A historical reflection on the discovery of human retroviruses

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Vahlne Anders

2009-05-01

Full Text Available Abstract The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined. The first human retroviruses (HTLV-I was first reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma and coworkers in 1981. These discoveries were in turn dependent on the previous discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor as it was called then. HTLV-II was described by Gallo's group in 1982. A human retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the morphology of a lentivirus was in my mind described for the first time by Luc Montagnier in an oral presentation at Cold Spring Harbor in September of 1983. This virus was isolated from a patient with lymphadenopathy using the protocol previously described for HTLV by Gallo. The first peer reviewed paper by Montagnier's group of such a retrovirus, isolated from two siblings of whom one with AIDS, appeared in Lancet in April of 1984. However, the proof that a new human retrovirus (HIV-1 was the cause of AIDS was first established in four publications by Gallo's group in the May 4th issue of Science in 1984.

Review of the twelfth West Coast retrovirus meeting

Directory of Open Access Journals (Sweden)

Melar Marta

2005-11-01

Full Text Available Abstract Every year the Cancer Research Institute from University of California at Irvine organizes the West Coast Retrovirus Meeting where participants have a chance to discuss the latest progress in understanding the pathology of retroviruses. The 12th meeting was held at the Hyatt Regency Suites in Palm Springs, California from October 6th to October 9th 2005, with the major focus on human immunodeficiency virus (HIV pathogenesis. Philippe Gallay from The Scripps Research Institute and Thomas J. Hope from Northwestern University organized the meeting, which covered all the steps involved in the lifecycle of retroviruses with an emphasis on virus:host interactions. The trend in research appeared to be on the restriction of viral infection, both by the endogenous, cellular restriction factors, as well as by the potential antimicrobial compounds of known or unknown mechanisms. Additionally, new stories on the inevitable feedback from the host immune system were presented as well. HIV still represents a challenge that an army of motivated people has been working on for over 20 years. And yet, the field has not reached the plateau in knowledge nor enthusiasm, which was proven again in October 2005 in Palm Springs.

Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

Science.gov (United States)

Rebollo, Rita; Mager, Dixie L

2016-01-01

Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

Complex Codon Usage Pattern and Compositional Features of Retroviruses

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Sourav RoyChoudhury

2013-01-01

Full Text Available Retroviruses infect a wide range of organisms including humans. Among them, HIV-1, which causes AIDS, has now become a major threat for world health. Some of these viruses are also potential gene transfer vectors. In this study, the patterns of synonymous codon usage in retroviruses have been studied through multivariate statistical methods on ORFs sequences from the available 56 retroviruses. The principal determinant for evolution of the codon usage pattern in retroviruses seemed to be the compositional constraints, while selection for translation of the viral genes plays a secondary role. This was further supported by multivariate analysis on relative synonymous codon usage. Thus, it seems that mutational bias might have dominated role over translational selection in shaping the codon usage of retroviruses. Codon adaptation index was used to identify translationally optimal codons among genes from retroviruses. The comparative analysis of the preferred and optimal codons among different retroviral groups revealed that four codons GAA, AAA, AGA, and GGA were significantly more frequent in most of the retroviral genes inspite of some differences. Cluster analysis also revealed that phylogenetically related groups of retroviruses have probably evolved their codon usage in a concerted manner under the influence of their nucleotide composition.

A novel approach to achieving modular retrovirus clearance for a parvovirus filter.

Science.gov (United States)

Stuckey, Juliana; Strauss, Daniel; Venkiteshwaran, Adith; Gao, Jinxin; Luo, Wen; Quertinmont, Michelle; O'Donnell, Sean; Chen, Dayue

2014-01-01

Viral filtration is routinely incorporated into the downstream purification processes for the production of biologics produced in mammalian cell cultures (MCC) to remove potential viral contaminants. In recent years, the use of retentive filters designed for retaining parvovirus (~20 nm) has become an industry standard in a conscious effort to further improve product safety. Since retentive filters remove viruses primarily by the size exclusion mechanism, it is expected that filters designed for parvovirus removal can effectively clear larger viruses such as retroviruses (~100 nm). In an attempt to reduce the number of viral clearance studies, we have taken a novel approach to demonstrate the feasibility of claiming modular retrovirus clearance for Asahi Planova 20N filters. Porcine parvovirus (PPV) and xenotropic murine leukemia virus (XMuLV) were co-spiked into six different feedstreams and then subjected to laboratory scale Planova 20N filtration. Our results indicate that Planova 20N filters consistently retain retroviruses and no retrovirus has ever been detected in the filtrates even when significant PPV breakthrough is observed. Based on the data from multiple in-house viral validation studies and the results from the co-spiking experiments, we have successfully claimed a modular retrovirus clearance of greater than 6 log10 reduction factors (LRF) to support clinical trial applications in both USA and Europe. © 2013 American Institute of Chemical Engineers.

Innate imune response against retrovirus.

OpenAIRE

Lucia González; Natalia Ibañez; Marcelo Mateus; Karina Romero; Otto Pritsch

2015-01-01

Los retrovirus son un diverso grupo de virus que se encuentran en los vertebrados. Su importancia biomédica radica en que son capaces de infectar humanos, produciendo importantes problemas de salud. El virus de la inmunodeficiencia humana (VIH) es capaz de producir un estado de inmunodeficiencia en el huésped determinando el desarrollo de enfermedades oportunistas en estadio avanzados de la enfermedad. Frente a la entrada de un retrovirus al organismo, nuestro sistema inmune presenta como pri...

Simultaneous presence of endogenous retrovirus and herpes virus antigens has profound effect on cell-mediated immune responses: implications for multiple sclerosis

DEFF Research Database (Denmark)

Brudek, T.; Christensen, T.; Hansen, H.J.

2004-01-01

Retroviruses have been suggested as possible pathogenic factors in multiple sclerosis (MS), supported by the observation that endogenous retroviruses are activated in MS patients. Different members of the herpes family of which several are neurotropic have also been suggested as factors in MS pat...

Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element

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Dudley Jaquelin P

2009-02-01

Full Text Available Abstract Background Mouse mammary tumor virus (MMTV encodes the Rem protein, an HIV Rev-like protein that enhances nuclear export of unspliced viral RNA in rodent cells. We have shown that Rem is expressed from a doubly spliced RNA, typical of complex retroviruses. Several recent reports indicate that MMTV can infect human cells, suggesting that MMTV might interact with human retroviruses, such as human immunodeficiency virus (HIV, human T-cell leukemia virus (HTLV, and human endogenous retrovirus type K (HERV-K. In this report, we test whether the export/regulatory proteins of human complex retroviruses will increase expression from vectors containing the Rem-responsive element (RmRE. Results MMTV Rem, HIV Rev, and HTLV Rex proteins, but not HERV-K Rec, enhanced expression from an MMTV-based reporter plasmid in human T cells, and this activity was dependent on the RmRE. No RmRE-dependent reporter gene expression was detectable using Rev, Rex, or Rec in HC11 mouse mammary cells. Cell fractionation and RNA quantitation experiments suggested that the regulatory proteins did not affect RNA stability or nuclear export in the MMTV reporter system. Rem had no demonstrable activity on export elements from HIV, HTLV, or HERV-K. Similar to the Rem-specific activity in rodent cells, the RmRE-dependent functions of Rem, Rev, or Rex in human cells were inhibited by a dominant-negative truncated nucleoporin that acts in the Crm1 pathway of RNA and protein export. Conclusion These data argue that many retroviral regulatory proteins recognize similar complex RNA structures, which may depend on the presence of cell-type specific proteins. Retroviral protein activity on the RmRE appears to affect a post-export function of the reporter RNA. Our results provide additional evidence that MMTV is a complex retrovirus with the potential for viral interactions in human cells.

On the general theory of the origins of retroviruses

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Wayengera Misaki

2010-02-01

Full Text Available Abstract Background The order retroviridae comprises viruses based on ribonucleic acids (RNA. Some, such as HIV and HTLV, are human pathogens. Newly emerged human retroviruses have zoonotic origins. As far as has been established, both repeated infections (themselves possibly responsible for the evolution of viral mutations (Vm and host adaptability (Ha; along with interplay between inhibitors and promoters of cell tropism, are needed to effect retroviral cross-species transmissions. However, the exact modus operadi of intertwine between these factors at molecular level remains to be established. Knowledge of such intertwine could lead to a better understanding of retrovirology and possibly other infectious processes. This study was conducted to derive the mathematical equation of a general theory of the origins of retroviruses. Methods and results On the basis of an arbitrarily non-Euclidian geometrical "thought experiment" involving the cross-species transmission of simian foamy virus (sfv from a non-primate species Xy to Homo sapiens (Hs, initially excluding all social factors, the following was derived. At the port of exit from Xy (where the species barrier, SB, is defined by the Index of Origin, IO, sfv shedding is (1 enhanced by two transmitting tensors (Tt, (i virus-specific immunity (VSI and (ii evolutionary defenses such as APOBEC, RNA interference pathways, and (when present expedited therapeutics (denoted e2D; and (2 opposed by the five accepting scalars (At: (a genomic integration hot spots, gIHS, (b nuclear envelope transit (NMt vectors, (c virus-specific cellular biochemistry, VSCB, (d virus-specific cellular receptor repertoire, VSCR, and (e pH-mediated cell membrane transit, (↓pH CMat. Assuming As and Tt to be independent variables, IO = Tt/As. The same forces acting in an opposing manner determine SB at the port of sfv entry (defined here by the Index of Entry, IE = As/Tt. Overall, If sfv encounters no unforeseen effects on

Koala retrovirus: a genome invasion in real time

OpenAIRE

Stoye, Jonathan P

2006-01-01

Koalas are currently undergoing a wave of germline infections by the retrovirus KoRV. Study of this phenomenon not only provides an opportunity for understanding the processes regulating retrovirus endogenization but may also be essential to preventing the extinction of the species.

Convergent evolution of ribonuclease h in LTR retrotransposons and retroviruses.

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Ustyantsev, Kirill; Novikova, Olga; Blinov, Alexander; Smyshlyaev, Georgy

2015-05-01

Ty3/Gypsy long terminals repeat (LTR) retrotransposons are structurally and phylogenetically close to retroviruses. Two notable structural differences between these groups of genetic elements are 1) the presence in retroviruses of an additional envelope gene, env, which mediates infection, and 2) a specific dual ribonuclease H (RNH) domain encoded by the retroviral pol gene. However, similar to retroviruses, many Ty3/Gypsy LTR retrotransposons harbor additional env-like genes, promoting concepts of the infective mode of these retrotransposons. Here, we provide a further line of evidence of similarity between retroviruses and some Ty3/Gypsy LTR retrotransposons. We identify that, together with their additional genes, plant Ty3/Gypsy LTR retrotransposons of the Tat group have a second RNH, as do retroviruses. Most importantly, we show that the resulting dual RNHs of Tat LTR retrotransposons and retroviruses emerged independently, providing strong evidence for their convergent evolution. The convergent resemblance of Tat LTR retrotransposons and retroviruses may indicate similar selection pressures acting on these diverse groups of elements and reveal potential evolutionary constraints on their structure. We speculate that dual RNH is required to accelerate retrotransposon evolution through increased rates of strand transfer events and subsequent recombination events. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Characterizing novel endogenous retroviruses from genetic variation inferred from short sequence reads

DEFF Research Database (Denmark)

Mourier, Tobias; Mollerup, Sarah; Vinner, Lasse

2015-01-01

From Illumina sequencing of DNA from brain and liver tissue from the lion, Panthera leo, and tumor samples from the pike-perch, Sander lucioperca, we obtained two assembled sequence contigs with similarity to known retroviruses. Phylogenetic analyses suggest that the pike-perch retrovirus belongs...... to the epsilonretroviruses, and the lion retrovirus to the gammaretroviruses. To determine if these novel retroviral sequences originate from an endogenous retrovirus or from a recently integrated exogenous retrovirus, we assessed the genetic diversity of the parental sequences from which the short Illumina reads...

Plant retroviruses: structure, evolution and future applications | Zaki ...

African Journals Online (AJOL)

Until recently, retroviruses were thought to be restricted to vertebrates. Plant sequencing projects revealed that plant genomes contain retroviral-like sequences. This review aims to address the structure and evolution of plant retroviruses. In addition, it proposes future applications for these important key components of plant ...

Multiple groups of endogenous epsilon-like retroviruses conserved across primates.

Science.gov (United States)

Brown, Katherine; Emes, Richard D; Tarlinton, Rachael E

2014-11-01

Several types of cancer in fish are caused by retroviruses, including those responsible for major outbreaks of disease, such as walleye dermal sarcoma virus and salmon swim bladder sarcoma virus. These viruses form a phylogenetic group often described as the epsilonretrovirus genus. Epsilon-like retroviruses have become endogenous retroviruses (ERVs) on several occasions, integrating into germ line cells to become part of the host genome, and sections of fish and amphibian genomes are derived from epsilon-like retroviruses. However, epsilon-like ERVs have been identified in very few mammals. We have developed a pipeline to screen full genomes for ERVs, and using this pipeline, we have located over 800 endogenous epsilon-like ERV fragments in primate genomes. Genomes from 32 species of mammals and birds were screened, and epsilon-like ERV fragments were found in all primate and tree shrew genomes but no others. These viruses appear to have entered the genome of a common ancestor of Old and New World monkeys between 42 million and 65 million years ago. Based on these results, there is an ancient evolutionary relationship between epsilon-like retroviruses and primates. Clearly, these viruses had the potential to infect the ancestors of primates and were at some point a common pathogen in these hosts. Therefore, this result raises questions about the potential of epsilonretroviruses to infect humans and other primates and about the evolutionary history of these retroviruses. Epsilonretroviruses are a group of retroviruses that cause several important diseases in fish. Retroviruses have the ability to become a permanent part of the DNA of their host by entering the germ line as endogenous retroviruses (ERVs), where they lose their infectivity over time but can be recognized as retroviruses for millions of years. Very few mammals are known to have epsilon-like ERVs; however, we have identified over 800 fragments of endogenous epsilon-like ERVs in the genomes of all major

Long-term reinfection of the human genome by endogenous retroviruses

Czech Academy of Sciences Publication Activity Database

Belshaw, R.; Pereira, V.; Katzourakis, A.; Talbot, G.; Pačes, Jan; Burt, A.

2004-01-01

Roč. 101, č. 14 (2004), s. 4894-4899 ISSN 0027-8424 R&D Projects: GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5052915 Keywords : endogenous retroviruses * human genome * HERV Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.452, year: 2004

Host-virus interactions of mammalian endogenous retroviruses

OpenAIRE

Farkašová, Helena

2017-01-01

Endogenous retroviruses (ERVs) originate by germline infection and subsequent mendelian inheritance of their exogenous counterparts. With notable exceptions, all mammalian ERVs are evolutionarily old and fixed in the population of its host species. Some groups of retroviruses were believed not to be able to form endogenous copies. We discovered an additional endogenous Lentivirus and a first endogenous Deltaretrovirus. Both of these groups were previously considered unable to form endogenous ...

Avian endogenous provirus (ev-3) env gene sequencing: implication for pathogenic retrovirus origination.

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Tikhonenko, A T; Lomovskaya, O L

1990-02-01

The avian endogenous env gene product blocks the surface receptor and, as a result, cells become immune to related exogenous retroviruses. On the other hand, the same sequence can be included in the pathogenic retrovirus genome, as shown by oligonucleotide mapping. However, since the complete env gene sequence was not known, the comparison of genomic nucleotide sequences was not possible. Therefore an avian endogenous provirus with an intact env gene was cloned from a chicken gene bank and the regions coding for the C terminus of the gp85 and gp37 proteins were sequenced. Comparison of this sequence with those of other retroviruses proved that one of the pathogenic viruses associated with osteopetrosis is a cross between avian endogenous virus and Rous sarcoma virus. Retroviruses and, especially, endogenous retroviruses are traditionally of the most developed models of viral carcinogenesis. Many endogenous retroviruses are implicated in neoplastic transformation of the cell. For instance, endogenous mouse mammary tumor virus of some inbred lines appears to be the only causative agent in these mammary cancers. Other even nonpathogenic murine endogenous retroviruses are involved in the origination of MCF-type recombinant acute leukosis viruses. Some endogenous retroviruses are implicated in the transduction or activation of cellular protooncogenes. Our interest in endogenous viruses is based on their ability to make cells resistant to exogenous retroviruses. Expression of their major envelope glycoprotein leads to cellular surface receptor blockage and imparts immunity to infection by the related leukemia retroviruses. This problem is quite elaborated for chicken endogenous virus RAV-O (7-9).(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of cell culture process changes on endogenous retrovirus expression.

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Brorson, Kurt; De Wit, Christina; Hamilton, Elizabeth; Mustafa, Mehnaz; Swann, Patrick G; Kiss, Robert; Taticek, Ron; Polastri, Gian; Stein, Kathryn E; Xu, Yuan

2002-11-05

Cell culture process changes (e.g., changes in scale, medium formulation, operational conditions) and cell line changes are common during the development life cycle of a therapeutic protein. To ensure that the impact of such process changes on product quality and safety is minimal, it is standard practice to compare critical product quality and safety attributes before and after the changes. One potential concern introduced by cell culture process improvements is the possibility of increased endogenous retrovirus expression to a level above the clearance capability of the subsequent purification process. To address this, retrovirus expression was measured in scaled down and full production scaled Chinese hamster ovary (CHO) cell cultures of four monoclonal antibodies and one recombinant protein before and after process changes. Two highly sensitive, quantitative (Q)-PCR-based assays were used to measure endogenous retroviruses. It is shown that cell culture process changes that primarily alter media components, nutrient feed volume, seed density, cell bank source (i.e., master cell bank vs. working cell bank), and vial size, or culture scale, singly or in combination, do not impact the rate of retrovirus expression to an extent greater than the variability of the Q-PCR assays (0.2-0.5 log(10)). Cell culture changes that significantly alter the metabolic state of the cells and/or rates of protein expression (e.g., pH and temperature shifts, NaButyrate addition) measurably impact the rate of retrovirus synthesis (up to 2 log(10)). The greatest degree of variation in endogenous retrovirus expression was observed between individual cell lines (up to 3 log(10)). These data support the practice of measuring endogenous retrovirus output for each new cell line introduced into manufacturing or after process changes that significantly increase product-specific productivity or alter the metabolic state, but suggest that reassessment of retrovirus expression after other

Expression and function of endogenous retroviruses in the placenta.

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Denner, Joachim

2016-01-01

Although the expression of endogenous retroviruses in the placenta of numerous species was observed a long time ago, their physiological function during gestation was demonstrated only very recently. Expression of retroviral envelope proteins, also called syncytins, in the placenta allows generation of the multinuclear syncytiotrophoblast as an outer cellular layer of the placenta by fusion of the trophoblast cells. This fusion process is crucial for the development of the placenta and for successful pregnancy. It is still unclear whether the immunosuppressive properties of the transmembrane envelope protein of the endogenous retroviruses expressed in the placenta contribute to immunosuppression to prevent the rejection of the semiallotransplant embryo. The presence of placenta cells expressing retroviral envelope proteins surrounded by immune cells deep in the maternal tissue supports an immunosuppressive function. It is important to emphasize that during evolution different species utilized ('enslaved') different endogenous retroviruses and that two or more endogenous retroviruses are involved in placentogenesis in each species. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Demethylation of host-cell DNA at the site of avian retrovirus integration

Czech Academy of Sciences Publication Activity Database

Hejnar, Jiří; Elleder, Daniel; Hájková, P.; Walter, J.; Blažková, Jana; Svoboda, Jan

2003-01-01

Roč. 2003, č. 311 (2003), s. 641-648 ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915 Keywords : DNA methylation and demethylation * integration of retroviruses * gene silencing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.836, year: 2003

Rapid modification of retroviruses using lipid conjugates

International Nuclear Information System (INIS)

Mukherjee, Nimisha G; Le Doux, Joseph M; Andrew Lyon, L

2009-01-01

Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

KOALA RETROVIRUS: A REVIEW.

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Kinney, Matthew E; Pye, Geoffrey W

2016-06-01

Koala retrovirus (KoRV) is a gammaretrovirus that has been identified in both captive and free-ranging koalas ( Phascolarctos cinereus ) with variable geographic distribution in Australia. KoRV is capable of both exogenous and endogenous transmission, which provides an interesting research platform for scientists to study active retrovirus endogenization into a host genome and offers veterinary scientists an opportunity to examine the clinical consequences of KoRV infection in koalas. Causation between KoRV and frequently recognized clinical conditions associated with immune suppression and neoplasia in koalas has not been definitively established, however research continues to evaluate a potential association. Three KoRV variants, KoRV-A, KoRV-B, and KoRV-J, have been the most thoroughly described and preliminary evidence suggests KoRV variability may be fundamental in host pathogenicity. In addition to reviewing what is currently known about KoRV, this article discusses treatment, management, and future research directions.

Friends-enemies: endogenous retroviruses are major transcriptional regulators of human DNA

Science.gov (United States)

Buzdin, Anton A.; Prassolov, Vladimir; Garazha, Andrew V.

2017-06-01

Endogenous retroviruses are mobile genetic elements hardly distinguishable from infectious, or “exogenous”, retroviruses at the time of insertion in the host DNA. Human endogenous retroviruses (HERVs) are not rare. They gave rise to multiple families of closely related mobile elements that occupy 8% of the human genome. Together, they shape genomic regulatory landscape by providing at least 320,000 human transcription factor binding sites (TFBS) located on 110,000 individual HERV elements. The HERVs host as many as 155,000 mapped DNaseI hypersensitivity sites, which denote loci active in the regulation of gene expression or chromatin structure. The contemporary view of the HERVs evolutionary dynamics suggests that at the early stages after insertion, the HERV is treated by the host cells as a foreign genetic element, and is likely to be suppressed by the targeted methylation and mutations. However, at the later stages, when significant number of mutations has been already accumulated and when the retroviral genes are broken, the regulatory potential of a HERV may be released and recruited to modify the genomic balance of transcription factor binding sites. This process goes together with further accumulation and selection of mutations, which reshape the regulatory landscape of the human DNA. However, developmental reprogramming, stress or pathological conditions like cancer, inflammation and infectious diseases, can remove the blocks limiting expression and HERV-mediated host gene regulation. This, in turn, can dramatically alter the gene expression equilibrium and shift it to a newer state, thus further amplifying instability and exacerbating the stressful situation.

Association of ultraviolet-induced retrovirus expression with anchorage-independent survival in rat embryo cells

International Nuclear Information System (INIS)

Suk, W.A.

1985-01-01

The authors have shown in the AI assay that the nontransforming retrovirus increases the differential in enhanced survival response in infected cultures. To more fully understand this aspect of the system, they examined the effect of UV irradiation on infected and uninfected FRE cells. In this communication the authors report that UV irradiation induces AI survival in infected and uninfected cells;in uninfected cells there is a concomitant induction of endogenous retrovirus expression. The AI survival of both cell lines was determined using a previously described procedure. Anchorage-dependent media control and solvent control cells, when suspended in medium above an agar base layer, showed a rapid decline in cell survival;however, cells that had been treated with carcinogen did not undergo the destructive process that took place in control cells, indicating specificity

Biology and evolution of the endogenous koala retrovirus.

Science.gov (United States)

Tarlinton, R; Meers, J; Young, P

2008-11-01

Although endogenous retroviruses are ubiquitous features of all mammalian genomes, the process of initial germ line invasion and subsequent inactivation from a pathogenic element has not yet been observed in a wild species. Koala retrovirus (KoRV) provides a unique opportunity to study this process of endogenisation in action as it still appears to be spreading through the koala population. Ongoing expression of the endogenous sequence and consequent high levels of viraemia have been linked to neoplasia and immunosuppression in koalas. This apparently recent invader of the koala genome shares a remarkably close sequence relationship with the pathogenic exogenous Gibbon ape leukaemia virus (GALV), and comparative analyses of KoRV and GALVare helping to shed light on how retroviruses in general adapt to a relatively benign or at least less pathogenic existence within a new host genome. (Part of a multi-author review).

Induced prion protein controls immune-activated retroviruses in the mouse spleen.

Directory of Open Access Journals (Sweden)

Marius Lötscher

Full Text Available The prion protein (PrP is crucially involved in transmissible spongiform encephalopathies (TSE, but neither its exact role in disease nor its physiological function are known. Here we show for mice, using histological, immunochemical and PCR-based methods, that stimulation of innate resistance was followed by appearance of numerous endogenous retroviruses and ensuing PrP up-regulation in germinal centers of the spleen. Subsequently, the activated retroviruses disappeared in a PrP-dependent manner. Our results reveal the regular involvement of endogenous retroviruses in murine immune responses and provide evidence for an essential function of PrP in the control of the retroviral activity. The interaction between PrP and ubiquitous endogenous retroviruses may allow new interpretations of TSE pathophysiology and explain the evolutionary conservation of PrP.

Human endogenous retroviruses in neurologic disease.

Science.gov (United States)

Christensen, Tove

2016-01-01

Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Real-time quantitative PCR for retrovirus-like particle quantification in CHO cell culture.

