delivery of leukocyte-poor PRP (Lp-PRP) versus leukocyte-rich PRP (Lr-PRP) in a rabbit chronic tendinopathy model in vivo. Controlled laboratory study. Four weeks after a local injection of collagenase in the Achilles tendon, the following treatments were randomly administered on the lesions: injections of (1) 200 μL of Lp-PRP (n = 8), (2) 200 μL of Lr-PRP (n = 8), or (3) 200 μL of saline (n = 8). Healing outcomes were assessed at 4 weeks after therapy with magnetic resonance imaging (MRI), cytokine quantification, real-time polymerase chain reaction analysis of gene expression, histology, and transmission electron microscopy (TEM). MRI revealed that the Lr-PRP and saline groups displayed higher signal intensities compared with the Lp-PRP group with T2 mapping. Histologically, the Lp-PRP group displayed significantly better general scores compared with the Lr-PRP ( P = .001) and saline ( P < .001) groups. Additionally, TEM showed that the Lp-PRP group had larger collagen fibril diameters than the Lr-PRP group ( P < .001). Enzyme-linked immunosorbent assay showed a significantly lower level of catabolic cytokine IL-6 in the Lp-PRP group compared with the Lr-PRP ( P = .001) and saline ( P = .021) groups. The Lp-PRP group displayed significantly increased expression of collagen I compared with the saline group ( P = .004) but not the Lr-PRP group. Both the Lp-PRP and Lr-PRP groups exhibited significantly lower matrix metalloproteinase (MMP)-1 and MMP-3 expression levels compared with the saline group. However, only the Lp-PRP group displayed significantly higher

  3. The PRNP gene polymorphism in Rough-coated Pomeranian ...

    African Journals Online (AJOL)

    Prion protein (PrP) is a membrane glycoprotein whose abnormal form is believed to cause a group of disorders known as transmissible spongiform encephalopathies (TSEs), which affect the brain and nervous system of both human beings and animals. The most familiar TSEs are Creutzfeldt-Jakob Disease (CJD) in human ...

  4. 5S rRNA gene arrangements in protists: a case of nonadaptive evolution.

    Science.gov (United States)

    Drouin, Guy; Tsang, Corey

    2012-06-01

    Given their high copy number and high level of expression, one might expect that both the sequence and organization of eukaryotic ribosomal RNA genes would be conserved during evolution. Although the organization of 18S, 5.8S and 28S ribosomal RNA genes is indeed relatively well conserved, that of 5S rRNA genes is much more variable. Here, we review the different types of 5S rRNA gene arrangements which have been observed in protists. This includes linkages to the other ribosomal RNA genes as well as linkages to ubiquitin, splice-leader, snRNA and tRNA genes. Mapping these linkages to independently derived phylogenies shows that these diverse linkages have repeatedly been gained and lost during evolution. This argues against such linkages being the primitive condition not only in protists but also in other eukaryote species. Because the only characteristic the diverse genes with which 5S rRNA genes are found linked with is that they are tandemly repeated, these arrangements are unlikely to provide any selective advantage. Rather, the observed high variability in 5S rRNA genes arrangements is likely the result of the fact that 5S rRNA genes contain internal promoters, that these genes are often transposed by diverse recombination mechanisms and that these new gene arrangements are rapidly homogenized by unequal crossingovers and/or by gene conversions events in species with short generation times and frequent founder events.

  5. Effects of platelet-rich plasma in a model of bovine endometrial inflammation in vitro

    OpenAIRE

    Marini, M G; C.; Perrini; Esposti, P.; Corradetti, B.; Bizzaro, D.; Riccaboni, P.; Fantinato, E.; Urbani, G.; Gelati, G.; Cremonesi, F.; Lange-Consiglio, A.

    2016-01-01

    Background Endometritis reduces fertility and is responsible for major economic losses in beef and dairy industries. The aim of this study was to evaluate an alternative therapy using platelet-rich plasma (PRP). PRP was tested in vivo, after bovine intrauterine administration, and in vitro on endometrial cells. Methods Bovine endometrial cells were cultured until passage (P) 10 with 5?% or 10?% PRP. Effect of PRP on endometrial cell proliferation and on the expression of genes [prostaglandin-...

  6. Quantitative trait loci define genes and pathways underlying genetic variation in longevity.

    Science.gov (United States)

    Shmookler Reis, Robert J; Kang, Ping; Ayyadevara, Srinivas

    2006-10-01

    Quantitative trait locus (QTL) mapping provides a means to discover and roughly position regions of the genome that harbor genes responsible for natural variation in a complex trait. QTL mapping has been utilized extensively in the pursuit of genes contributing to longevity, chiefly in two animal models, the nematode Caenorhabditis elegans and the dipteran insect Drosophila melanogaster. Research on both species has demonstrated that a relatively small set of loci accounts for most of their genetic variance in lifespan. QTL mapping complements the discovery of longevity genes by mutagenesis screens, because the two procedures are predicted to unveil overlapping but distinct types of genes. We argue that information gained from animal models, even invertebrates, can greatly facilitate the process of gene identification and testing of homologous genes in humans.

  7. Health, inequality and the politics of genes.

    Science.gov (United States)

    Whittle, Patrick M

    2010-08-13

    Research into the possible genetic basis of health inequalities between different ethnic or racial groups raises many scientific, ethical and political concerns. Proponents of such research point to the possible benefits for marginalised groups of understanding genetic influences on health outcomes; opponents indicate the potential social costs, citing historical use of Darwinian concepts to explain and justify inequalities between different peoples. Many health researchers may avoid the subject due to its potential for controversy--e.g. the recent media furore over the so-called 'warrior gene', and its apparent genetic explanations for negative health and social statistics among Maori. This article argues for a more nuanced account of the evolutionary history of marginalised groups such as Maori, one that accepts the possibility of relevant genetic differences between sub-populations, but which also acknowledges genuine ethical and political concerns. Such an account may assist health researchers in addressing the politically sensitive subject of 'race' and social inequality.

  8. Human Gene Therapy: Genes without Frontiers?

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  9. Associations among child abuse, mental health, and epigenetic modifications in the proopiomelanocortin gene (POMC) : a study with children in Tanzania

    OpenAIRE

    Hecker, Tobias; Radtke, Karl M.; Hermenau, Katharin; Papassotiropoulos, Andreas; Elbert, Thomas

    2016-01-01

    Child abuse is associated with a number of emotional and behavioral problems. Nevertheless, it has been argued that these adverse consequences may not hold for societies in which many of the specific acts of abuse are culturally normed. Epigenetic modifications in the genes of the hypothalamus-pituitary-adrenal axis may provide a potential mechanism translating abuse into altered gene expression, which subsequently results in behavioral changes. Our investigation took place in Tanzania, a soc...

  10. Genes and Hearing Loss

    Science.gov (United States)

    ... Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient Health Information News media interested in ... One of the most common birth defects is hearing loss or deafness (congenital), which can affect as ...

  11. Epigenetics: beyond genes

    CSIR Research Space (South Africa)

    Fossey, A

    2009-06-01

    Full Text Available Gene regulatory processes lead to differential gene expression and are referred to as epigenetic phenomena; these are ubiquitous processes in the biological world. These reversible heritable changes concern DNA and RNA, their interactions...

  12. Polydactyly and genes

    National Research Council Canada - National Science Library

    Phadke, Shubha R; Sankar, V H

    2010-01-01

    .... A lot of information about genes involved in development is available now. Genetics of hand development and genes involved in polydactyly syndromes is discussed in this article as a prototype to know about genetics of malformations...

  13. Evolution of gene expression after gene amplification.

    Science.gov (United States)

    Garcia, Nelson; Zhang, Wei; Wu, Yongrui; Messing, Joachim

    2015-04-24

    We took a rather unique approach to investigate the conservation of gene expression of prolamin storage protein genes across two different subfamilies of the Poaceae. We took advantage of oat plants carrying single maize chromosomes in different cultivars, called oat-maize addition (OMA) lines, which permitted us to determine whether regulation of gene expression was conserved between the two species. We found that γ-zeins are expressed in OMA7.06, which carries maize chromosome 7 even in the absence of the trans-acting maize prolamin-box-binding factor (PBF), which regulates their expression. This is likely because oat PBF can substitute for the function of maize PBF as shown in our transient expression data, using a γ-zein promoter fused to green fluorescent protein (GFP). Despite this conservation, the younger, recently amplified prolamin genes in maize, absent in oat, are not expressed in the corresponding OMAs. However, maize can express the oldest prolamin gene, the wheat high-molecular weight glutenin Dx5 gene, even when maize Pbf is knocked down (through PbfRNAi), and/or another maize transcription factor, Opaque-2 (O2) is knocked out (in maize o2 mutant). Therefore, older genes are conserved in their regulation, whereas younger ones diverged during evolution and eventually acquired a new repertoire of suitable transcriptional activators. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. How Genes Evolve

    Indian Academy of Sciences (India)

    evolutionary history of duplicated genes within a given lineage. The timings of gene duplication events can be inferred ... evolutionary history of the creatures in which various globin genes are found, the timings of the ..... But I cannot find heart to give any part of my life for money-making purposes ... : In 1901, one of the large ...

  15. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  16. Platlet Rich Plasma (PRP) Improves Fat Grafting Outcomes

    OpenAIRE

    Modarressi Ghavami, Seyed Ali

    2013-01-01

    Autologous fat transfer offers many qualities of a ideal soft tissue filler. Main advantages of fat grafting ensue from the fact that the lipoaspirate tissue is an abundant source of regenerative pluripotential cells. However, the reported rates of fat cell survival vary greatly in the medical literature (10-90%). Different techniques of harvesting, processing, and reinjecting the fat cells are so claimed to be responsible for these differences, without any agreement concerning the best way t...

  17. Modularity beyond Perception: Evidence from the PRP Paradigm

    Science.gov (United States)

    Magen, Hagit; Cohen, Asher

    2010-01-01

    The Dimension Action (DA) model asserts that the visual system is modular, and that each task involves multiple-response mechanisms rather than a unitary-response selection mechanism. The model has been supported by evidence from single-task interference paradigms. We use the psychological refractory period paradigm and show that dual-task…

  18. Platelet-rich plasma (PRP applied during total knee arthroplasty

    Directory of Open Access Journals (Sweden)

    João Paulo Fernandes Guerreiro

    2015-04-01

    Full Text Available OBJECTIVE: To evaluate the efficacy of platelet-rich plasma regarding healing, pain and hemostasis after total knee arthroplasty, by means of a blinded randomized controlled and blinded clinical study.METHODS: Forty patients who were going to undergo implantation of a total knee prosthesis were selected and randomized. In 20 of these patients, platelet-rich plasma was applied before the joint capsule was closed. The hemoglobin (mg/dL and hematocrit (% levels were assayed before the operation and 24 and 48 h afterwards. The Womac questionnaire and a verbal pain scale were applied and knee range of motion measurements were made up to the second postoperative month. The statistical analysis compared the results with the aim of determining whether there were any differences between the groups at each of the evaluation times.RESULTS: The hemoglobin (mg/dL and hematocrit (% measurements made before the operation and 24 and 48 h afterwards did not show any significant differences between the groups (p > 0.05. The Womac questionnaire and the range of motion measured before the operation and up to the first two months also did not show any statistical differences between the groups (p > 0.05. The pain evaluation using the verbal scale showed that there was an advantage for the group that received platelet-rich plasma, 24 h, 48 h, one week, three weeks and two months after the operation (p < 0.05.CONCLUSIONS: In the manner in which the platelet-rich plasma was used, it was not shown to be effective for reducing bleeding or improving knee function after arthroplasty, in comparison with the controls. There was an advantage on the postoperative verbal pain scale.

  19. Infiltrative treatment with Platelet Rich Plasma (PRP) in gonarthrosis

    National Research Council Canada - National Science Library

    Mangone, Giuseppe; Orioli, Annalisa; Pinna, Angela; Pasquetti, Pietro

    2014-01-01

    The aim of the study is to evaluate and to quantify the effects on the quality of life and the decrease of pain in short and middle term in patients affected of gonarthrosis and treated with a series...

  20. Randomization techniques for assessing the significance of gene periodicity results

    Directory of Open Access Journals (Sweden)

    Vuokko Niko

    2011-08-01

    Full Text Available Abstract Background Modern high-throughput measurement technologies such as DNA microarrays and next generation sequencers produce extensive datasets. With large datasets the emphasis has been moving from traditional statistical tests to new data mining methods that are capable of detecting complex patterns, such as clusters, regulatory networks, or time series periodicity. Study of periodic gene expression is an interesting research question that also is a good example of challenges involved in the analysis of high-throughput data in general. Unlike for classical statistical tests, the distribution of test statistic for data mining methods cannot be derived analytically. Results We describe the randomization based approach to significance testing, and show how it can be applied to detect periodically expressed genes. We present four randomization methods, three of which have previously been used for gene cycle data. We propose a new method for testing significance of periodicity in gene expression short time series data, such as from gene cycle and circadian clock studies. We argue that the underlying assumptions behind existing significance testing approaches are problematic and some of them unrealistic. We analyze the theoretical properties of the existing and proposed methods, showing how our method can be robustly used to detect genes with exceptionally high periodicity. We also demonstrate the large differences in the number of significant results depending on the chosen randomization methods and parameters of the testing framework. By reanalyzing gene cycle data from various sources, we show how previous estimates on the number of gene cycle controlled genes are not supported by the data. Our randomization approach combined with widely adopted Benjamini-Hochberg multiple testing method yields better predictive power and produces more accurate null distributions than previous methods. Conclusions Existing methods for testing significance

  1. Horizontal gene transfer between Wolbachia and the mosquito Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Walker Thomas

    2009-01-01

    Full Text Available Abstract Background The evolutionary importance of horizontal gene transfer (HGT from Wolbachia endosymbiotic bacteria to their eukaryotic hosts is a topic of considerable interest and debate. Recent transfers of genome fragments from Wolbachia into insect chromosomes have been reported, but it has been argued that these fragments may be on an evolutionary trajectory to degradation and loss. Results We have discovered a case of HGT, involving two adjacent genes, between the genomes of Wolbachia and the currently Wolbachia-uninfected mosquito Aedes aegypti, an important human disease vector. The lower level of sequence identity between Wolbachia and insect, the transcription of all the genes involved, and the fact that we have identified homologs of the two genes in another Aedes species (Ae. mascarensis, suggest that these genes are being expressed after an extended evolutionary period since horizontal transfer, and therefore that the transfer has functional significance. The association of these genes with Wolbachia prophage regions also provides a mechanism for the transfer. Conclusion The data support the argument that HGT between Wolbachia endosymbiotic bacteria and their hosts has produced evolutionary innovation.

  2. Gene therapy in periodontics

    Science.gov (United States)

    Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

    2013-01-01

    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is ‘the use of genes as medicine’. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone. PMID:23869119

  3. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu

    2013-01-01

    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  4. Modelling prokaryote gene content

    Directory of Open Access Journals (Sweden)

    Edward Susko

    2006-01-01

    Full Text Available The patchy distribution of genes across the prokaryotes may be caused by multiple gene losses or lateral transfer. Probabilistic models of gene gain and loss are needed to distinguish between these possibilities. Existing models allow only single genes to be gained and lost, despite the empirical evidence for multi-gene events. We compare birth-death models (currently the only widely-used models, in which only one gene can be gained or lost at a time to blocks models (allowing gain and loss of multiple genes within a family. We analyze two pairs of genomes: two E. coli strains, and the distantly-related Archaeoglobus fulgidus (archaea and Bacillus subtilis (gram positive bacteria. Blocks models describe the data much better than birth-death models. Our models suggest that lateral transfers of multiple genes from the same family are rare (although transfers of single genes are probably common. For both pairs, the estimated median time that a gene will remain in the genome is not much greater than the time separating the common ancestors of the archaea and bacteria. Deep phylogenetic reconstruction from sequence data will therefore depend on choosing genes likely to remain in the genome for a long time. Phylogenies based on the blocks model are more biologically plausible than phylogenies based on the birth-death model.

  5. Retrieval with gene queries

    Directory of Open Access Journals (Sweden)

    Srinivasan Padmini

    2006-04-01

    Full Text Available Abstract Background Accuracy of document retrieval from MEDLINE for gene queries is crucially important for many applications in bioinformatics. We explore five information retrieval-based methods to rank documents retrieved by PubMed gene queries for the human genome. The aim is to rank relevant documents higher in the retrieved list. We address the special challenges faced due to ambiguity in gene nomenclature: gene terms that refer to multiple genes, gene terms that are also English words, and gene terms that have other biological meanings. Results Our two baseline ranking strategies are quite similar in performance. Two of our three LocusLink-based strategies offer significant improvements. These methods work very well even when there is ambiguity in the gene terms. Our best ranking strategy offers significant improvements on three different kinds of ambiguities over our two baseline strategies (improvements range from 15.9% to 17.7% and 11.7% to 13.3% depending on the baseline. For most genes the best ranking query is one that is built from the LocusLink (now Entrez Gene summary and product information along with the gene names and aliases. For others, the gene names and aliases suffice. We also present an approach that successfully predicts, for a given gene, which of these two ranking queries is more appropriate. Conclusion We explore the effect of different post-retrieval strategies on the ranking of documents returned by PubMed for human gene queries. We have successfully applied some of these strategies to improve the ranking of relevant documents in the retrieved sets. This holds true even when various kinds of ambiguity are encountered. We feel that it would be very useful to apply strategies like ours on PubMed search results as these are not ordered by relevance in any way. This is especially so for queries that retrieve a large number of documents.

  6. In vivo robustness analysis of cell division cycle genes in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Hisao Moriya

    2006-07-01

    Full Text Available Intracellular biochemical parameters, such as the expression level of gene products, are considered to be optimized so that a biological system, including the parameters, works effectively. Those parameters should have some permissible range so that the systems have robustness against perturbations, such as noise in gene expression. However, little is known about the permissible range in real cells because there has been no experimental technique to test it. In this study, we developed a genetic screening method, named "genetic tug-of-war" (gTOW that evaluates upper limit copy numbers of genes in a model eukaryote Saccharomyces cerevisiae, and we applied it for 30 cell-cycle related genes (CDC genes. The experiment provided unique quantitative data that could be used to argue the system-level properties of the cell cycle such as robustness and fragility. The data were used to evaluate the current computational model, and refinements to the model were suggested.

  7. Final Report: Regulation and Function of Two Cell Wall protein Genes in Me Dicago Roots and Root Nodules, August 1, 1995 - January 31, 1999

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, James B.

    2000-05-08

    During the period of DOE funding we synthesized several PRP peptides, generated rabbit antisera against two PRP repeats found in early nodulin PRPs, and developed confocal microscopy methods for root immunohistochemistry. Using the antibodies, we completed extensive descriptive studies of PRP deposition in medic and alfalfa roots showing that PRPs deposition is developmentally regulated in roots and spatially restricted within the walls of specific root tissues. Domain-specific antibodies were isolated from polyclonal sera using peptide affinity chromatography and were then used to demonstrate that nodule-specific epitopes are shared by several nodule-specific proteins. The following provides a more detailed summary of this work.

  8. Primetime for Learning Genes.

    Science.gov (United States)

    Keifer, Joyce

    2017-02-11

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

  9. Primetime for Learning Genes

    Directory of Open Access Journals (Sweden)

    Joyce Keifer

    2017-02-01

    Full Text Available Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF, by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be “poised” for rapid response to activate or repress gene expression depending on environmental stimuli.

  10. Viral gene therapy.

    Science.gov (United States)

    Mancheño-Corvo, P; Martín-Duque, P

    2006-12-01

    Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor. Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity. This review discusses current and emerging virusbased genetic engineering strategies for the delivery of therapeutic molecules or several approaches for cancer treatment.

  11. Two methods for improving performance of an HMM and their application for gene finding

    DEFF Research Database (Denmark)

    Krogh, Anders Stærmose

    1997-01-01

    . It is argued that the standard maximum likelihood estimation criterion is not optimal for training such a model. Instead of maximizing the probability of the DNA sequence, one should maximize the probability of the correct prediction. Such a criterion, called conditional maximum likelihood, is used...... for the gene finder `HMMgene'. A new (approximative) algorithm is described, which finds the most probable prediction summed over all paths yielding the same prediction. We show that these methods contribute significantly to the high performance of HMMgene....

  12. What is a gene, post-ENCODE? History and updated definition.

    Science.gov (United States)

    Gerstein, Mark B; Bruce, Can; Rozowsky, Joel S; Zheng, Deyou; Du, Jiang; Korbel, Jan O; Emanuelsson, Olof; Zhang, Zhengdong D; Weissman, Sherman; Snyder, Michael

    2007-06-01

    While sequencing of the human genome surprised us with how many protein-coding genes there are, it did not fundamentally change our perspective on what a gene is. In contrast, the complex patterns of dispersed regulation and pervasive transcription uncovered by the ENCODE project, together with non-genic conservation and the abundance of noncoding RNA genes, have challenged the notion of the gene. To illustrate this, we review the evolution of operational definitions of a gene over the past century--from the abstract elements of heredity of Mendel and Morgan to the present-day ORFs enumerated in the sequence databanks. We then summarize the current ENCODE findings and provide a computational metaphor for the complexity. Finally, we propose a tentative update to the definition of a gene: A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products. Our definition side-steps the complexities of regulation and transcription by removing the former altogether from the definition and arguing that final, functional gene products (rather than intermediate transcripts) should be used to group together entities associated with a single gene. It also manifests how integral the concept of biological function is in defining genes.

  13. Gene manupulations in invertebrates

    OpenAIRE

    Čermáková, Eliška

    2017-01-01

    Gene manipulations in invertebrates are based on the same approches used in vertebrates. The are applied for the development of new genotypes in model species, convenient as model systems of human hereditary diseases etc. Gene manipulations are important as well for practical purposes, which is shown by the example of trangenic mosquitoes. Recently, it has been proved that programmable nucleases can be successfully used in invertebrates. Key words: Gene manipulations, invertebrates, methods, ...