Science.gov (United States)

de Wit, C; Fautz, C; Xu, Y

2000-09-01

Chinese hamster ovary (CHO) cells have been widely used to manufacture recombinant proteins intended for human therapeutic uses. Retrovirus-like particles, which are apparently defective and non-infectious, have been detected in all CHO cells by electron microscopy (EM). To assure viral safety of CHO cell-derived biologicals, quantification of retrovirus-like particles in production cell culture and demonstration of sufficient elimination of such retrovirus-like particles by the down-stream purification process are required for product market registration worldwide. EM, with a detection limit of 1x10(6) particles/ml, is the standard retrovirus-like particle quantification method. The whole process, which requires a large amount of sample (3-6 litres), is labour intensive, time consuming, expensive, and subject to significant assay variability. In this paper, a novel real-time quantitative PCR assay (TaqMan assay) has been developed for the quantification of retrovirus-like particles. Each retrovirus particle contains two copies of the viral genomic particle RNA (pRNA) molecule. Therefore, quantification of retrovirus particles can be achieved by quantifying the pRNA copy number, i.e. every two copies of retroviral pRNA is equivalent to one retrovirus-like particle. The TaqMan assay takes advantage of the 5'-->3' exonuclease activity of Taq DNA polymerase and utilizes the PRISM 7700 Sequence Detection System of PE Applied Biosystems (Foster City, CA, U.S.A.) for automated pRNA quantification through a dual-labelled fluorogenic probe. The TaqMan quantification technique is highly comparable to the EM analysis. In addition, it offers significant advantages over the EM analysis, such as a higher sensitivity of less than 600 particles/ml, greater accuracy and reliability, higher sample throughput, more flexibility and lower cost. Therefore, the TaqMan assay should be used as a substitute for EM analysis for retrovirus-like particle quantification in CHO cell

One Hundred Twenty Years of Koala Retrovirus Evolution Determined from Museum Skins

OpenAIRE

?vila-Arcos, Mar?a C.; Ho, Simon Y.W.; Ishida, Yasuko; Nikolaidis, Nikolas; Tsangaras, Kyriakos; H?nig, Karin; Medina, Rebeca; Rasmussen, Morten; Fordyce, Sarah L.; Calvignac-Spencer, S?bastien; Willerslev, Eske; Gilbert, M. Thomas P.; Helgen, Kristofer M.; Roca, Alfred L.; Greenwood, Alex D.

2013-01-01

Although endogenous retroviruses are common across vertebrate genomes, the koala retrovirus (KoRV) is the only retrovirus known to be currently invading the germ line of its host. KoRV is believed to have first infected koalas in northern Australia less than two centuries ago. We examined KoRV in 28 koala museum skins collected in the late 19th and 20th centuries and deep sequenced the complete proviral envelope region from five northern Australian specimens. Strikingly, KoRV env sequences we...

The retrovirus MA and PreTM proteins follow immature MVL cores

DEFF Research Database (Denmark)

Andersen, Klaus Bahl

2013-01-01

Detergent can dissolve retrovirus, exept the immature core. Here we show that the Matrix protein (MA) and the Transmembrane protein in its immature form (PreTM) bind to the retrovirus core. These attachments explain the attachment in the virus particle and the dynamics of the ability to fuse with...

Mutational definition of functional domains within the Rev homolog encoded by human endogenous retrovirus K.

Science.gov (United States)

Bogerd, H P; Wiegand, H L; Yang, J; Cullen, B R

2000-10-01

Nuclear export of the incompletely spliced mRNAs encoded by several complex retroviruses, including human immunodeficiency virus type 1 (HIV-1), is dependent on a virally encoded adapter protein, termed Rev in HIV-1, that directly binds both to a cis-acting viral RNA target site and to the cellular Crm1 export factor. Human endogenous retrovirus K, a family of ancient endogenous retroviruses that is not related to the exogenous retrovirus HIV-1, was recently shown to also encode a Crm1-dependent nuclear RNA export factor, termed K-Rev. Although HIV-1 Rev and K-Rev display little sequence identity, they share the ability not only to bind to Crm1 and to RNA but also to form homomultimers and shuttle between nucleus and cytoplasm. We have used mutational analysis to identify sequences in the 105-amino-acid K-Rev protein required for each of these distinct biological activities. While mutations in K-Rev that inactivate any one of these properties also blocked K-Rev-dependent nuclear RNA export, several K-Rev mutants were comparable to wild type when assayed for any of these individual activities yet nevertheless defective for RNA export. Although several nonfunctional K-Rev mutants acted as dominant negative inhibitors of K-Rev-, but not HIV-1 Rev-, dependent RNA export, these were not defined by their inability to bind to Crm1, as is seen with HIV-1 Rev. In total, this analysis suggests a functional architecture for K-Rev that is similar to, but distinct from, that described for HIV-1 Rev and raises the possibility that viral RNA export mediated by the approximately 25 million-year-old K-Rev protein may require an additional cellular cofactor that is not required for HIV-1 Rev function.

Viral and cellular requirements for the budding of Feline Endogenous Retrovirus RD-114

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Fukuma Aiko

2011-12-01

Full Text Available Abstract Background RD-114 virus is a feline endogenous retrovirus and produced as infectious viruses in some feline cell lines. Recently, we reported the contamination of an infectious RD-114 virus in a proportion of live attenuated vaccines for dogs and cats. It is very difficult to completely knock out the RD-114 proviruses from cells, as endogenous retroviruses are usually integrated multiply into the host genome. However, it may be possible to reduce the risk of contamination of RD-114 virus by regulating the viral release from cells. Results In this study, to understand the molecular mechanism of RD-114 virus budding, we attempted to identify the viral and cellular requirements for RD-114 virus budding. Analyses of RD-114 L-domain mutants showed that the PPPY sequence in the pp15 region of Gag plays a critical role in RD-114 virus release as viral L-domain. Furthermore, we investigated the cellular factors required for RD-114 virus budding. We demonstrated that RD-114 virus release was inhibited by overexpression of dominant negative mutants of Vps4A, Vps4B, and WWP2. Conclusions These results strongly suggest that RD-114 budding utilizes the cellular multivesicular body sorting pathway similar to many other retroviruses.

The role of human endogenous retroviruses in brain development and function.

Science.gov (United States)

Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

2016-01-01

Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Interspecies radioimmunoassay for the major structural proteins of primate type-D retroviruses

International Nuclear Information System (INIS)

Colcher, D.; Teramoto, Y.A.; Schlom, J.

1977-01-01

A competition radioimmunoassay has been developed in which type-D retroviruses from three primate species compete. The assay utilizes the major structural protein (36,000 daltons) of the endogenous squirrel monkey retrovirus and antisera directed against the major structural protein (27,000 daltons) of the Mason-Pfizer monkey virus isolated from rhesus monkeys. Purified preparations of both viruses grown in heterologous cells, as well as extracts of heterologous cells infected with squirrel monkey retrovirus or Mason-Pfizer monkey virus, compete completely in the assay. Addition of an endogenous virus of the langur monkey also results in complete blocking. No blocking in the assay is observed with type-C baboon viruses, woolly monkey virus, and gibbon virus. Various other type-C and type-B viruses also showed no reactivity. An interspecies assay has thus been developed that recognizes the type-D retroviruses from both Old World monkey (rhesus and langur) and New World monkey (squirrel) species

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

International Nuclear Information System (INIS)

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

1997-01-01

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

Retrovirus-mediated in vitro gene transfer into chicken male germ line cells

Czech Academy of Sciences Publication Activity Database

Kalina, J.; Šenigl, Filip; Mičáková, A.; Mucksová, J.; Blažková, Jana; Haifeng, Y.; Poplštejn, M.; Hejnar, Jiří; Trefil, P.

2007-01-01

Roč. 134, č. 3 (2007), s. 445-453 ISSN 1470-1626 R&D Projects: GA ČR GA523/04/0569 Grant - others:GA MŠk(CZ) 1P05ME722 Institutional research plan: CEZ:AV0Z50520514 Keywords : Transgenic spermatozoa * infection of testicular cells with retrovirus * transgenesis in chicken Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.962, year: 2007

Molecular characterization of full-length MLV-related endogenous retrovirus ChiRV1 from the chicken, Gallus gallus

Czech Academy of Sciences Publication Activity Database

Borysenko, L.; Stepanets, Volodymyr; Rynditch, A.V.

2008-01-01

Roč. 376, č. 1 (2008), s. 199-204 ISSN 0042-6822 Institutional research plan: CEZ:AV0Z50520514 Keywords : endogenous retrovirus * chicken * phylogeny Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.539, year: 2008

Human endogenous retroviruses and ADHD.

Science.gov (United States)

Balestrieri, Emanuela; Pitzianti, Mariabernarda; Matteucci, Claudia; D'Agati, Elisa; Sorrentino, Roberta; Baratta, Antonia; Caterina, Rosa; Zenobi, Rossella; Curatolo, Paolo; Garaci, Enrico; Sinibaldi-Vallebona, Paola; Pasini, Augusto

2014-08-01

Several lines of evidences suggest that human endogenous retroviruses (HERVs) are implicated in the development of many complex diseases with a multifactorial aetiology and a strong heritability, such as neurological and psychiatric diseases. Attention deficit hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that results from a complex interaction of environmental, biological and genetic factors. Our aim was to analyse the expression levels of three HERV families (HERV-H, K and W) in patients with ADHD. The expression of retroviral mRNAs from the three HERV families was evaluated in peripheral blood mononuclear cells (PBMCs) from 30 patients with ADHD and 30 healthy controls by quantitative RT-PCR. The expression levels of HERV-H are significantly higher in patients with ADHD compared to healthy controls, while there are no differences in the expression levels of HERV-K and W. Since the ADHD aetiology is due to a complex interaction of environmental, biological and genetic factors, HERVs may represent one link among these factors and clinical phenotype of ADHD. A future confirmation of HERV-H overexpression in a larger number of ADHD patients will make possible to identify it as a new parameter for this clinical condition, also contributing to deepen the study on the role of HERVs in the neurodevelopment diseases.

Single-Particle Discrimination of Retroviruses from Extracellular Vesicles by Nanoscale Flow Cytometry.

Science.gov (United States)

Tang, Vera A; Renner, Tyler M; Fritzsche, Anna K; Burger, Dylan; Langlois, Marc-André

2017-12-19

Retroviruses and small EVs overlap in size, buoyant densities, refractive indices and share many cell-derived surface markers making them virtually indistinguishable by standard biochemical methods. This poses a significant challenge when purifying retroviruses for downstream analyses or for phenotypic characterization studies of markers on individual virions given that EVs are a major contaminant of retroviral preparations. Nanoscale flow cytometry (NFC), also called flow virometry, is an adaptation of flow cytometry technology for the analysis of individual nanoparticles such as extracellular vesicles (EVs) and retroviruses. In this study we systematically optimized NFC parameters for the detection of retroviral particles in the range of 115-130 nm, including viral production, sample labeling, laser power and voltage settings. By using the retroviral envelope glycoprotein as a selection marker, and evaluating a number of fluorescent dyes and labeling methods, we demonstrate that it is possible to confidently distinguish retroviruses from small EVs by NFC. Our findings make it now possible to individually phenotype genetically modified retroviral particles that express a fluorescent envelope glycoprotein without removing EV contaminants from the sample.

Koala retroviruses: characterization and impact on the life of koalas

OpenAIRE

Denner, Joachim; Young, Paul R

2013-01-01

Koala retroviruses (KoRV) have been isolated from wild and captive koalas in Australia as well as from koala populations held in zoos in other countries. They are members of the genus Gammaretrovirus, are most closely related to gibbon ape leukemia virus (GaLV), feline leukemia virus (FeLV) and porcine endogenous retrovirus (PERV) and are likely the result of a relatively recent trans-species transmission from rodents or bats. The first KoRV to be isolated, KoRV-A, is widely distributed in th...

Human retroviruses and AIDS 1994

Energy Technology Data Exchange (ETDEWEB)

Myers, G.; Korber, B. [Los Alamos National Lab., NM (United States); Wain-Hobson, S.; Jeang, Kuan-Teh; Henderson, L.E.; Pavlakis, G.N. [eds.

1995-01-01

This compendium, including accompanying floppy diskettes, is the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts it comprises: (I) Nucleic Acid Alignments and Sequences; (II) Amino Acid Alignments; (III) Analysis; (IV) Related Sequences; (V) Database communications.

The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis.

Science.gov (United States)

Dolei, Antonina

2018-01-01

Two human endogenous retroviruses of the HERV-W family are proposed as multiple sclerosis (MS) co-factors: MS-associated retrovirus (MSRV) and ERVWE1, whose env proteins showed several potentially neuropathogenic features, in vitro and in animal models. Phase II clinical trials against HERV-Wenv are ongoing. HERV-W/MSRV was repeatedly found in MS patients, in striking parallel with MS stages, active/remission phases, and therapy outcome. The HERV-Wenv protein is highly expressed in active MS plaques. Early MSRV presence in spinal fluids predicted worst MS progression 10 years in advance. Effective anti-MS therapies strongly reduced MSRV/Syncytin-1/HERV-W expression. The Epstein-Barr virus (EBV) activates HERV-W/MSRV in vitro and in vivo, in patients with infectious mononucleosis and controls with high anti-EBNA1-IgG titers. Thus, the two main EBV/MS links (infectious mononucleosis and high anti-EBNA1-IgG titers) are paralleled by activation of HERV-W/MSRV. It is hypothesized that EBV may act as initial trigger of future MS, years later, by activating MSRV, which would act as direct neuropathogenic effector, before and during MS.

Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

Science.gov (United States)

Tönjes, Ralf R.

2012-01-01

Summary: Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference. PMID:22491774

Endogenous retrovirus sequences expressed in male mammalian ...

African Journals Online (AJOL)

Objectives: To review the research findings on the expression of endogenous retroviruses and retroviral-related particles in male mammalian reproductive tissues, and to discuss their possible role in normal cellular events and association with disease conditions in male reproductive tissues. Data sources: Published ...

How Active Are Porcine Endogenous Retroviruses (PERVs?

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Joachim Denner

2016-08-01

Full Text Available Porcine endogenous retroviruses (PERVs represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs, which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated nuclease (CRISPR/Cas technology.

High copy number in human endogenous retrovirus families is associated with copying mechanisms in addition to reinfection

Czech Academy of Sciences Publication Activity Database

Belshaw, R.; Katzourakis, A.; Pačes, Jan; Burt, A.; Tristem, M.

2005-01-01

Roč. 22, č. 4 (2005), s. 814-817 ISSN 0737-4038 R&D Projects: GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z50520514 Keywords : human endogenous retrovirus * reinfection * retrotransposition Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.233, year: 2005

Endogenous retroviruses are associated with autoimmune diseases

DEFF Research Database (Denmark)

Nexø, Bjørn A; Bisgaard Jensen, Sara; Hansen, Bettina

2016-01-01

of transmission is called vertical. Viral variants of importance for development of disease must be more frequent among diseased persons than among healthy individuals. Multiple sclerosis, diabetes and rheumatoid arthritis are all associated with sets of endogenouos retroviruses but not the same sets. If a virus...

The role of BST2/tetherin in infection with the feline retroviruses

Science.gov (United States)

Dietrich, Isabelle; Hosie, Margaret J.; Willett, Brian J.

2014-01-01

The recently identified host restriction factor tetherin (BST-2, CD317) potently inhibits the release of nascent retrovirus particles from infected cells. Recently, we reported the identification and characterization of tetherin as a novel feline retroviral restriction factor. Based on homology to human tetherin we identified a putative tetherin gene in the genome of the domestic cat (Felis catus) which was found to be expressed in different feline cell lines both prior to and post treatment with either type I or type II interferon (IFN). The predicted structure of feline tetherin (feTHN) was that of a type II single-pass transmembrane protein encoding an N-terminal transmembrane anchor, central predicted coiled-coil bearing extracellular domain to promote dimerization, and a C-terminal GPI-anchor, consistent with conservation of structure between human and feline tetherin. FeTHN displayed potent inhibition of feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) particle release in single-cycle replication assays. Notably, feTHN activity was resistant to antagonism by HIV-1 Vpu. However, stable ectopic expression of feTHN mRNA in different feline cell lines had no inhibitory effect on the growth of diverse primary or cell culture-adapted strains of FIV. Hence, whereas feline tetherin efficiently blocks viral particle release in single-cycle replication assays, it might not prevent dissemination of feline retroviruses in vivo. PMID:21715020

One hundred twenty years of koala retrovirus evolution determined from museum skins

DEFF Research Database (Denmark)

Avila Arcos, Maria del Carmen; Ho, Simon Y. W.; Ishida, Yasuko

2013-01-01

Although endogenous retroviruses are common across vertebrate genomes, the koala retrovirus (KoRV) is the only retrovirus known to be currently invading the germ line of its host. KoRV is believed to have first infected koalas in northern Australia less than two centuries ago. We examined Ko......RV in 28 koala museum skins collected in the late 19th and 20th centuries and deep sequenced the complete proviral envelope region from five northern Australian specimens. Strikingly, KoRV env sequences were conserved among koalas collected over the span of a century, and two functional motifs that affect...... viral infectivity were fixed across the museum koala specimens. We detected only 20 env polymorphisms among the koalas, likely representing derived mutations subject to purifying selection. Among northern Australian koalas, KoRV was already ubiquitous by the late 19th century, suggesting that Ko...

Endogenous retroviruses in fish genomes: from relics of past infections to evolutionary innovations?

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Magali Naville

2016-08-01

Full Text Available The increasing availability of fish genome sequences has allowed to gain new insights into the diversity and host distribution of retroviruses in fish and other vertebrates. This distribution can be assessed through the identification and analysis of endogenous retroviruses, which are proviral remnants of past infections integrated in genomes. Retroviral sequences are probably important for evolution through their ability to induce rearrangements and to contribute regulatory and coding sequences; they may also protect their host against new infections. We argue that the current mass of genome sequences will soon strongly improve our understanding of retrovirus diversity and evolution in aquatic animals, with the identification of new/re-emerging elements and host resistance genes that restrict their infectivity.

Retrovirus D/New England and its relation to Mason-Pfizer monkey virus.

OpenAIRE

Desrosiers, R C; Daniel, M D; Butler, C V; Schmidt, D K; Letvin, N L; Hunt, R D; King, N W; Barker, C S; Hunter, E

1985-01-01

Seventeen isolates of retrovirus D/New England have been obtained from three species of macaques at the New England Regional Primate Research Center. Seven of the isolates were obtained from macaques who subsequently died with the macaque immunodeficiency syndrome; other isolates were obtained from macaques with less severe or other forms of illness. Attempts to isolate type D retrovirus from peripheral lymphocytes of 97 apparently healthy macaques have not been successful. Cloned DNA was pre...

Human-Specific Endogenous Retroviruses

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Anton Buzdin

2007-01-01

Full Text Available This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

Endogenous retrovirus sequences expressed in male mammalian ...

African Journals Online (AJOL)

In humans, one ERV family, human endogenous retrovirus- K (HERV-K) is abundantly expressed, and is associated with germ cell tumours, while ERV3 env is expressed in normal human testis. Conclusion: The expression of ERVs in male reproductive tissues suggests a possible role in normal and disease conditions ...

Packaging of human endogenous retrovirus sequences is undetectable in porcine endogenous retrovirus particles produced from human cells

International Nuclear Information System (INIS)

Suling, Kristen; Quinn, Gary; Wood, James; Patience, Clive

2003-01-01

The chronic shortage of human donor organs and tissues for allotransplantation could be relieved if clinical xenotransplantation were to become a viable clinical therapy. Balanced against the benefits of xenotransplantation are the possible consequences of zoonotic infections, and in particular, infection by porcine endogenous retrovirus (PERV). An often-proclaimed risk of PERV infection is the possible recombination of PERV with human endogenous retroviruses (HERV) . To address this issue, we examined the potential for HERV sequences to be cross-packaged into PERV particles produced from infected human 293 cells. Although HERV-K, W, E, R, and ERV-9 RNA transcripts are expressed in 293 cells, we did not detect cross-packaging of any of these HERV groups. Quantitative analysis indicated that less than approximately 1 in 10 4 -10 7 PERV particles might contain HERV sequences. In comparison, we found that murine leukemia virus (MLV)-based vector transcripts were cross-packaged at a rate of approximately one copy in 10 4 PERV particles. Our results indicate that the potential for recombination of PERV and HERV sequences is low and that novel viruses generated by this mechanism are unlikely to represent a significant risk for xenotransplantation

Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses.

Science.gov (United States)

Gao, Daxing; Wu, Jiaxi; Wu, You-Tong; Du, Fenghe; Aroh, Chukwuemika; Yan, Nan; Sun, Lijun; Chen, Zhijian J

2013-08-23

Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-β induction by the virus, suggesting that the reverse-transcribed HIV DNA triggers the innate immune response. Knockout or knockdown of cGAS in mouse or human cell lines blocked cytokine induction by HIV, murine leukemia virus, and simian immunodeficiency virus. These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses.

Making a virtue of necessity: the pleiotropic role of human endogenous retroviruses in cancer.

Science.gov (United States)

Kassiotis, George; Stoye, Jonathan P

2017-10-19

Like all other mammals, humans harbour an astonishing number of endogenous retroviruses (ERVs), as well as other retroelements, embedded in their genome. These remnants of ancestral germline infection with distinct exogenous retroviruses display various degrees of open reading frame integrity and replication capability. Modern day exogenous retroviruses, as well as the infectious predecessors of ERVs, are demonstrably oncogenic. Further, replication-competent ERVs continue to cause cancers in many other species of mammal. Moreover, human cancers are characterized by transcriptional activation of human endogenous retroviruses (HERVs). These observations conspire to incriminate HERVs as causative agents of human cancer. However, exhaustive investigation of cancer genomes suggests that HERVs have entirely lost the ability for re-infection and thus the potential for insertional mutagenic activity. Although there may be non-insertional mechanisms by which HERVs contribute to cancer development, recent evidence also uncovers potent anti-tumour activities exerted by HERV replication intermediates or protein products. On balance, it appears that HERVs, despite their oncogenic past, now represent potential targets for immune-mediated anti-tumour mechanisms.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase.

Science.gov (United States)

Xiao, Ran; Li, Shan; Cao, Qian; Wang, Xiuling; Yan, Qiujin; Tu, Xiaoning; Zhu, Ying; Zhu, Fan

2017-06-01

Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

A recombinant endogenous retrovirus amplified in a mouse neuroblastoma is involved in tumor growth in vivo.

Science.gov (United States)

Pothlichet, Julien; Heidmann, Thierry; Mangeney, Marianne

2006-08-15

The theory of immunoediting postulates that tumor cells exhibit a reduced immunogenicity to escape eradication by the host immune system. It has been proposed that endogenous retroviruses--provided that they are active--could play a role in this process, via the immunosuppressive domain carried by their envelope protein. Here, we demonstrate that the Neuro-2a tumor cell line--originating from a spontaneous A/J mouse neuroblastoma--produces an infectious retrovirus that most probably results from a recombination event between 2 mouse endogenous retroviral elements. This Neuro-2a-associated recombinant retrovirus derives from the unique ecotropic provirus located at the Emv-1 locus, but with a gag sequence conferring B-tropism, thus allowing its high-level amplification in Neuro-2a cells. We show that knocking down -by RNA interference- this endogenous retrovirus in Neuro-2a cells has no effect on the transformed phenotype of the cells, but results in delayed tumor growth and prolonged animal survival, following engraftment of the cells into immunocompetent mice. Recombination between endogenous retroviruses, amplification of the resulting element and high-level expression of its immunosuppressive activity are therefore likely steps of an immunoediting process, leading to an invading tumor. Copyright 2006 Wiley-Liss, Inc.

Human endogenous retrovirus type W (HERV-W) in schizophrenia: a new avenue of research at the gene-environment interface.

Science.gov (United States)

Leboyer, Marion; Tamouza, Ryad; Charron, Dominique; Faucard, Raphaél; Perron, Hervé

2013-03-01

Provide a synthetic review of recent studies evidencing an association between human endogenous retrovirus-W (HERV-W) and schizophrenia. Bibliography analysis and contextual synthesis. Epidemiological studies suggest that the aetiology of schizophrenia is complex and involves a complex interplay of genetic and environmental factors such as infections. Eight percentof the human genome consists of human endogenous retroviruses (HERV), and this part of the genome was previously thought to be without importance, but new research has refuted this. HERVs share similarities with viruses and it is assumed that HERVs are present in the genome as a result of retroviruses infecting germ line cells many million years ago. A specific type of HERVs, called HERV-W, has through several recent studies been associated with schizophrenia. Elevated transcription of HERV-W elements has been documented, and antigens of HERV-W envelope and capsid proteins have been found in blood samples from patients. Viruses that have been implicated in pathology of schizophrenia, such as herpes and influenza, have been shown to activate HERV-W elements, and such activation has been associated with elevated biomarkers of systemic inflammation. New research indicates that HERV-W may be an important genetic factor interplaying with the environmental risk factor of infections and that, through this, HERV-W may be important for disease pathogenesis. A lifelong scenario of a detrimental interaction between infectious agents and HERV-W genes may decipher the actual development and course of schizophrenia. Further research is needed to find out if specific treatment strategies could reduce the expression of HERV-W and if this will be associated with remission.

DNA hypomethylation and aberrant expression of the human endogenous retrovirus ERVWE1/syncytin-1 in seminomas

Czech Academy of Sciences Publication Activity Database

Benešová, Martina; Trejbalová, Kateřina; Kovářová, Denisa; Vernerová, Z.; Hron, Tomáš; Kučerová, Dana; Hejnar, Jiří

2017-01-01

Roč. 14, č. 1 (2017), č. článku 20. ISSN 1742-4690 R&D Projects: GA ČR GA13-37600S; GA MZd NT14601 Institutional support: RVO:68378050 Keywords : Human endogenous retrovirus * ERVWE1 * Germ cell tumor * Seminoma * Promoter DNA methylation * 5-Hydroxymethylcytosine * Transcription * RNA splicing Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Virology Impact factor: 3.867, year: 2016

Tracking the Continuous Evolutionary Processes of an Endogenous Retrovirus of the Domestic Cat: ERV-DC

Directory of Open Access Journals (Sweden)

Junna Kawasaki

2018-04-01

Full Text Available An endogenous retrovirus (ERV is a remnant of an ancient retroviral infection in the host genome. Although most ERVs have lost their viral productivity, a few ERVs retain their replication capacity. In addition, partially inactivated ERVs can present a potential risk to the host via their encoded virulence factors or the generation of novel viruses by viral recombination. ERVs can also eventually acquire a biological function, and this ability has been a driving force of host evolution. Therefore, the presence of an ERV can be harmful or beneficial to the host. Various reports about paleovirology have revealed each event in ERV evolution, but the continuous processes of ERV evolution over millions of years are mainly unknown. A unique ERV family, ERV-DC, is present in the domestic cat (Felis silvestris catus genome. ERV-DC proviruses are phylogenetically classified into three genotypes, and the specific characteristics of each genotype have been clarified: their capacity to produce infectious viruses; their recombination with other retroviruses, such as feline leukemia virus or RD-114; and their biological functions as host antiviral factors. In this review, we describe ERV-DC-related phenomena and discuss the continuous changes in the evolution of this ERV in the domestic cat.

Endogenous Jaagsiekte Sheep Retrovirus RNA is expressed by different cell types in ovine foetus and placenta

Directory of Open Access Journals (Sweden)

E Sanna

2010-01-01

Full Text Available The endogenous retroviruses are inherited elements transmitted trough the germline of most animal species and their biological role is still controversial. Ovine Pulmonary Carcinoma (OPC represents a good model for studying the interactions of endogenous retroviruses with their exogenous counterparts. The type D exogenous retrovirus known as Jaagsiekte Sheep Retro-Virus (JSRV is necessary and sufficient to cause OPC in domestic and wild sheep, but both affected and unaffected animals host in their genome 15 to 20 copies of related endogenous retroviruses named endogenous JSRV (enJSRV. In this study we evaluated the expression of enJSRV gag sequences in ovine foetal and placental tissues. RNA in situ hybridisation was performed on tissue sections of thymi, lymph nodes and lungs from ovine foetuses and related placentas, taken at a late stage of development. Reverse transcriptase- in situ polymerase chain reactions were also carried out on placental samples to better define the involved cells. In foetal tissues, specific signals were observed in the thymus medulla, lymph nodes and, at a lesser extent, in foetal bronchiolar cells. In the placental tissues, positive areas were detected in various cell types in the sincythium-and cyto-trophoblast. These data demonstrate that en JSRV RNA is largely expressed in a broad spectrum of cells including tissues which are critical for the development of the immune system.

Human endogenous retrovirus-R (ERV 3) env-like antigens ...

African Journals Online (AJOL)

Background: A substantial component of the vertebrate genome comprise of retrovirusrelated sequences named as endogenous retroviruses (ERVs). The role of these ERVrelated sequences in the biological processes of the host species is still unknown. However, they have been associated with tumourigenesis, ...

Revealing the history of domesticated sheep using retrovirus integrations

DEFF Research Database (Denmark)

Chessa, Bernado; Pereira, Filipe; Arnaud, Frederick

2009-01-01

The domestication of livestock represented a crucial step in human history. By using endogenous retroviruses as genetic markers, we found that sheep differentiated on the basis of their "retrotype" and morphological traits dispersed across Eurasia and Africa via separate migratory episodes. Relic...

The first sequenced carnivore genome shows complex host-endogenous retrovirus relationships.

Directory of Open Access Journals (Sweden)

Álvaro Martínez Barrio

Full Text Available Host-retrovirus interactions influence the genomic landscape and have contributed substantially to mammalian genome evolution. To gain further insights, we analyzed a female boxer (Canis familiaris genome for complexity and integration pattern of canine endogenous retroviruses (CfERV. Intriguingly, the first such in-depth analysis of a carnivore species identified 407 CfERV proviruses that represent only 0.15% of the dog genome. In comparison, the same detection criteria identified about six times more HERV proviruses in the human genome that has been estimated to contain a total of 8% retroviral DNA including solitary LTRs. These observed differences in man and dog are likely due to different mechanisms to purge, restrict and protect their genomes against retroviruses. A novel group of gammaretrovirus-like CfERV with high similarity to HERV-Fc1 was found to have potential for active retrotransposition and possibly lateral transmissions between dog and human as a result of close interactions during at least 10.000 years. The CfERV integration landscape showed a non-uniform intra- and inter-chromosomal distribution. Like in other species, different densities of ERVs were observed. Some chromosomal regions were essentially devoid of CfERVs whereas other regions had large numbers of integrations in agreement with distinct selective pressures at different loci. Most CfERVs were integrated in antisense orientation within 100 kb from annotated protein-coding genes. This integration pattern provides evidence for selection against CfERVs in sense orientation relative to chromosomal genes. In conclusion, this ERV analysis of the first carnivorous species supports the notion that different mammals interact distinctively with endogenous retroviruses and suggests that retroviral lateral transmissions between dog and human may have occurred.

Endogenous retrovirus and radiation-induced leukemia in the RMF mouse

International Nuclear Information System (INIS)

Tennant, R.W.; Boone, L.R.; Lalley, P.; Yang, W.K.

1982-01-01

The induction of myeloid leukemia in irradiated RFM/Un mice has been associated with retrovirus infection. However, two characteristics of this strain complicate efforts to define the role of the virus. This strain possesses only one inducible host range class of endogenous virus and a unique gene, in addition to the Fv-1/sup n/ locus, which specifically restricts exogenous infection by endogenous viruses. These characteristics possibly account for absence of recombinant viruses in this strain, even though virus is amply expressed during most of the animal's life span. We have examined further the distribution of retrovirus sequences and the chromosomal locus of the inducible virus in this strain. This report describes evidence for additional viral sequences in cells of a radiation-induced myeloid leukemia line and discusses the possible origin of these added copies

Escape from R-peptide deletion in a γ-retrovirus

International Nuclear Information System (INIS)

Schneider, Irene C.; Eckhardt, Manon; Brynza, Julia; Collins, Mary K.; Cichutek, Klaus; Buchholz, Christian J.

2011-01-01

The R peptide in the cytoplasmic tail (C-tail) of γ-retroviral envelope proteins (Env) prevents membrane fusion before budding. To analyse its role in the formation of replication competent, infectious particles, we developed chimeric murine leukaemia viruses (MLV) with unmodified or R-peptide deleted Env proteins of the gibbon ape leukaemia virus (GaLV). While titres of these viruses were unaffected, R-peptide deficiency led to strongly impaired spreading. Most remarkably, we isolated an escape mutant which had restored an open reading frame for a C-terminal extension of the truncated C-tail. A reconstituted virus encoding this escape C-tail replicated in cell culture. In contrast to R-peptide deficient Env, particle incorporation of the escape Env was effective due to an enhanced protein expression and restored intracellular co-localisation with Gag proteins. Our data demonstrate that the R peptide not only regulates membrane fusion but also mediates efficient Env protein particle incorporation in γ-retrovirus infected cells.

Cyclic GMP-AMP Synthase is an Innate Immune Sensor of HIV and Other Retroviruses

OpenAIRE

Gao, Daxing; Wu, Jiaxi; Wu, You-Tong; Du, Fenghe; Aroh, Chukwuemika; Yan, Nan; Sun, Lijun; Chen, Zhijian J.

2013-01-01

Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic-GMP-AMP (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type-I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-β induction by the virus, suggesting that the reverse transcribed HIV DNA triggers the...

Hamster endogenous retrovirus (HaER) - distinct properties of structural proteins and DNA polymerase

International Nuclear Information System (INIS)

Goldschmied-Reouven, A.; Yaniv, A.

1983-01-01

The structural proteins as well as some features of the RNA-dependent DNA polymerase of the hamster endogenous retrovirus (HaER) were examined. The polypeptide pattern of this virus is substantially different from that of other known retroviruses in containing major polypeptides with molecular weights of 68000, 59000, 27000, 24000 daltons. Double antibody competitive radioimmunoassays showed that the HaER particles do not share any detectable antigenic relatedness with the murine viruses' p30, but manifest a considerable relatedness with the feline leukemia virus p27 and a slight cross-reactivity with the rat virus major protein. The RNA-dependent DNA polymerase of HaER virus has a molecular size of approximately 73000 daltons and in contrast to other mammalian retroviruses shows no significant preference for Mn 2+ over Mg 2+ . Apart from the lack of antigenic relatedness between the HaER virus proteins and the p30 protein of murine viruses, there is also no antigenic relatedness between HaER and murine viruses insofar as their DNA polymerase is concerned. (Author)

Negative regulation of retrovirus expression in embryonal carcinoma cells mediated by an intragenic domain.

Science.gov (United States)

Loh, T P; Sievert, L L; Scott, R W

1988-11-01

An intragenic region spanning the tRNA primer binding site of a Moloney murine leukemia virus recombinant retrovirus was found to restrict expression specifically in embryonal carcinoma (EC) cells. When the inhibitory domain was present, the levels of steady-state RNA synthesized from integrated recombinant templates in stable cotransformation assays were reduced 20-fold in EC cells but not in C2 myoblast cells. Transient-cotransfection assays showed that repression of a template containing the EC-specific inhibitory component was relieved by an excess of specific competitor DNA. In addition, repression mediated by the inhibitory component was orientation independent. This evidence demonstrates the presence of a saturable, trans-acting negative regulatory factor(s) in EC cells and suggests that the interaction of the factor(s) with the intragenic inhibitory component occurs at the DNA level.

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

Science.gov (United States)

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

2018-01-01

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

Endogenous retroviruses of sheep: a model system for understanding physiological adaptation to an evolving ruminant genome.

Science.gov (United States)

Spencer, Thomas E; Palmarini, Massimo

2012-01-01

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. The sheep genome contains 27 endogenous betaretroviruses (enJSRVs) related to the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. The enJSRVs can protect their host against JSRV infection by blocking early and late steps of the JSRV replication cycle. In the female reproductive tract, enJSRVs are specifically expressed in the uterine luminal and glandular epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm and in utero loss-of-function experiments found the enJSRVs envelope (env) to be essential for conceptus elongation and trophectoderm growth and development. Collectively, available evidence in sheep and other mammals indicate that ERVs coevolved with their hosts for millions of years and were positively selected for biological roles in genome plasticity and evolution, protection of the host against infection of related pathogenic and exogenous retroviruses, and placental development.

Porcine Endogenous Retroviruses in Xenotransplantation—Molecular Aspects

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Magdalena C. Kimsa

2014-05-01

Full Text Available In the context of the shortage of organs and other tissues for use in human transplantation, xenotransplantation procedures with material taken from pigs have come under increased consideration. However, there are unclear consequences of the potential transmission of porcine pathogens to humans. Of particular concern are porcine endogenous retroviruses (PERVs. Three subtypes of PERV have been identified, of which PERV-A and PERV-B have the ability to infect human cells in vitro. The PERV-C subtype does not show this ability but recombinant PERV-A/C forms have demonstrated infectivity in human cells. In view of the risk presented by these observations, the International Xenotransplantation Association recently indicated the existence of four strategies to prevent transmission of PERVs. This article focuses on the molecular aspects of PERV infection in xenotransplantation and reviews the techniques available for the detection of PERV DNA, RNA, reverse transcriptase activity and proteins, and anti-PERV antibodies to enable carrying out these recommendations. These methods could be used to evaluate the risk of PERV transmission in human recipients, enhance the effectiveness and reliability of monitoring procedures, and stimulate discussion on the development of improved, more sensitive methods for the detection of PERVs in the future.

Porcine Endogenous Retroviruses in Xenotransplantation—Molecular Aspects

Science.gov (United States)

Kimsa, Magdalena C.; Strzalka-Mrozik, Barbara; Kimsa, Malgorzata W.; Gola, Joanna; Nicholson, Peter; Lopata, Krzysztof; Mazurek, Urszula

2014-01-01

In the context of the shortage of organs and other tissues for use in human transplantation, xenotransplantation procedures with material taken from pigs have come under increased consideration. However, there are unclear consequences of the potential transmission of porcine pathogens to humans. Of particular concern are porcine endogenous retroviruses (PERVs). Three subtypes of PERV have been identified, of which PERV-A and PERV-B have the ability to infect human cells in vitro. The PERV-C subtype does not show this ability but recombinant PERV-A/C forms have demonstrated infectivity in human cells. In view of the risk presented by these observations, the International Xenotransplantation Association recently indicated the existence of four strategies to prevent transmission of PERVs. This article focuses on the molecular aspects of PERV infection in xenotransplantation and reviews the techniques available for the detection of PERV DNA, RNA, reverse transcriptase activity and proteins, and anti-PERV antibodies to enable carrying out these recommendations. These methods could be used to evaluate the risk of PERV transmission in human recipients, enhance the effectiveness and reliability of monitoring procedures, and stimulate discussion on the development of improved, more sensitive methods for the detection of PERVs in the future. PMID:24828841

Human endogenous retroviruses and cancer prevention: evidence and prospects.

Science.gov (United States)

Cegolon, Luca; Salata, Cristiano; Weiderpass, Elisabete; Vineis, Paolo; Palù, Giorgio; Mastrangelo, Giuseppe

2013-01-03

Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues.Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system.HERV-K expression has been detected in different types of tumors.Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family.The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression.The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder and

Human endogenous retroviruses and cancer prevention: evidence and prospects

International Nuclear Information System (INIS)

Cegolon, Luca; Salata, Cristiano; Weiderpass, Elisabete; Vineis, Paolo; Palù, Giorgio; Mastrangelo, Giuseppe

2013-01-01

Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder

Expression of the pol gene of human endogenous retroviruses HERV-K and -W in leukemia patients.

Science.gov (United States)

Bergallo, Massimiliano; Montanari, Paola; Mareschi, Katia; Merlino, Chiara; Berger, Massimo; Bini, Ilaria; Daprà, Valentina; Galliano, Ilaria; Fagioli, Franca

2017-12-01

The human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that integrated into the germ cell DNA of primates over 30 million years ago. HERV expression seems impaired in several diseases, ranging from autoimmune to neoplastic disorders. The purpose of this study was to evaluate the overall endogenous retroviral transcription profile in bone marrow (BM) samples. A total of 30 paediatric high-risk leukaemia patients (lymphoid and myeloid malignancies) were tested for HERVs virus gene expression. Our findings show that HERV-K expression was significantly higher in leukaemia patients when compared to healthy donors of a similar median age. We observed a significantly high expression of HERV-K in acute lymphoblastic leukemia (ALL) patients. In this study, we also found a relative overexpression of the endogenous retrovirus HERV-K in BM cells from the majority of leukemia samples analyzed, in particular in ALL. This overexpression might be related to lymphatic leukemogenesis and it warrants further investigations.

Human retroviruses and AIDS, 1991. [CONTAINS GLOSSARY

Energy Technology Data Exchange (ETDEWEB)

Myers, G.; Korber, B. (eds.) (Los Alamos National Lab., NM (USA)); Berzofsky, J.A.; Pavlakis, G.N. (eds.) (National Cancer Inst., Bethesda, MD (USA)); Smith, R.F. (ed.) (Harvard Univ. (USA))

1991-05-01

This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses.The scope of the compendium and database is best summarized by the five parts that it comprises: (1) HIV and SIV Nucleotide Sequences; (2) Amino Acid Sequences; (3) Analyses; (4) Related Sequences; and (5) Database Communications. Information within all the parts is updated at least twice in each year, which accounts for the modes of binding and pagination in the compendium.

Serum Antibody Response to Koala Retrovirus Antigens Varies in Free-Ranging Koalas ( Phascolarctos cinereus ) in Australia: Implications for Vaccine Design.

Science.gov (United States)

Waugh, Courtney; Gillett, Amber; Polkinghorne, Adam; Timms, Peter

2016-04-28

Little is known about the immune response in the koala ( Phascolarctos cinereus ) to its retroviruses. Koala retroviruses (KoRVs) have been linked to neoplasia in wild and captive koalas, but there is no treatment available. We tested the KoRV-specific serum immunoglobulin G antibody response in nonimmunized and immunized koalas.

Improved vaccine protection against retrovirus infection after co-administration of adenoviral vectors encoding viral antigens and type I interferon subtypes

Directory of Open Access Journals (Sweden)

Groitl Peter

2011-09-01

Full Text Available Abstract Background Type I interferons (IFNs exhibit direct antiviral effects, but also distinct immunomodulatory properties. In this study, we analyzed type I IFN subtypes for their effect on prophylactic adenovirus-based anti-retroviral vaccination of mice against Friend retrovirus (FV or HIV. Results Mice were vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in combination with vectors encoding IFNα1, IFNα2, IFNα4, IFNα5, IFNα6, IFNα9 or IFNβ. Only the co-administration of adenoviral vectors encoding IFNα2, IFNα4, IFNα6 and IFNα9 resulted in strongly improved immune protection of vaccinated mice from subsequent FV challenge infection with high control over FV-induced splenomegaly and reduced viral loads. The level of protection correlated with augmented virus-specific CD4+ T cell responses and enhanced antibody titers. Similar results were obtained when mice were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol in combination with various type I IFN encoding vectors. Here mainly CD4+ T cell responses were enhanced by IFNα subtypes. Conclusions Our results indicate that certain IFNα subtypes have the potential to improve the protective effect of adenovirus-based vaccines against retroviruses. This correlated with augmented virus-specific CD4+ T cell and antibody responses. Thus, co-expression of select type I IFNs may be a valuable tool for the development of anti-retroviral vaccines.

A whole genome screen for HIV restriction factors

Directory of Open Access Journals (Sweden)

Liu Li

2011-11-01

Full Text Available Abstract Background Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme, p21 and tetherin are well characterised. Results To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. Conclusions We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.

Host restriction factors in retroviral infection: promises in virus-host interaction

Directory of Open Access Journals (Sweden)

Zheng Yong-Hui

2012-12-01

Full Text Available Abstract Retroviruses have an intricate life cycle. There is much to be learned from studying retrovirus-host interactions. Among retroviruses, the primate lentiviruses have one of the more complex genome structures with three categories of viral genes: structural, regulatory, and accessory genes. Over time, we have gained increasing understanding of the lentivirus life cycle from studying host factors that support virus replication. Similarly, studies on host restriction factors that inhibit viral replication have also made significant contributions to our knowledge. Here, we review recent progress on the rapidly growing field of restriction factors, focusing on the antiretroviral activities of APOBEC3G, TRIM5, tetherin, SAMHD1, MOV10, and cellular microRNAs (miRNAs, and the counter-activities of Vif, Vpu, Vpr, Vpx, and Nef.

Role of nucleocytoplasmic RNA transport during the life cycle of retroviruses

Directory of Open Access Journals (Sweden)

Hisatoshi eShida

2012-05-01

Full Text Available Retroviruses have evolved mechanisms for transporting their intron-containing RNAs (including genomic and messenger RNAs, which encode virion components from the nucleus to the cytoplasm of the infected cell. Human retroviruses, such as human immunodeficiency virus (HIV and human T cell leukemia virus type 1 (HTLV-1, encode the regulatory proteins Rev and Rex, which form a bridge between the viral RNA and the export receptor CRM1. Recent studies show that these transport systems are not only involved in RNA export, but also in the encapsidation of genomic RNA; furthermore, they influence subsequent events in the cytoplasm, including the translation of the cognate mRNA, transport of Gag proteins to the plasma membrane, and the formation of virus particles. Moreover, the mode of interaction between the viral and cellular RNA transport machinery underlies the species-specific propagation of HIV-1 and HTLV-1, forming the basis for constructing animal models of infection. This review article discusses recent progress regarding these issues.

Evolution of Foamy Viruses: The Most Ancient of All Retroviruses

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Jochen Bodem

2013-09-01

Full Text Available Recent evidence indicates that foamy viruses (FVs are the oldest retroviruses (RVs that we know and coevolved with their hosts for several hundred million years. This coevolution may have contributed to the non-pathogenicity of FVs, an important factor in development of foamy viral vectors in gene therapy. However, various questions on the molecular evolution of FVs remain still unanswered. The analysis of the spectrum of animal species infected by exogenous FVs or harboring endogenous FV elements in their genome is pivotal. Furthermore, animal studies might reveal important issues, such as the identification of the FV in vivo target cells, which than require a detailed characterization, to resolve the molecular basis of the accuracy with which FVs copy their genome. The issues of the extent of FV viremia and of the nature of the virion genome (RNA vs. DNA also need to be experimentally addressed.

The ability of multimerized cyclophilin A to restrict retrovirus infection

International Nuclear Information System (INIS)

Javanbakht, Hassan; Diaz-Griffero, Felipe; Yuan Wen; Yeung, Darwin F.; Li Xing; Song Byeongwoon; Sodroski, Joseph

2007-01-01

In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection

The population history of endogenous retroviruses in mule deer (Odocoileus heminous)

Science.gov (United States)

Kamath, Pauline L.; Elleder, Daniel; Bao, Le; Cross, Paul C.; Powell, John H.; Poss, Mary

2013-01-01

Mobile elements are powerful agents of genomic evolution and can be exceptionally informative markers for investigating species and population-level evolutionary history. While several studies have utilized retrotransposon-based insertional polymorphisms to resolve phylogenies, few population studies exist outside of humans. Endogenous retroviruses are LTR-retrotransposons derived from retroviruses that have become stably integrated in the host genome during past infections and transmitted vertically to subsequent generations. They offer valuable insight into host-virus co-evolution and a unique perspective on host evolutionary history because they integrate into the genome at a discrete point in time. We examined the evolutionary history of a cervid endogenous gammaretrovirus (CrERVγ) in mule deer (Odocoileus hemionus). We sequenced 14 CrERV proviruses (CrERV-in1 to -in14), and examined the prevalence and distribution of 13 proviruses in 262 deer among 15 populations from Montana, Wyoming, and Utah. CrERV absence in white-tailed deer (O. virginianus), identical 5′ and 3′ long terminal repeat (LTR) sequences, insertional polymorphism, and CrERV divergence time estimates indicated that most endogenization events occurred within the last 200000 years. Population structure inferred from CrERVs (F ST = 0.008) and microsatellites (θ = 0.01) was low, but significant, with Utah, northwestern Montana, and a Helena herd being particularly differentiated. Clustering analyses indicated regional structuring, and non-contiguous clustering could often be explained by known translocations. Cluster ensemble results indicated spatial localization of viruses, specifically in deer from northeastern and western Montana. This study demonstrates the utility of endogenous retroviruses to elucidate and provide novel insight into both ERV evolutionary history and the history of contemporary host populations.

The population history of endogenous retroviruses in mule deer (Odocoileus hemionus).

Science.gov (United States)

Kamath, Pauline L; Elleder, Daniel; Bao, Le; Cross, Paul C; Powell, John H; Poss, Mary

2014-01-01

Mobile elements are powerful agents of genomic evolution and can be exceptionally informative markers for investigating species and population-level evolutionary history. While several studies have utilized retrotransposon-based insertional polymorphisms to resolve phylogenies, few population studies exist outside of humans. Endogenous retroviruses are LTR-retrotransposons derived from retroviruses that have become stably integrated in the host genome during past infections and transmitted vertically to subsequent generations. They offer valuable insight into host-virus co-evolution and a unique perspective on host evolutionary history because they integrate into the genome at a discrete point in time. We examined the evolutionary history of a cervid endogenous gammaretrovirus (CrERVγ) in mule deer (Odocoileus hemionus). We sequenced 14 CrERV proviruses (CrERV-in1 to -in14), and examined the prevalence and distribution of 13 proviruses in 262 deer among 15 populations from Montana, Wyoming, and Utah. CrERV absence in white-tailed deer (O. virginianus), identical 5' and 3' long terminal repeat (LTR) sequences, insertional polymorphism, and CrERV divergence time estimates indicated that most endogenization events occurred within the last 200000 years. Population structure inferred from CrERVs (F ST = 0.008) and microsatellites (θ = 0.01) was low, but significant, with Utah, northwestern Montana, and a Helena herd being particularly differentiated. Clustering analyses indicated regional structuring, and non-contiguous clustering could often be explained by known translocations. Cluster ensemble results indicated spatial localization of viruses, specifically in deer from northeastern and western Montana. This study demonstrates the utility of endogenous retroviruses to elucidate and provide novel insight into both ERV evolutionary history and the history of contemporary host populations.