  14. Genes and Social Behavior

    OpenAIRE

    Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

    2008-01-01

    What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence beh...

  15. Patients, evidence and genes: an exploration of GPs' perspectives on gene-based personalized nutrition advice.

    Science.gov (United States)

    Bouwman, Laura; Te Molder, Hedwig; Hiddink, Gerrit

    2008-12-01

    Nutrigenomics science examines the response of individuals to food compounds using post-genomics technology. It is expected that in the future, personalized nutrition advice can be provided based on information about genetic make-up. Gene-based personalized nutrition advice emerges at the junction of different disciplines and technologies and may directly influence people's lives. Therefore, public concern is to be expected. Because GPs are gatekeepers of health care, their involvement in early stages of the development process is desirable. In 2006, 15 GPs were interviewed to collect their perceived barriers and opportunities towards involvement in gene-based nutrition advice. The interviews were qualitatively analysed with use of Atlas.ti, a qualitative analysis programme. The participants held a mostly critical view towards such personalized nutrition advice. They argued that findings of nutritional studies lacked robustness, were not based on patients' needs and were often equivocal. And that a patient central perspective urges them to question consequences for patients. Participants argued that GPs should be involved in selecting and monitoring patients in nutrigenomics studies. Early involvement of GPs in the development process is needed to allow for the integration of their practical, social and ethical considerations in the technical and scientific agendas. However, the background of their critical attitude towards nutrigenomics-based personalized nutrition, and nutrition advice more generally, has to be explored further. To facilitate a joint learning process and to improve socio-technical decision making with respect to this innovation, initiatives that allow different stakeholders to exchange their perspectives should be organized.

  16. History of gene therapy.

    Science.gov (United States)

    Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

    2013-08-10

    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Does Platelet-Rich Plasma Freeze-Thawing Influence Growth Factor Release and Their Effects on Chondrocytes and Synoviocytes?

    Directory of Open Access Journals (Sweden)

    Alice Roffi

    2014-01-01

    Full Text Available PRP cryopreservation remains a controversial point. Our purpose was to investigate the effect of freezing/thawing on PRP molecule release, and its effects on the metabolism of chondrocytes and synoviocytes. PRP was prepared from 10 volunteers, and a half volume underwent one freezing/thawing cycle. IL-1β, HGF, PDGF AB/BB, TGF-β1, and VEGF were assayed 1 hour and 7 days after activation. Culture media of chondrocytes and synoviocytes were supplemented with fresh or frozen PRP, and, at 7 days, proliferation, gene expression, and secreted proteins levels were evaluated. Results showed that in the freeze-thawed PRP the immediate and delayed molecule releases were similar or slightly lower than those in fresh PRP. TGF-β1 and PDGF AB/BB concentrations were significantly reduced after freezing both at 1 hour and at 7 days, whereas HGF concentration was significantly lower in frozen PRP at 7 days. In fresh PRP IL-1β and HGF concentrations underwent a significant further increase after 7 days. Similar gene expression was found in chondrocytes cultured with both PRPs, whereas in synoviocytes HGF gene expression was higher in frozen PRP. PRP cryopreservation is a safe procedure, which sufficiently preserves PRP quality and its ability to induce proliferation and the production of ECM components in chondrocytes and synoviocytes.

  18. Robustness and accuracy in sea urchin developmental gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Smadar eBen-Tabou De-Leon

    2016-02-01

    Full Text Available Developmental gene regulatory networks robustly control the timely activation of regulatory and differentiation genes. The structure of these networks underlies their capacity to buffer intrinsic and extrinsic noise and maintain embryonic morphology. Here I illustrate how the use of specific architectures by the sea urchin developmental regulatory networks enables the robust control of cell fate decisions. The Wnt-βcatenin signaling pathway patterns the primary embryonic axis while the BMP signaling pathway patterns the secondary embryonic axis in the sea urchin embryo and across bilateria. Interestingly, in the sea urchin in both cases, the signaling pathway that defines the axis controls directly the expression of a set of downstream regulatory genes. I propose that this direct activation of a set of regulatory genes enables a uniform regulatory response and a clear cut cell fate decision in the endoderm and in the dorsal ectoderm. The specification of the mesodermal pigment cell lineage is activated by Delta signaling that initiates a triple positive feedback loop that locks down the pigment specification state. I propose that the use of compound positive feedback circuitry provides the endodermal cells enough time to turn off mesodermal genes and ensures correct mesoderm vs. endoderm fate decision. Thus, I argue that understanding the control properties of repeatedly used regulatory architectures illuminates their role in embryogenesis and provides possible explanations to their resistance to evolutionary change.

  19. Robustness and Accuracy in Sea Urchin Developmental Gene Regulatory Networks.

    Science.gov (United States)

    Ben-Tabou de-Leon, Smadar

    2016-01-01

    Developmental gene regulatory networks robustly control the timely activation of regulatory and differentiation genes. The structure of these networks underlies their capacity to buffer intrinsic and extrinsic noise and maintain embryonic morphology. Here I illustrate how the use of specific architectures by the sea urchin developmental regulatory networks enables the robust control of cell fate decisions. The Wnt-βcatenin signaling pathway patterns the primary embryonic axis while the BMP signaling pathway patterns the secondary embryonic axis in the sea urchin embryo and across bilateria. Interestingly, in the sea urchin in both cases, the signaling pathway that defines the axis controls directly the expression of a set of downstream regulatory genes. I propose that this direct activation of a set of regulatory genes enables a uniform regulatory response and a clear cut cell fate decision in the endoderm and in the dorsal ectoderm. The specification of the mesodermal pigment cell lineage is activated by Delta signaling that initiates a triple positive feedback loop that locks down the pigment specification state. I propose that the use of compound positive feedback circuitry provides the endodermal cells enough time to turn off mesodermal genes and ensures correct mesoderm vs. endoderm fate decision. Thus, I argue that understanding the control properties of repeatedly used regulatory architectures illuminates their role in embryogenesis and provides possible explanations to their resistance to evolutionary change.

  20. A feasibility of useful cell-based therapy by bone regeneration with deciduous tooth stem cells, dental pulp stem cells, or bone-marrow-derived mesenchymal stem cells for clinical study using tissue engineering technology.

    Science.gov (United States)

    Yamada, Yoichi; Nakamura, Sayaka; Ito, Kenji; Sugito, Takayuki; Yoshimi, Ryoko; Nagasaka, Tetsuro; Ueda, Minoru

    2010-06-01

    This study investigated the effect of bone regeneration with dental pulp stem cells (DPSCs), deciduous tooth stem cells (DTSCs), or bone-marrow-derived mesenchymal stem cells (BMMSCs) for clinical study on hydroxyapatite-coated osseointegrated dental implants, using tissue engineering technology. In vitro, human DPSCs and DTSCs expressed STRO-1, CD13, CD29, CD 44, CD73, and osteogenic marker genes such as alkaline phosphatase, Runx2, and osteocalcin. In vivo, prepared bone defect model was implanted using graft materials as follows: platelet-rich plasma (PRP), PRP and canine BMMSCs (cBMMSCs), PRP and canine DPSCs (cDPSCs), PRP and puppy DTSCs (pDTSCs), and control (defect only). After 8 weeks, the dental implants were installed, and 16 weeks later the sections were evaluated histologically and histometrically. The cBMMSCs/PRP, cDPSCs/PRP, and pDTSCs/PRP groups had well-formed mature bone and neovascularization. Histometrically, the bone-implant contact was significantly different between the cBMMSCs/PRP, cDPSCs/PRP, pDTSCs/PRP groups, and the control and PRP groups (p < 0.01). These results demonstrated that these stem cells with PRP have the ability to form bone, and this bone formation activity might be useful for osseointegrated hydroxyapatite-coated dental implants with good levels of bone-implant contact.

  1. Informed consent in field trials of gene-drive mosquitoes.

    Science.gov (United States)

    Kolopack, Pamela A; Lavery, James V

    2017-12-11

    The US National Academies' (NAS) recent report 'Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values' examines the requirements of responsible conduct in research involving gene drives in non-human organisms. Many of the complex ethical issues raised by the introduction of gene drive technologies for mosquito population control have been anticipated during the development and field-testing of earlier-generation genetic engineering approaches with mosquitoes. One issue-the requirement for informed consent in field trials-is not addressed explicitly in the NAS' report. Some commentators have presumed that informed consent should play a role as a protection for research participants in studies of genetically modified mosquitoes. Others have argued that there are no human subjects of field trials, so the informed consent requirement does not apply. It is both ethically and practically important that these presumptions are adequately scrutinized to ensure that any applications of informed consent in these trials are properly justified. We argue that informed consent from individual research participants in gene drive trials may be required: (1) when blood and other forms of clinical data are collected from them, as will likely be the case in some studies involving epidemiological endpoints, such as the incidence of new infections with dengue and malaria; (2) when they participate in social science and/or behavioral research involving the completion of surveys and questionnaires; or (3) when their home or property is accessed and the location recorded as a spatial variable for the release or collection of mosquitoes because the precise location of the household is important for entomological reasons and these data constitute identifiable private information at the household level. Importantly, most regulations and guidelines allow these requirements to be waived or modified, to various degrees, according to the

  2. Chromatin loops, gene positioning, and gene expression

    NARCIS (Netherlands)

    Holwerda, S.; de Laat, W.

    2012-01-01

    Technological developments and intense research over the last years have led to a better understanding of the 3D structure of the genome and its influence on genome function inside the cell nucleus. We will summarize topological studies performed on four model gene loci: the alpha- and beta-globin

  3. One gene's shattering effects.

    Science.gov (United States)

    Olsen, Kenneth M

    2012-05-29

    A new study shows that three independent mutations in the Sh1 gene, which encodes a YABBY transcription factor, gave rise to the non-shattering seed phenotype in domesticated sorghum. This same gene may have also had a role in the domestication of other cereals, including maize and rice.

  4. Cytokinins act synergistically with salicylic acid to activate defense gene expression in rice.

    Science.gov (United States)

    Jiang, Chang-Jie; Shimono, Masaki; Sugano, Shoji; Kojima, Mikiko; Liu, Xinqiong; Inoue, Haruhiko; Sakakibara, Hitoshi; Takatsuji, Hiroshi

    2013-03-01

    Hormone crosstalk is pivotal in plant-pathogen interactions. Here, we report on the accumulation of cytokinins (CK) in rice seedlings after infection of blast fungus Magnaporthe oryzae and its potential significance in rice-M. oryzae interaction. Blast infection to rice seedlings increased levels of N(6)-(Δ(2)-isopentenyl) adenine (iP), iP riboside (iPR), and iPR 5'-phosphates (iPRP) in leaf blades. Consistent with this, CK signaling was activated around the infection sites, as shown by histochemical staining for β-glucuronidase activity driven by a CK-responsive OsRR6 promoter. Diverse CK species were also detected in the hyphae (mycelium), conidia, and culture filtrates of blast fungus, indicating that M. oryzae is capable of production as well as hyphal secretion of CK. Co-treatment of leaf blades with CK and salicylic acid (SA), but not with either one alone, markedly induced pathogenesis-related genes OsPR1b and probenazole-induced protein 1 (PBZ1). These effects were diminished by RNAi-knockdown of OsNPR1 or WRKY45, the key regulators of the SA signaling pathway in rice, indicating that the effects of CK depend on these two regulators. Taken together, our data imply a coevolutionary rice-M. oryzae interaction, wherein M. oryzae probably elevates rice CK levels for its own benefits such as nutrient translocation. Rice plants, on the other hand, sense it as an infection signal and activate defense reactions through the synergistic action with SA.

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

    Directory of Open Access Journals (Sweden)

    Jeong Byung-Hoon

    2011-08-01

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

  6. A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Burton, Mark; Thomassen, Mads

    2016-01-01

    been argued that simple blood tests, including the leukocyte count and plasma lactate dehydrogenase (LDH) may be useful tools to separate genuine ET from prePMF, the latter disease entity more often being featured by anemia, leukocytosis and elevated LDH. Whole blood gene expression profiling...... to the World Health Organization (WHO) 2008 classification, bone marrow histology is a major component in the distinction between these disease entities. However, the differential diagnosis between them may be challenging and several studies have not been able to distinguish between them. Most lately, it has......, CEACAM8, CRISP3, MS4A3, CEACAM6, HEMGN, and MMP8, which are genes known to be involved in inflammation, cell adhesion, differentiation and proliferation. Evaluation of bone marrow biopsies and the 7-gene signature showed a concordance rate of 71%, 79%, 62%, and 38%. Our 7-gene signature may be a useful...

  7. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    OpenAIRE

    Wold, William S. M.; Toth, Karoly

    2013-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  8. HOX gene complement and expression in the planarian Schmidtea mediterranea

    Directory of Open Access Journals (Sweden)

    Ko W. Currie

    2016-03-01

    Full Text Available Abstract Background Freshwater planarians are well known for their regenerative abilities. Less well known is how planarians maintain spatial patterning in long-lived adult animals or how they re-pattern tissues during regeneration. HOX genes are good candidates to regulate planarian spatial patterning, yet the full complement or genomic clustering of planarian HOX genes has not yet been described, primarily because only a few have been detectable by in situ hybridization, and none have given morphological phenotypes when knocked down by RNAi. Results Because the planarian Schmidtea mediterranea (S. mediterranea is unsegmented, appendage less, and morphologically simple, it has been proposed that it may have a simplified HOX gene complement. Here, we argue against this hypothesis and show that S. mediterranea has a total of 13 HOX genes, which represent homologs to all major axial categories, and can be detected by whole-mount in situ hybridization using a highly sensitive method. In addition, we show that planarian HOX genes do not cluster in the genome, yet 5/13 have retained aspects of axially restricted expression. Finally, we confirm HOX gene axial expression by RNA deep-sequencing 6 anterior–posterior “zones” of the animal, which we provide as a dataset to the community to discover other axially restricted transcripts. Conclusions Freshwater planarians have an unappreciated HOX gene complexity, with all major axial categories represented. However, we conclude based on adult expression patterns that planarians have a derived body plan and their asexual lifestyle may have allowed for large changes in HOX expression from the last common ancestor between arthropods, flatworms, and vertebrates. Using our in situ method and axial zone RNAseq data, it should be possible to further understand the pathways that pattern the anterior–posterior axis of adult planarians.

  9. HOX gene complement and expression in the planarian Schmidtea mediterranea.

    Science.gov (United States)

    Currie, Ko W; Brown, David D R; Zhu, Shujun; Xu, ChangJiang; Voisin, Veronique; Bader, Gary D; Pearson, Bret J

    2016-01-01

    Freshwater planarians are well known for their regenerative abilities. Less well known is how planarians maintain spatial patterning in long-lived adult animals or how they re-pattern tissues during regeneration. HOX genes are good candidates to regulate planarian spatial patterning, yet the full complement or genomic clustering of planarian HOX genes has not yet been described, primarily because only a few have been detectable by in situ hybridization, and none have given morphological phenotypes when knocked down by RNAi. Because the planarian Schmidtea mediterranea (S. mediterranea) is unsegmented, appendage less, and morphologically simple, it has been proposed that it may have a simplified HOX gene complement. Here, we argue against this hypothesis and show that S. mediterranea has a total of 13 HOX genes, which represent homologs to all major axial categories, and can be detected by whole-mount in situ hybridization using a highly sensitive method. In addition, we show that planarian HOX genes do not cluster in the genome, yet 5/13 have retained aspects of axially restricted expression. Finally, we confirm HOX gene axial expression by RNA deep-sequencing 6 anterior-posterior "zones" of the animal, which we provide as a dataset to the community to discover other axially restricted transcripts. Freshwater planarians have an unappreciated HOX gene complexity, with all major axial categories represented. However, we conclude based on adult expression patterns that planarians have a derived body plan and their asexual lifestyle may have allowed for large changes in HOX expression from the last common ancestor between arthropods, flatworms, and vertebrates. Using our in situ method and axial zone RNAseq data, it should be possible to further understand the pathways that pattern the anterior-posterior axis of adult planarians.

  10. Gene therapy flexes muscle.

    Science.gov (United States)

    VandenDriessche, Thierry

    2005-09-01

    This commentary highlights the promising results of recent studies in animal models of Duchenne muscular dystrophy and amyotrophic lateral sclerosis that have clearly demonstrated the potential of gene therapy for tackling these diseases. In the absence of effective drugs or other treatments, these advances in gene therapy technology represent the best hope for those patients and families that are blighted by these diseases. Diseases characterized by progressive muscle degeneration are often incurable and affect a relatively large number of individuals. The progressive deterioration of muscle function is like the sword of Damocles that constantly reminds patients suffering from these diseases of their tragic fate, since most of them will eventually die from cardiac or pulmonary dysfunction. Some of these disorders are due to mutations in genes that directly influence the integrity of muscle fibers, such as in Duchenne muscular dystrophy (DMD), a recessive X-linked genetic disease. Others result from a progressive neurodegeneration of the motoneurons that are essential for maintaining muscle function, such as in amyotrophic lateral sclerosis (ALS), also commonly known as Lou Gehrig's disease. The genetic basis of DMD is relatively well understood as it is due to mutations in the dystrophin gene that encodes the cognate sarcolemmal protein. In contrast, the cause of ALS is poorly defined, with the exception of some dominantly inherited familial cases of ALS that are due to gain-of-function mutations in the gene encoding superoxide dismutase (SODG93A). Gene therapy for these disorders has been hampered by the inability to achieve widespread gene transfer. Moreover, since familial ALS is due to a dominant gain-of-function mutation, inhibition of gene expression (rather than gene augmentation) would be required to correct the phenotype, which is particularly challenging. Copyright (c) 2005 John Wiley & Sons, Ltd.

  11. Comparative analysis of septic injury-inducible genes in phylogenetically distant model organisms of regeneration and stem cell research, the planarian Schmidtea mediterranea and the cnidarian Hydra vulgaris

    Directory of Open Access Journals (Sweden)

    Vilcinskas Andreas

    2008-04-01

    Full Text Available Abstract Background The planarian Schmidtea mediterranea and the cnidarian Hydra vulgaris have emerged as valuable model organisms in regeneration and stem cell research because of their prominent ability to regenerate a complete organism from any small body fragment. Under natural conditions wounding may result from predator attacks. These injuries open their innermost to a wide array of microbes present in the environment. Therefore, we established the hypothesis that regeneration processes may be linked to or at least accompanied by innate immune responses. In order to screen for septic wounding inducible genes we dissected individuals using a scalpel in the presence of a crude bacterial lipopolysaccharide preparation that is commonly used to elicit innate immune responses in animals and applied the suppression subtractive hybridization technique that selectively amplifies cDNAs of differentially expressed genes. Results This analysis revealed the induced expression of 27 genes in immune challenged Schmidtea and 35 genes in immune challenged Hydra. Identified genes from both animals encode proteins that share sequence similarities with potential homologues from other organisms known to be involved in signaling (e.g. calreticulin in Schmidtea and major vault protein in Hydra, stress responses (e.g. Hsp20 in Schmidtea and a PRP19/PSO4 DNA repair protein in Hydra, or to represent potential antimicrobial effectors (e.g. perforin-like protein in Schmidtea and PR-1-like protein and neutrophil cytosolic factor 1 in Hydra. As expected, septic wounding also induces expression of genes in Schmidtea and Hydra potentially involved in tissue remodeling associated with regeneration processes (e.g. matrix metalloproteinase in Schmidtea and a potential von Willebrand factor in Hydra. Conclusion We identified numerous immune-inducible genes in Hydra and Schmidtea that show a similar distribution corresponding to their physiological roles, although lineages of

  12. Impacts of a Digital Dialogue Game and Epistemic Beliefs on Argumentative Discourse and Willingness to Argue

    Science.gov (United States)

    Noroozi, Omid; McAlister, Simon; Mulder, Martin

    2016-01-01

    The goal of this study was to explore how students debate with their peers within a designed context using a digital dialogue game, and whether their epistemic beliefs are significant to the outcomes. Epistemic beliefs are known to colour student interactions within argumentative discourse, leading some students to hold back from interactions. By…

  13. Arguing sovereignty in Songhay Plaider la souveraineté en pays songhaï

    Directory of Open Access Journals (Sweden)

    Bruce S. Hall

    2013-05-01

    Full Text Available Recent archaeological, historical, and anthropological literature on the development of social and political complexity in Africa challenges older models of state formation that used to shape the understanding of medieval Sahelian empires, such as Songhay. As we now know, there were multiple paths to complexity that did not necessarily lead to state formation; and there was a heterarchical distribution of power in many African political formations. Nonetheless, the historiography of pre-colonial states in Sahelian West Africa, and of Islam’s role in these political formations, retains an attachment to a particular model of statehood derived from Arabic geographies and chronicles. Emphasis continues to be placed on military power and a largely ambivalent relation between Islam and indigenous forms of authority. In this article, a reinterpretation of the exercise and rhetoric of sovereignty in imperial Songhay is proposed that focuses on ways in which Islamic authority was claimed and contested byrulers. Songhay rulers claimed a religious authority that far outstripped their coercive power. Instead of an ambivalent relation between the Muslim religious estate and secular power, Islamic religious authority was the principal basis of Songhay rulers’ claims to extensive power.La littérature récente en archéologie, histoire et anthropologie à propos du développement de la complexité sociale et politique en Afrique lance un défi à nos modèles anciens de la formation de l’État, et notamment des empires médiévaux sahéliens, comme celui du Songhaï. Comme nous le savons, il y de multiples voies vers la complexité qui ne mènent pas forcément à la formation d’un État ; et il y avait une distribution hétérarchique du pouvoir dans plusieurs formations politiques africaines. Néanmoins, l’historiographie des États précoloniaux en Afrique de l'Ouest sahélienne et celle du rôle de l’islam dans ces formations politiques restent attachées à un modèle de l’État tiré des géographies et chroniques arabes. On y insiste encore sur le pouvoir militaire et sur un rapport ambivalent entre islam et des formes autochtones d’autorité. Dans cet article, nous proposons une réinterprétation de l’exercice de la souveraineté et de sa rhétorique dans l’empire songhaï qui met en avant les modalités par lesquelles les dirigeants pouvaient prétendre à une autorité islamique ou la mettre en cause. Les dirigeants songhaïs revendiquaient une autorité religieuse qui allait au-delà du pouvoir de coercition. Plutôt qu’un rapport ambivalent entre le domaine religieux musulman et le pouvoir séculier, l’autorité islamique constituait le principal fondement de la prétention par les souverains songhaïs à un pouvoir étendu.