Retroviruses as tools to study the immune system.

Science.gov (United States)

Lois, C; Refaeli, Y; Qin, X F; Van Parijs, L

2001-08-01

Retrovirus-based vectors provide an efficient means to introduce and express genes in cells of the immune system and have become a popular tool to study immune function. They are easy to manipulate and provide stable, long-term gene expression because they integrate into the genome. Current retroviral vectors do have limitations that affect their usefulness in certain applications. However, recent advances suggest a number of ways in which these vectors might be improved to extend their utility in immunological research.

Wolbachia influences the maternal transmission of the gypsy endogenous retrovirus in Drosophila melanogaster.

Science.gov (United States)

Touret, Franck; Guiguen, François; Terzian, Christophe

2014-09-02

The endosymbiotic bacteria of the genus Wolbachia are present in most insects and are maternally transmitted through the germline. Moreover, these intracellular bacteria exert antiviral activity against insect RNA viruses, as in Drosophila melanogaster, which could explain the prevalence of Wolbachia bacteria in natural populations. Wolbachia is maternally transmitted in D. melanogaster through a mechanism that involves distribution at the posterior pole of mature oocytes and then incorporation into the pole cells of the embryos. In parallel, maternal transmission of several endogenous retroviruses is well documented in D. melanogaster. Notably, gypsy retrovirus is expressed in permissive follicle cells and transferred to the oocyte and then to the offspring by integrating into their genomes. Here, we show that the presence of Wolbachia wMel reduces the rate of gypsy insertion into the ovo gene. However, the presence of Wolbachia does not modify the expression levels of gypsy RNA and envelope glycoprotein from either permissive or restrictive ovaries. Moreover, Wolbachia affects the pattern of distribution of the retroviral particles and the gypsy envelope protein in permissive follicle cells. Altogether, our results enlarge the knowledge of the antiviral activity of Wolbachia to include reducing the maternal transmission of endogenous retroviruses in D. melanogaster. Animals have established complex relationships with bacteria and viruses that spread horizontally among individuals or are vertically transmitted, i.e., from parents to offspring. It is well established that members of the genus Wolbachia, maternally inherited symbiotic bacteria present mainly in arthropods, reduce the replication of several RNA viruses transmitted horizontally. Here, we demonstrate for the first time that Wolbachia diminishes the maternal transmission of gypsy, an endogenous retrovirus in Drosophila melanogaster. We hypothesize that gypsy cannot efficiently integrate into the germ

Human endogenous retroviruses and cancer prevention: evidence and prospects

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Cegolon Luca

2013-01-01

Full Text Available Abstract Background Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity, hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Discussion Human endogenous retroviruses (HERVs are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well

A survey of endogenous retrovirus (ERV) sequences in the vicinity of multiple sclerosis (MS)-associated single nucleotide polymorphisms (SNPs).

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Brütting, Christine; Emmer, Alexander; Kornhuber, Malte; Staege, Martin S

2016-08-01

Although multiple sclerosis (MS) is one of the most common central nervous system diseases in young adults, little is known about its etiology. Several human endogenous retroviruses (ERVs) are considered to play a role in MS. We are interested in which ERVs can be identified in the vicinity of MS associated genetic marker to find potential initiators of MS. We analysed the chromosomal regions surrounding 58 single nucleotide polymorphisms (SNPs) that are associated with MS identified in one of the last major genome wide association studies. We scanned these regions for putative endogenous retrovirus sequences with large open reading frames (ORFs). We observed that more retrovirus-related putative ORFs exist in the relatively close vicinity of SNP marker indices in multiple sclerosis compared to control SNPs. We found very high homologies to HERV-K, HCML-ARV, XMRV, Galidia ERV, HERV-H/env62 and XMRV-like mouse endogenous retrovirus mERV-XL. The associated genes (CYP27B1, CD6, CD58, MPV17L2, IL12RB1, CXCR5, PTGER4, TAGAP, TYK2, ICAM3, CD86, GALC, GPR65 as well as the HLA DRB1*1501) are mainly involved in the immune system, but also in vitamin D regulation. The most frequently detected ERV sequences are related to the multiple sclerosis-associated retrovirus, the human immunodeficiency virus 1, HERV-K, and the Simian foamy virus. Our data shows that there is a relation between MS associated SNPs and the number of retroviral elements compared to control. Our data identifies new ERV sequences that have not been associated with MS, so far.

Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

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García-Montojo, Marta; Alcina, Antonio; Fedetz, María; Alloza, Iraide; Astobiza, Ianire; Leyva, Laura; Fernández, Oscar; Izquierdo, Guillermo; Antigüedad, Alfredo; Arroyo, Rafael; Álvarez-Lafuente, Roberto; Vandenbroeck, Koen; Matesanz, Fuencisla; Urcelay, Elena

2014-01-01

Background Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11–1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14–1.53)]. Conclusion Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts. PMID:24594754

Characterization of a Full-Length Endogenous Beta-Retrovirus, EqERV-Beta1, in the Genome of the Horse (Equus caballus

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Antoinette C. van der Kuyl

2011-06-01

Full Text Available Information on endogenous retroviruses fixed in the horse (Equus caballus genome is scarce. The recent availability of a draft sequence of the horse genome enables the detection of such integrated viruses by similarity search. Using translated nucleotide fragments from gamma-, beta-, and delta-retroviral genera for initial searches, a full-length beta-retrovirus genome was retrieved from a horse chromosome 5 contig. The provirus, tentatively named EqERV-beta1 (for the first equine endogenous beta-retrovirus, was 10434 nucleotide (nt in length with the usual retroviral genome structure of 5’LTR-gag-pro-pol-env-3’LTR. The LTRs were 1361 nt long, and differed approximately 1% from each other, suggestive of a relatively recent integration. Coding sequences for gag, pro and pol were present in three different reading-frames, as common for beta-retroviruses, and the reading frames were completely open, except that the env gene was interrupted by a single stopcodon. No reading frame was apparent downstream of the env gene, suggesting that EqERV-beta1 does not encode a superantigen like mouse mammary tumor virus (MMTV. A second proviral genome of EqERV-beta1, with no stopcodon in env, is additionally integrated on chromosome 5 downstream of the first virus. Single EqERV-beta1 LTRs were abundantly present on all chromosomes except chromosome 24. Phylogenetically, EqERV-beta1 most closely resembles an unclassified retroviral sequence from cattle (Bos taurus, and the murine beta-retrovirus MMTV.

An Evolutionarily Young Polar Bear (Ursus maritimus) Endogenous Retrovirus Identified from Next Generation Sequence Data.

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Tsangaras, Kyriakos; Mayer, Jens; Alquezar-Planas, David E; Greenwood, Alex D

2015-11-24

Transcriptome analysis of polar bear (Ursus maritimus) tissues identified sequences with similarity to Porcine Endogenous Retroviruses (PERV). Based on these sequences, four proviral copies and 15 solo long terminal repeats (LTRs) of a newly described endogenous retrovirus were characterized from the polar bear draft genome sequence. Closely related sequences were identified by PCR analysis of brown bear (Ursus arctos) and black bear (Ursus americanus) but were absent in non-Ursinae bear species. The virus was therefore designated UrsusERV. Two distinct groups of LTRs were observed including a recombinant ERV that contained one LTR belonging to each group indicating that genomic invasions by at least two UrsusERV variants have recently occurred. Age estimates based on proviral LTR divergence and conservation of integration sites among ursids suggest the viral group is only a few million years old. The youngest provirus was polar bear specific, had intact open reading frames (ORFs) and could potentially encode functional proteins. Phylogenetic analyses of UrsusERV consensus protein sequences suggest that it is part of a pig, gibbon and koala retrovirus clade. The young age estimates and lineage specificity of the virus suggests UrsusERV is a recent cross species transmission from an unknown reservoir and places the viral group among the youngest of ERVs identified in mammals.

An Evolutionarily Young Polar Bear (Ursus maritimus) Endogenous Retrovirus Identified from Next Generation Sequence Data

Science.gov (United States)

Tsangaras, Kyriakos; Mayer, Jens; Alquezar-Planas, David E.; Greenwood, Alex D.

2015-01-01

Transcriptome analysis of polar bear (Ursus maritimus) tissues identified sequences with similarity to Porcine Endogenous Retroviruses (PERV). Based on these sequences, four proviral copies and 15 solo long terminal repeats (LTRs) of a newly described endogenous retrovirus were characterized from the polar bear draft genome sequence. Closely related sequences were identified by PCR analysis of brown bear (Ursus arctos) and black bear (Ursus americanus) but were absent in non-Ursinae bear species. The virus was therefore designated UrsusERV. Two distinct groups of LTRs were observed including a recombinant ERV that contained one LTR belonging to each group indicating that genomic invasions by at least two UrsusERV variants have recently occurred. Age estimates based on proviral LTR divergence and conservation of integration sites among ursids suggest the viral group is only a few million years old. The youngest provirus was polar bear specific, had intact open reading frames (ORFs) and could potentially encode functional proteins. Phylogenetic analyses of UrsusERV consensus protein sequences suggest that it is part of a pig, gibbon and koala retrovirus clade. The young age estimates and lineage specificity of the virus suggests UrsusERV is a recent cross species transmission from an unknown reservoir and places the viral group among the youngest of ERVs identified in mammals. PMID:26610552

HTLV-3/4 and simian foamy retroviruses in humans: discovery, epidemiology, cross-species transmission and molecular virology.

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Gessain, Antoine; Rua, Réjane; Betsem, Edouard; Turpin, Jocelyn; Mahieux, Renaud

2013-01-05

Non-human primates are considered to be likely sources of viruses that can infect humans and thus pose a significant threat to human population. This is well illustrated by some retroviruses, as the simian immunodeficiency viruses and the simian T lymphotropic viruses, which have the ability to cross-species, adapt to a new host and sometimes spread. This leads to a pandemic situation for HIV-1 or an endemic one for HTLV-1. Here, we present the available data on the discovery, epidemiology, cross-species transmission and molecular virology of the recently discovered HTLV-3 and HTLV-4 deltaretroviruses, as well as the simian foamy retroviruses present in different human populations at risk, especially in central African hunters. We discuss also the natural history in humans of these retroviruses of zoonotic origin (magnitude and geographical distribution, possible inter-human transmission). In Central Africa, the increase of the bushmeat trade during the last decades has opened new possibilities for retroviral emergence in humans, especially in immuno-compromised persons. Copyright © 2012 Elsevier Inc. All rights reserved.

Retrovirus-mediated gene transfer of a human c-fos cDNA into mouse bone marrow stromal cells.

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Roux, P; Verrier, B; Klein, B; Niccolino, M; Marty, L; Alexandre, C; Piechaczyk, M

1991-11-01

A cDNA encoding a complete human c-fos protein was isolated and inserted into two different murine MoMuLV-derived recombinant retroviruses allowing expression of c-fos protein in different cell types. One c-fos-expressing retrovirus, chosen for its ability to express high levels of proteins in fibroblast-like cells, was shown to potentiate long-term cultures of mouse bone marrow stromal cells in vitro and therefore constitutes a potential tool for immortalizing such cells. Moreover, when tested in an in vitro differentiation assay, stromal cells constitutively expressing c-fos favor the granulocyte differentiation of hematopoietic precursors. Interestingly, retroviruses expressing v-src and v-abl oncogenes, included as controls in our experiments, do not produce any detectable effects, whereas those expressing polyoma virus middle T antigen facilitate long-term growth in vitro of stromal cells that favor the macrophage differentiation pathway of bone marrow stem cells. Our observation supports the idea that constitutive expression of some oncogenes, including c-fos and polyoma virus middle T antigen, may influence cytokine production by bone marrow stromal cells.

Experimental study of the occurence and properties of C-type retroviruses in radiation-induced osteosarcomas in mice

International Nuclear Information System (INIS)

Erfle, V.

1981-01-01

In the radiation induced osteosarcomas of the C 3 Hx101/F 1 -mouse C-type virus particles had been found regularly with a density of 1.16 g/cm 3 , with high molecular RNA, a reverse transcriptase and the murine group-specific antigen p 30. Osteosarcomas of the NMRI-mouse, however, had only p 30 protein and so-called intra-cisternal A-type particles. After 'in vitro' cultivation retroviruses had been liberated from the osteosarcoma cells of the C 3 Hx101/F 1 -mice as well as from the NMRI-mice type C. During the tumour latency period a virus expression of the C-type retroviruses had been found for a certain period in the first month after irradiation of the bone tissue had begun; then followed an antibody-reaction which continued to persist until the 8th month. Another virus expression was observed in the skeleton during the period when the osteosarcomas appeared. This virus expression was accompanied by a decrease in antibodies and a temporary increase of the viral p 30 protein in the serum. The viruses which had been isolated from the radiation induced osteosarcomas showed the properties which are typical for ecotropic C-type retroviruses of mice. After infection of new-born mice these viruses produced fibrosarcomas (C 3 Hx 101/F 1 -mice) or lymphomas and osteomas (NMRI-mice). The results make it obvious that the endogenetic C-type retroviruses participate in the formation of radiation-induced sarcomas in mice. (orig./MG) [de

Evolutionary relationships within a subgroup of HERV-K-related human endogenous retroviruses

NARCIS (Netherlands)

Zsíros, J.; Jebbink, M. F.; Lukashov, V. V.; Voûte, P. A.; Berkhout, B.

1998-01-01

The prototype endogenous retrovirus HERV-K10 was identified in the human genome by its homology to the exogenous mouse mammary tumour virus. By analysis of a short 244 bp segment of the reverse transcriptase (RT) gene of other HERV-K10-like sequences, it has become clear that these elements

The endogenous langur type D retrovirus PO-1-Lu and its exogenous counterparts in macaque and langur monkeys

International Nuclear Information System (INIS)

Sommerfelt, Maja A.; Harkestad, Nina; Hunter, Eric

2003-01-01

PO-1-Lu, the endogenous type D retrovirus of langurs (Trachypithecus obscurus) has previously been considered a progenitor to the prototype type D retrovirus, Mason Pfizer monkey virus (M-PMV/SRV-3), that became established in macaque monkeys (Macaca spp.) following a zoonosis. This study reevaluates this hypothesis to include other exogenous SRVs. New sequence information from the gp70(SU)-encoding region of PO-1-Lu shows striking similarity to the newly identified exogenous langur retrovirus, SRV-6, recently isolated from the Hanuman Langur (Semnopithecus entellus). An unrooted, bootstrapped neighbor-joining tree derived from env gene nucleotide sequences shows PO-1-Lu and SRV-6 appear more closely related genetically to SRV-2 than SRV-1 or SRV-3 (M-PMV). This is also reflected in our observations that the M-PMV envelope glycoprotein precursor gPr86 Env and gp70(SU) were antigenically distinct from PO-1-Lu, although the gp22(TM) glycoproteins were antigenically cross-reactive. The potential that SRV-6 represents an exogenous form of PO-1-Lu that has arisen following a recent zoonosis is discussed

An Evolutionarily Young Polar Bear (Ursus maritimus Endogenous Retrovirus Identified from Next Generation Sequence Data

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Kyriakos Tsangaras

2015-11-01

Full Text Available Transcriptome analysis of polar bear (Ursus maritimus tissues identified sequences with similarity to Porcine Endogenous Retroviruses (PERV. Based on these sequences, four proviral copies and 15 solo long terminal repeats (LTRs of a newly described endogenous retrovirus were characterized from the polar bear draft genome sequence. Closely related sequences were identified by PCR analysis of brown bear (Ursus arctos and black bear (Ursus americanus but were absent in non-Ursinae bear species. The virus was therefore designated UrsusERV. Two distinct groups of LTRs were observed including a recombinant ERV that contained one LTR belonging to each group indicating that genomic invasions by at least two UrsusERV variants have recently occurred. Age estimates based on proviral LTR divergence and conservation of integration sites among ursids suggest the viral group is only a few million years old. The youngest provirus was polar bear specific, had intact open reading frames (ORFs and could potentially encode functional proteins. Phylogenetic analyses of UrsusERV consensus protein sequences suggest that it is part of a pig, gibbon and koala retrovirus clade. The young age estimates and lineage specificity of the virus suggests UrsusERV is a recent cross species transmission from an unknown reservoir and places the viral group among the youngest of ERVs identified in mammals.

LTRs of Endogenous Retroviruses as a Source of Tbx6 Binding Sites.

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Yasuhiko, Yukuto; Hirabayashi, Yoko; Ono, Ryuichi

2017-01-01

Retrotransposons are abundant in mammalian genomes and can modulate the gene expression of surrounding genes by disrupting endogenous binding sites for transcription factors (TFs) or providing novel TFs binding sites within retrotransposon sequences. Here, we show that a (C/T)CACACCT sequence motif in ORR1A, ORR1B, ORR1C, and ORR1D, Long Terminal Repeats (LTRs) of MaLR endogenous retrovirus (ERV), is the direct target of Tbx6, an evolutionary conserved family of T-box TFs. Moreover, by comparing gene expression between control mice (Tbx6 +/-) and Tbx6-deficient mice (Tbx6 -/-), we demonstrate that at least four genes, Twist2, Pitx2, Oscp1 , and Nfxl1 , are down-regulated with Tbx6 deficiency. These results suggest that ORR1A, ORR1B, ORR1C and ORR1D may contribute to the evolution of mammalian embryogenesis.

Computational and Statistical Analyses of Insertional Polymorphic Endogenous Retroviruses in a Non-Model Organism

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Le Bao

2014-11-01

Full Text Available Endogenous retroviruses (ERVs are a class of transposable elements found in all vertebrate genomes that contribute substantially to genomic functional and structural diversity. A host species acquires an ERV when an exogenous retrovirus infects a germ cell of an individual and becomes part of the genome inherited by viable progeny. ERVs that colonized ancestral lineages are fixed in contemporary species. However, in some extant species, ERV colonization is ongoing, which results in variation in ERV frequency in the population. To study the consequences of ERV colonization of a host genome, methods are needed to assign each ERV to a location in a species’ genome and determine which individuals have acquired each ERV by descent. Because well annotated reference genomes are not widely available for all species, de novo clustering approaches provide an alternative to reference mapping that are insensitive to differences between query and reference and that are amenable to mobile element studies in both model and non-model organisms. However, there is substantial uncertainty in both identifying ERV genomic position and assigning each unique ERV integration site to individuals in a population. We present an analysis suitable for detecting ERV integration sites in species without the need for a reference genome. Our approach is based on improved de novo clustering methods and statistical models that take the uncertainty of assignment into account and yield a probability matrix of shared ERV integration sites among individuals. We demonstrate that polymorphic integrations of a recently identified endogenous retrovirus in deer reflect contemporary relationships among individuals and populations.

Human Endogenous Retrovirus W Activity in Cartilage of Osteoarthritis Patients

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Signy Bendiksen

2014-01-01

Full Text Available The etiology of viruses in osteoarthritis remains controversial because the prevalence of viral nucleic acid sequences in peripheral blood or synovial fluid from osteoarthritis patients and that in healthy control subjects are similar. Until now the presence of virus has not been analyzed in cartilage. We screened cartilage and chondrocytes from advanced and non-/early osteoarthritis patients for parvovirus B19, herpes simplex virus-1, Epstein Barr virus, cytomegalovirus, human herpes virus-6, hepatitis C virus, and human endogenous retroviruses transcripts. Endogenous retroviruses transcripts, but none of the other viruses, were detected in 15 out the 17 patients. Sequencing identified the virus as HERV-WE1 and E2. HERV-W activity was confirmed by high expression levels of syncytin, dsRNA, virus budding, and the presence of virus-like particles in all advanced osteoarthritis cartilages examined. Low levels of HERV-WE1, but not E2 envelope RNA, were observed in 3 out of 8 non-/early osteoarthritis patients, while only 3 out of 7 chondrocytes cultures displayed low levels of syncytin, and just one was positive for virus-like particles. This study demonstrates for the first time activation of HERV-W in cartilage of osteoarthritis patients; however, a causative role for HERV-W in development or deterioration of the disease remains to be proven.

Genomic Amplification of an Endogenous Retrovirus in Zebrafish T-Cell Malignancies

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J. Kimble Frazer

2012-01-01

Full Text Available Genomic instability plays a crucial role in oncogenesis. Somatically acquired mutations can disable some genes and inappropriately activate others. In addition, chromosomal rearrangements can amplify, delete, or even fuse genes, altering their functions and contributing to malignant phenotypes. Using array comparative genomic hybridization (aCGH, a technique to detect numeric variations between different DNA samples, we examined genomes from zebrafish (Danio rerio T-cell leukemias of three cancer-prone lines. In all malignancies tested, we identified recurring amplifications of a zebrafish endogenous retrovirus. This retrovirus, ZFERV, was first identified due to high expression of proviral transcripts in thymic tissue from larval and adult fish. We confirmed ZFERV amplifications by quantitative PCR analyses of DNA from wild-type fish tissue and normal and malignant D. rerio T cells. We also quantified ZFERV RNA expression and found that normal and neoplastic T cells both produce retrovirally encoded transcripts, but most cancers show dramatically increased transcription. In aggregate, these data imply that ZFERV amplification and transcription may be related to T-cell leukemogenesis. Based on these data and ZFERV’s phylogenetic relation to viruses of the murine-leukemia-related virus class of gammaretroviridae, we posit that ZFERV may be oncogenic via an insertional mutagenesis mechanism.

A New Approach to Establish a Cell Line with Reduced Risk of Endogenous Retroviruses

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Fukuma, Aiko; Yoshikawa, Rokusuke; Miyazawa, Takayuki; Yasuda, Jiro

2013-01-01

Endogenous retroviruses (ERVs) are integrated as DNA proviruses in the genomes of all mammalian species. Several ERVs are replication-competent and produced as fully infectious viruses from host cell. Thus, live-attenuated vaccines and biological substances have been prepared using the cell lines which may produce ERV. Indeed, we recently reported that several commercial live-attenuated vaccines for pets were contaminated with the infectious feline endogenous retrovirus, RD-114. In this study, to establish a cell line for vaccine manufacture with reduced risk of ERVs, we generated a cell line stably expressing human tetherin (Teth-CRFK cells). The release of infectious ERV from Teth-CRFK cells was suppressed to undetectable levels, while the production of parvovirus in Teth-CRFK cells was similar to that in parental CRFK cells. These observations suggest that Teth-CRFK cells will be useful as a cell line for the manufacture of live-attenuated vaccines or biological substances with reduced risk of ERV. PMID:23585909

A new approach to establish a cell line with reduced risk of endogenous retroviruses.

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Aiko Fukuma

Full Text Available Endogenous retroviruses (ERVs are integrated as DNA proviruses in the genomes of all mammalian species. Several ERVs are replication-competent and produced as fully infectious viruses from host cell. Thus, live-attenuated vaccines and biological substances have been prepared using the cell lines which may produce ERV. Indeed, we recently reported that several commercial live-attenuated vaccines for pets were contaminated with the infectious feline endogenous retrovirus, RD-114. In this study, to establish a cell line for vaccine manufacture with reduced risk of ERVs, we generated a cell line stably expressing human tetherin (Teth-CRFK cells. The release of infectious ERV from Teth-CRFK cells was suppressed to undetectable levels, while the production of parvovirus in Teth-CRFK cells was similar to that in parental CRFK cells. These observations suggest that Teth-CRFK cells will be useful as a cell line for the manufacture of live-attenuated vaccines or biological substances with reduced risk of ERV.

A new approach to establish a cell line with reduced risk of endogenous retroviruses.

Science.gov (United States)

Fukuma, Aiko; Yoshikawa, Rokusuke; Miyazawa, Takayuki; Yasuda, Jiro

2013-01-01

Endogenous retroviruses (ERVs) are integrated as DNA proviruses in the genomes of all mammalian species. Several ERVs are replication-competent and produced as fully infectious viruses from host cell. Thus, live-attenuated vaccines and biological substances have been prepared using the cell lines which may produce ERV. Indeed, we recently reported that several commercial live-attenuated vaccines for pets were contaminated with the infectious feline endogenous retrovirus, RD-114. In this study, to establish a cell line for vaccine manufacture with reduced risk of ERVs, we generated a cell line stably expressing human tetherin (Teth-CRFK cells). The release of infectious ERV from Teth-CRFK cells was suppressed to undetectable levels, while the production of parvovirus in Teth-CRFK cells was similar to that in parental CRFK cells. These observations suggest that Teth-CRFK cells will be useful as a cell line for the manufacture of live-attenuated vaccines or biological substances with reduced risk of ERV.