  14. There is no reason to argue about taste | Klosse | Research in ...

    African Journals Online (AJOL)

    This paper is a transcript of Prof Peter Klosse's inaugural speech, delivered at Stenden University, Leeuwarden. Set againstthe backdrop of a rapidly evolving industry, the message is of particular significance. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  15. Arguing for Democracy: A Multimodal Approach to Argumentative Writing Instruction in the Social Studies Classroom

    Science.gov (United States)

    Dingler, Matt

    2017-01-01

    Democratic societies require a citizenry skilled in argumentation. At present, the written argument maintains primacy among communicative modes. Because of its cognitive demands, written argumentation is often difficult to teach. A multimodal approach to writing instruction carries the potential to assist struggling learners. This article outlines…

  16. Arguing to learn: Supporting interactive argumentation through Computer-Supported Collaborative Learning

    NARCIS (Netherlands)

    Munneke-de Vries, E.L.

    2008-01-01

    Interactive argumentation gives students the opportunity to learn because it allows them to produce, explicate, articulate, verbalise their opinions and arguments, and construct and/or reconstruct knowledge through disagreement. However, argumentation can also be very difficult and needs support at

  17. Impacts of a digital dialogue game and epistemic beliefs on argumentative discourse and willingness to argue

    OpenAIRE

    Noroozi, O.; McAlister, S.; Mulder, M.

    2016-01-01

    The goal of this study was to explore how students debate with their peers within a designed context using a digital dialogue game, and whether their epistemic beliefs are significant to the outcomes. Epistemic beliefs are known to colour student interactions within argumentative discourse, leading some students to hold back from interactions. By designing an online small group activity based around an issue both important and controversial to the students, with multiple viewpoints in each gr...

  18. Impacts of a digital dialogue game and epistemic beliefs on argumentative discourse and willingness to argue

    NARCIS (Netherlands)

    Noroozi, O.; McAlister, S.; Mulder, M.

    2016-01-01

    The goal of this study was to explore how students debate with their peers within a designed context using a digital dialogue game, and whether their epistemic beliefs are significant to the outcomes. Epistemic beliefs are known to colour student interactions within argumentative discourse, leading

  19. Never Argue with a Kiwi: International Exchange Debating in New Zealand.

    Science.gov (United States)

    Saxon, John D.

    A report concerning the value of the international exchange debate tour of New Zealand sponsored by the Committee on International Discussion and Debate of the Speech Communication Association is given in this paper. The report provides an examination of the goals and benefits of international exchange debating, discusses how this particular tour…

  20. When children argue: the discursive construction of evidence use in inquiry science lessons

    Directory of Open Access Journals (Sweden)

    Luiz Gustavo Franco Silveira

    2017-12-01

    Full Text Available The aim of this study is to analyze the discursive construction of practices of evidence use during argumentation in science lessons in a 3rd grade classroom. We selected an event considered a telling case to analyze face-to-face interactions. We adopted elements of the ethnographic perspective in education and of the Pragma-dialectical Theory of Argumentation. Our results indicate that participants’ argumentation was organized around two foci: one generated by disagreements about directive questions, demanded presentation of points of view and arguments with evidence; the second one, generated by disagreements about metacognitive questions, led to discussions around evidence use. In addition, we indicate the complexity of the process of relating evidence to a particular claim through an interaction in which opposite points of view were supported by the same observations. We examine our results in the light of research on argumentation at elementary school, and we suggest implications for teaching practice and research in science education.

  1. "Teach Your Children Well": Arguing in Favor of Pedagogically Justifiable Hospitality Education

    Science.gov (United States)

    Potgieter, Ferdinand J.

    2016-01-01

    This paper is a sequel to the paper which I delivered at last year's BCES conference in Sofia. Making use of hermeneutic phenomenology and constructive interpretivism as methodological apparatus, I challenge the pedagogic justifiability of the fashionable notion of religious tolerance. I suggest that we need, instead, to reflect "de…

  2. Expert Testimony, "Regular People," and Public Values: Arguing Common Sense at a Death Penalty Trial.

    Science.gov (United States)

    Chappell, Virginia A.

    1995-01-01

    Presents a case study of a particular courtroom case dealing with the death penalty. Analyzes the processes and communications of the trial jury. Discusses the interplay of common-sense and expert claims at three crucial stages of the trial. (HB)

  3. Paris vs. Prague: A "Suspicion of Fraud": Ernst Mach Argues over Photographs and Epistemological Prerequisites.

    Science.gov (United States)

    Hoffmann, Christoph

    2016-12-01

    Argument In spring 1888, an anonymous critic raised severe doubts about Ernst Mach's and Peter Salcher's studies, published one year before, on the processes in the air caused by very rapid projectiles. Paraphrasing the experiments for the French popular science magazine La Nature, the critic insinuated that the photographs upon which Mach and Salcher's argument were ostensibly based must have been of such low quality that they did not allow any well-founded conclusion. The critic did not deny the phenomena Mach and Salcher had presented in their article; he denied that the photographs taken in the course of the experiments could permit any observation of the phenomena. I take the resulting quarrel as a window into the actors' ideas on the requirements of "good observations" and the role of technical devices in this case. In particular I enquire how the various arguments relate to Lorraine Daston's and Peter Galison's framing of photography as an emblem of "mechanical objectivity." We will see that in the case under debate, actors considered naked-eye observation, observation by telescope and photography mainly with regard to the challenges of the particular research object.

  4. Learning to Argue with Intermediate Macro Theory: A Semester-Long Team Writing Project

    Science.gov (United States)

    Strasser, Georg; Wolfe, Marketa Halova

    2014-01-01

    The authors describe their experience with integrating a semester-long economic analysis project into an intermediate macroeconomic theory course. Students work in teams of "economic advisors" to write a series of nested reports that analyze the current state of the economy, and propose and evaluate policies for a decision-maker. The…

  5. "Pay Now, Argue Later" Rule – Before and After the Tax ...

    African Journals Online (AJOL)

    The South African Revenue Service (SARS) is entrusted with the duty of collecting tax on behalf of the South African government. In order to ensure effective and prompt collection of taxes, the payment of tax is not suspended pending an objection or an appeal, unless directed otherwise. This is also known as the "pay now, ...

  6. Fermilab Physicists don't see higgs, argue they should keep looking

    CERN Multimedia

    Cho, Adrian

    2010-01-01

    "This year's International Conference on High Energy Physics was a case study in irony. The meeting was billed as the coming-out party for the Large Hadron Collider (LHC), the gigantic European atom smasher that started taking data in March, but the buzz surrounded results form the older Tevatron collider at Fermi National Accelerator Laboratory (Fermilab) in Batavia, Illinois." (1 page)

  7. Observations on the occurrence of the fish louse Argu/us japonicus ...

    African Journals Online (AJOL)

    407-417. HOBSON. E.S. 1974. Feeding relationships of teleostean fishes on coral reefs in Kona Hawaii. Fishery Bull. Fish Wildt. Serv. U.S.. 72: 915 - 1031. LASIAK, T.A. 1982. Structural and functional aspects of the surf- zone fish community in the Eastern Cape. Ph.D. thesis. University of Port Elizabeth. SMITH. J.L.B. 1965.

  8. Metabolic pathway redundancy within the apicomplexan-dinoflagellate radiation argues against an ancient chromalveolate plastid

    KAUST Repository

    Waller, Ross F.

    2015-12-08

    The chromalveolate hypothesis presents an attractively simple explanation for the presence of red algal-derived secondary plastids in 5 major eukaryotic lineages: “chromista” phyla, cryptophytes, haptophytes and ochrophytes; and alveolate phyla, dinoflagellates and apicomplexans. It posits that a single secondary endosymbiotic event occurred in a common ancestor of these diverse groups, and that this ancient plastid has since been maintained by vertical inheritance only. Substantial testing of this hypothesis by molecular phylogenies has, however, consistently failed to provide support for the predicted monophyly of the host organisms that harbour these plastids—the “chromalveolates.” This lack of support does not disprove the chromalveolate hypothesis per se, but rather drives the proposed endosymbiosis deeper into the eukaryotic tree, and requires multiple plastid losses to have occurred within intervening aplastidic lineages. An alternative perspective on plastid evolution is offered by considering the metabolic partnership between the endosymbiont and its host cell. A recent analysis of metabolic pathways in a deep-branching dinoflagellate indicates a high level of pathway redundancy in the common ancestor of apicomplexans and dinoflagellates, and differential losses of these pathways soon after radiation of the major extant lineages. This suggests that vertical inheritance of an ancient plastid in alveolates is highly unlikely as it would necessitate maintenance of redundant pathways over very long evolutionary timescales.

  9. Learning to Argue as a Biotechnologist: Disprivileging Opposition to Genetically Modified Food

    Science.gov (United States)

    Solli, Anne; Bach, Frank; Åkerman, Björn

    2014-01-01

    In the public discussion of genetically modified (GM) food the representations of science as a social good, conducted in the public interest to solve major problems are being subjected to intense scrutiny and questioning. Scientists working in these areas have been seen to struggle for the position of science in society. However few in situ…

  10. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...... to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how...

  11. Gene Therapy for Hemophilia.

    Science.gov (United States)

    Nathwani, Amit C; Davidoff, Andrew M; Tuddenham, Edward G D

    2017-10-01

    The best currently available treatments for hemophilia A and B (factor VIII or factor IX deficiency, respectively) require frequent intravenous infusion of highly expensive proteins that have short half-lives. Factor levels follow a saw-tooth pattern that is seldom in the normal range and falls so low that breakthrough bleeding occurs. Most hemophiliacs worldwide do not have access to even this level of care. In stark contrast, gene therapy holds out the hope of a cure by inducing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene to replace the hemophilic patient's own defective gene. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Platelet-Rich Plasma Activates Proinflammatory Signaling Pathways and Induces Oxidative Stress in Tendon Fibroblasts.

    Science.gov (United States)

    Hudgens, Joshua L; Sugg, Kristoffer B; Grekin, Jeremy A; Gumucio, Jonathan P; Bedi, Asheesh; Mendias, Christopher L

    2016-08-01

    Tendon injuries are one of the most common musculoskeletal conditions in active patients. Platelet-rich plasma (PRP) has shown some promise in the treatment of tendon disorders, but little is known as to the mechanisms by which PRP can improve tendon regeneration. PRP contains numerous different growth factors and cytokines that activate various cellular signaling cascades, but it has been difficult to determine precisely which signaling pathways and cellular responses are activated after PRP treatment. Additionally, macrophages play an important role in modulating tendon regeneration, but the influence of PRP on determining whether macrophages assume a proinflammatory or anti-inflammatory phenotype remains unknown. To use genome-wide expression profiling, bioinformatics, and protein analysis to determine the cellular pathways activated in fibroblasts treated with PRP. The effect of PRP on macrophage polarization was also evaluated. Controlled laboratory study. Tendon fibroblasts or macrophages from rats were cultured and treated with either platelet-poor plasma (PPP) or PRP. RNA or protein was isolated from cells and analyzed using microarrays, quantitative polymerase chain reaction, immunoblotting, or bioinformatics techniques. Pathway analysis determined that the most highly induced signaling pathways in PRP-treated tendon fibroblasts were TNFα and NFκB pathways. PRP also downregulated the expression of extracellular matrix genes and induced the expression of autophagy-related genes and reactive oxygen species (ROS) genes and protein markers in tendon fibroblasts. PRP failed to have a major effect on markers of macrophage polarization. PRP induces an inflammatory response in tendon fibroblasts, which leads to the formation of ROS and the activation of oxidative stress pathways. PRP does not appear to significantly modulate macrophage polarization. PRP might act by inducing a transient inflammatory event, which could then trigger a tissue regeneration response

  13. Genes underlying altruism.

    Science.gov (United States)

    Thompson, Graham J; Hurd, Peter L; Crespi, Bernard J

    2013-01-01

    William D. Hamilton postulated the existence of 'genes underlying altruism', under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system polymorphisms, between alleles for altruism and alleles for non-social cognition. Such trade-offs between self-oriented and altruistic behaviour may influence the evolution of phenotypic diversity across all social animals.

  14. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  15. Evidence for homosexuality gene

    Energy Technology Data Exchange (ETDEWEB)

    Pool, R.

    1993-07-16

    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  16. Gene genealogies indicates abundant gene conversions and independent evolutionary histories of the mating-type chromosomes in the evolutionary history of Neurospora tetrasperma

    Directory of Open Access Journals (Sweden)

    Whittle Carrie A

    2010-07-01

    Full Text Available Abstract Background The self-fertile filamentous ascomycete Neurospora tetrasperma contains a large (~7 Mbp and young (mat chromosomes. The objective of the present study is to reveal the evolutionary history, including key genomic events, associated with the various regions of the mat chromosomes among ten strains representing all the nine known species (lineages contained within the N. tetrasperma species complex. Results Comparative analysis of sequence divergence among alleles of 24 mat-linked genes (mat A and mat a indicates that a large region of suppressed recombination exists within the mat chromosome for each of nine lineages of N. tetrasperma sensu latu. The recombinationally suppressed region varies in size and gene composition among lineages, and is flanked on both ends by normally recombining regions. Genealogical analyses among lineages reveals that eight gene conversion events have occurred between homologous mat A and mat a-linked alleles of genes located within the region of restricted recombination during the evolutionary history of N. tetrasperma. Conclusions We conclude that the region of suppressed recombination in the mat chromosomes has likely been subjected to independent contraction and/or expansion during the evolutionary history of the N. tetrasperma species complex. Furthermore, we infer that gene conversion events are likely a common phenomenon within this recombinationally suppressed genomic region. We argue that gene conversions might provide an efficient mechanism of adaptive editing of functional genes, including the removal of deleterious mutations, within the young recombinationally suppressed region of the mat chromosomes.

  17. Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

    National Research Council Canada - National Science Library

    Adegoke, Olufemi

    2003-01-01

    The objective of this CDA is to evaluate the gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS...

  18. Associations of P2Y12R gene polymorphisms with susceptibility to coronary heart disease and clinical efficacy of antiplatelet treatment with clopidogrel.

    Science.gov (United States)

    Yang, Hong-Hui; Chen, Yan; Gao, Chuan-Yu

    2016-12-01

    To investigate the correlations of three P2Y12 receptor (P2Y12R) gene polymorphisms (rs7428575 T>G, rs2046934 C>T, and rs3732759 A>G) with susceptibility to coronary artery disease (CHD) and clinical efficacy of clopidogrel treatment for CHD. From May 2014 to May 2015, 178 CHD patients (the case group) and 182 healthy controls (the control group) were selected from our hospital. The platelet-rich plasma (PRP) turbidimetry was used to measure the rate of adenosine diphosphate (ADP)-induced platelet aggregation before and after clopidogrel treatment. Clopidogrel-sensitive group was defined as a 10% or greater decrease in the rate of platelet aggregation after 10 days of clopidogrel treatment, while clopidogrel-resistant group was defined as a T and rs3732759 A>G between the case and control groups (all Pclopidogrel-sensitive group had higher frequencies of TT genotype of rs2046934 C>T and lower frequencies of GG genotype of rs3732759 A>G than those in the clopidogrel-resistant group (both PT and rs3732759 A>G polymorphisms might be associated with the risk of CHD and the efficacy of clopidogrel treatment for CHD. © 2016 John Wiley & Sons Ltd.

  19. Cell type-specific neuroprotective activity of untranslocated prion protein.

    Directory of Open Access Journals (Sweden)

    Elena Restelli

    2010-10-01

    Full Text Available A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions.Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells.These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  20. Neonatal maternal deprivation response and developmental changes in gene expression revealed by hypothalamic gene expression profiling in mice.

    Directory of Open Access Journals (Sweden)

    Feng Ding

    Full Text Available Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS. Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period.

  1. Bootstrapping of gene-expression data improves and controls the false discovery rate of differentially expressed genes

    Directory of Open Access Journals (Sweden)

    Goddard Mike E

    2004-03-01

    Full Text Available Abstract The ordinary-, penalized-, and bootstrap t-test, least squares and best linear unbiased prediction were compared for their false discovery rates (FDR, i.e. the fraction of falsely discovered genes, which was empirically estimated in a duplicate of the data set. The bootstrap-t-test yielded up to 80% lower FDRs than the alternative statistics, and its FDR was always as good as or better than any of the alternatives. Generally, the predicted FDR from the bootstrapped P-values agreed well with their empirical estimates, except when the number of mRNA samples is smaller than 16. In a cancer data set, the bootstrap-t-test discovered 200 differentially regulated genes at a FDR of 2.6%, and in a knock-out gene expression experiment 10 genes were discovered at a FDR of 3.2%. It is argued that, in the case of microarray data, control of the FDR takes sufficient account of the multiple testing, whilst being less stringent than Bonferoni-type multiple testing corrections. Extensions of the bootstrap simulations to more complicated test-statistics are discussed.

  2. The Mycoplasma hominis vaa gene displays a mosaic gene structure

    DEFF Research Database (Denmark)

    Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.

    1998-01-01

    Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular...

  3. Characteristic differences between the promoters of intron-containing and intronless ribosomal protein genes in yeast

    Directory of Open Access Journals (Sweden)

    Vingron Martin

    2008-10-01

    Full Text Available Abstract Background More than two thirds of the highly expressed ribosomal protein (RP genes in Saccharomyces cerevisiae contain introns, which is in sharp contrast to the genome-wide five percent intron-containing genes. It is well established that introns carry regulatory sequences and that the transcription of RP genes is extensively and coordinately regulated. Here we test the hypotheses that introns are innately associated with heavily transcribed genes and that introns of RP genes contribute regulatory TF binding sequences. Moreover, we investigate whether promoter features are significantly different between intron-containing and intronless RP genes. Results We find that directly measured transcription rates tend to be lower for intron-containing compared to intronless RP genes. We do not observe any specifically enriched sequence motifs in the introns of RP genes other than those of the branch point and the two splice sites. Comparing the promoters of intron-containing and intronless RP genes, we detect differences in number and position of Rap1-binding and IFHL motifs. Moreover, the analysis of the length distribution and the folding free energies suggest that, at least in a sub-population of RP genes, the 5' untranslated sequences are optimized for regulatory function. Conclusion Our results argue against the direct involvement of introns in the regulation of transcription of highly expressed genes. Moreover, systematic differences in motif distributions suggest that RP transcription factors may act differently on intron-containing and intronless gene promoters. Thus, our findings contribute to the decoding of the RP promoter architecture and may fuel the discussion on the evolution of introns.

  4. Ribosomal genes in focus

    Science.gov (United States)

    Koberna, Karel; Malínský, Jan; Pliss, Artem; Mašata, Martin; Večeřová, Jaromíra; Fialová, Markéta; Bednár, Jan; Raška, Ivan

    2002-01-01

    T he organization of transcriptionally active ribosomal genes in animal cell nucleoli is investigated in this study in order to address the long-standing controversy with regard to the intranucleolar localization of these genes. Detailed analyses of HeLa cell nucleoli include direct localization of ribosomal genes by in situ hybridization and their indirect localization via nascent ribosomal transcript mappings. On the light microscopy (LM) level, ribosomal genes map in 10–40 fluorescence foci per nucleus, and transcription activity is associated with most foci. We demonstrate that each nucleolar focus observed by LM corresponds, on the EM level, to an individual fibrillar center (FC) and surrounding dense fibrillar components (DFCs). The EM data identify the DFC as the nucleolar subcompartment in which rRNA synthesis takes place, consistent with detection of rDNA within the DFC. The highly sensitive method for mapping nascent transcripts in permeabilized cells on ultrastructural level provides intense and unambiguous clustered immunogold signal over the DFC, whereas very little to no label is detected over the FC. This signal is strongly indicative of nascent “Christmas trees” of rRNA associated with individual rDNA genes, sampled on the surface of thin sections. Stereological analysis of the clustered transcription signal further suggests that these Christmas trees may be contorted in space and exhibit a DNA compaction ratio on the order of 4–5.5. PMID:12034768

  5. On sports and genes.

    Science.gov (United States)

    Zilberman-Schapira, Gili; Chen, Jieming; Gerstein, Mark

    2012-12-01

    Our genes influence our athletic ability. However, the causal genetic factors and mechanisms, and the extent of their effects, remain largely elusive. Many studies investigate this association between specific genes and athletic performance. Such studies have increased in number over the past few years, as recent developments and patents in DNA sequencing have made large amounts of sequencing data available for such analysis. In this paper, we consider four of the most intensively studied genes in relation to athletic ability: angiotensin I-converting enzyme, alpha-actinin 3, peroxismose proliferator-activator receptor alpha and nitric oxide synthase 3. We investigate the connection between genotype and athletic phenotype in the context of these four genes in various sport fields and across different ethnicities and genders. We do an extensive literature survey on these genes and the polymorphisms (single nucleotide polymorphisms or indels) found to be associated with athletic performance. We also present, for each of these polymorphisms, the allele frequencies in the different ethnicities reported in the pilot phase of the 1000 Genomes Project - arguably the largest human genome-sequencing endeavor to date. We discuss the considerable success, and significant drawbacks, of past research along these lines, and propose interesting directions for future research.