Hybridization Capture Reveals Evolution and Conservation across the Entire Koala Retrovirus Genome

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Ishida, Yasuko; Cui, Pin; Vielgrader, Hanna; Helgen, Kristofer M.; Roca, Alfred L.; Greenwood, Alex D.

2014-01-01

The koala retrovirus (KoRV) is the only retrovirus known to be in the midst of invading the germ line of its host species. Hybridization capture and next generation sequencing were used on modern and museum DNA samples of koala (Phascolarctos cinereus) to examine ca. 130 years of evolution across the full KoRV genome. Overall, the entire proviral genome appeared to be conserved across time in sequence, protein structure and transcriptional binding sites. A total of 138 polymorphisms were detected, of which 72 were found in more than one individual. At every polymorphic site in the museum koalas, one of the character states matched that of modern KoRV. Among non-synonymous polymorphisms, radical substitutions involving large physiochemical differences between amino acids were elevated in env, potentially reflecting anti-viral immune pressure or avoidance of receptor interference. Polymorphisms were not detected within two functional regions believed to affect infectivity. Host sequences flanking proviral integration sites were also captured; with few proviral loci shared among koalas. Recently described variants of KoRV, designated KoRV-B and KoRV-J, were not detected in museum samples, suggesting that these variants may be of recent origin. PMID:24752422

Hybridization capture reveals evolution and conservation across the entire Koala retrovirus genome.

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Kyriakos Tsangaras

Full Text Available The koala retrovirus (KoRV is the only retrovirus known to be in the midst of invading the germ line of its host species. Hybridization capture and next generation sequencing were used on modern and museum DNA samples of koala (Phascolarctos cinereus to examine ca. 130 years of evolution across the full KoRV genome. Overall, the entire proviral genome appeared to be conserved across time in sequence, protein structure and transcriptional binding sites. A total of 138 polymorphisms were detected, of which 72 were found in more than one individual. At every polymorphic site in the museum koalas, one of the character states matched that of modern KoRV. Among non-synonymous polymorphisms, radical substitutions involving large physiochemical differences between amino acids were elevated in env, potentially reflecting anti-viral immune pressure or avoidance of receptor interference. Polymorphisms were not detected within two functional regions believed to affect infectivity. Host sequences flanking proviral integration sites were also captured; with few proviral loci shared among koalas. Recently described variants of KoRV, designated KoRV-B and KoRV-J, were not detected in museum samples, suggesting that these variants may be of recent origin.

Proliferation of Endogenous Retroviruses in the Early Stages of a Host Germ Line Invasion

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Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D.; Roca, Alfred L.

2015-01-01

Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire–dam–progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5′- and 3′-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5′-LTR sequence was identical to the 3′-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200–49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. PMID:25261407

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

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Sudhir Kumar Rai

2017-12-01

Full Text Available Retroviruses and Long Terminal Repeat (LTR-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

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Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak; Levin, Henry L

2017-12-01

Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

Proliferation of endogenous retroviruses in the early stages of a host germ line invasion.

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Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D; Roca, Alfred L

2015-01-01

Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5'- and 3'-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5'-LTR sequence was identical to the 3'-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200-49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The MHC-II transactivator CIITA, a restriction factor against oncogenic HTLV-1 and HTLV-2 retroviruses: similarities and differences in the inhibition of Tax-1 and Tax-2 viral transactivators

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Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S.; Tosi, Giovanna

2013-01-01

The activation of CD4+ T helper cells is strictly dependent on the presentation of antigenic peptides by MHC class II (MHC-II) molecules. MHC-II expression is primarily regulated at the transcriptional level by the AIR-1 gene product CIITA (class II transactivator). Thus, CIITA plays a pivotal role in the triggering of the adaptive immune response against pathogens. Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against HTLV-1 (human T cell lymphotropic virus type 1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively. Here we review our findings on CIITA-mediated inhibition of viral replication and discuss similarities and differences in the molecular mechanisms by which CIITA specifically counteracts the function of Tax-1 and Tax-2 molecules. The dual function of CIITA as a key regulator of adaptive and intrinsic immunity represents a rather unique example of adaptation of host-derived factors against pathogen infections during evolution. PMID:23986750

Endogenous Retrovirus 3 – History, Physiology, and Pathology

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Bustamante Rivera, Yomara Y.; Brütting, Christine; Schmidt, Caroline; Volkmer, Ines; Staege, Martin S.

2018-01-01

Endogenous viral elements (EVE) seem to be present in all eukaryotic genomes. The composition of EVE varies between different species. The endogenous retrovirus 3 (ERV3) is one of these elements that is present only in humans and other Catarrhini. Conservation of ERV3 in most of the investigated Catarrhini and the expression pattern in normal tissues suggest a putative physiological role of ERV3. On the other hand, ERV3 has been implicated in the pathogenesis of auto-immunity and cancer. In the present review we summarize knowledge about this interesting EVE. We propose the model that expression of ERV3 (and probably other EVE loci) under pathological conditions might be part of a metazoan SOS response. PMID:29379485

Endogenous Retrovirus 3 – History, Physiology, and Pathology

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Yomara Y. Bustamante Rivera

2018-01-01

Full Text Available Endogenous viral elements (EVE seem to be present in all eukaryotic genomes. The composition of EVE varies between different species. The endogenous retrovirus 3 (ERV3 is one of these elements that is present only in humans and other Catarrhini. Conservation of ERV3 in most of the investigated Catarrhini and the expression pattern in normal tissues suggest a putative physiological role of ERV3. On the other hand, ERV3 has been implicated in the pathogenesis of auto-immunity and cancer. In the present review we summarize knowledge about this interesting EVE. We propose the model that expression of ERV3 (and probably other EVE loci under pathological conditions might be part of a metazoan SOS response.

Infection with koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging koalas (Phascolarctos cinereus)

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Waugh, Courtney A.; Hanger, Jonathan; Loader, Joanne; King, Andrew; Hobbs, Matthew; Johnson, Rebecca; Timms, Peter

2017-01-01

The virulence of chlamydial infection in wild koalas is highly variable between individuals. Some koalas can be infected (PCR positive) with Chlamydia for long periods but remain asymptomatic, whereas others develop clinical disease. Chlamydia in the koala has traditionally been studied without regard to coinfection with other pathogens, although koalas are usually subject to infection with koala retrovirus (KoRV). Retroviruses can be immunosuppressive, and there is evidence of an immunosuppr...

Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA.

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Prats, A C; Sarih, L; Gabus, C; Litvak, S; Keith, G; Darlix, J L

1988-06-01

Retrovirus virions carry a diploid genome associated with a large number of small viral finger protein molecules which are required for encapsidation. Our present results show that finger protein p12 of Rous sarcoma virus (RSV) and p10 of murine leukaemia virus (MuLV) positions replication primer tRNA on the replication initiation site (PBS) at the 5' end of the RNA genome. An RSV mutant with a Val-Pro insertion in the finger motif of p12 is able to partially encapsidate genomic RNA but is not infectious because mutated p12 is incapable of positioning the replication primer, tRNATrp. Since all known replication competent retroviruses, and the plant virus CaMV, code for finger proteins analogous to RSV p12 or MuLV p10, the initial stage of reverse transcription in avian, mammalian and human retroviruses and in CaMV is probably controlled in an analogous way.

Association of endogenous retroviruses and long terminal repeats with human disorders

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Iyoko eKatoh

2013-09-01

Full Text Available Since the human genome sequences became available in 2001, our knowledge about the human transposable elements which comprise ~40% of the total nucleotides has been expanding. Non- LTR (long terminal repeat retrotransposons are actively transposing in the present-day human genome, and have been found to cause ~100 identified clinical cases of varied disorders. In contrast, almost all of the human endogenous retroviruses (HERVs originating from ancient infectious retroviruses lost their infectivity and transposing activity at various times before the human-chimpanzee speciation (~6 million years ago, and no known HERV is presently infectious. Insertion of HERVs and mammalian apparent LTR retrotransposons (MaLRs into the chromosomal DNA influenced a number of host genes in various modes during human evolution. Apart from the aspect of genome evolution, HERVs and solitary LTRs being suppressed in normal biological processes can potentially act as extra transcriptional apparatuses of cellular genes by re-activation in individuals. There has been a reasonable prediction that aberrant LTR activation could trigger malignant disorders and autoimmune responses if epigenetic changes including DNA hypomethylation occur in somatic cells. Evidence supporting this hypothesis has begun to emerge only recently: a MaLR family LTR activation in the pathogenesis of Hodgkin’s lymphoma and a HERV-E antigen expression in an anti-renal cell carcinoma immune response. This mini review addresses the impacts of the remnant-form LTR retrotransposons on human pathogenesis.

Sequence variation of koala retrovirus transmembrane protein p15E among koalas from different geographic regions

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Ishida, Yasuko; McCallister, Chelsea; Nikolaidis, Nikolas; Tsangaras, Kyriakos; Helgen, Kristofer M.; Greenwood, Alex D.; Roca, Alfred L.

2014-01-01

The koala retrovirus (KoRV), which is transitioning from an exogenous to an endogenous form, has been associated with high mortality in koalas. For other retroviruses, the envelope protein p15E has been considered a candidate for vaccine development. We therefore examined proviral sequence variation of KoRV p15E in a captive Queensland and three wild southern Australian koalas. We generated 163 sequences with intact open reading frames, which grouped into 39 distinct haplotypes. Sixteen distinct haplotypes comprising 139 of the sequences (85%) coded for the same polypeptide. Among the remaining 23 haplotypes, 22 were detected only once among the sequences, and each had 1 or 2 non-synonymous differences from the majority sequence. Several analyses suggested that p15E was under purifying selection. Important epitopes and domains were highly conserved across the p15E sequences and in previously reported exogenous KoRVs. Overall, these results support the potential use of p15E for KoRV vaccine development. PMID:25462343

Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.

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Wang, Jichang; Xie, Gangcai; Singh, Manvendra; Ghanbarian, Avazeh T; Raskó, Tamás; Szvetnik, Attila; Cai, Huiqiang; Besser, Daniel; Prigione, Alessandro; Fuchs, Nina V; Schumann, Gerald G; Chen, Wei; Lorincz, Matthew C; Ivics, Zoltán; Hurst, Laurence D; Izsvák, Zsuzsanna

2014-12-18

Naive embryonic stem cells hold great promise for research and therapeutics as they have broad and robust developmental potential. While such cells are readily derived from mouse blastocysts it has not been possible to isolate human equivalents easily, although human naive-like cells have been artificially generated (rather than extracted) by coercion of human primed embryonic stem cells by modifying culture conditions or through transgenic modification. Here we show that a sub-population within cultures of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) manifests key properties of naive state cells. These naive-like cells can be genetically tagged, and are associated with elevated transcription of HERVH, a primate-specific endogenous retrovirus. HERVH elements provide functional binding sites for a combination of naive pluripotency transcription factors, including LBP9, recently recognized as relevant to naivety in mice. LBP9-HERVH drives hESC-specific alternative and chimaeric transcripts, including pluripotency-modulating long non-coding RNAs. Disruption of LBP9, HERVH and HERVH-derived transcripts compromises self-renewal. These observations define HERVH expression as a hallmark of naive-like hESCs, and establish novel primate-specific transcriptional circuitry regulating pluripotency.

Koala retroviruses: characterization and impact on the life of koalas

Science.gov (United States)

2013-01-01

Koala retroviruses (KoRV) have been isolated from wild and captive koalas in Australia as well as from koala populations held in zoos in other countries. They are members of the genus Gammaretrovirus, are most closely related to gibbon ape leukemia virus (GaLV), feline leukemia virus (FeLV) and porcine endogenous retrovirus (PERV) and are likely the result of a relatively recent trans-species transmission from rodents or bats. The first KoRV to be isolated, KoRV-A, is widely distributed in the koala population in both integrated endogenous and infectious exogenous forms with evidence from museum specimens older than 150 years, indicating a relatively long engagement with the koala population. More recently, additional subtypes of KoRV that are not endogenized have been identified based on sequence differences and host cell receptor specificity (KoRV-B and KoRV-J). A specific association with fatal lymphoma and leukemia has been recently suggested for KoRV-B. In addition, it has been proposed that the high viral loads found in many animals may lead to immunomodulation resulting in a higher incidence of diseases such as chlamydiosis. Although the molecular basis of this immunomodulation is still unclear, purified KoRV particles and a peptide corresponding to a highly conserved domain in the envelope protein have been shown to modulate cytokine expression in vitro, similar to that induced by other gammaretroviruses. While much is still to be learned, KoRV induced lymphoma/leukemia and opportunistic disease arising as a consequence of immunomodulation are likely to play an important role in the stability of koala populations both in the wild and in captivity. PMID:24148555

Koala retroviruses: characterization and impact on the life of koalas.

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Denner, Joachim; Young, Paul R

2013-10-23

Koala retroviruses (KoRV) have been isolated from wild and captive koalas in Australia as well as from koala populations held in zoos in other countries. They are members of the genus Gammaretrovirus, are most closely related to gibbon ape leukemia virus (GaLV), feline leukemia virus (FeLV) and porcine endogenous retrovirus (PERV) and are likely the result of a relatively recent trans-species transmission from rodents or bats. The first KoRV to be isolated, KoRV-A, is widely distributed in the koala population in both integrated endogenous and infectious exogenous forms with evidence from museum specimens older than 150 years, indicating a relatively long engagement with the koala population. More recently, additional subtypes of KoRV that are not endogenized have been identified based on sequence differences and host cell receptor specificity (KoRV-B and KoRV-J). A specific association with fatal lymphoma and leukemia has been recently suggested for KoRV-B. In addition, it has been proposed that the high viral loads found in many animals may lead to immunomodulation resulting in a higher incidence of diseases such as chlamydiosis. Although the molecular basis of this immunomodulation is still unclear, purified KoRV particles and a peptide corresponding to a highly conserved domain in the envelope protein have been shown to modulate cytokine expression in vitro, similar to that induced by other gammaretroviruses. While much is still to be learned, KoRV induced lymphoma/leukemia and opportunistic disease arising as a consequence of immunomodulation are likely to play an important role in the stability of koala populations both in the wild and in captivity.

Restriction genes for retroviruses influence the risk of multiple sclerosis

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Nexø, Bjørn A; Hansen, Bettina; Nissen, Kari K

2013-01-01

known for a long time. Today human restriction genes for retroviruses include amongst others TRIMs, APOBEC3s, BST2 and TREXs. We have therefore looked for a role of these retroviral restriction genes in MS using genetic epidemiology. We here report that markers in two TRIMs, TRIM5 and TRIM22...... and a marker in BST2, associated statistically with the risk of getting MS, while markers in or near APOBEC3s and TREXs showed little or no effect. This indicates that the two TRIMs and BST2 influence the risk of disease and thus supports the hypothesis of a viral involvement....

Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency

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B.E. Strauss

2007-05-01

Full Text Available A successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence.

The NHLBI Retrovirus Epidemiology Donor Studies (REDS and REDS-II): Twenty years of research to advance blood product safety and availability

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Kleinman, Steven; King, Melissa R; Busch, Michael P; Murphy, Edward L; Glynn, Simone A.

2012-01-01

The Retrovirus Epidemiology Donor Study (REDS), conducted from 1989–2001, and the Retrovirus Epidemiology Donor Study-II (REDS-II), conducted from 2004–2012, were National Heart Lung and Blood Institute (NHLBI) funded multicenter programs focused on improving blood safety and availability in the United States. REDS-II also included international study sites in Brazil and China. The three major research domains of REDS/REDS-II have been infectious disease risk evaluation, blood donation availability, and blood donor characterization. Both programs have made significant contributions to transfusion medicine research methodology by the use of mathematical modeling, large-scale donor surveys, innovative methods of repository sample storage, and establishing an infrastructure that responded to potential emerging blood safety threats such as XMRV. Blood safety studies have included protocols evaluating epidemiologic and/or laboratory aspects of HIV, HTLV I/II, HCV, HBV, WNV, CMV, HHV-8, B19V, malaria, CJD, influenza, and T. cruzi infections. Other analyses have characterized: blood donor demographics, motivations to donate, factors influencing donor return, behavioral risk factors, donors’ perception of the blood donation screening process, and aspects of donor deferral. In REDS-II, two large-scale blood donor protocols examined iron deficiency in donors and the prevalence of leukocyte antibodies. This review describes the major study results from over 150 peer-reviewed articles published by these two REDS programs. In 2011, a new seven year program, the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III), was launched. REDS-III expands beyond donor-based research to include studies of blood transfusion recipients in the hospital setting, and adds a third country, South Africa, to the international program. PMID:22633182

Dysfunction of bovine endogenous retrovirus K2 envelope glycoprotein is related to unsuccessful intracellular trafficking.

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Nakaya, Yuki; Miyazawa, Takayuki

2014-06-01

Endogenous retroviruses (ERVs) are the remnants of retroviral infection of ancestral germ cells. Mutations introduced into ERVs halt the production of infectious agents, but their effects on the function of retroviral proteins are not fully understood. Retroviral envelope glycoproteins (Envs) are utilized in membrane fusion during viral entry, and we recently identified intact coding sequences for bovine endogenous retrovirus K1 (BERV-K1) and BERV-K2 Envs. Amino acid sequences of BERV-K1 Env (also called Fematrin-1) and BERV-K2 Env are similar, and both viruses are classified in the genus Betaretrovirus. While Fematrin-1 plays an important role in cell-to-cell fusion in bovine placenta, the BERV-K2 envelope gene is marginally expressed in vivo, and its recombinant Env protein is defective in membrane fusion due to inefficient cleavage of surface (SU) and transmembrane subunits. Here, we conducted chimeric analyses of Fematrin-1 and BERV-K2 Envs and revealed that defective maturation of BERV-K2 Env contributed to failed intracellular trafficking. Fluorescence microscopy and flow cytometric analysis suggested that in contrast to Fematrin-1 Env, BERV-K2 Env could not be transported from the endoplasmic reticulum to the trans-Golgi network, where cellular proteases required for processing retroviral Envs are localized. We also identified that one of the responsive regions of this phenomenon resided within a 65-amino-acid region of BERV-K2 SU. This is the first report to identify that retroviral Env SU is involved in the regulation of intracellular trafficking, and it may help to elucidate the maturation process of Fematrin-1 and other related Envs. Retroviruses utilize envelope glycoproteins (Envs) to enter host target cells. Mature retroviral Env is a heterodimer, which consists of surface (SU) and transmembrane (TM) subunits that are generated by the cleavage of an Env precursor protein in the trans-Golgi network. SU and TM mediate the recognition of the entry

REVEALING THE HISTORY OF SHEEP DOMESTICATION USING RETROVIRUS INTEGRATIONS

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Chessa, B.; Pereira, F.; Arnaud, F.; Amorim, A.; Goyache, F.; Mainland, I.; Kao, R.R.; Pemberton, J. M.; Beraldi, D.; Stear, M.; Alberti, A.; Pittau, M.; Iannuzzi, L.; Banabazi, M.H.; Kazwala, R.; Zhang, Y.-P.; Arranz, J.J.; Ali, B.A.; Wang, Z.; Uzun, M.; Dione, M.; Olsaker, I.; Holm, L.-E.; Saarma, U.; Ahmad, S.; Marzanov, N.; Eythorsdottir, E.; Holland, M.J.; Ajmone-Marsan, P.; Bruford, M.W.; Kantanen, J.; Spencer, T.E.; Palmarini, M.

2011-01-01

The domestication of livestock represented a crucial step in human history. By using endogenous retroviruses as genetic markers, we found that sheep differentiated on the basis of their “retrotype” and morphological traits, dispersed across Eurasia and Africa via separate migratory episodes. Relicts of the first migrations include the Mouflon, as well as breeds previously recognized as “primitive” on the basis of their morphology, such as the Orkney, Soay and the Nordic short-tailed sheep now confined to the periphery of NW Europe. A later migratory episode, involving sheep with improved production traits, shaped the vast majority of present-day breeds. The ability to differentiate genetically primitive sheep from more modern breeds provides valuable insights into the history of sheep domestication. PMID:19390051

Revealing the history of sheep domestication using retrovirus integrations.

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Chessa, Bernardo; Pereira, Filipe; Arnaud, Frederick; Amorim, Antonio; Goyache, Félix; Mainland, Ingrid; Kao, Rowland R; Pemberton, Josephine M; Beraldi, Dario; Stear, Michael J; Alberti, Alberto; Pittau, Marco; Iannuzzi, Leopoldo; Banabazi, Mohammad H; Kazwala, Rudovick R; Zhang, Ya-Ping; Arranz, Juan J; Ali, Bahy A; Wang, Zhiliang; Uzun, Metehan; Dione, Michel M; Olsaker, Ingrid; Holm, Lars-Erik; Saarma, Urmas; Ahmad, Sohail; Marzanov, Nurbiy; Eythorsdottir, Emma; Holland, Martin J; Ajmone-Marsan, Paolo; Bruford, Michael W; Kantanen, Juha; Spencer, Thomas E; Palmarini, Massimo

2009-04-24

The domestication of livestock represented a crucial step in human history. By using endogenous retroviruses as genetic markers, we found that sheep differentiated on the basis of their "retrotype" and morphological traits dispersed across Eurasia and Africa via separate migratory episodes. Relicts of the first migrations include the Mouflon, as well as breeds previously recognized as "primitive" on the basis of their morphology, such as the Orkney, Soay, and the Nordic short-tailed sheep now confined to the periphery of northwest Europe. A later migratory episode, involving sheep with improved production traits, shaped the great majority of present-day breeds. The ability to differentiate genetically primitive sheep from more modern breeds provides valuable insights into the history of sheep domestication.

Deletion of the pluripotency-associated Tex19.1 gene causes activation of endogenous retroviruses and defective spermatogenesis in mice

DEFF Research Database (Denmark)

Ollinger, Rupert; Childs, Andrew J; Burgess, Hannah M

2008-01-01

. During male spermatogenesis, Tex19.1 expression is highest in mitotic spermatogonia and diminishes as these cells differentiate and progress through meiosis. In pluripotent stem cells, Tex19.1 expression is also downregulated upon differentiation. However, it is not clear whether Tex19.1 has an essential...... spermatogenesis. Immunostaining and histological analysis revealed defects in meiotic chromosome synapsis, the persistence of DNA double-strand breaks during meiosis, and a loss of post-meiotic germ cells in the testis. Furthermore, expression of a class of endogenous retroviruses is upregulated during meiosis...... in the Tex19.1(-/-) testes. Increased transposition of endogenous retroviruses in the germline of Tex19.1(-/-) mutant mice, and the concomitant increase in DNA damage, may be sufficient to disrupt the normal processes of recombination and chromosome synapsis during meiosis and cause defects...

Gypsy endogenous retrovirus maintains potential infectivity in several species of Drosophilids

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de Frutos Rosa

2008-10-01

Full Text Available Abstract Background Sequences homologous to the gypsy retroelement from Drosophila melanogaster are widely distributed among drosophilids. The structure of gypsy includes an open reading frame resembling the retroviral gene env, which is responsible for the infectious properties of retroviruses. Results In this study we report molecular and phylogeny analysis of the complete env gene from ten species of the obscura group of the genus Drosophila and one species from the genus Scaptomyza. Conclusion The results indicate that in most cases env sequences could produce a functional Env protein and therefore maintain the infectious capability of gypsy in these species.

Retrovirus endógenos humanos: Significado biológico e implicaciones evolutivas

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Sentís, Carlos

2002-05-01

Full Text Available El genoma humano contiene un importante número de retrovirus endógenos (HERVs, es decir, secuencias derivadas de pasadas infecciones retrovirales insertadas de forma permanente; y secuencias similares se pueden observar en prácticamente todos los organismos eucariontes. Muchos de estos HERVs se transcriben y traducen en condiciones fisiológicas normales, llegando a formar partículas virales completas, y participando en procesos tan complejos como la placentación. Por su capacidad de retrotransposición y recombinación entre ellos son una fuente importante de remodelación genómica y, junto con otros retroelementos, participan en la generación de retrogenes y retropseudogenes, que suponen un sustrato de variabilidad informacional fundamental para la aparición de nuevas estructuras y funciones. Puesto que su actividad responde también a las condiciones ambientales, los cambios genómicos generados por ellos no son graduales, sino que aparecen en oleadas, de modo que se puede producir una variedad fenotípica muy extensa en momentos evolutivos concretos, coincidiendo con situaciones ambientales críticas. La consideración de los HERVs como parte integral y consustancial de nuestro genoma obliga a replantearse la utilización de vectores retrovirales en protocolos de terapia génica, así como la utilización de órganos animales -con sus propios retrovirus endógenos- para xenotrasplantes.

Characterization of a nucleocapsid-like region and of two distinct primer tRNALys,2 binding sites in the endogenous retrovirus Gypsy.