  6. Recombination in immunoglobulin gene loci

    Directory of Open Access Journals (Sweden)

    Komisarenko S. V.

    2009-02-01

    Full Text Available Gene network of the lymphoid cell differentiation coordinates precisely the recombination process in immunoglobulin gene loci. In our opinion, cellular microRNAs can contribute to the allelic exclusion through microRNA-directed DNA methylation and participate in retargeting recombinases activity from the gene loci of heavy immunoglobulin chains to the gene loci of light chains

  7. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  8. Gene decay in archaea

    Directory of Open Access Journals (Sweden)

    M. W. J. van Passel

    2007-01-01

    Full Text Available The gene-dense chromosomes of archaea and bacteria were long thought to be devoid of pseudogenes, but with the massive increase in available genome sequences, whole genome comparisons between closely related species have identified mutations that have rendered numerous genes inactive. Comparative analyses of sequenced archaeal genomes revealed numerous pseudogenes, which can constitute up to 8.6% of the annotated coding sequences in some genomes. The largest proportion of pseudogenes is created by gene truncations, followed by frameshift mutations. Within archaeal genomes, large numbers of pseudogenes contain more than one inactivating mutation, suggesting that pseudogenes are deleted from the genome more slowly in archaea than in bacteria. Although archaea seem to retain pseudogenes longer than do bacteria, most archaeal genomes have unique repertoires of pseudogenes.

  9. Why not “just for the money”? An experimental vignette study of the cognitive price effects and crowding effects of performance-related pay

    DEFF Research Database (Denmark)

    Jacobsen, Christian Bøtcher; Jensen, Lars Engelbrecht

    2017-01-01

    Motivation crowding theory (MCT) argues that performance-related pay (PRP) can crowd out intrinsic motivation with detrimental consequences for the employees’ willingness to exert effort, but this mechanism is only expected, when PRP is perceived to be controlling. However, no studies have tested......-controlling, the importance of intrinsic motivation can actually increase. The implications of this study are that PRP is not necessarily harmful, and that managers should pay close attention to how their employees perceive performance-based pay systems.......Motivation crowding theory (MCT) argues that performance-related pay (PRP) can crowd out intrinsic motivation with detrimental consequences for the employees’ willingness to exert effort, but this mechanism is only expected, when PRP is perceived to be controlling. However, no studies have tested...

  10. Mechanisms of Horizontal Gene Transfer

    OpenAIRE

    Cafini Barrado, Fabio; Medrano Romero, Verónica; Morikawa, Kazuya

    2017-01-01

    Horizontal gene transfer plays important roles in the evolution of S. aureus, and indeed, a variety of virulence factors and antibiotic resistance genes are embedded in a series of mobile genetic elements. In this chapter, we review the mechanisms of horizontal gene transfer, including recent findings on the natural genetic competence. Then, we consider the transfer of two important antibiotic resistance genes: the methicillin resistance gene, mecA (in Staphylococcal Cassette Chromosome) and ...

  11. Idiomatic (gene) expressions.

    Science.gov (United States)

    Rockman, Matthew V

    2003-05-01

    Hidden among the myriad nucleotide variants that constitute each species' gene pool are a few variants that contribute to phenotypic variation. Many of these differences that make a difference are non-coding cis-regulatory variants, which, unlike coding variants, can only be identified through laborious experimental analysis. Recently, Cowles et al.1 described a screening method that does an end-run around this problem by searching for genes whose cis regulation varies without having to find the polymorphic nucleotides that influence transcription. While we will continue to require a diverse arsenal of experimental methods, this versatile method will speed the identification of functional genetic variation. Copyright 2003 Wiley Periodicals, Inc.

  12. A Bayesian approach to gene-gene and gene-environment interactions in chronic fatigue syndrome.

    Science.gov (United States)

    Lin, Eugene; Hsu, Sen-Yen

    2009-01-01

    In the study of genomics, it is essential to address gene-gene and gene-environment interactions for describing the complex traits that involves disease-related mechanisms. In this work, our goal is to detect gene-gene and gene-environment interactions resulting from the analysis of chronic fatigue syndrome patients' genetic and demographic factors including SNPs, age, gender and BMI. We employed the dataset that was original to the previous study by the Centers for Disease Control and Prevention Chronic Fatigue Syndrome Research Group. To investigate gene-gene and gene-environment interactions, we implemented a Bayesian based method for identifying significant interactions between factors. Here, we employed a two-stage Bayesian variable selection methodology based on Markov Chain Monte Carlo approaches. By applying our Bayesian based approach, NR3C1 was found in the significant two-locus gene-gene effect model, as well as in the significant two-factor gene-environment effect model. Furthermore, a significant gene-environment interaction was identified between NR3C1 and gender. These results support the hypothesis that NR3C1 and gender may play a role in biological mechanisms associated with chronic fatigue syndrome. We demonstrated that our Bayesian based approach is a promising method to assess the gene-gene and gene-environment interactions in chronic fatigue syndrome patients by using genetic factors, such as SNPs, and demographic factors such as age, gender and BMI.

  13. Neighboring Genes Show Correlated Evolution in Gene Expression

    Science.gov (United States)

    Ghanbarian, Avazeh T.; Hurst, Laurence D.

    2015-01-01

    When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

  14. Gene Therapy and Children (For Parents)

    Science.gov (United States)

    ... Needs a Kidney Transplant Vision Facts and Myths Gene Therapy and Children KidsHealth > For Parents > Gene Therapy and ... by a "bad" gene. continue Two Types of Gene Therapy The two forms of gene therapy are: Somatic ...

  15. Ultrasound mediated gene transfection

    Science.gov (United States)

    Williamson, Rene G.; Apfel, Robert E.; Brandsma, Janet L.

    2002-05-01

    Gene therapy is a promising modality for the treatment of a variety of human diseases both inherited and acquired, such as cystic fibrosis and cancer. The lack of an effective, safe method for the delivery of foreign genes into the cells, a process known as transfection, limits this effort. Ultrasound mediated gene transfection is an attractive method for gene delivery since it is a noninvasive technique, does not introduce any viral particles into the host and can offer very good temporal and spatial control. Previous investigators have shown that sonication increases transfection efficiency with and without ultrasound contrast agents. The mechanism is believed to be via a cavitation process where collapsing bubble nuclei permeabilize the cell membrane leading to increased DNA transfer. The research is focused on the use of pulsed wave high frequency focused ultrasound to transfect DNA into mammalian cells in vitro and in vivo. A better understanding of the mechanism behind the transfection process is also sought. A summary of some in vitro results to date will be presented, which includes the design of a sonication chamber that allows us to model the in vivo case more accurately.

  16. What is a Gene?

    Indian Academy of Sciences (India)

    His other interests include reading, photography and listening to classical music. The first part of this general article appeared in April 1997. S C Lakhotia. The first part of this article traced the evolution of the concept of a gene from Mendel's times to the middle of this century: starting from the imaginary factors of Mendel, the.

  17. Genes in mammalian reproduction

    Energy Technology Data Exchange (ETDEWEB)

    Gwatkin, R.B.L. [ed.

    1996-11-01

    This is an informative book which deals mainly with genomic imprinting, the role of steroid hormones in development, the expression of a variety of genes during development and the link to hereditary diseases. It is an up-to-date review in a field that is quickly changing and provides valuable basic information and current research trends.

  18. (FIE) gene from soybean

    African Journals Online (AJOL)

    DR. NJ TONUKARI

    2012-04-17

    Apr 17, 2012 ... Harb. Protoc. doi:10.1101/pdb.prot4666. Xu H, Li Y, Yan Y, Wang K, Gao Y, Hu Y (2010). Genome-scale identification of Soybean BURP domain-containing genes and their expression under stress treatments. BMC Plant Biol. 10: 197. Yadegari R, Kinoshita T, Lotan O, Cohen G, Katz A, Choi Y, Nakashima.

  19. Silence of the Genes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 4. Silence of the Genes - 2006 Nobel Prize in Physiology or Medicine. Utpal Nath Saumitra Das. General Article Volume 12 Issue 4 April 2007 pp 6-18. Fulltext. Click here to view fulltext PDF. Permanent link:

  20. Silence of the Genes

    Indian Academy of Sciences (India)

    Srimath

    research for several decades (See Resonance, Vol. 12, pp.47–53,. March 2007). RNA interference (RNAi) is a novel mechanism for controlling gene expression. In this mechanism, tiny double-stranded RNA molecules called 'small interfering RNA' (siRNA) degrade cellu- lar mRNA that has sequence similarity with them.

  1. Gene therapy in pancreatic cancer

    Science.gov (United States)

    Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

    2014-01-01

    Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC. PMID:25309069

  2. Genes2FANs: connecting genes through functional association networks

    Directory of Open Access Journals (Sweden)

    Dannenfelser Ruth

    2012-07-01

    Full Text Available Abstract Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs, researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our

  3. Text Mining to Support Gene Ontology Curation and Vice Versa.

    Science.gov (United States)

    Ruch, Patrick

    2017-01-01

    In this chapter, we explain how text mining can support the curation of molecular biology databases dealing with protein functions. We also show how curated data can play a disruptive role in the developments of text mining methods. We review a decade of efforts to improve the automatic assignment of Gene Ontology (GO) descriptors, the reference ontology for the characterization of genes and gene products. To illustrate the high potential of this approach, we compare the performances of an automatic text categorizer and show a large improvement of +225 % in both precision and recall on benchmarked data. We argue that automatic text categorization functions can ultimately be embedded into a Question-Answering (QA) system to answer questions related to protein functions. Because GO descriptors can be relatively long and specific, traditional QA systems cannot answer such questions. A new type of QA system, so-called Deep QA which uses machine learning methods trained with curated contents, is thus emerging. Finally, future advances of text mining instruments are directly dependent on the availability of high-quality annotated contents at every curation step. Databases workflows must start recording explicitly all the data they curate and ideally also some of the data they do not curate.

  4. Sexy sons: a dead end for cytoplasmic genes.

    Science.gov (United States)

    Zeh, Jeanne A

    2004-08-07

    Critics of sexual conflict theory argue that females may gain a net reproductive benefit from mating with manipulative males because the direct costs that they suffer may be offset by the production of sexy, i.e. manipulative, sons. However, this exclusive focus on nuclear gene effects represents an incomplete view of female fitness. Females differ fundamentally from males in transmitting not only nuclear genes but also a wide range of cytoplasmic genetic elements (CGEs) that can have profound effects, from male killing to influencing development of the nervous system and cognitive ability. Maternal transmission of CGEs has two major implications for sexual selection. First, the evolution of male fitness traits, such as sperm competitive ability, may be constrained because response to selection on mitochondrial genomes can occur only through the female line. Second, CGEs bear the direct costs of male manipulation but gain no indirect benefits when females produce sexy sons. This should result in perpetual antagonistic coevolution between nuclear genes involved in male manipulation and CGEs that promote female resistance to male sexually selected traits. Explicit consideration of the consequences of selection acting on CGEs is therefore necessary for a better understanding of the relationship between sexual selection and sexual conflict.

  5. Staunch protections: the ethics of haemophilia gene transfer research.

    Science.gov (United States)

    Kimmelman, J

    2008-01-01

    Haemophilia has long been considered an ideal system for validating human gene transfer (GT). However, haemophilia GT trials present a particular ethical challenge because they involve subjects whose medical condition is stabilized by standard therapies. Below, I review the ethics and risks of haemophilia GT clinical research. I propose several conditions and practices that strengthen the ethical basis for such trials. These include consultation with haemophilia advocacy organizations as trials are designed and executed, high standards of supporting evidence before trials are initiated, pretrial publication of this evidence, and the offer of indemnification for participants. I further argue against the conduct of paediatric haemophilia GT studies at this time, and raise questions about the fairness of recruiting economically disadvantaged subjects into studies that are primarily directed towards the health needs of persons in the developed world.

  6. Using gene expression noise to understand gene regulation

    NARCIS (Netherlands)

    Munsky, B.; Neuert, G.; van Oudenaarden, A.

    2012-01-01

    Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a

  7. Gene set analysis for longitudinal gene expression data

    Directory of Open Access Journals (Sweden)

    Piepho Hans-Peter

    2011-07-01

    Full Text Available Abstract Background Gene set analysis (GSA has become a successful tool to interpret gene expression profiles in terms of biological functions, molecular pathways, or genomic locations. GSA performs statistical tests for independent microarray samples at the level of gene sets rather than individual genes. Nowadays, an increasing number of microarray studies are conducted to explore the dynamic changes of gene expression in a variety of species and biological scenarios. In these longitudinal studies, gene expression is repeatedly measured over time such that a GSA needs to take into account the within-gene correlations in addition to possible between-gene correlations. Results We provide a robust nonparametric approach to compare the expressions of longitudinally measured sets of genes under multiple treatments or experimental conditions. The limiting distributions of our statistics are derived when the number of genes goes to infinity while the number of replications can be small. When the number of genes in a gene set is small, we recommend permutation tests based on our nonparametric test statistics to achieve reliable type I error and better power while incorporating unknown correlations between and within-genes. Simulation results demonstrate that the proposed method has a greater power than other methods for various data distributions and heteroscedastic correlation structures. This method was used for an IL-2 stimulation study and significantly altered gene sets were identified. Conclusions The simulation study and the real data application showed that the proposed gene set analysis provides a promising tool for longitudinal microarray analysis. R scripts for simulating longitudinal data and calculating the nonparametric statistics are posted on the North Dakota INBRE website http://ndinbre.org/programs/bioinformatics.php. Raw microarray data is available in Gene Expression Omnibus (National Center for Biotechnology Information with

  8. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis

    Science.gov (United States)

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

  9. Genes, stress, and depression.

    Science.gov (United States)

    Wurtman, Richard J

    2005-05-01

    A relationship between genetic makeup and susceptibility to major depressive disorder (MDD) has long been suspected on the basis of family and twin studies. A metaanalysis of reports on the basis of twin studies has estimated MDD's degree of heritability to be 0.33 (confidence interval, 0.26-0.39). Among families exhibiting an increased prevalence of MDD, risk of developing the illness was enhanced in members exposed to a highly stressful environment. Aberrant genes can predispose to depression in a number of ways, for example, by diminishing production of growth factors that act during brain development. An aberrant gene could also increase or decrease a neurotransmitter's release into synapses, its actions, or its duration of activity. The gene products of greatest interest at present are those involved in the synthesis and actions of serotonin; among them, the serotonin-uptake protein localized within the terminals and dendrites of serotonin-releasing neurons. It has been found that the Vmax of platelet serotonin uptake is low in some patients with MDD; also, Vmax is highly correlated in twins. Antidepressant drugs such as the selective serotonin reuptake inhibitors act on this uptake protein. The specific genetic locus causing serotonin uptake to be lower in some patients with major depression involves a polymorphic region (5-HTTLPR) in the promoter region of the gene for the uptake protein. The gene itself exists as several alleles, the short "S" allele and the long "L" allele. The S variant is associated with less, and the L variant with more, of the uptake protein. The effect of stressful life events on depressive symptoms in young adults was found to be significantly stronger among SS or SL subjects than among LL subjects. Neuroimaging studies showed that people with the SS or SL alleles exhibited a greater activation of the amygdala in response to fearful stimuli than those with LL. It has been reported recently that mutations in the gene that controls

  10. Vertebrate gene predictions and the problem of large genes

    DEFF Research Database (Denmark)

    Wang, Jun; Li, ShengTing; Zhang, Yong

    2003-01-01

    To find unknown protein-coding genes, annotation pipelines use a combination of ab initio gene prediction and similarity to experimentally confirmed genes or proteins. Here, we show that although the ab initio predictions have an intrinsically high false-positive rate, they also have a consistent...

  11. Expression of isgylation related genes in regenerating rat liver

    Directory of Open Access Journals (Sweden)

    Kuklin A. V.

    2015-10-01

    Full Text Available Our recent studies have revealed the early up-regulated expression of interferon alpha (IFNα in the liver, induced by partial hepatectomy. The role of this cytokine of innate immune response in liver regeneration is still controversial. Aim. To analyze expression of canonical interferon-stimulated genes Ube1l, Ube2l6, Trim25, Usp18 and Isg15 during the liver transition from quiescence to proliferation induced by partial hepatectomy, and acute phase response induced by laparotomy. These genes are responsible for posttranslational modification of proteins by ISGylation. The expression of genes encoding TATA binding protein (TBP and 18S rRNA served as indirect general markers of transcriptional and translational activities. Methods. The abundance of investigated RNAs was assessed in total liver RNA by real time RT–qPCR. Results. Partial hepatecomy induced steady upregulation of the Tbp and 18S rRNA genes expression during 12 hours post-surgery and downregulation or no change in expression of ISGylation-related genes during the first 3 hours followed by slight upregulation at 12 hours. The level of Isg15 transcripts was permanently below that of the control during the prereplicative period. Laparotomy induced a continuous downregulation of Tbp and 18S rRNA expression and early (1–3h upregulation of ISGylation–related transcripts followed by a sharp drop at 6 hours and slight increase/decrease at 12 hours. The changes in the abundance of Ifnα and ISGylation-related mRNAs were oppositely directed at each stage of the response to partial hepatectomy and laparotomy. Conclusion. We suggest that the expression of ISGylation-related genes does not depend on the expression of Ifnα gene after both surgeries. The indirect indices of transcription and translation as well as the expression of ISGylation-relaled genes are principally different in response to partial hepatectomy and laparotomy and argue for the high specificity of innate immune response.

  12. Gene Therapy for Lung Cancer.

    Science.gov (United States)

    Lara-Guerra, Humberto; Roth, Jack A

    2016-01-01

    Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible. To overcome these difficulties, various gene therapy strategies have been adopted, including immune stimulation, transfer of suicide genes, inhibition of driver oncogenes, replacement of tumor-suppressor genes that could mediate apoptosis or anti-angiogenesis, and transfer of genes that enhance conventional treatments such as radiotherapy and chemotherapy. Some of these strategies have been tested successfully in non-small-cell lung cancer patients and the results of laboratory studies and clinical trials are reviewed herein.

  13. Gene therapy in keratoconus

    Directory of Open Access Journals (Sweden)

    Mahgol Farjadnia

    2015-01-01

    Full Text Available Keratoconus (KC is the most common ectasia of the cornea and is a common reason for corneal transplant. Therapeutic strategies that can arrest the progression of this disease and modify the underlying pathogenesis are getting more and more popularity among scientists. Cumulating data represent strong evidence of a genetic role in the pathogenesis of KC. Different loci have been identified, and certain mutations have also been mapped for this disease. Moreover, Biophysical properties of the cornea create an appropriate candidate of this tissue for gene therapy. Immune privilege, transparency and ex vivo stability are among these properties. Recent advantage in vectors, besides the ability to modulate the corneal milieu for accepting the target gene for a longer period and fruitful translation, make a big hope for stupendous results reasonable.

  14. The sulfatase gene family.

    Science.gov (United States)

    Parenti, G; Meroni, G; Ballabio, A

    1997-06-01

    During the past few years, molecular analyses have provided important insights into the biochemistry and genetics of the sulfatase family of enzymes, identifying the molecular bases of inherited diseases caused by sulfatase deficiencies. New members of the sulfatase gene family have been identified in man and other species using a genomic approach. These include the gene encoding arylsulfatase E, which is involved in X-linked recessive chondrodysplasia punctata, a disorder of cartilage and bone development. Another important breakthrough has been the discovery of the biochemical basis of multiple sulfatase deficiency, an autosomal recessive disorder characterized by a severe of all sulfatase activities. These discoveries, together with the resolution of the crystallographic structure of sulfatases, have improved our understanding of the function and evolution of this fascinating family of enzymes.

  15. Brains, Genes and Primates

    Science.gov (United States)

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

    2015-01-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  16. PRRT2 gene mutations

    Science.gov (United States)

    Gardiner, Alice R.; Bhatia, Kailash P.; Stamelou, Maria; Dale, Russell C.; Kurian, Manju A.; Schneider, Susanne A.; Wali, G.M.; Counihan, Tim; Schapira, Anthony H.; Spacey, Sian D.; Valente, Enza-Maria; Silveira-Moriyama, Laura; Teive, Hélio A.G.; Raskin, Salmo; Sander, Josemir W.; Lees, Andrew; Warner, Tom; Kullmann, Dimitri M.; Wood, Nicholas W.; Hanna, Michael

    2012-01-01

    ABSTRACT Objective: The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such as epilepsy, migraine, and paroxysmal movement disorders, often coexist and are thought to have a shared channel-related etiology. To investigate further the frequency, spectrum, and phenotype of PRRT2 mutations, we analyzed this gene in 3 large series of episodic neurologic disorders with PKD/IC, episodic ataxia (EA), and hemiplegic migraine (HM). Methods: The PRRT2 gene was sequenced in 58 family probands/sporadic individuals with PKD/IC, 182 with EA, 128 with HM, and 475 UK and 96 Asian controls. Results: PRRT2 genetic mutations were identified in 28 out of 58 individuals with PKD/IC (48%), 1/182 individuals with EA, and 1/128 individuals with HM. A number of loss-of-function and coding missense mutations were identified; the most common mutation found was the p.R217Pfs*8 insertion. Males were more frequently affected than females (ratio 52:32). There was a high proportion of PRRT2 mutations found in families and sporadic cases with PKD associated with migraine or HM (10 out of 28). One family had EA with HM and another large family had typical HM alone. Conclusions: This work expands the phenotype of mutations in the PRRT2 gene to include the frequent occurrence of migraine and HM with PKD/IC, and the association of mutations with EA and HM and with familial HM alone. We have also extended the PRRT2 mutation type and frequency in PKD and other episodic neurologic disorders. PMID:23077024

  17. Gene Porter Bridwell

    Science.gov (United States)

    1994-01-01

    Gene Porter Bridwell served as the director of the Marshall Space Flight Center from January 6, 1994 until February 3, 1996, when he retired from NASA after thirty-four years service. Bridwell, a Marshall employee since 1962, had been Marshall's Space Shuttle Projects Office Director and Space Station Redesign Team deputy manager. Under Bridwell, Marshall worked to develop its role as a Center of Excellence for propulsion and for providing access to space.

  18. Genealogy and gene trees.

    Science.gov (United States)

    Rasmuson, Marianne

    2008-02-01

    Heredity can be followed in persons or in genes. Persons can be identified only a few generations back, but simplified models indicate that universal ancestors to all now living persons have occurred in the past. Genetic variability can be characterized as variants of DNA sequences. Data are available only from living persons, but from the pattern of variation gene trees can be inferred by means of coalescence models. The merging of lines backwards in time leads to a MRCA (most recent common ancestor). The time and place of living for this inferred person can give insights in human evolutionary history. Demographic processes are incorporated in the model, but since culture and customs are known to influence demography the models used ought to be tested against available genealogy. The Icelandic data base offers a possibility to do so and points to some discrepancies. Mitochondrial DNA and Y chromosome patterns give a rather consistent view of human evolutionary history during the latest 100 000 years but the earlier epochs of human evolution demand gene trees with longer branches. The results of such studies reveal as yet unsolved problems about the sources of our genome.

  19. Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.

    Directory of Open Access Journals (Sweden)

    Ming-Wei Su

    Full Text Available BACKGROUND: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1, the gene coding interleukin-4 receptor alpha chain (IL4Ra and the gene coding insulin induced gene 2 (INSIG2 on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2, signal transducer and activator of transcription 6 (STAT6. We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk.

  20. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  1. Independent Gene Discovery and Testing

    Science.gov (United States)

    Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

    2010-01-01

    A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

  2. Gene probes: principles and protocols

    National Research Council Canada - National Science Library

    Rapley, Ralph; Aquino de Muro, Marilena

    2002-01-01

    ... of labeled DNA has allowed genes to be mapped to single chromosomes and in many cases to a single chromosome band, promoting significant advance in human genome mapping. Gene Probes: Principles and Protocols presents the principles for gene probe design, labeling, detection, target format, and hybridization conditions together with detailed protocols, accom...

  3. Compositional gradients in Gramineae genes

    DEFF Research Database (Denmark)

    Wong, Gane Ka-Shu; Wang, Jun; Tao, Lin

    2002-01-01

    In this study, we describe a property of Gramineae genes, and perhaps all monocot genes, that is not observed in eudicot genes. Along the direction of transcription, beginning at the junction of the 5'-UTR and the coding region, there are gradients in GC content, codon usage, and amino-acid usage...

  4. Optimal gene partition into operons correlates with gene functional order

    Science.gov (United States)

    Zaslaver, Alon; Mayo, Avi; Ronen, Michal; Alon, Uri

    2006-09-01

    Gene arrangement into operons varies between bacterial species. Genes in a given system can be on one operon in some organisms and on several operons in other organisms. Existing theories explain why genes that work together should be on the same operon, since this allows for advantageous lateral gene transfer and accurate stoichiometry. But what causes the frequent separation into multiple operons of co-regulated genes that act together in a pathway? Here we suggest that separation is due to benefits made possible by differential regulation of each operon. We present a simple mathematical model for the optimal distribution of genes into operons based on a balance of the cost of operons and the benefit of regulation that provides 'just-when-needed' temporal order. The analysis predicts that genes are arranged such that genes on the same operon do not skip functional steps in the pathway. This prediction is supported by genomic data from 137 bacterial genomes. Our work suggests that gene arrangement is not only the result of random historical drift, genome re-arrangement and gene transfer, but has elements that are solutions of an evolutionary optimization problem. Thus gene functional order may be inferred by analyzing the operon structure across different genomes.

  5. Neo-Darwinism, the modern synthesis and selfish genes: are they of use in physiology?

    Science.gov (United States)

    Noble, Denis

    2011-03-01

    This article argues that the gene-centric interpretations of evolution, and more particularly the selfish gene expression of those interpretations, form barriers to the integration of physiological science with evolutionary theory. A gene-centred approach analyses the relationships between genotypes and phenotypes in terms of differences (change the genotype and observe changes in phenotype). We now know that, most frequently, this does not correctly reveal the relationships because of extensive buffering by robust networks of interactions. By contrast, understanding biological function through physiological analysis requires an integrative approach in which the activity of the proteins and RNAs formed from each DNA template is analysed in networks of interactions. These networks also include components that are not specified by nuclear DNA. Inheritance is not through DNA sequences alone. The selfish gene idea is not useful in the physiological sciences, since selfishness cannot be defined as an intrinsic property of nucleotide sequences independently of gene frequency, i.e. the 'success' in the gene pool that is supposed to be attributable to the 'selfish' property. It is not a physiologically testable hypothesis.

  6. Adaptive evolution in the Arabidopsis MADS-box gene family inferred from its complete resolved phylogeny

    Science.gov (United States)

    Martínez-Castilla, León Patricio; Alvarez-Buylla, Elena R.

    2003-01-01

    Gene duplication is a substrate of evolution. However, the relative importance of positive selection versus relaxation of constraints in the functional divergence of gene copies is still under debate. Plant MADS-box genes encode transcriptional regulators key in various aspects of development and have undergone extensive duplications to form a large family. We recovered 104 MADS sequences from the Arabidopsis genome. Bayesian phylogenetic trees recover type II lineage as a monophyletic group and resolve a branching sequence of monophyletic groups within this lineage. The type I lineage is comprised of several divergent groups. However, contrasting gene structure and patterns of chromosomal distribution between type I and II sequences suggest that they had different evolutionary histories and support the placement of the root of the gene family between these two groups. Site-specific and site-branch analyses of positive Darwinian selection (PDS) suggest that different selection regimes could have affected the evolution of these lineages. We found evidence for PDS along the branch leading to flowering time genes that have a direct impact on plant fitness. Sites with high probabilities of having been under PDS were found in the MADS and K domains, suggesting that these played important roles in the acquisition of novel functions during MADS-box diversification. Detected sites are targets for further experimental analyses. We argue that adaptive changes in MADS-domain protein sequences have been important for their functional divergence, suggesting that changes within coding regions of transcriptional regulators have influenced phenotypic evolution of plants. PMID:14597714

  7. The gene patent controversy on Twitter: a case study of Twitter users' responses to the CHEO lawsuit against Long QT gene patents.

    Science.gov (United States)

    Du, Li; Kamenova, Kalina; Caulfield, Timothy

    2015-08-25

    The recent Canadian lawsuit on patent infringement, filed by the Children's Hospital of Eastern Ontario (CHEO), has engendered a significant public debate on whether patenting genes should be legal in Canada. In part, this public debate has involved the use of social networking sites, such as Twitter. This case provides an opportunity to examine how Twitter was used in the context of this gene patent controversy. We collected 310 English-language tweets that contained the keyword "gene patents" by using TOPSY.com and Twitter's built-in search engine. A content analysis of the messages was conducted to establish the users' perspectives on both CHEO's court challenge and the broader controversy over the patenting of human DNA. More specifically, we analyzed the users' demographics, geographic locations, and attitudes toward the CHEO position on gene patents and the patentability of human genes in principle. Our analysis has shown that messages tweeted by news media and health care organizations were re-tweeted most frequently in Twitter discussions regarding both the CHEO patent infringement lawsuit and gene patents in general. 34.8% of tweets were supportive of CHEO, with 52.8% of the supportive tweets suggesting that gene patents contravene patients' rights to health care access. 17.6% of the supportive tweets cited ethical and social concerns against gene patents. Nearly 40% of tweets clearly expressed that human genes should not be patentable, and there were no tweets that presented perspectives favourable toward the patenting of human genes. Access to healthcare and the use of genetic testing were the most important concerns raised by Twitter users in the context of the CHEO case. Our analysis of tweets reveals an expectation that the CHEO lawsuit will provide an opportunity to clear the confusion on gene patents by establishing a legal precedent on the patentability of human genes in Canada. In general, there were no tweets arguing in favour of gene patents

  8. A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Burton, Mark; Thomassen, Mads

    2016-01-01

    to the World Health Organization (WHO) 2008 classification, bone marrow histology is a major component in the distinction between these disease entities. However, the differential diagnosis between them may be challenging and several studies have not been able to distinguish between them. Most lately, it has...... been argued that simple blood tests, including the leukocyte count and plasma lactate dehydrogenase (LDH) may be useful tools to separate genuine ET from prePMF, the latter disease entity more often being featured by anemia, leukocytosis and elevated LDH. Whole blood gene expression profiling...

  9. Characterization of the ptr5{sup +} gene involved in nuclear mRNA export in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Nobuyoshi; Ikeda, Terumasa; Mizuki, Fumitaka [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kurokami, Kumamoto 860-8555 (Japan); Tani, Tokio, E-mail: ttani@sci.kumamoto-u.ac.jp [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kurokami, Kumamoto 860-8555 (Japan)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer We cloned the ptr5{sup +} gene involved in nuclear mRNA export in fission yeast. Black-Right-Pointing-Pointer The ptr5{sup +} gene was found to encode nucleoporin 85 (Nup85). Black-Right-Pointing-Pointer Seh1p and Mlo3p are multi-copy suppressors for the ptr5 mutation. Black-Right-Pointing-Pointer Ptr5p/Nup85p functions in nuclear mRNA export through the mRNA export factor Rae1p. Black-Right-Pointing-Pointer Ptr5p/Nup85p interacts genetically with pre-mRNA splicing factors. -- Abstract: To analyze the mechanisms of mRNA export from the nucleus to the cytoplasm, we have isolated eleven mutants, ptr [poly(A){sup +} RNA transport] 1 to 11, which accumulate poly(A){sup +} RNA in the nucleus at a nonpermissive temperature in Schizosaccharomyces pombe. Of those, the ptr5-1 mutant shows dots- or a ring-like accumulation of poly(A){sup +} RNA at the nuclear periphery after shifting to the nonpermissive temperature. We cloned the ptr5{sup +} gene and found that it encodes a component of the nuclear pore complex (NPC), nucleoporin 85 (Nup85). The ptr5-1 mutant shows no defects in protein transport, suggesting the specific involvement of Ptr5p/Nup85p in nuclear mRNA export in S. pombe. We identified Seh1p, a nucleoporin interacting with Nup85p, an mRNA-binding protein Mlo3p, and Sac3p, a component of the TREX-2 complex involved in coupling of nuclear mRNA export with transcription, as multi-copy suppressors for the ptr5-1 mutation. In addition, we found that the ptr5-1 mutation is synthetically lethal with a mutation of the mRNA export factor Rae1p, and that the double mutant exaggerates defective nuclear mRNA export, suggesting that Ptr5p/Nup85p is involved in nuclear mRNA export through Rae1p. Interestingly, the ptr5-1 mutation also showed synthetic effects with several prp pre-mRNA splicing mutations, suggesting a functional linkage between the NPCs and the splicing apparatus in the yeast nucleus.

  10. Somatic gene therapy for dyslipidemias.

    Science.gov (United States)

    Belalcazar, M; Chan, L

    1999-09-01

    Somatic gene transfer is a valuable tool for the in vivo evaluation of lipoprotein metabolism. It has been used to dissect metabolic pathways, to establish structure-function relationships of various gene products, and to evaluate conventional lipid-lowering and novel therapeutic genes for the treatment of lipoprotein disorders. In this article we review some general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. We highlight some recent advances in adenoviral vector development that make this vector an attractive system for clinical trials.

  11. Gene electrotransfer in clinical trials

    DEFF Research Database (Denmark)

    Gehl, Julie

    2014-01-01

    Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapte...... describes how gene therapy may be performed using electric pulses to enhance uptake and expression.......Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapter...

  12. Tumor-suppressing gene therapy.

    Science.gov (United States)

    Fang, Bingliang; Roth, Jack A

    2003-01-01

    Tumor-suppressor genes play pivotal roles in maintaining genome integrity and in regulating cell proliferation, differentiation, and apoptosis. Their loss-of-function mutations are related directly to tumorigenesis. Thus, use of tumor-suppressor genes as anticancer therapeutics has been investigated rigorously in both experimental and clinical researches. Transfer of various tumor-suppressor genes directly to cancer cells has been demonstrated to suppress tumor growth via induction of apoptosis and cell-cycle arrest and, in some cases, with evidence for bystander effects. Various studies also have shown that combination of tumor-suppressor gene therapy with conventional anticancer therapy can yield synergistic therapeutic benefits. Clinical trials with tumor-suppressor genes, especially the p53 gene, have demonstrated that the treatment is well tolerated, and; favorable clinical responses, including a pathologically complete responses, have been observed in a subset of patients with advanced disease or with cancers resistant to conventional therapy. Yet, current gene replacement approaches in cancer gene therapy must be improved if they are to have a broader clinical impact. Efficient systemic gene delivery systems will be required ultimately for treatment of metastatic disease. In this review, we have recently summarized achievements in tumor-suppressor gene therapy with a focus on the p53 gene.

  13. Horizontal gene transfer in choanoflagellates.

    Science.gov (United States)

    Tucker, Richard P

    2013-01-01

    Horizontal gene transfer (HGT), also known as lateral gene transfer, results in the rapid acquisition of genes from another organism. HGT has long been known to be a driving force in speciation in prokaryotes, and there is evidence for HGT from symbiotic and infectious bacteria to metazoans, as well as from protists to bacteria. Recently, it has become clear that as many as a 1,000 genes in the genome of the choanoflagellate Monosiga brevicollis may have been acquired by HGT. Interestingly, these genes reportedly come from algae, bacteria, and other choanoflagellate prey. Some of these genes appear to have allowed an ancestral choanoflagellate to exploit nutrient-poor environments and were not passed on to metazoan descendents. However, some of these genes are also found in animal genomes, suggesting that HGT into a common ancestor of choanozoans and animals may have contributed to metazoan evolution. Copyright © 2012 Wiley Periodicals, Inc.

  14. Gene finding in novel genomes

    Directory of Open Access Journals (Sweden)

    Korf Ian

    2004-05-01

    Full Text Available Abstract Background Computational gene prediction continues to be an important problem, especially for genomes with little experimental data. Results I introduce the SNAP gene finder which has been designed to be easily adaptable to a variety of genomes. In novel genomes without an appropriate gene finder, I demonstrate that employing a foreign gene finder can produce highly inaccurate results, and that the most compatible parameters may not come from the nearest phylogenetic neighbor. I find that foreign gene finders are more usefully employed to bootstrap parameter estimation and that the resulting parameters can be highly accurate. Conclusion Since gene prediction is sensitive to species-specific parameters, every genome needs a dedicated gene finder.

  15. Driven to extinction? The ethics of eradicating mosquitoes with gene-drive technologies.

    Science.gov (United States)

    Pugh, Jonathan

    2016-09-01

    Mosquito-borne diseases represent a significant global disease burden, and recent outbreaks of such diseases have led to calls to reduce mosquito populations. Furthermore, advances in 'gene-drive' technology have raised the prospect of eradicating certain species of mosquito via genetic modification. This technology has attracted a great deal of media attention, and the idea of using gene-drive technology to eradicate mosquitoes has been met with criticism in the public domain. In this paper, I shall dispel two moral objections that have been raised in the public domain against the use of gene-drive technologies to eradicate mosquitoes. The first objection invokes the concept of the 'sanctity of life' in order to claim that we should not drive an animal to extinction. In response, I follow Peter Singer in raising doubts about general appeals to the sanctity of life, and argue that neither individual mosquitoes nor mosquitoes species considered holistically are appropriately described as bearing a significant degree of moral status. The second objection claims that seeking to eradicate mosquitoes amounts to displaying unacceptable degrees of hubris. Although I argue that this objection also fails, I conclude by claiming that it raises the important point that we need to acquire more empirical data about, inter alia, the likely effects of mosquito eradication on the ecosystem, and the likelihood of gene-drive technology successfully eradicating the intended mosquito species, in order to adequately inform our moral analysis of gene-drive technologies in this context. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Progress in gene targeting and gene therapy for retinitis pigmentosa

    Energy Technology Data Exchange (ETDEWEB)

    Farrar, G.J.; Humphries, M.M.; Erven, A. [Trinity College, Dublin (Ireland)] [and others

    1994-09-01

    Previously, we localized disease genes involved in retinitis pigmentosa (RP), an inherited retinal degeneration, close to the rhodopsin and peripherin genes on 3q and 6p. Subsequently, we and others identified mutations in these genes in RP patients. Currently animal models for human retinopathies are being generated using gene targeting by homologous recombination in embryonic stem (ES) cells. Genomic clones for retinal genes including rhodopsin and peripherin have been obtained from a phage library carrying mouse DNA isogenic with the ES cell line (CC1.2). The peripherin clone has been sequenced to establish the genomic structure of the mouse gene. Targeting vectors for rhodopsin and peripherin including a neomycin cassette for positive selection and thymidine kinase genes enabling selection against random intergrants are under construction. Progress in vector construction will be presented. Simultaneously we are developing systems for delivery of gene therapies to retinal tissues utilizing replication-deficient adenovirus (Ad5). Efficacy of infection subsequent to various methods of intraocular injection and with varying viral titers is being assayed using an adenovirus construct containing a CMV promoter LacZ fusion as reporter and the range of tissues infected and the level of duration of LacZ expression monitored. Viral constructs with the LacZ reporter gene under the control of retinal specific promoters such as rhodopsin and IRBP cloned into pXCJL.1 are under construction. An update on developments in photoreceptor cell-directed expression of virally delivered genes will be presented.

  17. From gene expression to gene regulatory networks in Arabidopsis thaliana.

    Science.gov (United States)

    Needham, Chris J; Manfield, Iain W; Bulpitt, Andrew J; Gilmartin, Philip M; Westhead, David R

    2009-09-03

    The elucidation of networks from a compendium of gene expression data is one of the goals of systems biology and can be a valuable source of new hypotheses for experimental researchers. For Arabidopsis, there exist several thousand microarrays which form a valuable resource from which to learn. A novel Bayesian network-based algorithm to infer gene regulatory networks from gene expression data is introduced and applied to learn parts of the transcriptomic network in Arabidopsis thaliana from a large number (thousands) of separate microarray experiments. Starting from an initial set of genes of interest, a network is grown by iterative addition to the model of the gene, from another defined set of genes, which gives the 'best' learned network structure. The gene set for iterative growth can be as large as the entire genome. A number of networks are inferred and analysed; these show (i) an agreement with the current literature on the circadian clock network, (ii) the ability to model other networks, and (iii) that the learned network hypotheses can suggest new roles for poorly characterized genes, through addition of relevant genes from an unconstrained list of over 15,000 possible genes. To demonstrate the latter point, the method is used to suggest that particular GATA transcription factors are regulators of photosynthetic genes. Additionally, the performance in recovering a known network from different amounts of synthetically generated data is evaluated. Our results show that plausible regulatory networks can be learned from such gene expression data alone. This work demonstrates that network hypotheses can be generated from existing gene expression data for use by experimental biologists.

  18. Gene circuit analysis of the terminal gap gene huckebein.

    Directory of Open Access Journals (Sweden)

    Maksat Ashyraliyev

    2009-10-01

    Full Text Available The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network.

  19. The Caenorhabditis chemoreceptor gene families

    Directory of Open Access Journals (Sweden)

    Robertson Hugh M

    2008-10-01

    Full Text Available Abstract Background Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  20. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  1. Genetic rhetoric: Science, authority, and genes

    Science.gov (United States)

    Shea, Elizabeth Parthenia

    This dissertation is an analysis of how the cultural authority of genetics works through language. An analysis of the rhetorical construction of knowledge and authority in cultural contexts, the study is intended to contribute to a larger discussion aimed at keeping the intersections of science and culture within the realm of rhetoric, that is within the realm of communication and dialogue. Of special concern is the influence of genetic rhetoric on the cultural momentum of biological determinism to explain away social organization, class inequalities, racial differences, gender differences, and stigmatized behaviors by rooting them in the construct of the biological individual. This study separates questions of legitimacy from questions of authority and focuses on the way that authority of genetics works through language. With authority defined as the function of resisting challenges to legitimacy and/or power, the study consists of three parts. First, a historical analysis of the terms science, genetics, and gene, shows how these words came to refer not only to areas and objects of study but also to sources of epistemological legitimacy outside culture and language. The relationships between these words and their referents are examined in socio-historical context to illustrate how the function of signaling authority was inscribed in the literal definition of these terms. Second, introductory chapters of contemporary Genetics textbooks are examined. In these texts the foundations of legitimacy associated with genetics and science are maintained as the authors articulate idealized views of science and genetics in relation to society. Finally, articles in the popular press reporting on and discussing recent research correlating genetics and homosexuality are examined. The popular press reports of "gay gene" research serve as textual examples of figurative representations of genetics concepts shaping discourse about social issues. I argue that the cultural authority

  2. The evolutionary trajectory of the mating-type (mat genes in Neurospora relates to reproductive behavior of taxa

    Directory of Open Access Journals (Sweden)

    Johannesson Hanna

    2008-04-01

    Full Text Available Abstract Background Comparative sequencing studies among a wide range of taxonomic groups, including fungi, have led to the discovery that reproductive genes evolve more rapidly than other genes. However, for fungal reproductive genes the question has remained whether the rapid evolution is a result of stochastic or deterministic processes. The mating-type (mat genes constitute the master regulators of sexual reproduction in filamentous ascomycetes and here we present a study of the molecular evolution of the four mat-genes (mat a-1, mat A-1, mat A-2 and mat A-3 of 20 Neurospora taxa. Results We estimated nonsynonymous and synonymous substitution rates of genes to infer their evolutionary rate, and confirmed that the mat-genes evolve rapidly. Furthermore, the evolutionary trajectories are related to the reproductive modes of the taxa; likelihood methods revealed that positive selection acting on specific codons drives the diversity in heterothallic taxa, while among homothallic taxa the rapid evolution is due to a lack of selective constraint. The latter finding is supported by presence of stop codons and frame shift mutations disrupting the open reading frames of mat a-1, mat A-2 and mat A-3 in homothallic taxa. Lower selective constraints of mat-genes was found among homothallic than heterothallic taxa, and comparisons with non-reproductive genes argue that this disparity is not a nonspecific, genome-wide phenomenon. Conclusion Our data show that the mat-genes evolve rapidly in Neurospora. The rapid divergence is due to either adaptive evolution or lack of selective constraints, depending on the reproductive mode of the taxa. This is the first instance of positive selection acting on reproductive genes in the fungal kingdom, and illustrates how the evolutionary trajectory of reproductive genes can change after a switch in reproductive behaviour of an organism.