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Gabus, Caroline; Ivanyi-Nagy, Roland; Depollier, Julien; Bucheton, Alain; Pelisson, Alain; Darlix, Jean-Luc

2006-01-01

Mobile LTR-retroelements comprising retroviruses and LTR-retrotransposons form a large part of eukaryotic genomes. Their mode of replication and abundance favour the notion that they are major actors in eukaryote evolution. The Gypsy retroelement can spread in the germ line of the fruit fly Drosophila melanogaster via both env-independent and env-dependent processes. Thus, Gypsy is both an active retrotransposon and an infectious retrovirus resembling the gammaretrovirus MuLV. However, unlike gammaretroviruses, the Gypsy Gag structural precursor is not processed into Matrix, Capsid and Nucleocapsid (NC) proteins. In contrast, it has features in common with Gag of the ancient yeast TY1 retroelement. These characteristics of Gypsy make it a very interesting model to study replication of a retroelement at the frontier between ancient retrotransposons and retroviruses. We investigated Gypsy replication using an in vitro model system and transfection of insect cells. Results show that an unstructured domain of Gypsy Gag has all the properties of a retroviral NC. This NC-like peptide forms ribonucleoparticle-like complexes upon binding Gypsy RNA and directs the annealing of primer tRNA(Lys,2) to two distinct primer binding sites (PBS) at the genome 5' and 3' ends. Only the 5' PBS is indispensable for cDNA synthesis in vitro and in Drosophila cells.

Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

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Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

2017-07-01

The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

Human endogenous retroviruses and chosen disease parameters in morphea

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Dańczak-Pazdrowska, Aleksandra; Szramka-Pawlak, Beata; Żaba, Ryszard; Osmola-Mańkowska, Agnieszka; Silny, Wojciech

2017-01-01

Introduction Morphea (localized scleroderma) is a relatively rare disease characterized by excessive skin fibrosis. Human endogenous retroviruses (HERV) are largely distributed within the human genome with hundreds of thousands of elements. The HERV have been widely studied in autoimmune disorders, yet hardly ever assessed in diseases with a good prognosis such as morphea. Aim In this study we focus on the possible relations between the expression of chosen HERV and factors influencing the pathomechanism of the disease, such as age, sex, titres of anti-nuclear antibodies, as well as duration, activity, and severity of the disease (LoSSI index). Material and methods Real-time polymerase chain reaction (PCR) targeting six HERV sequences of interest were performed on samples derived from peripheral blood mononuclear cells (PBMC) and skin biopsies. Results In PBMC we found a statistically significant negative correlation between HERV-W env expression and LoSSI index (p = 0.01). Additionally, HERV-W env was downregulated in patients with the active form of morphea. In all other cases we found no correlation whatsoever nor statistically significant differences below the p = 0.05 threshold. Conclusions Morphea seems to be an autoimmune disease where the impact of HERV is not so apparent. It seems that probing many patients for the expression of just a few sequences is not as effective as previously expected. For initial studies of HERV in other diseases we recommend high throughput techniques such as HERV-dedicated DNA microarrays or massive parallel sequencing. PMID:28261031

Human endogenous retroviruses and chosen disease parameters in morphea

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Michał J. Kowalczyk

2017-02-01

Full Text Available Introduction: Morphea (localized scleroderma is a relatively rare disease characterized by excessive skin fibrosis. Human endogenous retroviruses (HERV are largely distributed within the human genome with hundreds of thousands of elements. The HERV have been widely studied in autoimmune disorders, yet hardly ever assessed in diseases with a good prognosis such as morphea. Aim: In this study we focus on the possible relations between the expression of chosen HERV and factors influencing the pathomechanism of the disease, such as age, sex, titres of anti-nuclear antibodies, as well as duration, activity, and severity of the disease (LoSSI index. Material and methods: Real-time polymerase chain reaction (PCR targeting six HERV sequences of interest were performed on samples derived from peripheral blood mononuclear cells (PBMC and skin biopsies. Results: In PBMC we found a statistically significant negative correlation between HERV-W env expression and LoSSI index (p = 0.01. Additionally, HERV-W env was downregulated in patients with the active form of morphea. In all other cases we found no correlation whatsoever nor statistically significant differences below the p = 0.05 threshold. Conclusions : Morphea seems to be an autoimmune disease where the impact of HERV is not so apparent. It seems that probing many patients for the expression of just a few sequences is not as effective as previously expected. For initial studies of HERV in other diseases we recommend high throughput techniques such as HERV-dedicated DNA microarrays or massive parallel sequencing.

Human endogenous retroviruses and multiple sclerosis: innocent bystanders or disease determinants?

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Antony, Joseph M; Deslauriers, Andre M; Bhat, Rakesh K; Ellestad, Kristofer K; Power, Christopher

2011-02-01

Human endogenous retroviruses (HERVs) constitute 5-8% of human genomic DNA and are replication incompetent despite expression of individual HERV genes from different chromosomal loci depending on the specific tissue. Several HERV genes have been detected as transcripts and proteins in the central nervous system, frequently in the context of neuroinflammation. The HERV-W family has received substantial attention in large part because of associations with diverse syndromes including multiple sclerosis (MS) and several psychiatric disorders. A HERV-W-related retroelement, multiple sclerosis retrovirus (MSRV), has been reported in MS patients to be both a biomarker as well as an effector of aberrant immune responses. HERV-H and HERV-K have also been implicated in MS and other neurological diseases but await delineation of their contributions to disease. The HERV-W envelope-encoded glycosylated protein, syncytin-1, is encoded by chromosome 7q21 and exhibits increased glial expression within MS lesions. Overexpression of syncytin-1 in glia induces endoplasmic reticulum stress leading to neuroinflammation and the induction of free radicals, which damage proximate cells. Syncytin-1's receptor, ASCT1 is a neutral amino acid transporter expressed on glia and is suppressed in white matter of MS patients. Of interest, antioxidants ameliorate syncytin-1's neuropathogenic effects raising the possibility of using these agents as therapeutics for neuroinflammatory diseases. Given the multiple insertion sites of HERV genes as complete and incomplete open reading frames, together with their differing capacity to be expressed and the complexities of individual HERVs as both disease markers and bioactive effectors, HERV biology is a compelling area for understanding neuropathogenic mechanisms and developing new therapeutic strategies. 2010 Elsevier B.V. All rights reserved.

RNAi and retroviruses: are they in RISC?

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Vasselon, Thierry; Bouttier, Manuella; Saumet, Anne; Lecellier, Charles-Henri

2013-02-01

RNA interference (RNAi) is a potent cellular system against viruses in various organisms. Although common traits are observed in plants, insects, and nematodes, the situation observed in mammals appears more complex. In mammalian somatic cells, RNAi is implicated in endonucleolytic cleavage mediated by artificially delivered small interfering RNAs (siRNAs) as well as in translation repression mediated by microRNAs (miRNAs). Because siRNAs and miRNAs recognize viral mRNAs, RNAi inherently limits virus production and participates in antiviral defense. However, several observations made in the cases of hepatitis C virus and retroviruses (including the human immunodeficiency virus and the primate foamy virus) bring evidence that this relationship is much more complex and that certain components of the RNAi effector complex [called the RNA-induced silencing complex (RISC)], such as AGO2, are also required for viral replication. Here, we summarize recent discoveries that have revealed this dual implication in virus biology. We further discuss their potential implications for the functions of RNAi-related proteins, with special emphasis on retrotransposition and genome stability.

THE ROLE OF EPSTEIN-BARR VIRUS AND HUMAN ENDOGENOUS RETROVIRUSES IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS

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Zelenska, A. D.

2018-04-01

Full Text Available Multiple sclerosis (MS is an autoimmune demyelinating disease of the central nervous system (CNS, the development of which is associated with the action of a large number of pathogenetic factors which role can vary significantly at different stages of the disease. Although the etiology of MS still remains unclear, in recent years the hypothesis of the pathogenetic role of Epstein-Barr virus (EBV and human endogenous retroviruses, such as MSRV / HERV-W, is actively considered. EBV has a unique ability to infect, activate, and latently persist within B lymphocytes during human life. Immune control of EBV infection in healthy organisms is realized through humoral and cellular mechanisms – EBV virions are destroyed by neutralizing antibodies, and proliferating and lytically active EBV-infected B cells are the targets of specific CD8+ T cells. At the same time, EBV remains latent for most of the life of the infected individual, expressing a single gene (EBNA1 within memory B cells. EBNA1 protein is not well recognized by CD8+ T cells, allowing infected memory B cells to avoid detection. In addition to epidemiological data, association of EBV with MS is indicated by a significant increase in IgG titres to EBV antigens, mainly to EBNA1, in serum of patients a few years before the onset of clinical manifestations of the disease. Although the data on the presence of EBV in the CNS remain controversial due to a number of methodological difficulties, a number of studies have shown the presence of EBV-infected B cells in the CNS, as well as effector CD8+ T cells specific for them in meningeal inflammatory infiltrates and white matter lesions in brain samples of MS patients. At the same time, the EBV bystander damage hypothesis which considers CNS damage in multiple sclerosis as a result of EBV-targeted cytotoxic reactions of CD8+ T cells, does not explain the autoimmune nature of MS, although secondary autoimmune responses could develop as a result of

Evolution of the retroviral restriction gene Fv1: inhibition of non-MLV retroviruses.

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Melvyn W Yap

2014-03-01

Full Text Available Fv1 is the prototypic restriction factor that protects against infection by the murine leukemia virus (MLV. It was first identified in cells that were derived from laboratory mice and was found to be homologous to the gag gene of an endogenous retrovirus (ERV. To understand the evolution of the host restriction gene from its retroviral origins, Fv1s from wild mice were isolated and characterized. Most of these possess intact open reading frames but not all restricted N-, B-, NR-or NB-tropic MLVs, suggesting that other viruses could have played a role in the selection of the gene. The Fv1s from Mus spretus and Mus caroli were found to restrict equine infectious anemia virus (EIAV and feline foamy virus (FFV respectively, indicating that Fv1 could have a broader target range than previously thought, including activity against lentiviruses and spumaviruses. Analyses of the Fv1 sequences revealed a number of residues in the C-terminal region that had evolved under positive selection. Four of these selected residues were found to be involved in the novel restriction by mapping studies. These results strengthen the similarities between the two capsid binding restriction factors, Fv1 and TRIM5α, which support the hypothesis that Fv1 defended mice against waves of retroviral infection possibly including non-MLVs as well as MLVs.

Establishment of a high production system for AIDS retroviruses with a human T-leukemic cell line Molt-4

International Nuclear Information System (INIS)

Koyanagi, Yoshio; Harada, Shinji; Yamamoto, Naoki

1986-01-01

A cell culture system was developed for the continuous and efficient production of acquired immune deficiency syndrome (AIDS) retrovirus. After infection of a human T-cell line Molt-4 with HTLV-III and LAV the cells grow permanently and produce large amounts of virus continuously. The yields of production of virus were assessed either with reverse transcriptase activity or a newly established biological quantitation assay of active virus. The amounts of virus with this cell system were much higher than those of the H9 cell system. This procedure enabled us first to compare the two viral isolates HTLV-III and LAV directly in the same cell lines. Establishment of the culture system, allowing efficient production of AIDS retroviruses, provides a useful tool for the isolation of the virus from patients with AIDS and for more basic research, such as the mechanisms of immune destruction caused by the virus leading to the occurence of various malignancies (author)

Activation of endogenous retrovirus reverse transcriptase in multiple sclerosis patient lymphocytes by inactivated HSV-1, HHV-6 and VZV

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Brudek, Tomasz; Lühdorf, Pernille; Christensen, Tove

2007-01-01

Human endogenous retroviruses (HERVs) and herpesviruses have been associated with the development of multiple sclerosis (MS). These virus groups interact with each other and have been shown to induce synergistic immune responses. Here, we focus on the possible role of herpesviruses as contributing...

Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

DEFF Research Database (Denmark)

Christensen, Tove

2005-01-01

may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation...... and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS. Copyright (c) 2005 ...

Investigation of Human Cancers for Retrovirus by Low-Stringency Target Enrichment and High-Throughput Sequencing

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Vinner, Lasse; Mourier, Tobias; Friis-Nielsen, Jens

2015-01-01

-stringency in-solution hybridization method enables detection of discovery of hitherto unknown viral sequences by high-throughput sequencing. The sensitivity was sufficient to detect retroviral...... sequences in clinical samples. We used this method to conduct an investigation for novel retrovirus in samples from three cancer types. In accordance with recent studies our investigation revealed no retroviral infections in human B-cell lymphoma cells, cutaneous T-cell lymphoma or colorectal cancer...

Functional hierarchy of two L domains in porcine endogenous retrovirus (PERV) that influence release and infectivity

International Nuclear Information System (INIS)

Marcucci, Katherine T.; Martina, Yuri; Harrison, Frank; Wilson, Carolyn A.; Salomon, Daniel R.

2008-01-01

The porcine endogenous retrovirus (PERV) Gag protein contains two late (L) domain motifs, PPPY and P(F/S)AP. Using viral release assays we demonstrate that PPPY is the dominant L domain involved in PERV release. PFAP represents a novel retroviral L domain variant and is defined by abnormal viral assembly phenotypes visualized by electron microscopy and attenuation of early PERV release as measured by viral genomes. PSAP is functionally dominant over PFAP in early PERV release. PSAP virions are 3.5-fold more infectious in vitro by TCID 50 and in vivo results in more RNA positive tissues and higher levels of proviral DNA using our human PERV-A receptor (HuPAR-2) transgenic mouse model [Martina, Y., Marcucci, K.T., Cherqui, S., Szabo, A., Drysdale, T., Srinivisan, U., Wilson, C.A., Patience, C., Salomon, D.R., 2006. Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection. J. Virol. 80 (7), 3135-3146]. The functional hierarchies displayed by PERV L domains, demonstrates that L domain selection in viral evolution exists to promote efficient viral assembly, release and infectivity in the virus-host context

Evaluation of factors important to enhance productivity

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Sanjay Kumar

2016-12-01

Full Text Available Productivity as a measure for output is important to industry and academia. In this research, factors to enhance productivity have been identified from the literature by reviewing various international and national sources to explore this evergreen field of research that is “productivity,” which has always been an increasingly interesting area of research for researchers over decades or perhaps over centuries. In total, 15 number of factors have been identified to enhance productivity. Analytic hierarchy process approach has been appropriately chosen to rank these factors because of its simplicity and effectiveness. The tool has been used by taking perception of experts from the Indian manufacturing industry. Positive attitude and involvement of management, proactive employees, and good working conditions have been ranked as top three factors as per the experts’ opinion. The ranking of factors to enhance productivity, categorization of the factors into four perspectives, and hierarchy of perspective and action plan as a final outcome of the paper may help academia and operations managers toward effective management of “operations and production activities of firms/supply chains.”

Presence of a Shared 5'-Leader Sequence in Ancestral Human and Mammalian Retroviruses and Its Transduction into Feline Leukemia Virus.

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Kawasaki, Junna; Kawamura, Maki; Ohsato, Yoshiharu; Ito, Jumpei; Nishigaki, Kazuo

2017-10-15

Recombination events induce significant genetic changes, and this process can result in virus genetic diversity or in the generation of novel pathogenicity. We discovered a new recombinant feline leukemia virus (FeLV) gag gene harboring an unrelated insertion, termed the X region, which was derived from Felis catus endogenous gammaretrovirus 4 (FcERV-gamma4). The identified FcERV-gamma4 proviruses have lost their coding capabilities, but some can express their viral RNA in feline tissues. Although the X-region-carrying recombinant FeLVs appeared to be replication-defective viruses, they were detected in 6.4% of tested FeLV-infected cats. All isolated recombinant FeLV clones commonly incorporated a middle part of the FcERV-gamma4 5'-leader region as an X region. Surprisingly, a sequence corresponding to the portion contained in all X regions is also present in at least 13 endogenous retroviruses (ERVs) observed in the cat, human, primate, and pig genomes. We termed this shared genetic feature the commonly shared (CS) sequence. Despite our phylogenetic analysis indicating that all CS-sequence-carrying ERVs are classified as gammaretroviruses, no obvious closeness was revealed among these ERVs. However, the Shannon entropy in the CS sequence was lower than that in other parts of the provirus genome. Notably, the CS sequence of human endogenous retrovirus T had 73.8% similarity with that of FcERV-gamma4, and specific signals were detected in the human genome by Southern blot analysis using a probe for the FcERV-gamma4 CS sequence. Our results provide an interesting evolutionary history for CS-sequence circulation among several distinct ancestral viruses and a novel recombined virus over a prolonged period. IMPORTANCE Recombination among ERVs or modern viral genomes causes a rapid evolution of retroviruses, and this phenomenon can result in the serious situation of viral disease reemergence. We identified a novel recombinant FeLV gag gene that contains an unrelated

Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

DEFF Research Database (Denmark)

Brudek, Tomasz; Christensen, Tove; Hansen, Hans Jacob

2008-01-01

Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...

Widespread and highly persistent gene transfer to the CNS by retrovirus vector in utero: implication for gene therapy to Krabbe disease.

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Shen, Jin-Song; Meng, Xing-Li; Yokoo, Takashi; Sakurai, Ken; Watabe, Kazuhiko; Ohashi, Toya; Eto, Yoshikatsu

2005-05-01

Brain-directed prenatal gene therapy may benefit some lysosomal storage diseases that affect the central nervous system (CNS) before birth. Our previous study showed that intrauterine introduction of recombinant adenoviruses into cerebral ventricles results in efficient gene transfer to the CNS in the mouse. However, transgene expression decreased with time due to the non-integrative property of adenoviral vectors. In this study, in order to obtain permanent gene transduction, we investigated the feasibility of retrovirus-mediated in utero gene transduction. Concentrated retrovirus encoding the LacZ gene was injected into the cerebral ventricles of the embryos of normal and twitcher mice (a murine model of Krabbe disease) at embryonic day 12. The distribution and maintenance of the transgene expression in the recipient brain were analyzed histochemically, biochemically and by the quantitative polymerase chain reaction method pre- and postnatally. Efficient and highly persistent gene transduction to the brain was achieved both in normal and the twitcher mouse. Transduced neurons, astrocytes and oligodendrocytes were distributed throughout the brain. The transduced LacZ gene, its transcript and protein expression in the brain were maintained for 14 months without decrement. In addition, gene transduction to multiple tissues other than the brain was also detected at low levels. This study suggests that brain-directed in utero gene transfer using retrovirus vector may be beneficial to the treatment of lysosomal storage diseases with severe brain damage early in life, such as Krabbe disease. Copyright (c) 2005 John Wiley & Sons, Ltd.

Generation of neutralising antibodies against porcine endogenous retroviruses (PERVs)

International Nuclear Information System (INIS)

Kaulitz, Danny; Fiebig, Uwe; Eschricht, Magdalena; Wurzbacher, Christian; Kurth, Reinhard; Denner, Joachim

2011-01-01

Antibodies neutralising porcine endogenous retroviruses (PERVs) were induced in different animal species by immunisation with the transmembrane envelope protein p15E. These antibodies recognised epitopes, designated E1, in the fusion peptide proximal region (FPPR) of p15E, and E2 in the membrane proximal external region (MPER). E2 is localised in a position similar to that of an epitope in the transmembrane envelope protein gp41 of the human immunodeficiency virus-1 (HIV-1), recognised by the monoclonal antibody 4E10 that is broadly neutralising. To detect neutralising antibodies specific for PERV, a novel assay was developed, which is based on quantification of provirus integration by real-time PCR. In addition, for the first time, highly effective neutralising antibodies were obtained by immunisation with the surface envelope protein of PERV. These data indicate that neutralising antibodies can be induced by immunisation with both envelope proteins.

Detection of the human endogenous retrovirus ERV3-encoded Env-protein in human tissues using antibody-based proteomics.

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Fei, Chen; Atterby, Christina; Edqvist, Per-Henrik; Pontén, Fredrik; Zhang, Wei Wei; Larsson, Erik; Ryan, Frank P

2014-01-01

There is growing evidence to suggest that human endogenous retroviruses (HERVs) have contributed to human evolution, being expressed in development, normal physiology and disease. A key difficulty in the scientific evaluation of this potential viral contribution is the accurate demonstration of virally expressed protein in specific human cells and tissues. In this study, we have adopted the endogenous retrovirus, ERV3, as our test model in developing a reliable high-capacity methodology for the expression of such endogenous retrovirus-coded protein. Two affinity-purified polyclonal antibodies to ERV3 Env-encoded protein were generated to detect the corresponding protein expression pattern in specific human cells, tissues and organs. Sampling included normal tissues from 144 individuals ranging from childhood to old age. This included more than forty different tissues and organs and some 216 different cancer tissues representing the twenty commonest forms of human cancer. The Rudbeck Laboratory, Uppsala University and Uppsala University Hospital, Uppsala, Sweden. The potential expression at likely physiological level of the ERV3Env encoded protein in a wide range of human cells, tissues and organs. We found that ERV3 encoded Env protein is expressed at substantive levels in placenta, testis, adrenal gland, corpus luteum, Fallopian tubes, sebaceous glands, astrocytes, bronchial epithelium and the ducts of the salivary glands. Substantive expression was also seen in a variety of epithelial cells as well as cells known to undergo fusion in inflammation and in normal physiology, including fused macrophages, myocardium and striated muscle. This contrasted strongly with the low levels expressed in other tissues types. These findings suggest that this virus plays a significant role in human physiology and may also play a possible role in disease. This technique can now be extended to the study of other HERV genomes within the human chromosomes that may have contributed to

Computational Evaluation of the Strict Master and Random Template Models of Endogenous Retrovirus Evolution

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Nascimento, Fabrícia F.; Rodrigo, Allen G.

2016-01-01

Transposable elements (TEs) are DNA sequences that are able to replicate and move within and between host genomes. Their mechanism of replication is also shared with endogenous retroviruses (ERVs), which are also a type of TE that represent an ancient retroviral infection within animal genomes. Two models have been proposed to explain TE proliferation in host genomes: the strict master model (SMM), and the random template (or transposon) model (TM). In SMM only a single copy of a given TE lineage is able to replicate, and all other genomic copies of TEs are derived from that master copy. In TM, any element of a given family is able to replicate in the host genome. In this paper, we simulated ERV phylogenetic trees under variations of SMM and TM. To test whether current phylogenetic programs can recover the simulated ERV phylogenies, DNA sequence alignments were simulated and maximum likelihood trees were reconstructed and compared to the simulated phylogenies. Results indicate that visual inspection of phylogenetic trees alone can be misleading. However, if a set of statistical summaries is calculated, we are able to distinguish between models with high accuracy by using a data mining algorithm that we introduce here. We also demonstrate the use of our data mining algorithm with empirical data for the porcine endogenous retrovirus (PERV), an ERV that is able to replicate in human and pig cells in vitro. PMID:27649303

Endogenous retroviruses mobilized during friend murine leukemia virus infection.

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Boi, Stefano; Rosenke, Kyle; Hansen, Ethan; Hendrick, Duncan; Malik, Frank; Evans, Leonard H

2016-12-01

We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses. Published by Elsevier Inc.

Correction of acid beta-galactosidase deficiency in GM1 gangliosidosis human fibroblasts by retrovirus vector-mediated gene transfer: higher efficiency of release and cross-correction by the murine enzyme.

Science.gov (United States)

Sena-Esteves, M; Camp, S M; Alroy, J; Breakefield, X O; Kaye, E M

2000-03-20

Mutations in the lysosomal acid beta-galactosidase (EC 3.2.1.23) underlie two different disorders: GM1 gangliosidosis, which involves the nervous system and visceral organs to varying extents, and Morquio's syndrome type B (Morquio B disease), which is a skeletal-connective tissue disease without any CNS symptoms. This article shows that transduction of human GM1 gangliosidosis fibroblasts with retrovirus vectors encoding the human acid beta-galactosidase cDNA leads to complete correction of the enzymatic deficiency. The newly synthesized enzyme is correctly processed and targeted to the lysosomes in transduced cells. Cross-correction experiments using retrovirus-modified cells as enzyme donors showed, however, that the human enzyme is transferred at low efficiencies. Experiments using a different retrovirus vector carrying the human cDNA confirmed this observation. Transduction of human GM1 fibroblasts and mouse NIH 3T3 cells with a retrovirus vector encoding the mouse beta-galactosidase cDNA resulted in high levels of enzymatic activity. Furthermore, the mouse enzyme was found to be transferred to human cells at high efficiency. Enzyme activity measurements in medium conditioned by genetically modified cells suggest that the human beta-galactosidase enzyme is less efficiently released to the extracellular space than its mouse counterpart. This study suggests that lysosomal enzymes, contrary to the generalized perception in the field of gene therapy, may differ significantly in their properties and provides insights for design of future gene therapy interventions in acid beta-galactosidase deficiency.

Expression and activation by Epstein Barr virus of human endogenous retroviruses-W in blood cells and astrocytes: inference for multiple sclerosis.