  3. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata

    2015-01-01

    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene...... expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles...... for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying...

  4. Molecular mechanism of the priming by jasmonic acid of specific dehydration stress response genes in Arabidopsis.

    Science.gov (United States)

    Liu, Ning; Avramova, Zoya

    2016-01-01

    Plant genes that provide a different response to a similar dehydration stress illustrate the concept of transcriptional 'dehydration stress memory'. Pre-exposing a plant to a biotic stress or a stress-signaling hormone may increase transcription from response genes in a future stress, a phenomenon known as 'gene priming'. Although known that primed transcription is preceded by accumulation of H3K4me3 marks at primed genes, what mechanism provides for their appearance before the transcription was unclear. How augmented transcription is achieved, whether/how the two memory phenomena are connected at the transcriptional level, and whether similar molecular and/or epigenetic mechanisms regulate them are fundamental questions about the molecular mechanisms regulating gene expression. Although the stress hormone jasmonic acid (JA) was unable to induce transcription of tested dehydration stress response genes, it strongly potentiated transcription from specific ABA-dependent 'memory' genes. We elucidate the molecular mechanism causing their priming, demonstrate that stalled RNA polymerase II and H3K4me3 accumulate as epigenetic marks at the JA-primed ABA-dependent genes before actual transcription, and describe how these events occur mechanistically. The transcription factor MYC2 binds to the genes in response to both dehydration stress and to JA and determines the specificity of the priming. The MEDIATOR subunit MED25 links JA-priming with dehydration stress response pathways at the transcriptional level. Possible biological relevance of primed enhanced transcription from the specific memory genes is discussed. The biotic stress hormone JA potentiated transcription from a specific subset of ABA-response genes, revealing a novel aspect of the JA- and ABA-signaling pathways' interactions. H3K4me3 functions as an epigenetic mark at JA-primed dehydration stress response genes before transcription. We emphasize that histone and epigenetic marks are not synonymous and argue

  5. The infinitely many genes model with horizontal gene transfer

    OpenAIRE

    Baumdicker, Franz; Pfaffelhuber, Peter

    2013-01-01

    The genome of bacterial species is much more flexible than that of eukaryotes. Moreover, the distributed genome hypothesis for bacteria states that the total number of genes present in a bacterial population is greater than the genome of every single individual. The pangenome, i.e. the set of all genes of a bacterial species (or a sample), comprises the core genes which are present in all living individuals, and accessory genes, which are carried only by some individuals. In order to use acce...

  6. Are TMEM genes potential candidate genes for panic disorder?

    DEFF Research Database (Denmark)

    NO, Gregersen; Buttenschøn, Henriette Nørmølle; Hedemand, Anne

    2014-01-01

    We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12, a previou......We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12...

  7. Parenting in the Age of Preimplantation Gene Editing.

    Science.gov (United States)

    Klipstein, Sigal

    2017-12-01

    Medical science at its core aims to preserve health and eliminate disease, but a common theme in scientific discovery is the application of findings in ways that were not the primary intent. The development of diagnostic modalities to predict the health of resulting children has been a fundamental aim underpinning research into prenatal and preimplantation diagnostic modalities; however, the knowledge gained has in some cases been utilized for nonmedical purposes. As an example, amniocentesis developed to determine whether the pregnancy is chromosomally normal also provides information about the sex of the fetus, which normally does not affect health. The emerging gene-editing technologies that could be used to repair mutated disease-causing genes in an embryo will presumably also be able to be used to alter traits unrelated to disease. And yet, I will argue, the desire to preserve the mystery of reproduction remains a central value in humans' quest to reproduce. This yearning to maintain the mysteries will likely temper the development of strategies to alter our genome and affect the genetic identities of our offspring. In my experience as an obstetrician and reproductive endocrinology and infertility subspecialist, people want to have, not the best possible baby, but rather their own baby. © 2017 The Hastings Center.

  8. Gene therapy for psychiatric disorders.

    Science.gov (United States)

    Gelfand, Yaroslav; Kaplitt, Michael G

    2013-01-01

    Gene therapy has become of increasing interest in clinical neurosurgery with the completion of numerous clinical trials for Parkinson disease, Alzheimer disease, and pediatric genetic disorders. With improved understanding of the dysfunctional circuitry mediating various psychiatric disorders, deep brain stimulation for refractory psychiatric diseases is being increasingly explored in human patients. These factors are likely to facilitate development of gene therapy for psychiatric diseases. Because delivery of gene therapy agents would require the same surgical techniques currently being employed for deep brain stimulation, neurosurgeons are likely to lead the development of this field, as has occurred in other areas of clinical gene therapy for neurologic disorders. We review the current state of gene therapy for psychiatric disorders and focus specifically on particular areas of promising research that may translate into human trials for depression, drug addiction, obsessive-compulsive disorder, and schizophrenia. Issues that are relatively unique to psychiatric gene therapy are also discussed. Copyright © 2013. Published by Elsevier Inc.

  9. Selection for the compactness of highly expressed genes in Gallus gallus

    Directory of Open Access Journals (Sweden)

    Zhou Ming

    2010-05-01

    (n = 1105, and compared the first intron length and the average intron length between highly expressed genes (top 5% expressed genes and weakly expressed genes (bottom 5% expressed genes. We found that the first intron length and the average intron length in highly expressed genes are not different from that in weakly expressed genes. We also made a comparison between ubiquitously expressed genes and narrowly expressed somatic genes with similar expression levels. Our data demonstrated that ubiquitously expressed genes are less compact than narrowly expressed genes with the similar expression levels. Obviously, these observations can not be explained by mutational bias hypotheses either. We also found that the significant trend between genes' compactness and expression level could not be affected by local mutational biases. We argued that the selection of economy model is most likely one to explain the relationship between gene expression and gene characteristics in chicken genome. Conclusion Natural selection appears to favor the compactness of highly expressed genes in chicken genome. This observation can be explained by the selection of economy model. Reviewers This article was reviewed by Dr. Gavin Huttley, Dr. Liran Carmel (nominated by Dr. Eugene V. Koonin and Dr. Araxi Urrutia (nominated by Dr. Laurence D. Hurst.

  10. Gene set analysis for GWAS

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette

    2014-01-01

    Abstract We discuss the use of modified Kolmogorov-Smirnov (KS) statistics in the context of gene set analysis and review corresponding null and alternative hypotheses. Especially, we show that, when enhancing the impact of highly significant genes in the calculation of the test statistic...... parameter and the genesis and distribution of the gene-level statistics, and illustrate the effects of differential weighting in a real-life example....

  11. A genetic ensemble approach for gene-gene interaction identification

    Directory of Open Access Journals (Sweden)

    Ho Joshua WK

    2010-10-01

    Full Text Available Abstract Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA and an ensemble of classifiers (called genetic ensemble. Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR and is slightly better than Polymorphism Interaction Analysis (PIA, which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of

  12. Prion protein gene frequencies in three Sicilian dairy sheep populations

    Directory of Open Access Journals (Sweden)

    Santo Caracappa

    2010-01-01

    Full Text Available The objective of this paper was to investigate the prion protein (PrP genotype and haplotype frequencies in three Sicilian dairy sheep populations. The three populations were: (1 1096 Valle del Belice animals, (2 1143 Comisana animals, and (3 1771 individuals from 5 flocks with scrapie outbreaks, in which the animals were crossbreds derived from indigenous Sicilian dairy breeds. PrP genotypes are described for the three codons 136 (Alanine or Valine; A, V, 154 (Histidine or Arginine; H, R, and 171 (Glutamine, Arginine or Histidine; Q, R, H which represent polymorphisms known to be linked with scrapie susceptibility. The Valle del Belice haplotype frequencies were 32.3% ARR, 6.5% AHQ, 1.0% ARH, 58.8% ARQ, and 1.4% VRQ. The Comisana frequencies were 39.4% ARR, 2.9% AHQ, 2.9% ARH, 50.9% ARQ, and 3.9% VRQ. In the flocks with scrapie outbreaks the frequencies were 32.8% ARR, 2.4% AHQ, 1.7% ARH, 59.1% ARQ, and 3.9% VRQ. In all three populations ARQ and ARR were the most frequent haplotypes. Multiple generations of strong selection will be needed to fixate the most resistant ARR haplotype.

  13. Gene therapy for hemophilia

    Science.gov (United States)

    Rogers, Geoffrey L.; Herzog, Roland W.

    2015-01-01

    Hemophilia is an X-linked inherited bleeding disorder consisting of two classifications, hemophilia A and hemophilia B, depending on the underlying mutation. Although the disease is currently treatable with intravenous delivery of replacement recombinant clotting factor, this approach represents a significant cost both monetarily and in terms of quality of life. Gene therapy is an attractive alternative approach to the treatment of hemophilia that would ideally provide life-long correction of clotting activity with a single injection. In this review, we will discuss the multitude of approaches that have been explored for the treatment of both hemophilia A and B, including both in vivo and ex vivo approaches with viral and nonviral delivery vectors. PMID:25553466

  14. Introduction: Cancer Gene Networks.

    Science.gov (United States)

    Clarke, Robert

    2017-01-01

    Constructing, evaluating, and interpreting gene networks generally sits within the broader field of systems biology, which continues to emerge rapidly, particular with respect to its application to understanding the complexity of signaling in the context of cancer biology. For the purposes of this volume, we take a broad definition of systems biology. Considering an organism or disease within an organism as a system, systems biology is the study of the integrated and coordinated interactions of the network(s) of genes, their variants both natural and mutated (e.g., polymorphisms, rearrangements, alternate splicing, mutations), their proteins and isoforms, and the organic and inorganic molecules with which they interact, to execute the biochemical reactions (e.g., as enzymes, substrates, products) that reflect the function of that system. Central to systems biology, and perhaps the only approach that can effectively manage the complexity of such systems, is the building of quantitative multiscale predictive models. The predictions of the models can vary substantially depending on the nature of the model and its inputoutput relationships. For example, a model may predict the outcome of a specific molecular reaction(s), a cellular phenotype (e.g., alive, dead, growth arrest, proliferation, and motility), a change in the respective prevalence of cell or subpopulations, a patient or patient subgroup outcome(s). Such models necessarily require computers. Computational modeling can be thought of as using machine learning and related tools to integrate the very high dimensional data generated from modern, high throughput omics technologies including genomics (next generation sequencing), transcriptomics (gene expression microarrays; RNAseq), metabolomics and proteomics (ultra high performance liquid chromatography, mass spectrometry), and "subomic" technologies to study the kinome, methylome, and others. Mathematical modeling can be thought of as the use of ordinary

  15. Pompe disease gene therapy

    Science.gov (United States)

    Byrne, Barry J.; Falk, Darin J.; Pacak, Christina A.; Nayak, Sushrusha; Herzog, Roland W.; Elder, Melissa E.; Collins, Shelley W.; Conlon, Thomas J.; Clement, Nathalie; Cleaver, Brian D.; Cloutier, Denise A.; Porvasnik, Stacy L.; Islam, Saleem; Elmallah, Mai K.; Martin, Anatole; Smith, Barbara K.; Fuller, David D.; Lawson, Lee Ann; Mah, Cathryn S.

    2011-01-01

    Pompe disease is an autosomal recessive metabolic myopathy caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase and results in cellular lysosomal and cytoplasmic glycogen accumulation. A wide spectrum of disease exists from hypotonia and severe cardiac hypertrophy in the first few months of life due to severe mutations to a milder form with the onset of symptoms in adulthood. In either condition, the involvement of several systems leads to progressive weakness and disability. In early-onset severe cases, the natural history is characteristically cardiorespiratory failure and death in the first year of life. Since the advent of enzyme replacement therapy (ERT), the clinical outcomes have improved. However, it has become apparent that a new natural history is being defined in which some patients have substantial improvement following ERT, while others develop chronic disability reminiscent of the late-onset disease. In order to improve on the current clinical outcomes in Pompe patients with diminished clinical response to ERT, we sought to address the cause and potential for the treatment of disease manifestations which are not amenable to ERT. In this review, we will focus on the preclinical studies that are relevant to the development of a gene therapy strategy for Pompe disease, and have led to the first clinical trial of recombinant adeno-associated virus-mediated gene-based therapy for Pompe disease. We will cover the preliminary laboratory studies and rationale for a clinical trial, which is based on the treatment of the high rate of respiratory failure in the early-onset patients receiving ERT. PMID:21518733

  16. A perspective on the economic valorization of gene manipulated biotechnology: Past and future.

    Science.gov (United States)

    Knockaert, Mirjam; Manigart, Sophie; Cattoir, Sofie; Verstraete, Willy

    2015-06-01

    Three distinct fields of gene manipulated biotechnology have so far been economically exploited: medical biotechnology, plant biotechnology and industrial biotechnology. This article analyzes the economic evolution and its drivers in the three fields over the past decades, highlighting strong divergences. Product and market characteristics, affecting firms' financing options, are shown to be important enablers or inhibitors. Subsequently, the lack of commercialization in a fourth type of gene manipulated biotechnology, namely environmental biotechnology, is explained by the existence of strong barriers. Given the latter's great promises for environmental sustainability, we argue for a need to push the commercial valorization of environmental biotechnology. Our research has strong implications for (technology) management research in biotechnology, pointing to a need to control for and/or distinguish between different biotechnology fields.

  17. Vancomycin gene selection in the microbiome of urban Rattus norvegicus from hospital environment

    DEFF Research Database (Denmark)

    Arn Hansen, Thomas; Joshi, Tejal; Larsen, Anders Rhod

    2016-01-01

    Widespread use of antibiotics has resulted in selection pressure on genes that make bacteria non-responsive to antibiotics. These antibiotic-resistant bacteria are currently a major threat to global health. There are various possibilities for the transfer of antibiotic resistance genes. It has be....... norvegicus microbiome, potentially driven by the outflow of antibiotics and antibiotic-resistant bacteria into the wastewater systems. Carriage of vancomycin resistance may suggest that R. norvegicus is acting as a reservoir for possible transmission to the human population....... argued that animal vectors such as Rattus norvegicus (R. norvegicus) living in hospital sewage systems are ideal for carrying pathogens responsible for fatal diseases in humans. Using a metagenomic sequencing approach, we investigated faecal samples of R. norvegicus from three major cities...

  18. Responsible innovation in human germline gene editing: Background document to the recommendations of ESHG and ESHRE.

    Science.gov (United States)

    De Wert, Guido; Heindryckx, Björn; Pennings, Guido; Clarke, Angus; Eichenlaub-Ritter, Ursula; van El, Carla G; Forzano, Francesca; Goddijn, Mariëtte; Howard, Heidi C; Radojkovic, Dragica; Rial-Sebbag, Emmanuelle; Dondorp, Wybo; Tarlatzis, Basil C; Cornel, Martina C

    2018-01-12

    Technological developments in gene editing raise high expectations for clinical applications, including editing of the germline. The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. This document provides the background to the Recommendations. Germline gene editing is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if germline gene editing would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique could help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? This Background document summarizes the scientific developments and expectations regarding germline gene editing, legal regulations at the European level, and ethics for three different settings (basic research, preclinical research and clinical applications). In ethical terms, we argue that the deontological objections (e.g., gene editing goes against nature) do not seem convincing while consequentialist objections (e.g., safety for the children thus conceived and following generations) require research, not all of which is allowed in the current legal situation in European countries. Development of this Background document and Recommendations reflects the responsibility to help society understand and debate the full range of possible implications of the new technologies, and to contribute to regulations that are adapted to the dynamics of the field while taking account of ethical considerations and societal concerns.

  19. Vancomycin gene selection in the microbiome of urban Rattus norvegicus from hospital environment.

    Science.gov (United States)

    Hansen, Thomas Arn; Joshi, Tejal; Larsen, Anders Rhod; Andersen, Paal Skytt; Harms, Klaus; Mollerup, Sarah; Willerslev, Eske; Fuursted, Kurt; Nielsen, Lars Peter; Hansen, Anders Johannes

    2016-01-01

    Widespread use of antibiotics has resulted in selection pressure on genes that make bacteria non-responsive to antibiotics. These antibiotic-resistant bacteria are currently a major threat to global health. There are various possibilities for the transfer of antibiotic resistance genes. It has been argued that animal vectors such as Rattus norvegicus (R. norvegicus) living in hospital sewage systems are ideal for carrying pathogens responsible for fatal diseases in humans. Using a metagenomic sequencing approach, we investigated faecal samples of R. norvegicus from three major cities for the presence of antibiotic resistance genes. We show that despite the shared resistome within samples from the same geographic locations, samples from hospital area carry significantly abundant vancomycin resistance genes. The observed pattern is consistent with a selection for vancomycin genes in the R. norvegicus microbiome, potentially driven by the outflow of antibiotics and antibiotic-resistant bacteria into the wastewater systems. Carriage of vancomycin resistance may suggest that R. norvegicus is acting as a reservoir for possible transmission to the human population. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  20. Gene therapy for meningioma : improved gene delivery with targeted adenoviruses

    NARCIS (Netherlands)

    Dirven, CMF; Grill, J; Lamfers, MLM; Van der Valk, P; Leonhart, AM; Van Beusechem, VW; Haisma, HJ; Pinedo, HM; Curiel, DT; Vandertop, WP; Gerritsen, WR

    Object. Due to their surgical inaccessibility or aggressive behavior, some meningiomas cannot be cured with current treatment strategies. Gene therapy is an emerging strategy for the treatment of brain tumors, which the authors investigated to determine whether adenoviruses could be used for gene

  1. Gene-gene Interaction Analyses for Atrial Fibrillation

    NARCIS (Netherlands)

    H. Lin (Honghuang); M. Mueller-Nurasyid; A.V. Smith (Albert Vernon); D.E. Arking (Dan); J. Barnard (John); T.M. Bartz (Traci M.); K.L. Lunetta (Kathryn); K. Lohman (Kurt); M.E. Kleber (Marcus); S.A. Lubitz (Steven); Geelhoed, B. (Bastiaan); S. Trompet (Stella); M.N. Niemeijer (Maartje); T. Kacprowski (Tim); D.I. Chasman (Daniel); Klarin, D. (Derek); M.F. Sinner (Moritz); M. Waldenberger (Melanie); T. Meitinger (Thomas); T.B. Harris (Tamara); L.J. Launer (Lenore); E.Z. Soliman (Elsayed Z.); L. Chen (Lin); J.D. Smith (Jonathan); D.R. van Wagoner (David); Rotter, J.I. (Jerome I.); B.M. Psaty (Bruce); Xie, Z. (Zhijun); A.E. Hendricks (Audrey E.); Ding, J. (Jingzhong); G.E. Delgado (Graciela E.); N. Verweij (Niek); P. van der Harst (Pim); P.W. MacFarlane (Peter); I. Ford (Ian); A. Hofman (Albert); A.G. Uitterlinden (André); J. Heeringa (Jan); O.H. Franco (Oscar); J.A. Kors (Jan); Weiss, S. (Stefan); H. Völzke (Henry); L.M. Rose (Lynda); Natarajan, P. (Pradeep); S. Kathiresan (Sekar); S. Kääb (Stefan); V. Gudnason (Vilmundur); A. Alonso (Alvaro); M.K. Chung (Mina); S.R. Heckbert (Susan); E.J. Benjamin (Emelia); Y. Liu (Yongmei); W. März (Winfried); S.A. Rienstra; J.W. Jukema (Jan Wouter); B.H.Ch. Stricker (Bruno); M. Dörr (Marcus); C.M. Albert (Christine); P.T. Ellinor (Patrick)

    2016-01-01

    textabstractAtrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility.

  2. Gene-gene Interaction Analyses for Atrial Fibrillation

    NARCIS (Netherlands)

    Lin, Honghuang; Mueller-Nurasyid, Martina; Smith, Albert V.; Arking, Dan E.; Barnard, John; Bartz, Traci M.; Lunetta, Kathryn L.; Lohman, Kurt; Kleber, Marcus E.; Lubitz, Steven A.; Geelhoed, Bastiaan; Trompet, Stella; Niemeijer, Maartje N.; Kacprowski, Tim; Chasman, Daniel I.; Klarin, Derek; Sinner, Moritz F.; Waldenberger, Melanie; Meitinger, Thomas; Harris, Tamara B.; Launer, Lenore J.; Soliman, Elsayed Z.; Chen, Lin Y.; Smith, Jonathan D.; Van Wagoner, David R.; Rotter, Jerome I.; Psaty, Bruce M.; Xie, Zhijun; Hendricks, Audrey E.; Ding, Jingzhong; Delgado, Graciela E.; Verweij, Niek; van der Harst, Pim; Macfarlane, Peter W.; Ford, Ian; Hofman, Albert; Uitterlinden, Andre; Heeringa, Jan; Franco, Oscar H.; Kors, Jan A.; Weiss, Stefan; Volzke, Henry; Rose, Lynda M.; Natarajan, Pradeep; Kathiresan, Sekar; Kaab, Stefan; Gudnason, Vilmundur; Alonso, Alvaro; Chung, Mina K.; Heckbert, Susan R.; Benjamin, Emelia J.; Liu, Yongmei; Marz, Winfried; Rienstra, Michiel; Jukema, J. Wouter; Stricker, Bruno H.; Dorr, Marcus; Albert, Christine M.; Ellinor, Patrick T.