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Giuseppe Mameli

Full Text Available BACKGROUND: Proposed co-factors triggering the pathogenesis of multiple sclerosis (MS are the Epstein Barr virus (EBV, and the potentially neuropathogenic MSRV (MS-associated retrovirus and syncytin-1, of the W family of human endogenous retroviruses. METHODOLOGY/PRINCIPAL FINDINGS: In search of links, the expression of HERV-W/MSRV/syncytin-1, with/without exposure to EBV or to EBV glycoprotein350 (EBVgp350, was studied on peripheral blood mononuclear cells (PBMC from healthy volunteers and MS patients, and on astrocytes, by discriminatory env-specific RT-PCR assays, and by flow cytometry. Basal expression of HERV-W/MSRV/syncytin-1 occurs in astrocytes and in monocytes, NK, and B, but not in T cells. This uneven expression is amplified in untreated MS patients, and dramatically reduced during therapy. In astrocytes, EBVgp350 stimulates the expression of HERV-W/MSRV/syncytin-1, with requirement of the NF-κB pathway. In EBVgp350-treated PBMC, MSRVenv and syncytin-1 transcription is activated in B cells and monocytes, but not in T cells, nor in the highly expressing NK cells. The latter cells, but not the T cells, are activated by proinflammatory cytokines. CONCLUSIONS/SIGNIFICANCE: In vitro EBV activates the potentially immunopathogenic and neuropathogenic HERV-W/MSRV/syncytin-1, in cells deriving from blood and brain. In vivo, pathogenic outcomes would depend on abnormal situations, as in late EBV primary infection, that is often symptomatic, or/and in the presence of particular host genetic backgrounds. In the blood, HERV-Wenv activation might induce immunopathogenic phenomena linked to its superantigenic properties. In the brain, toxic mechanisms against oligodendrocytes could be established, inducing inflammation, demyelination and axonal damage. Local stimulation by proinflammatory cytokines and other factors might activate further HERV-Ws, contributing to the neuropathogenity. In MS pathogenesis, a possible model could include EBV as

A transcriptome resource for the koala (Phascolarctos cinereus): insights into koala retrovirus transcription and sequence diversity.

Science.gov (United States)

Hobbs, Matthew; Pavasovic, Ana; King, Andrew G; Prentis, Peter J; Eldridge, Mark D B; Chen, Zhiliang; Colgan, Donald J; Polkinghorne, Adam; Wilkins, Marc R; Flanagan, Cheyne; Gillett, Amber; Hanger, Jon; Johnson, Rebecca N; Timms, Peter

2014-09-11

The koala, Phascolarctos cinereus, is a biologically unique and evolutionarily distinct Australian arboreal marsupial. The goal of this study was to sequence the transcriptome from several tissues of two geographically separate koalas, and to create the first comprehensive catalog of annotated transcripts for this species, enabling detailed analysis of the unique attributes of this threatened native marsupial, including infection by the koala retrovirus. RNA-Seq data was generated from a range of tissues from one male and one female koala and assembled de novo into transcripts using Velvet-Oases. Transcript abundance in each tissue was estimated. Transcripts were searched for likely protein-coding regions and a non-redundant set of 117,563 putative protein sequences was produced. In similarity searches there were 84,907 (72%) sequences that aligned to at least one sequence in the NCBI nr protein database. The best alignments were to sequences from other marsupials. After applying a reciprocal best hit requirement of koala sequences to those from tammar wallaby, Tasmanian devil and the gray short-tailed opossum, we estimate that our transcriptome dataset represents approximately 15,000 koala genes. The marsupial alignment information was used to look for potential gene duplications and we report evidence for copy number expansion of the alpha amylase gene, and of an aldehyde reductase gene.Koala retrovirus (KoRV) transcripts were detected in the transcriptomes. These were analysed in detail and the structure of the spliced envelope gene transcript was determined. There was appreciable sequence diversity within KoRV, with 233 sites in the KoRV genome showing small insertions/deletions or single nucleotide polymorphisms. Both koalas had sequences from the KoRV-A subtype, but the male koala transcriptome has, in addition, sequences more closely related to the KoRV-B subtype. This is the first report of a KoRV-B-like sequence in a wild population. This transcriptomic

Clinical Aspects of Feline Retroviruses: A Review

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Katrin Hartmann

2012-10-01

Full Text Available Feline leukemia virus (FeLV and feline immunodeficiency virus (FIV are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma, bone marrow suppression syndromes (mainly anemia, and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats.

Human retroviruses and AIDS 1997

Energy Technology Data Exchange (ETDEWEB)

Korber, B.; Foley, B.; Leitner, T. [eds.] [and others

1997-12-01

This compendium is the result of an effort to compile, organize, and rapidly publish as much relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses as possible. The scope of the compendium and database is best summarized by the four parts that it comprises: (1) Nucleic Acid Alignments, (2) Amino Acid Alignments, (3) Reviews and Analyses, and (4) Related Sequences. Information within all the parts is updated throughout the year on the Web site, http://hiv-web.lanl.gov. This year we are not including floppy diskettes as the entire compendium is available both at our Web site and at our ftp site. If you need floppy diskettes please contact either Bette Korber (btk@t10.lanl.gov) or Kersti Rock (karm@t10.lanl.gov) by email or fax ((505) 665-4453). While this publication could take the form of a review or sequence monograph, it is not so conceived. Instead, the literature from which the database is derived has simply been summarized and some elementary computational analyses have been performed upon the data. Interpretation and commentary have been avoided insofar as possible so that the reader can form his or her own judgments concerning the complex information. The exception to this are reviews submitted by experts in areas deemed of particular and basic importance to research involving AIDS viral sequence information. These are included in Part III, and are contributed by scientists with particular expertise in the area of interest. In addition to the general descriptions below of the parts of the compendium, the user should read the individual introductions for each part.

Multivariable analysis of clinical influence factors on liver enhancement of Gd-EOB-DTPA-enhanced 3T MRI

International Nuclear Information System (INIS)

Verloh, N.; Haimerl, M.; Stroszczynski, C.; Fellner, C.; Wiggermann, P.; Zeman, F.; Teufel, A.; Lang, S.

2015-01-01

The purpose of this study was to identify clinical factors influencing Gd-EOB-DTPA liver uptake in patients with healthy liver parenchyma. A total of 124 patients underwent contrast-enhanced MRI with a hepatocyte-specific contrast agent at 3T. T1-weighted volume interpolated breath-hold examination (VIBE) sequences with fat suppression were acquired before and 20 minutes after contrast injection. The relative enhancement (RE) between plain and contrast-enhanced signal intensity was calculated. Simple and multiple linear regression analyses were performed to evaluate clinical factors influencing the relative enhancement. Patients were subdivided into three groups according to their relative liver enhancement (HRE, RE ≥ 100 %; MRE, 100 % > RE > 50 %; NRE, RE ≤ 50 %) and were analyzed according to the relevant risk factors. Simple regression analyses revealed patient age, transaminases (AST, ALT, GGT), liver, spleen and delta-liver volume (the difference between the volumetrically measured liver volume and the estimated liver volume based on body weight) as significant factors influencing relative enhancement. In the multiple analysis the transaminase AST, spleen and delta liver volume remained significant factors influencing relative enhancement. Delta liver volume showed a significant difference between all analyzed groups. Liver enhancement in the hepatobiliary phase depends on a variety of factors. Body weight-adapted administration of Gd-EOB-DTPA may lead to inadequate liver enhancement after 20 minutes especially when the actual liver volume differs from the expected volume.

Human endogenous retrovirus K Gag coassembles with HIV-1 Gag and reduces the release efficiency and infectivity of HIV-1.

Science.gov (United States)

Monde, Kazuaki; Contreras-Galindo, Rafael; Kaplan, Mark H; Markovitz, David M; Ono, Akira

2012-10-01

Human endogenous retroviruses (HERVs), which are remnants of ancestral retroviruses integrated into the human genome, are defective in viral replication. Because activation of HERV-K and coexpression of this virus with HIV-1 have been observed during HIV-1 infection, it is conceivable that HERV-K could affect HIV-1 replication, either by competition or by cooperation, in cells expressing both viruses. In this study, we found that the release efficiency of HIV-1 Gag was 3-fold reduced upon overexpression of HERV-K(CON) Gag. In addition, we observed that in cells expressing Gag proteins of both viruses, HERV-K(CON) Gag colocalized with HIV-1 Gag at the plasma membrane. Furthermore, HERV-K(CON) Gag was found to coassemble with HIV-1 Gag, as demonstrated by (i) processing of HERV-K(CON) Gag by HIV-1 protease in virions, (ii) coimmunoprecipitation of virion-associated HERV-K(CON) Gag with HIV-1 Gag, and (iii) rescue of a late-domain-defective HERV-K(CON) Gag by wild-type (WT) HIV-1 Gag. Myristylation-deficient HERV-K(CON) Gag localized to nuclei, suggesting cryptic nuclear trafficking of HERV-K Gag. Notably, unlike WT HERV-K(CON) Gag, HIV-1 Gag failed to rescue myristylation-deficient HERV-K(CON) Gag to the plasma membrane. Efficient colocalization and coassembly of HIV-1 Gag and HERV-K Gag also required nucleocapsid (NC). These results provide evidence that HIV-1 Gag heteromultimerizes with HERV-K Gag at the plasma membrane, presumably through NC-RNA interaction. Intriguingly, HERV-K Gag overexpression reduced not only HIV-1 release efficiency but also HIV-1 infectivity in a myristylation- and NC-dependent manner. Altogether, these results indicate that Gag proteins of endogenous retroviruses can coassemble with HIV-1 Gag and modulate the late phase of HIV-1 replication.

Proviral amplification of the Gypsy endogenous retrovirus of Drosophila melanogaster involves env-independent invasion of the female germline.

OpenAIRE

Chalvet, F; Teysset, L; Terzian, C; Prud'homme, N; Santamaria, P; Bucheton, A; Pélisson, A

1999-01-01

Gypsy is an infectious endogenous retrovirus of Drosophila melanogaster. The gypsy proviruses replicate very efficiently in the genome of the progeny of females homozygous for permissive alleles of the flamenco gene. This replicative transposition is correlated with derepression of gypsy expression, specifically in the somatic cells of the ovaries of the permissive mothers. The determinism of this amplification was studied further by making chimeric mothers containing different permissive/res...

Diaspora, a large family of Ty3-gypsy retrotransposons in Glycine max, is an envelope-less member of an endogenous plant retrovirus lineage.

Science.gov (United States)

Yano, Sho T; Panbehi, Bahman; Das, Arpita; Laten, Howard M

2005-05-05

The chromosomes of higher plants are littered with retrotransposons that, in many cases, constitute as much as 80% of plant genomes. Long terminal repeat retrotransposons have been especially successful colonizers of the chromosomes of higher plants and examinations of their function, evolution, and dispersal are essential to understanding the evolution of eukaryotic genomes. In soybean, several families of retrotransposons have been identified, including at least two that, by virtue of the presence of an envelope-like gene, may constitute endogenous retroviruses. However, most elements are highly degenerate and are often sequestered in regions of the genome that sequencing projects initially shun. In addition, finding potentially functional copies from genomic DNA is rare. This study provides a mechanism to surmount these issues to generate a consensus sequence that can then be functionally and phylogenetically evaluated. Diaspora is a multicopy member of the Ty3-gypsy-like family of LTR retrotransposons and comprises at least 0.5% of the soybean genome. Although the Diaspora family is highly degenerate, and with the exception of this report, is not represented in the Genbank nr database, a full-length consensus sequence was generated from short overlapping sequences using a combination of experimental and in silico methods. Diaspora is 11,737 bp in length and contains a single 1892-codon ORF that encodes a gag-pol polyprotein. Phylogenetic analysis indicates that it is closely related to Athila and Calypso retroelements from Arabidopsis and soybean, respectively. These in turn form the framework of an endogenous retrovirus lineage whose members possess an envelope-like gene. Diaspora appears to lack any trace of this coding region. A combination of empirical sequencing and retrieval of unannotated Genome Survey Sequence database entries was successfully used to construct a full-length representative of the Diaspora family in Glycine max. Diaspora is presently the

Gold nanodisc arrays as near infrared metal-enhanced fluorescence platforms with tuneable enhancement factors

KAUST Repository

Pang, J.; Theodorou, I. G.; Centeno, A.; Petrov, P. K.; Alford, N. M.; Ryan, M. P.; Xie, F.

2016-01-01

Metal enhanced fluorescence (MEF) is a physical effect through which the near-field interaction of fluorophores with metallic nanoparticles can lead to large fluorescence enhancement. MEF can be exploited in many fluorescence-based biomedical applications, with potentially significant improvement in detection sensitivity and contrast enhancement. Offering lower autofluorescence and minimal photoinduced damage, the development of effective and multifunctional MEF platforms in the near-infrared (NIR) region, is particularly desirable. In this work, the enhancement of NIR fluorescence caused by interaction with regular arrays of cylindrical gold (Au) nanoparticles (nanodiscs), fabricated through nanosphere lithography, is reported. Significant MEF of up to 235 times is obtained, with tuneable enhancement factors. The effect of array structure on fluorescence enhancement is investigated by semi-quantitatively de-convoluting excitation enhancement from emission enhancement, and modelling the local electric field enhancement. By considering arrays of Au nanodiscs with the same extinction maximum, it is shown that the excitation enhancement, due to increased electric field, is not significantly different for the particle sizes and separation distances considered. Rather, it is seen that the emission from the fluorophore is strongly enhanced, and is dependent on the topography, in particular particle size. The results show that the structural characteristics of Au nanodisc arrays can be manipulated to tune their enhancement factor, and hence their sensitivity.

Gold nanodisc arrays as near infrared metal-enhanced fluorescence platforms with tuneable enhancement factors

KAUST Repository

Pang, J.

2016-12-28

Metal enhanced fluorescence (MEF) is a physical effect through which the near-field interaction of fluorophores with metallic nanoparticles can lead to large fluorescence enhancement. MEF can be exploited in many fluorescence-based biomedical applications, with potentially significant improvement in detection sensitivity and contrast enhancement. Offering lower autofluorescence and minimal photoinduced damage, the development of effective and multifunctional MEF platforms in the near-infrared (NIR) region, is particularly desirable. In this work, the enhancement of NIR fluorescence caused by interaction with regular arrays of cylindrical gold (Au) nanoparticles (nanodiscs), fabricated through nanosphere lithography, is reported. Significant MEF of up to 235 times is obtained, with tuneable enhancement factors. The effect of array structure on fluorescence enhancement is investigated by semi-quantitatively de-convoluting excitation enhancement from emission enhancement, and modelling the local electric field enhancement. By considering arrays of Au nanodiscs with the same extinction maximum, it is shown that the excitation enhancement, due to increased electric field, is not significantly different for the particle sizes and separation distances considered. Rather, it is seen that the emission from the fluorophore is strongly enhanced, and is dependent on the topography, in particular particle size. The results show that the structural characteristics of Au nanodisc arrays can be manipulated to tune their enhancement factor, and hence their sensitivity.

Evidence of simian retrovirus type D by polymerase chain reaction.

Science.gov (United States)

Hwa, Christian Z R; Tsai, Sheung Pun; Yee, JoAnn L; Van Rompay, Koen K; Roberts, Jeffrey A

2017-06-01

Over the past few years, there have been reports of finding Simian retrovirus type D (SRV) in macaque colonies where some animals were characterized as antibody positive but virus negative raising questions about how SRV was transmitted or whether there is a variant strain detected by antibody but not polymerase chain reaction (PCR) in current use. We developed a three-round nested PCR assay using degenerate primers targeting the pol gene to detect for SRV serotypes 1-5 and applied this newly validated PCR assay to test macaque DNA samples collected in China from 2010 to 2015. Using the nested PCR assay validated in this study, we found 0.15% of the samples archived on FTA ® cards were positive. The source of SRV infection identified within domestic colonies might have originated from imported macaques. The multiplex nested PCR assay developed here may supplement the current assays for SRV. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Model calculation of the scanned field enhancement factor of CNTs

International Nuclear Information System (INIS)

Ahmad, Amir; Tripathi, V K

2006-01-01

The field enhancement factor of a carbon nanotube (CNT) placed in a cluster of CNTs is smaller than an isolated CNT because the electric field on one tube is screened by neighbouring tubes. This screening depends on the length of the CNTs and the spacing between them. We have derived an expression to compute the field enhancement factor of CNTs under any positional distribution of CNTs using a model of a floating sphere between parallel anode and cathode plates. Using this expression we can compute the field enhancement factor of a CNT in a cluster (non-uniformly distributed CNTs). This expression is used to compute the field enhancement factor of a CNT in an array (uniformly distributed CNTs). Comparison has been shown with experimental results and existing models

Transcriptional Modulation of Human Endogenous Retroviruses in Primary CD4+ T Cells Following Vorinostat Treatment

Directory of Open Access Journals (Sweden)

Cory H. White

2018-04-01

Full Text Available The greatest obstacle to a cure for HIV is the provirus that integrates into the genome of the infected cell and persists despite antiretroviral therapy. A “shock and kill” approach has been proposed as a strategy for an HIV cure whereby drugs and compounds referred to as latency-reversing agents (LRAs are used to “shock” the silent provirus into active replication to permit “killing” by virus-induced pathology or immune recognition. The LRA most utilized to date in clinical trials has been the histone deacetylase (HDAC inhibitor—vorinostat. Potentially, pathological off-target effects of vorinostat may result from the activation of human endogenous retroviruses (HERVs, which share common ancestry with exogenous retroviruses including HIV. To explore the effects of HDAC inhibition on HERV transcription, an unbiased pharmacogenomics approach (total RNA-Seq was used to evaluate HERV expression following the exposure of primary CD4+ T cells to a high dose of vorinostat. Over 2,000 individual HERV elements were found to be significantly modulated by vorinostat, whereby elements belonging to the ERVL family (e.g., LTR16C and LTR33 were predominantly downregulated, in contrast to LTR12 elements of the HERV-9 family, which exhibited the greatest signal, with the upregulation of 140 distinct elements. The modulation of three different LTR12 elements by vorinostat was confirmed by droplet digital PCR along a dose–response curve. The monitoring of LTR12 expression during clinical trials with vorinostat may be indicated to assess the impact of this HERV on the human genome and host immunity.

A soluble envelope protein of endogenous retrovirus (FeLIX) present in serum of domestic cats mediates infection of a pathogenic variant of feline leukemia virus.

Science.gov (United States)

Sakaguchi, Shoichi; Shojima, Takayuki; Fukui, Daisuke; Miyazawa, Takayuki

2015-03-01

T-lymphotropic feline leukemia virus (FeLV-T), a highly pathogenic variant of FeLV, induces severe immunosuppression in cats. FeLV-T is fusion defective because in its PHQ motif, a gammaretroviral consensus motif in the N terminus of an envelope protein, histidine is replaced with aspartate. Infection by FeLV-T requires FeLIX, a truncated envelope protein encoded by an endogenous FeLV, for transactivation of infectivity and Pit1 for binding FeLIX. Although Pit1 is present in most tissues in cats, the expression of FeLIX is limited to certain cells in lymphoid organs. Therefore, the host cell range of FeLV-T was thought to be restricted to cells expressing FeLIX. However, because FeLIX is a soluble factor and is expressed constitutively in lymphoid organs, we presumed it to be present in blood and evaluated its activities in sera of various mammalian species using a pseudotype assay. We demonstrated that cat serum has FeLIX activity at a functional level, suggesting that FeLIX is present in the blood and that FeLV-T may be able to infect cells expressing Pit1 regardless of the expression of FeLIX in vivo. In addition, FeLIX activities in sera were detected only in domestic cats and not in other feline species tested. To our knowledge, this is the first report to prove that a large amount of truncated envelope protein of endogenous retrovirus is circulating in the blood to facilitate the infection of a pathogenic exogenous retrovirus. © 2015 The Authors.

Loss of retrovirus production in JB/RH melanoma cells transfected with H-2Kb and TAP-1 genes.

Science.gov (United States)

Li, M; Xu, F; Muller, J; Huang, X; Hearing, V J; Gorelik, E

1999-01-20

JB/RH1 melanoma cells, as well as other melanomas of C57BL/6 mice (B16 and JB/MS), express a common melanoma-associated antigen (MAA) encoded by an ecotropic melanoma-associated retrovirus (MelARV). JB/RH1 cells do not express the H-2Kb molecules due to down-regulation of the H-2Kb and TAP-1 genes. When JB/RH1 cells were transfected with the H-2Kb and cotransfected with the TAP-1 gene, it resulted in the appearance of H-2Kb molecules and an increase in their immunogenicity, albeit they lost expression of retrovirus-encoded MAA recognized by MM2-9B6 mAb. Loss of MAA was found to result from a complete and stable elimination of ecotropic MelARV production in the H-2Kb/TAP-1-transfected JB/RH1 cells. Northern blot analysis showed no differences in ecotropic retroviral messages in MelARV-producing and -nonproducing melanoma cells, suggesting that loss of MelARV production was not due to down-regulation of MelARV transcription. Southern blot analysis revealed several rearrangements in the proviral DNA of H-2Kb-positive JB/RH1 melanoma cells. Sequence analysis of the ecotropic proviral DNA from these cells showed numerous nucleotide substitutions, some of which resulted in the appearance of a novel intraviral PstI restriction site and the loss of a HindIII restriction site in the pol region. PCR amplification of the proviral DNAs indicates that an ecotropic provirus found in the H-2Kb-positive cells is novel and does not preexist in the parental H-2Kb-negative melanoma cells. Conversely, the ecotropic provirus of the parental JB/RH1 cells was not amplifable from the H-2Kb-positive cells. Our data indicate that stable loss of retroviral production in the H-2Kb/TAP-1-transfected melanoma cells is probably due to the induction of recombination between a productive ecotropic MelARV and a defective nonecotropic provirus leading to the generation of a defective ecotropic provirus and the loss of MelARV production and expression of the retrovirus-encoded MAA. Copyright 1999

Genetic alterations of the long terminal repeat of an ecotropic porcine endogenous retrovirus during passage in human cells

International Nuclear Information System (INIS)

Denner, Joachim; Specke, Volker; Thiesen, Ulla; Karlas, Alexander; Kurth, Reinhard

2003-01-01

Human-tropic porcine endogenous retroviruses (PERV) such as PERV-A and PERV-B can infect human cells and are therefore a potential risk to recipients of xenotransplants. A similar risk is posed by recombinant viruses containing the receptor-binding site of PERV-A and large parts of the genome of the ecotropic PERV-C including its long terminal repeat (LTR). We describe here the unique organization of the PERV-C LTR and its changes during serial passage of recombinant virus in human cells. An increase in virus titer correlated with an increase in LTR length, caused by multiplication of 37-bp repeats containing nuclear factor Y binding sites. Luciferase dual reporter assays revealed a correlation between the number of repeats and the extent of expression. No alterations have been observed in the receptor-binding site, indicating that the increased titer is due to the changes in the LTR. These data indicate that recombinant PERVs generated during infection of human cells can adapt and subsequently replicate with greater efficiency

Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

Science.gov (United States)

Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

2002-11-01

Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

Vaccination directed against the human endogenous retrovirus-K envelope protein inhibits tumor growth in a murine model system.

Science.gov (United States)

Kraus, Benjamin; Fischer, Katrin; Büchner, Sarah M; Wels, Winfried S; Löwer, Roswitha; Sliva, Katja; Schnierle, Barbara S

2013-01-01

Human endogenous retrovirus (HERV) genomes are chromosomally integrated in all cells of an individual. They are normally transcriptionally silenced and transmitted only vertically. Enhanced expression of HERV-K accompanied by the emergence of anti-HERV-K-directed immune responses has been observed in tumor patients and HIV-infected individuals. As HERV-K is usually not expressed and immunological tolerance development is unlikely, it is an appropriate target for the development of immunotherapies. We generated a recombinant vaccinia virus (MVA-HKenv) expressing the HERV-K envelope glycoprotein (ENV), based on the modified vaccinia virus Ankara (MVA), and established an animal model to test its vaccination efficacy. Murine renal carcinoma cells (Renca) were genetically altered to express E. coli beta-galactosidase (RLZ cells) or the HERV-K ENV gene (RLZ-HKenv cells). Intravenous injection of RLZ-HKenv cells into syngenic BALB/c mice led to the formation of pulmonary metastases, which were detectable by X-gal staining. A single vaccination of tumor-bearing mice with MVA-HKenv drastically reduced the number of pulmonary RLZ-HKenv tumor nodules compared to vaccination with wild-type MVA. Prophylactic vaccination of mice with MVA-HKenv precluded the formation of RLZ-HKenv tumor nodules, whereas wild-type MVA-vaccinated animals succumbed to metastasis. Protection from tumor formation correlated with enhanced HERV-K ENV-specific killing activity of splenocytes. These data demonstrate for the first time that HERV-K ENV is a useful target for vaccine development and might offer new treatment opportunities for diverse types of cancer.

Assay of mouse-cell clones for retrovirus p30 protein by use of an automated solid-state radioimmunoassay

International Nuclear Information System (INIS)

Kennel, S.J.; Tnnant, R.W.