    2016-01-01

    Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed

  3. Horizontal gene transfer and nucleotide compositional anomaly in large DNA viruses

    Directory of Open Access Journals (Sweden)

    Ogata Hiroyuki

    2007-12-01

    Full Text Available Abstract Background DNA viruses have a wide range of genome sizes (5 kb up to 1.2 Mb, compared to 0.16 Mb to 1.5 Mb for obligate parasitic bacteria that do not correlate with their virulence or the taxonomic distribution of their hosts. The reasons for such large variation are unclear. According to the traditional view of viruses as gifted "gene pickpockets", large viral genome sizes could originate from numerous gene acquisitions from their hosts. We investigated this hypothesis by studying 67 large DNA viruses with genome sizes larger than 150 kb, including the recently characterized giant mimivirus. Given that horizontally transferred DNA often have anomalous nucleotide compositions differing from the rest of the genome, we conducted a detailed analysis of the inter- and intra-genome compositional properties of these viruses. We then interpreted their compositional heterogeneity in terms of possible causes, including strand asymmetry, gene function/expression, and horizontal transfer. Results We first show that the global nucleotide composition and nucleotide word usage of viral genomes are species-specific and distinct from those of their hosts. Next, we identified compositionally anomalous (cA genes in viral genomes, using a method based on Bayesian inference. The proportion of cA genes is highly variable across viruses and does not exhibit a significant correlation with genome size. The vast majority of the cA genes were of unknown function, lacking homologs in the databases. For genes with known homologs, we found a substantial enrichment of cA genes in specific functional classes for some of the viruses. No significant association was found between cA genes and compositional strand asymmetry. A possible exogenous origin for a small fraction of the cA genes could be confirmed by phylogenetic reconstruction. Conclusion At odds with the traditional dogma, our results argue against frequent genetic transfers to large DNA viruses from their

  4. Combination of platelet-rich plasma within periodontal ligament stem cell sheets enhances cell differentiation and matrix production.

    Science.gov (United States)

    Xu, Qiu; Li, Bei; Yuan, Lin; Dong, Zhiwei; Zhang, Hao; Wang, Han; Sun, Jin; Ge, Song; Jin, Yan

    2017-03-01

    The longstanding goal of periodontal therapy is to regenerate periodontal tissues. Although platelet-rich plasma (PRP) has been gaining increasing popularity for use in the orofacial region, whether PRP is useful for periodontal regeneration is still unknown. The purpose of this study was to determine whether a mixture of periodontal ligament stem cell (PDLSC) sheets and PRP promoted bone regeneration, one of the most important measurement indices of periodontal tissue regenerative capability in vitro and in vivo. In this study, we evaluated the effects of different doses of PRP on the differentiation of human PDLSCs. Then cell sheet formation, extracellular matrix deposition and osteogenic gene expression in response to different doses of PRP treatment during sheet grafting was investigated. Furthermore, we implanted PDLSC sheets treated with 1% PRP subcutaneously into immunocompromised mice to evaluate their bone-regenerative capability. The results revealed that 1% PRP significantly enhanced the osteogenic differentiation of PDLSCs. Based on the production of extracellular matrix proteins, the results of scanning electron microscopy and the expression of the osteogenic genes ALP, Runx2, Col-1 and OCN, the provision of 1% PRP for PDLSC sheets was the most effective PRP administration mode for cell sheet formation. The results of in vivo transplantation showed that 1% PRP-mediated PDLSC sheets exhibited better periodontal tissue regenerative capability than those obtained without PRP intervention. These data suggest that a suitable concentration of PRP stimulation may enhance extracellular matrix production and positively affect cell behaviour in PDLSC sheets. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning

    Directory of Open Access Journals (Sweden)

    Tsatsoulis Costas

    2010-05-01

    Full Text Available Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. Results We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80 of the classification rules produced. Conclusions We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.

  6. Consequences of population topology for studying gene flow using link-based landscape genetic methods.

    Science.gov (United States)

    van Strien, Maarten J

    2017-07-01

    Many landscape genetic studies aim to determine the effect of landscape on gene flow between populations. These studies frequently employ link-based methods that relate pairwise measures of historical gene flow to measures of the landscape and the geographical distance between populations. However, apart from landscape and distance, there is a third important factor that can influence historical gene flow, that is, population topology (i.e., the arrangement of populations throughout a landscape). As the population topology is determined in part by the landscape configuration, I argue that it should play a more prominent role in landscape genetics. Making use of existing literature and theoretical examples, I discuss how population topology can influence results in landscape genetic studies and how it can be taken into account to improve the accuracy of these results. In support of my arguments, I have performed a literature review of landscape genetic studies published during the first half of 2015 as well as several computer simulations of gene flow between populations. First, I argue why one should carefully consider which population pairs should be included in link-based analyses. Second, I discuss several ways in which the population topology can be incorporated in response and explanatory variables. Third, I outline why it is important to sample populations in such a way that a good representation of the population topology is obtained. Fourth, I discuss how statistical testing for link-based approaches could be influenced by the population topology. I conclude the article with six recommendations geared toward better incorporating population topology in link-based landscape genetic studies.

  7. The Monopolization Hypothesis and the dispersal gene flow paradox in aquatic organisms

    Science.gov (United States)

    De Meester, Luc; Gómez, Africa; Okamura, Beth; Schwenk, Klaus

    2002-06-01

    Many aquatic organisms rely on passive transport of resting stages for their dispersal. In this review, we provide evidence pointing to the high dispersal capacity of both animals (cladocerans, rotifers and bryozoans) and aquatic macrophytes inhabiting lentic habitats. This evidence includes direct observation of dispersal by vectors such as wind and waterfowl and the rapid colonization of new habitats. Such high dispersal capacity contrasts with the abundant evidence of pronounced genetic differentiation among neighbouring populations in many pond-dwelling organisms. We provide an overview of the potential mechanisms causing a discrepancy between high dispersal rates and reduced levels of gene flow. We argue that founder events combined with rapid local adaptation may underlie the striking patterns of genetic differentiation for neutral markers in many aquatic organisms. Rapid population growth and local adaptation upon colonization of a new habitat result in the effective monopolization of resources, yielding a strong priority effect. Once a population is locally adapted, the presence of a large resting propagule bank provides a powerful buffer against newly invading genotypes, so enhancing priority effects. Under this Monopolization Hypothesis, high genetic differentiation among nearby populations largely reflects founder events. Phylogeographic data support a scenario of low effective dispersal among populations and persistent effects of historical colonization in cyclical parthenogens. A comparison of patterns of gene flow in taxa with different life cycles suggests an important role of local adaptation in reducing gene flow among populations. We argue that patterns of regional genetic differentiation may often reflect historical colonization of new habitats rather than contemporary gene flow.

  8. Expectations and beliefs in science communication: Learning from three European gene therapy discussions of the early 1990s.

    Science.gov (United States)

    Meyer, Gitte

    2016-04-01

    There is widespread agreement that the potential of gene therapy was oversold in the early 1990s. This study, however, comparing written material from the British, Danish and German gene therapy discourses of the period finds significant differences: Over-optimism was not equally strong everywhere; gene therapy was not universally hyped. Against that background, attention is directed towards another area of variation in the material: different basic assumptions about science and scientists. Exploring such culturally rooted assumptions and beliefs and their possible significance to science communication practices, it is argued that deep beliefs may constitute drivers of hype that are particularly difficult to deal with. To participants in science communication, the discouragement of hype, viewed as a practical-ethical challenge, can be seen as a learning exercise that includes critical attention to internalised beliefs. © The Author(s) 2014.

  9. Electro-acupuncture-mediated gene transfer.

    Science.gov (United States)

    Zhang, J; Qin, Y; Fu, A; Tang, J; Chen, G; Cai, D; Han, J

    1998-10-01

    Gene transfer is one of the key techniques in gene therapy application. Unfortunately, it seems that by now, there still exists no approach with simplicity, easiness, efficiency and safety. A novel method for gene delivery, electro-acupuncture needle-mediated gene transfer which combined the Chinese traditional acupuncture with modem gene introduction, was developed. With acupuncture needle carrying exogenous gene into muscle after direct electronic stimuli, efficient gene delivery was achieved.

  10. Determining Semantically Related Significant Genes.

    Science.gov (United States)

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  11. Uncovering trends in gene naming

    OpenAIRE

    Seringhaus, Michael R.; Cayting, Philip D; Gerstein, Mark B.

    2008-01-01

    We take stock of current genetic nomenclature and attempt to organize strange and notable gene names. We categorize, for instance, those that involve a naming system transferred from another context (for example, Pavlov’s dogs). We hope this analysis provides clues to better steer gene naming in the future.

  12. Uncovering trends in gene naming.

    Science.gov (United States)

    Seringhaus, Michael R; Cayting, Philip D; Gerstein, Mark B

    2008-01-31

    We take stock of current genetic nomenclature and attempt to organize strange and notable gene names. We categorize, for instance, those that involve a naming system transferred from another context (for example, Pavlov's dogs). We hope this analysis provides clues to better steer gene naming in the future.

  13. Gene Synthesis with HG Khorana

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 17; Issue 12. Gene Synthesis with H G Khorana. Marvin H Caruthers. General Article Volume 17 Issue 12 December 2012 pp ... Keywords. Chemical synthesis of genes for yeast alanine tRNA and E. coli supressor tRNA; Khorana's philosophy on science.

  14. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    2005-01-01

    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  15. On meme--gene coevolution.

    Science.gov (United States)

    Bull, L; Holland, O; Blackmore, S

    2000-01-01

    In this article we examine the effects of the emergence of a new replicator, memes, on the evolution of a pre-existing replicator, genes. Using a version of the NKCS model we examine the effects of increasing the rate of meme evolution in relation to the rate of gene evolution, for various degrees of interdependence between the two replicators. That is, the effects of memes' (suggested) more rapid rate of evolution in comparison to that of genes is investigated using a tunable model of coevolution. It is found that, for almost any degree of interdependence between the two replicators, as the rate of meme evolution increases, a phase transition-like dynamic occurs under which memes have a significantly detrimental effect on the evolution of genes, quickly resulting in the cessation of effective gene evolution. Conversely, the memes experience a sharp increase in benefit from increasing their rate of evolution. We then examine the effects of enabling genes to reduce the percentage of gene-detrimental evolutionary steps taken by memes. Here a critical region emerges as the comparative rate of meme evolution increases, such that if genes cannot effectively select memes a high percentage of the time, they suffer from meme evolution as if they had almost no selective capability.

  16. Ancestral and novel roles of Pax family genes in mollusks.

    Science.gov (United States)

    Scherholz, Maik; Redl, Emanuel; Wollesen, Tim; de Oliveira, André Luiz; Todt, Christiane; Wanninger, Andreas

    2017-03-16

    Pax genes are transcription factors with significant roles in cell fate specification and tissue differentiation during animal ontogeny. Most information on their tempo-spatial mode of expression is available from well-studied model organisms where the Pax-subfamilies Pax2/5/8, Pax6, and Paxα/β are mainly involved in the development of the central nervous system (CNS), the eyes, and other sensory organs. In certain taxa, Pax2/5/8 seems to be additionally involved in the development of excretion organs. Data on expression patterns in lophotrochozoans, and in particular in mollusks, are very scarce for all the above-mentioned Pax-subfamilies, which hampers reconstruction of their putative ancestral roles in bilaterian animals. Thus, we studied the developmental expression of Pax2/5/8, Pax6, and the lophotrochozoan-specific Paxβ in the worm-shaped mollusk Wirenia argentea, a member of Aplacophora that together with Polyplacophora forms the Aculifera, the proposed sister taxon to all primarily single-shelled mollusks (Conchifera). All investigated Pax genes are expressed in the developing cerebral ganglia and in the ventral nerve cords, but not in the lateral nerve cords of the tetraneural nervous system. Additionally, Pax2/5/8 is expressed in epidermal spicule-secreting or associated cells of the larval trunk and in the region of the developing protonephridia. We found no indication for an involvement of the investigated Pax genes in the development of larval or adult sensory organs of Wirenia argentea. Pax2/5/8 seems to have a conserved role in the development of the CNS, whereas expression in the spicule-secreting tissues of aplacophorans and polyplacophorans suggests co-option in aculiferan skeletogenesis. The Pax6 expression pattern in Aculifera largely resembles the common bilaterian expression during CNS development. All data available on Paxβ expression argue for a common role in lophotrochozoan neurogenesis.

  17. Homeobox gene expression in Brachiopoda

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Martinez, Pedro; Wanninger, Andreas

    2011-01-01

    The molecular control that underlies brachiopod ontogeny is largely unknown. In order to contribute to this issue we analyzed the expression pattern of two homeobox containing genes, Not and Cdx, during development of the rhynchonelliform (i.e., articulate) brachiopod Terebratalia transversa....... Not is a homeobox containing gene that regulates the formation of the notochord in chordates, while Cdx (caudal) is a ParaHox gene involved in the formation of posterior tissues of various animal phyla. The T. transversa homolog, TtrNot, is expressed in the ectoderm from the beginning of gastrulation until...... formation. TtrNot expression is absent in unfertilized eggs, in embryos prior to gastrulation, and in settled individuals during and after metamorphosis. Comparison with the expression patterns of Not genes in other metazoan phyla suggests an ancestral role for this gene in gastrulation and germ layer...

  18. CNS Genes Implicated in Relapse

    Directory of Open Access Journals (Sweden)

    Willard M. Freeman

    2008-01-01

    Full Text Available Drug abuse is a condition that impacts not only the individual drug user, but society as a whole. Although prevention of initial drug use is the most effective way to prevent addiction, avoiding relapse is a crucial component of drug addiction recovery. Recent studies suggest that there is a set of genes whose expression is robustly and stably altered following drug use and ensuing abstinence. Such stable changes in gene expression correlate with ultrastructural changes in brain as well as alterations in behavior. As persistent molecular changes, these genes may provide targets for the development of therapeutics. Developing a list of well-characterized candidate genes and examining the effect of manipulating these genes will contribute to the ultimate goal of developing effective treatments to prevent relapse to drug use.

  19. Gene Discovery Methods from Large-Scale Gene Expression Data

    Science.gov (United States)

    Shimizu, Akifumi; Yano, Kentaro

    2010-01-01

    Microarrays provide genome-wide gene expression changes. In current analyses, the majority of genes on the array are frequently eliminated for further analysis just in order for computational effort to be affordable. This strategy risks failure to discover whole sets of genes related to a quantitative trait of interest, which is generally controlled by several loci that might be eliminated in current approaches. Here, we describe a high-throughput gene discovery method based on correspondence analysis with a new index for expression ratios [arctan (1/ratio)] and three artificial marker genes. This method allows us to quickly analyze the whole microarray dataset without elimination and discover up/down-regulated genes related to a trait of interest. We employed an example dataset to show the theoretical advantage of this method. We then used the method to identify 88 cancer-related genes from a published microarray data from patients with breast cancer. This method can be easily performed and the result is also visible in three-dimensional viewing software that we have developed. Our method is useful for revaluating the wealth of microarray data available from web-sites.

  20. Gene recognition by combination of several gene-finding programs.

    Science.gov (United States)

    Murakami, K; Takagi, T

    1998-01-01

    A number of programs have been developed to predict the eukaryotic gene structures in DNA sequences. However, gene finding is still a challenging problem. We have explored the effectiveness when the results of several gene-finding programs were re-analyzed and combined. We studied several methods with four programs (FEXH, GeneParser3, GEN-SCAN and GRAIL2). By HIGHEST-policy combination method or BOUNDARY method, approximate correlation (AC) improved by 3-5% in comparison with the best single gene-finding program. From another viewpoint, OR-based combination of the four programs is the most reliable to know whether a candidate exon overlaps with the real exon or not, although it is less sensitive than GENSCAN for exon-intron boundaries. Our methods can easily be extended to combine other programs. We have developed a server program (Shirokane System) and a client program (GeneScope) to use the methods. GeneScope is available through a WWW site (http://gf.genome.ad.jp/). (katsu,takagi)@ims.u-tokyo.ac.jp

  1. Reference gene screening for analyzing gene expression across goat tissue.

    Science.gov (United States)

    Zhang, Yu; Zhang, Xiao-Dong; Liu, Xing; Li, Yun-Sheng; Ding, Jian-Ping; Zhang, Xiao-Rong; Zhang, Yun-Hai

    2013-12-01

    Real-time quantitative PCR (qRT-PCR) is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2) in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

  2. Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2013-12-01

    Full Text Available Real-time quantitative PCR (qRT-PCR is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2 in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

  3. Phylogenetic analysis of gene expression.

    Science.gov (United States)

    Dunn, Casey W; Luo, Xi; Wu, Zhijin

    2013-11-01

    Phylogenetic analyses of gene expression have great potential for addressing a wide range of questions. These analyses will, for example, identify genes that have evolutionary shifts in expression that are correlated with evolutionary changes in morphological, physiological, and developmental characters of interest. This will provide entirely new opportunities to identify genes related to particular phenotypes. There are, however, 3 key challenges that must be addressed for such studies to realize their potential. First, data on gene expression must be measured from multiple species, some of which may be field-collected, and parameterized in such a way that they can be compared across species. Second, it will be necessary to develop comparative phylogenetic methods suitable for large multidimensional datasets. In most phylogenetic comparative studies to date, the number n of independent observations (independent contrasts) has been greater than the number p of variables (characters). The behavior of comparative methods for these classic problems is now well understood under a wide variety of conditions. In studies of gene expression, and in studies based on other high-throughput tools, the number n of samples is dwarfed by the number p of variables. The estimated covariance matrices will be singular, complicating their analysis and interpretation, and prone to spurious results. Third, new approaches are needed to investigate the expression of the many genes whose phylogenies are not congruent with species phylogenies due to gene loss, gene duplication, and incomplete lineage sorting. Here we outline general considerations of project design for phylogenetic analyses of gene expression and suggest solutions to these three categories of challenges. These topics are relevant to high-throughput phenotypic data well beyond gene expression.

  4. Gene Prediction Using Multinomial Probit Regression with Bayesian Gene Selection

    Science.gov (United States)

    Zhou, Xiaobo; Wang, Xiaodong; Dougherty, Edward R.

    2004-12-01

    A critical issue for the construction of genetic regulatory networks is the identification of network topology from data. In the context of deterministic and probabilistic Boolean networks, as well as their extension to multilevel quantization, this issue is related to the more general problem of expression prediction in which we want to find small subsets of genes to be used as predictors of target genes. Given some maximum number of predictors to be used, a full search of all possible predictor sets is combinatorially prohibitive except for small predictors sets, and even then, may require supercomputing. Hence, suboptimal approaches to finding predictor sets and network topologies are desirable. This paper considers Bayesian variable selection for prediction using a multinomial probit regression model with data augmentation to turn the multinomial problem into a sequence of smoothing problems. There are multiple regression equations and we want to select the same strongest genes for all regression equations to constitute a target predictor set or, in the context of a genetic network, the dependency set for the target. The probit regressor is approximated as a linear combination of the genes and a Gibbs sampler is employed to find the strongest genes. Numerical techniques to speed up the computation are discussed. After finding the strongest genes, we predict the target gene based on the strongest genes, with the coefficient of determination being used to measure predictor accuracy. Using malignant melanoma microarray data, we compare two predictor models, the estimated probit regressors themselves and the optimal full-logic predictor based on the selected strongest genes, and we compare these to optimal prediction without feature selection.

  5. Gene Prediction Using Multinomial Probit Regression with Bayesian Gene Selection

    Directory of Open Access Journals (Sweden)

    Wang Xiaodong

    2004-01-01

    Full Text Available A critical issue for the construction of genetic regulatory networks is the identification of network topology from data. In the context of deterministic and probabilistic Boolean networks, as well as their extension to multilevel quantization, this issue is related to the more general problem of expression prediction in which we want to find small subsets of genes to be used as predictors of target genes. Given some maximum number of predictors to be used, a full search of all possible predictor sets is combinatorially prohibitive except for small predictors sets, and even then, may require supercomputing. Hence, suboptimal approaches to finding predictor sets and network topologies are desirable. This paper considers Bayesian variable selection for prediction using a multinomial probit regression model with data augmentation to turn the multinomial problem into a sequence of smoothing problems. There are multiple regression equations and we want to select the same strongest genes for all regression equations to constitute a target predictor set or, in the context of a genetic network, the dependency set for the target. The probit regressor is approximated as a linear combination of the genes and a Gibbs sampler is employed to find the strongest genes. Numerical techniques to speed up the computation are discussed. After finding the strongest genes, we predict the target gene based on the strongest genes, with the coefficient of determination being used to measure predictor accuracy. Using malignant melanoma microarray data, we compare two predictor models, the estimated probit regressors themselves and the optimal full-logic predictor based on the selected strongest genes, and we compare these to optimal prediction without feature selection.

  6. Therapeutic genes for anti-HIV/AIDS gene therapy.

    Science.gov (United States)

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  7. RESONANCEI

    Indian Academy of Sciences (India)

    the DNA that encodes them. There is a genetically inherited form of human prion disease, known as Gerstmann-Straussler-. Scheinker syndrome (GSS). GSS is accompanied by a single amino acid change in the normal PrP. When the corresponding change is introduced into the mouse PrP gene, it leads to spontanous ...

  8. Evidence based selection of housekeeping genes

    NARCIS (Netherlands)

    de Jonge, Hendrik J. M.; Fehrmann, Rudolf S. N.; de Bont, Eveline S. J. M.; Hofstra, Robert M. W.; Gerbens, Frans; Kamps, Willem A.; de Vries, Elisabeth G. E.; van der Zee, Ate G. J.; te Meerman, Gerard J.; ter Elst, Arja

    2007-01-01

    For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes (reference or internal control genes) is required. It is known that commonly used housekeeping genes (e. g. ACTB, GAPDH, HPRT1, and B2M) vary considerably under different experimental

  9. Human Lacrimal Gland Gene Expression.

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Aakalu

    Full Text Available The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development.We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix ® gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium.The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described.Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.

  10. GENES IN SPORT AND DOPING

    Science.gov (United States)

    Kaliszewski, P.; Majorczyk, E.; Zembroń-Łacny, A.

    2013-01-01

    Genes control biological processes such as muscle production of energy, mitochondria biogenesis, bone formation, erythropoiesis, angiogenesis, vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic variations that may be associated with endurance ability, muscle performance and power exercise, tendon susceptibility to injuries and psychological aptitude. Already, over 200 genes relating to physical performance have been identified by several research groups. Athletes’ genotyping is developing as a tool for the formulation of personalized training and nutritional programmes to optimize sport training as well as for the prediction of exercise-related injuries. On the other hand, development of molecular technology and gene therapy creates a risk of non-therapeutic use of cells, genes and genetic elements to improve athletic performance. Therefore, the World Anti-Doping Agency decided to include prohibition of gene doping within their World Anti-Doping Code in 2003. In this review article, we will provide a current overview of genes for use in athletes’ genotyping and gene doping possibilities, including their development and detection techniques. PMID:24744482

  11. GENES IN SPORT AND DOPING

    Directory of Open Access Journals (Sweden)

    Andrzej Pokrywka

    2013-06-01

    Full Text Available Genes control biological processes such as muscle production of energy, mitochondria biogenesis, bone formation erythropoiesis, angiogenesis, vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic variations that may be associated with endurance ability, muscle performance and power exercise, tendon susceptibility to injuries and psychological aptitude. Already, over 200 genes relating to physical performance have been identified by several research groups. Athletes’ genotyping is developing as a tool for the formulation of personalized training and nutritional programmes to optimize sport training as well as for the prediction of exercise-related injuries. On the other hand, development of molecular technology and gene therapy creates a risk of non-therapeutic use of cells, genes and genetic elements to improve athletic performance. Therefore, the World Anti-Doping Agency decided to include prohibition of gene doping within their World Anti-Doping Code in 2003. In this review article, we will provide a current overview of genes for use in athletes’ genotyping and gene doping possibilities, including their development and detection techniques.

  12. Synergistic interactions of biotic and abiotic environmental stressors on gene expression.

    Science.gov (United States)

    Altshuler, Ianina; McLeod, Anne M; Colbourne, John K; Yan, Norman D; Cristescu, Melania E

    2015-03-01

    Understanding the response of organisms to multiple stressors is critical for predicting if populations can adapt to rapid environmental change. Natural and anthropogenic stressors often interact, complicating general predictions. In this study, we examined the interactive and cumulative effects of two common environmental stressors, lowered calcium concentration, an anthropogenic stressor, and predator presence, a natural stressor, on the water flea Daphnia pulex. We analyzed expression changes of five genes involved in calcium homeostasis - cuticle proteins (Cutie, Icp2), calbindin (Calb), and calcium pump and channel (Serca and Ip3R) - using real-time quantitative PCR (RT-qPCR) in a full factorial experiment. We observed strong synergistic interactions between low calcium concentration and predator presence. While the Ip3R gene was not affected by the stressors, the other four genes were affected in their transcriptional levels by the combination of the stressors. Transcriptional patterns of genes that code for cuticle proteins (Cutie and Icp2) and a sarcoplasmic calcium pump (Serca) only responded to the combination of stressors, changing their relative expression levels in a synergistic response, while a calcium-binding protein (Calb) responded to low calcium stress and the combination of both stressors. The expression pattern of these genes (Cutie, Icp2, and Serca) were nonlinear, yet they were dose dependent across the calcium gradient. Multiple stressors can have complex, often unexpected effects on ecosystems. This study demonstrates that the dominant interaction for the set of tested genes appears to be synergism. We argue that gene expression patterns can be used to understand and predict the type of interaction expected when organisms are exposed simultaneously to natural and anthropogenic stressors.

  13. Limited pattern of TCR delta chain gene rearrangement on the RNA level in multiple sclerosis.

    Science.gov (United States)

    Nowak, J; Januszkiewicz, D; Pernak, M; Hertmanowska, H; Nowicka-Kujawska, K; Rembowska, J; Lewandowski, K; Nowak, T; Wender, M

    2001-01-01

    Susceptibility to multiple sclerosis (MS) is most likely affected by a number of genes, including HLA and T-cell receptor (TCR) genes. T cells expressing gamma/delta receptors seem to contribute to autoagression in MS, as evidenced by their localization in the MS plaques in the brain. The aim of this study was to analyse the TCRdelta chain gene rearrangement at the RNA (cDNA) level and compare to the DNA pattern rearrangement. TCRdelta gene rearrangement was analysed in MS patients and healthy individuals with the use of primers specific for Vdelta1-6 and Jdelta1 genes (at the DNA level) and specific for Vdelta1-6 and Cdelta1 genes (at the cDNA level). The size of PCR products was analysed on agarose gel and by ALF-Express (Pharmacia). Additionally, the lymphocyte surface immunophenotype was studied with specific monoclonal antibodies. At the DNA level a restricted pattern of Vdelta3-Jdelta1 and Vdelta5-Jdelta1 was found only in MS patients. Contrary to DNA, mono-, oligoclonal RNA (cDNA) rearrangements were limited to Vdelta1-Cdelta1, Vdelta2-Cdelta1 and Vdelta3-Cdelta1 only in MS patients as well. Surface immunophenotype analysis revealed in MS a much higher frequency of activated gamma/delta T lymphocytes, i.e. expressing HLA-DR and CD25. An elevated level of CD56 positive cells in MS was recorded. Mono-oligoclonal pattern of TCRdelta gene rearrangement at the RNA level, along with increase in activated gamma/delta T cells, strongly argue for a significant role of gamma/delta T lymphocytes in the pathogenesis of MS.

  14. Gene expression profiles in skeletal muscle after gene electrotransfer

    DEFF Research Database (Denmark)

    Hojman, Pernille; Zibert, John R; Gissel, Hanne

    2007-01-01

    BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... therefore investigated transcriptional changes through gene expression profile analyses, morphological changes by histological analysis, and physiological changes by force generation measurements. DNA electrotransfer was obtained using a combination of a short high voltage pulse (HV, 1000 V/cm, 100 mus......) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...

  15. Cloning and selection of reference genes for gene expression ...

    African Journals Online (AJOL)

    Full length mRNA sequences of Ac-β-actin and Ac-gapdh, and partial mRNA sequences of Ac-18SrRNA and Ac-ubiquitin were cloned from pineapple in this study. The four genes were tested as housekeeping genes in three experimental sets. GeNorm and NormFinder analysis revealed that β-actin was the most ...

  16. Gene therapy of cancer by vaccines carrying inserted immunostimulatory genes

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2007-01-01

    Roč. 53, č. 3 (2007), s. 71-73 ISSN 0015-5500 Grant - others:EU-FP6 NoE Clinigene(XE) 018933; Liga proti rakovině, Praha(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : gene therapy * immunostimulatory genes * vaccine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.596, year: 2007

  17. Correction of gene expression data

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin

    2014-01-01

    This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

  18. Gene Therapy Approaches to Hemoglobinopathies.

    Science.gov (United States)

    Ferrari, Giuliana; Cavazzana, Marina; Mavilio, Fulvio

    2017-10-01

    Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting as well as engraftment. These hurdles need be addressed for gene therapy for hemoglobinopathies to become a clinical reality. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Panspermia and horizontal gene transfer

    Science.gov (United States)

    Klyce, Brig

    2009-08-01

    Evidence that extremophiles are hardy and ubiquitous is helping to make panspermia a respectable theory. But even if life on Earth originally came from space, biologists assume that the subsequent evolution of life is still governed by the darwinian paradigm. In this review we show how panspermia could amend darwinism and point to a cosmic source for, not only extremophiles but, all of life. This version of panspermia can be called "strong panspermia." To support this theory we will discuss recent evidence pertaining to horizontal gene transfer, viruses, genes apparently older than the Earthly evolution of the features they encode, and primate-specific genes without identifiable precursors.

  20. Genomics screens for metastasis genes

    Science.gov (United States)

    Yan, Jinchun; Huang, Qihong

    2014-01-01

    Metastasis is responsible for most cancer mortality. The process of metastasis is complex, requiring the coordinated expression and fine regulation of many genes in multiple pathways in both the tumor and host tissues. Identification and characterization of the genetic programs that regulate metastasis is critical to understanding the metastatic process and discovering molecular targets for the prevention and treatment of metastasis. Genomic approaches and functional genomic analyses can systemically discover metastasis genes. In this review, we summarize the genetic tools and methods that have been used to identify and characterize the genes that play critical roles in metastasis. PMID:22684367

  1. American Society of Gene & Cell Therapy

    Science.gov (United States)

    ... Chicago Learn More Close The American Society of Gene & Cell Therapy ASGCT is the primary membership organization for scientists, ... Therapeutics Official Journal of the American Society of Gene & Cell Therapy Molecular Therapy is the leading journal for gene ...

  2. Gene Expression Analysis of Breast Cancer Progression

    National Research Council Canada - National Science Library

    Gerald, Wiliam L

    2004-01-01

    ... to identify genes, gene expression profiles and molecular pathways associated with metastatic BC we have performed genome-wide gene expression analysis of a large number of breast cancer samples...

  3. Autologous leukocyte-reduced platelet-rich plasma therapy for Achilles tendinopathy induced by collagenase in a rabbit model

    Science.gov (United States)

    González, Juan C.; López, Catalina; Álvarez, María E.; Pérez, Jorge E.; Carmona, Jorge U.

    2016-01-01

    Leukocyte-reduced platelet-rich plasma (LR-PRP) is a therapy for tendinopathy of the Achilles tendon (TAT); however, there is scarce information regarding LR-PRP effects in rabbit models of TAT. We compared, at 4 and 12 weeks (w), the LR-PRP and placebo (PBS) effects on ultrasonography, histology and relative gene expression of collagen types I (COL1A1) and III (COL3A1) and vascular endothelial growth factor (VEGF) in 24 rabbits with TAT induced by collagenase. The rabbits (treated with both treatments) were euthanatised after either 4 or 12 w. A healthy group (HG (n = 6)) was included. At 4 and 12 w, the LR-PRP group had a no statistically different histology score to the HG. At w 4, the COL1A1 expression was significantly higher in the LR-PRP group when compared to HG, and the expression of COL3A1from both LR-PRP and PBS-treated tendons was significantly higher when compared to the HG. At w 12, the expression of COL3A1 remained significantly higher in the PBS group in comparison to the LR-PRP group and the HG. At w 4, the LR-PRP group presented a significantly higher expression of VEGF when compared to the PBS group and the HG. In conclusion, LR-PRP treatment showed regenerative properties in rabbits with TAT. PMID:26781753

  4. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol...

  5. Candidate genes in panic disorder

    DEFF Research Database (Denmark)

    Howe, A. S.; Buttenschön, Henriette N; Bani-Fatemi, A.

    2016-01-01

    The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered...

  6. Sleep deprivation and gene expression.

    Science.gov (United States)

    da Costa Souza, Annie; Ribeiro, Sidarta

    2015-01-01

    Sleep occurs in a wide range of animal species as a vital process for the maintenance of homeostasis, metabolic restoration, physiological regulation, and adaptive cognitive functions in the central nervous system. Long-term perturbations induced by the lack of sleep are mostly mediated by changes at the level of transcription and translation. This chapter reviews studies in humans, rodents, and flies to address the various ways by which sleep deprivation affects gene expression in the nervous system, with a focus on genes related to neuronal plasticity, brain function, and cognition. However, the effects of sleep deprivation on gene expression and the functional consequences of sleep loss are clearly not restricted to the cognitive domain but may include increased inflammation, expression of stress-related genes, general impairment of protein translation, metabolic imbalance, and thermal deregulation.

  7. Gene Therapy for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Rachel Denyer

    2012-01-01

    Full Text Available Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

  8. Rhythms and synchronization patterns in gene expression in the Aedes aegypti mosquito

    Directory of Open Access Journals (Sweden)

    Carlson Jonathan O

    2011-03-01

    Full Text Available Abstract Background Aedes aegypti is arguably the most studied of all mosquito species in the laboratory and is the primary vector of both Dengue and Yellow Fever flaviviruses in the field. A large number of transcriptional studies have been made in the species and these usually report transcript quantities observed at a certain age or stage of development. However, circadian oscillation is an important characteristic of gene expression in many animals and plants, modulating both their physiology and behavior. Circadian gene expression in mosquito species has been previously reported but for only a few genes directly involved in the function of the molecular clock. Results Herein we analyze the transcription profiles of 21,494 messenger RNAs using an Ae. aegypti Agilent® microarray. Transcripts were quantified in adult female heads at 24 hours and then again at 72 hours and eight subsequent time points spaced four hours apart. We document circadian rhythms in multiple molecular pathways essential for growth, development, immune response, detoxification/pesticide resistance. Circadian rhythms were also noted in ribosomal protein genes used for normalization in reverse transcribed PCR (RT-PCR to determine transcript abundance. We report pervasive oscillations and intricate synchronization patterns relevant to all known biological pathways. Conclusion These results argue strongly that transcriptional analyses either need to be made over time periods rather than confining analyses to a single time point or development stage or exceptional care needs to be made to synchronize all mosquitoes to be analyzed and compared among treatment groups.

  9. Are SCN1A gene mutations responsible for genetic susceptibility to subacute sclerosing panencephalitis?

    Science.gov (United States)

    Garg, Ravindra Kumar

    2012-02-01

    Dravet syndrome, characterized predominantly by myoclonus, has a striking clinical resemblance to subacute sclerosing panencephalitis (SSPE). Patients with Dravet syndrome develop significant mental decline with advancing age of affected child like in SSPE. It is well established that SCN1A gene mutations are associated with Dravet syndrome. Even periodic EEG complexes have been described in Dravet syndrome. In addition to Dravet syndrome, several other types of acute and subacute encephalopathic syndromes having clinical and electroencephalographic resemblance to SSPE are associated with SCN1A gene mutations. SSPE is a devastating progressive inflammatory disorder of the central nervous system. It is caused by persistent infection of the brain by an aberrant measles virus. Only a few of a vast number of measles infected pediatric population develop SSPE. There are several reports describing presence of SSPE is close relatives and it has been described previously in sibling and twin pairs. A genetic susceptibility for development of SSPE is likely. In fact, a variety of genetic abnormalities have already been described in patients with SSPE. It can also be argued that because of striking clinical resemblance between Dravet and various epileptic and encephalopathic syndromes associated with SCN1A gene mutations and SSPE, SCN1A gene abnormalities may also be responsible for susceptibility to SSPE in measles infected children. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial Processing.

    Science.gov (United States)

    Miller, Jessica K; McDougall, Siné; Thomas, Sarah; Wiener, Jan

    2017-11-27

    The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD) continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene, given its impact on the integrity of the hippocampal memory system. Research into human navigation also considers the BDNF gene in relation to hippocampal dependent spatial processing. This speculative paper brings together trauma and spatial processing for the first time and presents exploratory research into their interactions with BDNF. We propose that quantifying the impact of BDNF on trauma and spatial processing is critical and may well explain individual differences in clinical trauma treatment outcomes and in navigation performance. Research has already shown that the BDNF gene influences PTSD severity and prevalence as well as navigation behaviour. However, more data are required to demonstrate the precise hippocampal dependent processing mechanisms behind these influences in different populations and environmental conditions. This paper provides insight from recent studies and calls for further research into the relationship between allocentric processing, trauma processing and BDNF. We argue that research into these neural mechanisms could transform PTSD clinical practice and professional support for individuals in trauma-exposing occupations such as emergency response, law enforcement and the military.

  11. Deregulated genes in sporadic vestibular schwannomas

    DEFF Research Database (Denmark)

    Cayé-Thomasen, Per; Helweg-Larsen, Rehannah Holga Andrea; Stangerup, Sven-Eric

    2010-01-01

    In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology....

  12. Gene expression based cancer classification

    OpenAIRE

    Sara Tarek; Reda Abd Elwahab; Mahmoud Shoman

    2017-01-01

    Cancer classification based on molecular level investigation has gained the interest of researches as it provides a systematic, accurate and objective diagnosis for different cancer types. Several recent researches have been studying the problem of cancer classification using data mining methods, machine learning algorithms and statistical methods to reach an efficient analysis for gene expression profiles. Studying the characteristics of thousands of genes simultaneously offered a deep in...

  13. Transgenic Arabidopsis Gene Expression System

    Science.gov (United States)

    Ferl, Robert; Paul, Anna-Lisa

    2009-01-01

    The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

  14. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben

    2015-01-01

    is associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due....... This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value....

  15. Rice Multi-Gene Analysis

    Indian Academy of Sciences (India)

    gdyang

    Maps of all the intronic MIR genes analyzed using MPSS database in rice. Click here for a legend that explains the icons and colors in the image below. Click here to jump in the page below to the specific gene. osa-MIR159f osa-MIR399i osa-MIR418 osa-MIR437 osa-MIR439b osa-MIR439j osa-MIR440 osa-MIR442.

  16. Degradable Polymers for Gene Delivery

    Science.gov (United States)

    Sunshine, Joel; Bhise, Nupura; Green, Jordan J.

    2014-01-01

    Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure led to significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than Lipofectamine 2000 or polyethylenimine for gene delivery to cancerous fibroblasts or human primary fibroblasts. These materials may be useful for cancer therapeutics and regenerative medicine. PMID:19964958

  17. Cationic Bolaamphiphiles for Gene Delivery

    Science.gov (United States)

    Tan, Amelia Li Min; Lim, Alisa Xue Ling; Zhu, Yiting; Yang, Yi Yan; Khan, Majad

    2014-05-01

    Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

  18. ASPM gene expression in medulloblastoma.

    Science.gov (United States)

    Vulcani-Freitas, Tânia M; Saba-Silva, Najsla; Cappellano, Andréa; Cavalheiro, Sérgio; Marie, Sueli K N; Oba-Shinjo, Sueli M; Malheiros, Suzana M F; de Toledo, Sílvia Regina Caminada

    2011-01-01

    Medulloblastomas are the most common malignant tumors of the central nervous system in childhood. The incidence is about 19-20% between children younger than 16 years old with peak incidence between 4 and 7 years. Despite its sensibility to no specific therapeutic means like chemotherapy and radiotherapy, the treatment is very aggressive and frequently results in regression, growth deficit, and endocrine dysfunction. From this point of view, new treatment approaches are needed such as molecular targeted therapies. Studies in glioblastoma demonstrated that ASPM gene was overexpressed when compared to normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM gene as a potential molecular target in glioblastoma. The aim of this work was to evaluate ASPM expression in medulloblastoma fragment samples, and to compare the results with the patient clinical features. Analysis of gene expression was performed by quantitative PCR real time using SYBR Green system in tumor samples from 37 children. The t test was used to analyze the gene expression, and Mann-Whitney test was performed to analyze the relationship between gene expressions and clinical characteristics. Kaplan-Meier test evaluated curve survival. All samples overexpressed ASPM gene more than 40-fold. However, we did not find any association between the overexpressed samples and the clinical parameters. ASPM overexpression may modify the ability of stem cells to differentiate during the development of the central nervous system, contributing to the development of medulloblastoma, a tumor of embryonic origin from cerebellar progenitor cells.

  19. New Gene Evolution: Little Did We Know

    Science.gov (United States)

    Long, Manyuan; VanKuren, Nicholas W.; Chen, Sidi; Vibranovski, Maria D.

    2014-01-01

    Genes are perpetually added to and deleted from genomes during evolution. Thus, it is important to understand how new genes are formed and evolve as critical components of the genetic systems determining the biological diversity of life. Two decades of effort have shed light on the process of new gene origination, and have contributed to an emerging comprehensive picture of how new genes are added to genomes, ranging from the mechanisms that generate new gene structures to the presence of new genes in different organisms to the rates and patterns of new gene origination and the roles of new genes in phenotypic evolution. We review each of these aspects of new gene evolution, summarizing the main evidence for the origination and importance of new genes in evolution. We highlight findings showing that new genes rapidly change existing genetic systems that govern various molecular, cellular and phenotypic functions. PMID:24050177

  20. Novel gene transfer systems: intelligent gene transfer vectors for gene medicines.

    Science.gov (United States)

    Nakajima, Toshihiro

    2012-01-01

    Drug delivery systems for gene transfer are called 'vectors'. These systems were originally invented as a delivery system for the transfection in vitro or in vivo. Several vectors are then developed for clinical use of gene medicines and currently some of them are approved as animal drugs. Conventional drug delivery system generally consists of approved (existing) materials to avoid additional pre-clinical or clinical studies. However, current vectors contain novel materials to improve an efficacy of gene medicines. Thus, these vectors have functions more than a mere delivery of active ingredients. For example some vectors have immunological functions such as adjuvants in vaccines. These new types of vectors are called 'intelligent' or 'innovative' vector system', since the concept or strategy for the development is completely different from conventional drug delivery systems. In this article, we described a current status of 'intelligent gene transfer vectors and discussed on the potentials of them.