1979-01-01

A solid-state radioimmunoassay system has been developed that is useful for automated analysis of samples in microtiter plates. Assays for interspecies and type-specific antigenic determinants of the C-type retrovirus protein, p30, have been used to identify clones of cells producing this protein. This method allows testing of at least 1000 clones a day, making it useful for studies of frequencies of virus protein induction, defective virus production, and formation of recombinant viruses

Endogenous Retroviruses: With Us and Against Us

Science.gov (United States)

Meyer, Thomas J.; Rosenkrantz, Jimi L.; Carbone, Lucia; Chavez, Shawn L.

2017-04-01

Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe the roles ERVs may play in somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

Expression of human adenosine deaminase in mice reconstituted with retrovirus-transduced hematopoietic stem cells

International Nuclear Information System (INIS)

Wilson, J.M.; Danos, O.; Grossman, M.; Raulet, D.H.; Mulligan, R.C.

1990-01-01

Recombinant retroviruses encoding human adenosine deaminase have been used to infect murine hematopoietic stem cells. In bone marrow transplant recipients reconstituted with the genetically modified cells, human ADA was detected in peripheral blood mononuclear cells of the recipients for at least 6 months after transplantation. In animals analyzed in detail 4 months after transplantation, human ADA and proviral sequences were detected in all hematopoietic lineages; in several cases, human ADA activity exceeded the endogenous activity. These studies demonstrate the feasibility of introducing a functional human ADA gene into hematopoietic stem cells and obtaining expression in multiple hematopoietic lineages long after transplantation. This approach should be helpful in designing effective gene therapies for severe combined immunodeficiency syndromes in humans

Novel endogenous retrovirus-derived transcript expressed in the bovine placenta is regulated by WNT signaling.

Science.gov (United States)

Sakurai, Toshihiro; Nakagawa, So; Bai, Hanako; Bai, Rulan; Kusama, Kazuya; Ideta, Atsushi; Aoyagi, Yoshito; Kaneko, Kazuyuki; Iga, Kosuke; Yasuda, Jiro; Miyazawa, Takayuki; Imakawa, Kazuhiko

2017-10-10

Endogenous retroviruses (ERVs) are involved in placentation; perhaps, the most well-known ERV s are the syncytins, actively transcribed env genes involved in cell-cell fusion and possible morphological variations. However, ERVs other than syncytins that play an important role in placental development have not been well characterized. To identify ERV genes expressed during the onset of placentation in the bovine species, we characterized the expression profiles of bovine conceptus transcripts during the peri-attachment period using RNA-seq analysis, and confirming some candidates through real-time PCR. Using in silico and PCR analyses, we identified a novel ERV proviral sequence derived from a gag region, designated bovine endogenous retroviruses (BERV)-K3, containing Gag _p10 and Gag _p24, zinc finger domain. Initial expression of this ERV in bovine conceptuses was on day 20 (day 0 = day of estrus), soon after conceptus attachment to the endometrial epithelium, and its high placental expression was maintained up to the middle of pregnancy. The BERV-K3 transcript was also found in the uterine luminal and glandular epithelia, liver, kidney, intestine, and skin. BERV-K3 is located on chromosome 7 and integrated within LOC100848658 , from which noncoding RNA could be transcribed. Furthermore, the expression of endogenous BERV-K3 in bovine trophoblast cell lines was induced by a WNT agonist, a signaling system common to genes expressed in placentas. These data support the argument that during the evolutionary process, mammals incorporated not only similar ERV sequences, but also ERV s unique to individual species. BERV-K3 is in the latter case, likely providing functions unique to ruminant gestation. © 2017 The Author(s).

Toxicity and efficacy of 2',3'-dideoxycytidine in clinical trials of pigtailed macaques infected with simian retrovirus type 2.

OpenAIRE

Tsai, C C; Follis, K E; Yarnall, M; Blakley, G A

1989-01-01

Four dosing regimens of 2',3'-dideoxycytidine (ddC) were administered intravenously for 10 to 28 days to 18 pigtailed macaques with simian acquired immunodeficiency syndrome. Ten macaques naturally infected with simian acquired immunodeficiency syndrome retrovirus serotype 2 (SRV-2), the etiologic agent of simian acquired immunodeficiency syndrome, received ddC by continuous intravenous infusion or by a daily bolus injection for 10 to 12 days. Another eight macaques that were negative for SRV...

V-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas

International Nuclear Information System (INIS)

Langdon, W.Y.; Klinken, S.P.; Hartley, J.W.; Morse, H.C. III; Ruscetti, S.K.

1989-01-01

Cas NS-1 is an acutely transforming murine retrovirus that induces pre-B and pro-B cell lymphomas. Molecular cloning showed it was generated from the ecotropic Cas-Br-M virus by sequential recombinations with endogenous retroviral sequences and a cellular oncogene. The oncogene sequence shows no homology with known oncogenes but some similarity to the yeast transcriptional activator GCN4. A 100-kDa gag-cbl fusion protein, with no detectable kinase activity, is responsible for the cellular transformation. The cellular homologue of v-cbl, present in mouse and human DNA, is expressed in a range of hemopoietic lineages

Alterations in Mesenteric Lymph Node T Cell Phenotype and Cytokine Secretion are Associated with Changes in Thymocyte Phenotype after LP-BM5 Retrovirus Infection

Directory of Open Access Journals (Sweden)

Maria C. Lopez

2005-01-01

Full Text Available In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5 retrovirus infection were studied. A decrease in the percentage of IL-7+ cells and an increase in the percentage of IL-16+ cells in the MLN indicated that secretion of these cytokines was also altered after LP-BM5 infection. The percentage of MLN T cells expressing IL-7 receptors was significantly reduced, while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine secretion was done in an attempt to understand whether the deregulation of IFN-Υ secretion could be ascribed to a defined cell phenotype, concluding that all T cell subsets studied increased IFN-Υ secretion after retrovirus infection. Finally, thymocyte phenotype was further analyzed trying to correlate changes in thymocyte phenotype with MLN cell phenotype. The results indicated that the increase in single positive either CD4+CD8- or CD4- CD8+ cells was due to accumulation of both immature (CD3- and mature (CD3+ single positive thymocytes. Moreover, single positive mature thymocytes presented a phenotype similar to the phenotype previously seen on MLN T cells. In summary, we can conclude that LP-BM5 uses the immune system to reach the thymus where it interferes with the generation of functionally mature T cells, favoring the development of T cells with an abnormal phenotype. These new T cells are activated to secrete several cytokines that in turn will favor retrovirus replication and inhibit any attempt of the immune system to control infection.

Endogenous Retrovirus ev21 Dose Not Recombine with ALV-J and Induces the Expression of ISGs in the Host.

Science.gov (United States)

Feng, Min; Tan, Yan; Dai, Manman; Li, Yuanfang; Xie, Tingting; Li, Hongmei; Shi, Meiqing; Zhang, Xiquan

2016-01-01

Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Endogenous viruses integrate into host genomes and can recombine with exogenous avian leukosis virus (ALV). In this study, we analyzed the interaction of endogenous retrovirus 21 ( ev21 ) with the ALV-J in late-feathering Chinese yellow chicken. Two ALV-J strains M180 and K243 were isolated from late-feathering and fast-feathering Chinese yellow chicken flocks, respectively. The env gene of the two strains showed 94.2-94.8% nucleotide identity with reference ALV-J strains. Compared with the env gene and the LTR of ev21 and M180, the nucleotide identity of LTR was 69.7% and env gene was 58.4%, respectively, especially the amino acid identity of env gene as low as 14.2%. Phylogenetic analysis of the nucleotide sequence of the env gene and the 3'LTR showed that M180 was closely related to ALV-J, and was located in a distinct group with ev21 in the phylogenetic tree. Using co-immunoprecipitation (co-IP), we next demonstrate that the envelope protein of ev21 does not interact with the M180 envelope protein. We further show that the envelope protein of ev21 cannot activate ALV-J LTR promoter activity using luciferase-reporter assays. qPCR and western blot analysis revealed that envelope protein of endogenous ev21 can facilitate the expression of PKR at 6h post ALV-J infection (hpi) and facilitate the expression of ISG12 and CH25H at 24 hpi. However, the expression of the env gene of M180 strain was not significantly at 6 and 24 hpi. We conclude that there is no evidence of recombination between endogenous retrovirus ev21 and ALV-J strain M180 in late-feathering Chinese yellow chicken, and envelope protein of ev21 can affect the expression of host ISGs, but appears not to influence the replication of ALV-J strain M180. This is the first report of interaction among the endogenous retrovirus ev21, ALV-J and the late-feathering chicken.

Identification and characterization of avian retroviruses in chicken embryo-derived yellow fever vaccines: investigation of transmission to vaccine recipients.

Science.gov (United States)

Hussain, Althaf I; Johnson, Jeffrey A; Da Silva Freire, Marcos; Heneine, Walid

2003-01-01

All currently licensed yellow fever (YF) vaccines are propagated in chicken embryos. Recent studies of chick cell-derived measles and mumps vaccines show evidence of two types of retrovirus particles, the endogenous avian retrovirus (EAV) and the endogenous avian leukosis virus (ALV-E), which originate from the chicken embryonic fibroblast substrates. In this study, we investigated substrate-derived avian retrovirus contamination in YF vaccines currently produced by three manufacturers (YF-vax [Connaught Laboratories], Stamaril [Aventis], and YF-FIOCRUZ [FIOCRUZ-Bio-Manguinhos]). Testing for reverse transcriptase (RT) activity was not possible because of assay inhibition. However, Western blot analysis of virus pellets with anti-ALV RT antiserum detected three distinct RT proteins in all vaccines, indicating that more than one source is responsible for the RTs present in the vaccines. PCR analysis of both chicken substrate DNA and particle-associated RNA from the YF vaccines showed no evidence of the long terminal repeat sequences of exogenous ALV subgroups A to D in any of the vaccines. In contrast, both ALV-E and EAV particle-associated RNA were detected at equivalent titers in each vaccine by RT-PCR. Quantitative real-time RT-PCR revealed 61,600, 348,000, and 1,665,000 ALV-E RNA copies per dose of Stamaril, YF-FIOCRUZ, and YF-vax vaccines, respectively. ev locus-specific PCR testing of the vaccine-associated chicken substrate DNA was positive both for the nondefective ev-12 locus in two vaccines and for the defective ev-1 locus in all three vaccines. Both intact and ev-1 pol sequences were also identified in the particle-associated RNA. To investigate the risks of transmission, serum samples from 43 YF vaccine recipients were studied. None of the samples were seropositive by an ALV-E-based Western blot assay or had detectable EAV or ALV-E RNA sequences by RT-PCR. YF vaccines produced by the three manufacturers all have particles containing EAV genomes and

Overexpression of TGF-β1 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Yong Il; Ryu, Jae-Sung; Yeo, Jee Eun; Choi, Yun Jin; Kim, Yong Sang [Center for Stem Cell and Arthritis Research, Department of Orthopedic Surgery, Yonsei Sarang Hospital, Seoul (Korea, Republic of); Ko, Kinarm [Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul 143-701 (Korea, Republic of); Koh, Yong-Gon, E-mail: yonseranglab@daum.net [Center for Stem Cell and Arthritis Research, Department of Orthopedic Surgery, Yonsei Sarang Hospital, Seoul (Korea, Republic of)

2014-08-08

Highlights: • Continuous TGF-β1 overexpression in hSD-MSCs did not influence their phenotypes. • Retroviral-mediated transduction of TGFB1 in hSD-MSCs enhances cell proliferation. • TGF-β1 overexpression did not effect to adipo- or osteogenic potential of hSD-MSCs. • TGF-β1 overexpression in hSD-MSCs could stimulate and accelerate chondrogenesis. - Abstract: Transforming growth factor-beta (TGF-β) superfamily proteins play a critical role in proliferation, differentiation, and other functions of mesenchymal stem cells (MSCs). During chondrogenic differentiation of MSCs, TGF-β up-regulates chondrogenic gene expression by enhancing the expression of the transcription factor SRY (sex-determining region Y)-box9 (Sox9). In this study, we investigated the effect of continuous TGF-β1 overexpression in human synovium-derived MSCs (hSD-MSCs) on immunophenotype, differentiation potential, and proliferation rate. hSD-MSCs were transduced with recombinant retroviruses (rRV) encoding TGF-β1. The results revealed that continuous overexpression of TGF-β1 did not affect their phenotype as evidenced by flow cytometry and reverse transcriptase PCR (RT-PCR). In addition, continuous TGF-β1 overexpression strongly enhanced cell proliferation of hSD-MSCs compared to the control groups. Also, induction of chondrogenesis was more effective in rRV-TGFB-transduced hSD-MSCs as shown by RT-PCR for chondrogenic markers, toluidine blue staining and glycosaminoglycan (GAG)/DNA ratio. Our data suggest that overexpression of TGF-β1 positively enhances the proliferation and chondrogenic potential of hSD-MSCs.

Overexpression of TGF-β1 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cells

International Nuclear Information System (INIS)

Kim, Yong Il; Ryu, Jae-Sung; Yeo, Jee Eun; Choi, Yun Jin; Kim, Yong Sang; Ko, Kinarm; Koh, Yong-Gon

2014-01-01

Highlights: • Continuous TGF-β1 overexpression in hSD-MSCs did not influence their phenotypes. • Retroviral-mediated transduction of TGFB1 in hSD-MSCs enhances cell proliferation. • TGF-β1 overexpression did not effect to adipo- or osteogenic potential of hSD-MSCs. • TGF-β1 overexpression in hSD-MSCs could stimulate and accelerate chondrogenesis. - Abstract: Transforming growth factor-beta (TGF-β) superfamily proteins play a critical role in proliferation, differentiation, and other functions of mesenchymal stem cells (MSCs). During chondrogenic differentiation of MSCs, TGF-β up-regulates chondrogenic gene expression by enhancing the expression of the transcription factor SRY (sex-determining region Y)-box9 (Sox9). In this study, we investigated the effect of continuous TGF-β1 overexpression in human synovium-derived MSCs (hSD-MSCs) on immunophenotype, differentiation potential, and proliferation rate. hSD-MSCs were transduced with recombinant retroviruses (rRV) encoding TGF-β1. The results revealed that continuous overexpression of TGF-β1 did not affect their phenotype as evidenced by flow cytometry and reverse transcriptase PCR (RT-PCR). In addition, continuous TGF-β1 overexpression strongly enhanced cell proliferation of hSD-MSCs compared to the control groups. Also, induction of chondrogenesis was more effective in rRV-TGFB-transduced hSD-MSCs as shown by RT-PCR for chondrogenic markers, toluidine blue staining and glycosaminoglycan (GAG)/DNA ratio. Our data suggest that overexpression of TGF-β1 positively enhances the proliferation and chondrogenic potential of hSD-MSCs

Determination and applications of enhancement factors for positron and ortho-positronium annihilations

International Nuclear Information System (INIS)

Mitroy, J.

2005-01-01

Electron-positron annihilation rates calculated directly from the electron and positron densities are known to underestimate the true annihilation rate. A correction factor, known as the enhancement factor, allows for the local increase of the electron density around the positron caused by the attractive electron-positron interaction. Enhancement factors are given for positrons annihilating with the 1s electron in H, He + , He, Li 2+ , and Li + . The enhancement factor for a free positron annihilating with He + and He is found to be close to that of ortho-positronium (i.e., Ps in its triplet state) annihilating with these atoms. The enhancement factor for Ps-He scattering is used in conjunction with the known annihilation rate for pickoff annihilation to derive a scattering length of 1.47a 0 for Ps-He scattering. Further, enhancement factors for e + -Ne and e + -Ar annihilation are used in conjunction with the pickoff annihilation rate to estimate scattering lengths of 1.46a 0 for Ps-Ne scattering and 1.75a 0 for Ps-Ar scattering

Minimally invasive esthetic ridge preservation with growth-factor enhanced bone matrix.

Science.gov (United States)

Nevins, Marc L; Said, Sherif

2017-12-28

Extraction socket preservation procedures are critical to successful esthetic implant therapy. Conventional surgical approaches are technique sensitive and often result in alteration of the soft tissue architecture, which then requires additional corrective surgical procedures. This case series report presents the ability of flapless surgical techniques combined with a growth factor-enhanced bone matrix to provide esthetic ridge preservation at the time of extraction for compromised sockets. When considering esthetic dental implant therapy, preservation, or further enhancement of the available tissue support at the time of tooth extraction may provide an improved esthetic outcome with reduced postoperative sequelae and decreased treatment duration. Advances in minimally invasive surgical techniques combined with recombinant growth factor technology offer an alternative for bone reconstruction while maintaining the gingival architecture for enhanced esthetic outcome. The combination of freeze-dried bone allograft (FDBA) and rhPDGF-BB (platelet-derived growth factor-BB) provides a growth-factor enhanced matrix to induce bone and soft tissue healing. The use of a growth-factor enhanced matrix is an option for minimally invasive ridge preservation procedures for sites with advanced bone loss. Further studies including randomized clinical trials are needed to better understand the extent and limits of these procedures. The use of minimally invasive techniques with growth factors for esthetic ridge preservation reduces patient morbidity associated with more invasive approaches and increases the predictability for enhanced patient outcomes. By reducing the need for autogenous bone grafts the use of this technology is favorable for patient acceptance and ease of treatment process for esthetic dental implant therapy. © 2017 Wiley Periodicals, Inc.

Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses.

Directory of Open Access Journals (Sweden)

Jumpei Ito

2017-07-01

Full Text Available Human endogenous retroviruses (HERVs and other long terminal repeat (LTR-type retrotransposons (HERV/LTRs have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs. Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified "HERV/LTR-shared regulatory element (HSRE," defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG, embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2, hematopoietic TFs (e.g., SPI1 (PU1, GATA1/2, and TAL1, and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/. This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into

Conservation of a proteinase cleavage site between an insect retrovirus (gypsy) Env protein and a baculovirus envelope fusion protein

International Nuclear Information System (INIS)

Pearson, Margot N.; Rohrmann, George F.

2004-01-01

The predicted Env protein of insect retroviruses (errantiviruses) is related to the envelope fusion protein of a major division of the Baculoviridae. The highest degree of homology is found in a region that contains a furin cleavage site in the baculovirus proteins and an adjacent sequence that has the properties of a fusion peptide. In this investigation, the homologous region in the Env protein of the gypsy retrovirus of Drosophila melanogaster (DmegypV) was investigated. Alteration of the predicted DmegypV Env proteinase cleavage site from RIAR to AIAR significantly reduced cleavage of Env in both Spodoptera frugiperda (Sf-9) and D. melanogaster (S2) cell lines. When the predicted DmegypV Env cleavage site RIAR was substituted for the cleavage sequence RRKR in the Lymantria dispar nucleopolyhedrovirus fusion protein (LD130) sequence, cleavage of the hybrid LD130 molecules still occurred, although at a reduced level. The conserved 21-amino acid sequence just downstream of the cleavage site, which is thought to be the fusion peptide in LD130, was also characterized. When this sequence from DmegypV Env was substituted for the homologous sequence in LD130, cleavage still occurred, but no fusion was observed in either cell type. In addition, although a DmegypV-Env-green fluorescent protein construct localized to cell membranes, no cell fusion was observed

Retroviruses As Myeloid Cell Riders: What Natural Human Siglec-1 “Knockouts” Tell Us About Pathogenesis

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Javier Martinez-Picado

2017-11-01

Full Text Available Myeloid cells initiate immune responses and are crucial to control infections. In the case of retroviruses, however, myeloid cells also promote pathogenesis by enabling viral dissemination; a process extensively studied in vitro using human immunodeficiency virus type 1 (HIV-1. This viral hijacking mechanism does not rely on productive myeloid cell infection but requires HIV-1 capture via Siglec-1/CD169, a receptor expressed on myeloid cells that facilitates the infection of bystander target cells. Murine retroviruses are also recognized by Siglec-1, and this interaction is required for robust retroviral infection in vivo. Yet, the relative contribution of Siglec-1-mediated viral dissemination to HIV-1 disease progression remains unclear. The identification of human null individuals lacking working copies of a particular gene enables studying how this loss affects disease progression. Moreover, it can reveal novel antiviral targets whose blockade might be therapeutically effective and safe, since finding null individuals in natura uncovers dispensable functions. We previously described a loss-of-function variant in SIGLEC-1. Analysis of a large cohort of HIV-1-infected individuals identified homozygous and heterozygous subjects, whose cells were functionally null or partially defective for Siglec-1 activity in HIV-1 capture and transmission ex vivo. Nonetheless, analysis of the effect of Siglec-1 truncation on progression to AIDS was not conclusive due to the limited cohort size, the lack of complete clinical records, and the restriction to study only off-therapy periods. Here, we review how the study of loss-of-function variants might serve to illuminate the role of myeloid cells in viral pathogenesis in vivo and the challenges ahead.

Comparative Methylation of ERVWE1/Syncytin-1 and Other Human Endogenous Retrovirus LTRs in Placenta Tissues

Science.gov (United States)

Gimenez, Juliette; Montgiraud, Cécile; Oriol, Guy; Pichon, Jean-Philippe; Ruel, Karine; Tsatsaris, Vassilis; Gerbaud, Pascale; Frendo, Jean-Louis; Evain-Brion, Danièle; Mallet, François

2009-01-01

Human endogenous retroviruses (HERVs) are globally silent in somatic cells. However, some HERVs display high transcription in physiological conditions. In particular, ERVWE1, ERVFRDE1 and ERV3, three proviruses of distinct families, are highly transcribed in placenta and produce envelope proteins associated with placenta development. As silencing of repeated elements is thought to occur mainly by DNA methylation, we compared the methylation of ERVWE1 and related HERVs to appreciate whether HERV methylation relies upon the family, the integration site, the tissue, the long terminal repeat (LTR) function or the associated gene function. CpG methylation of HERV-W LTRs in placenta-associated tissues was heterogeneous but a joint epigenetic control was found for ERVWE1 5′LTR and its juxtaposed enhancer, a mammalian apparent LTR retrotransposon. Additionally, ERVWE1, ERVFRDE1 and ERV3 5′LTRs were all essentially hypomethylated in cytotrophoblasts during pregnancy, but showed distinct and stage-dependent methylation profiles. In non-cytotrophoblastic cells, they also exhibited different methylation profiles, compatible with their respective transcriptional activities. Comparative analyses of transcriptional activity and LTR methylation in cell lines further sustained a role for methylation in the control of functional LTRs. These results suggest that HERV methylation might not be family related but copy-specific, and related to the LTR function and the tissue. In particular, ERVWE1 and ERV3 could be developmentally epigenetically regulated HERVs. PMID:19561344

Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone

International Nuclear Information System (INIS)

Adachi, A.; Gendelman, H.E.; Koenig, S.; Folks, T.; Willey, R.; Rabson, A.; Martin, M.A.

1986-01-01

The authors considered an infectious molecular clone of acquired immunodeficiency syndrome-associated retrovirus. Upon transfection, this clone directed the production of infectious virus particles in a wide variety of cells in addition to human T4 cells. The progeny, infectious virions, were synthesized in mouse, mink, monkey, and several human non-T cell lines, indicating the absence of any intracellular obstacle to viral RNA or protein production or assembly. During the course of these studies, a human colon carcinoma cell line, exquisitely sensitive to DNA transfection, was identified

Maintenance of vascular endothelial cell-specific properties after immortalization with an amphotrophic replication-deficient retrovirus containing human papilloma virus 16 E6/E7 DNA

NARCIS (Netherlands)

Fontijn, R.; Hop, C.; Brinkman, H. J.; Slater, R.; Westerveld, A.; van Mourik, J. A.; Pannekoek, H.

1995-01-01

Primary human vascular endothelial cells were immortalized by the integration of a single DNA copy of an amphotrophic, replication-deficient retrovirus containing the E6/E7 genes of human papilloma virus. To date, the resulting cell lines, designated EC-RF7 and EC-RF24, have been cultured for more

Supramolecular Nanofibers Enhance Growth Factor Signaling by Increasing Lipid Raft Mobility

Energy Technology Data Exchange (ETDEWEB)

Newcomb, Christina J.; Sur, Shantanu; Lee, Sungsoo S.; Yu, Jeong Min; Zhou, Yan; Snead, Malcolm L.; Stupp, Samuel I. (NWU); (USC)

2016-04-12

The nanostructures of self-assembling biomaterials have been previously designed to tune the release of growth factors in order to optimize biological repair and regeneration. We report here on the discovery that weakly cohesive peptide nanostructures in terms of intermolecular hydrogen bonding, when combined with low concentrations of osteogenic growth factor, enhance both BMP-2 and Wnt mediated signaling in myoblasts and bone marrow stromal cells, respectively. Conversely, analogous nanostructures with enhanced levels of internal hydrogen bonding and cohesion lead to an overall reduction in BMP-2 signaling. We propose that the mechanism for enhanced growth factor signaling by the nanostructures is related to their ability to increase diffusion within membrane lipid rafts. The phenomenon reported here could lead to new nanomedicine strategies to mediate growth factor signaling for translational targets.

Characterization of an endogenous retrovirus class in elephants and their relatives

Directory of Open Access Journals (Sweden)

Englbrecht Claudia C

2004-10-01

Full Text Available Abstract Background Endogenous retrovirus-like elements (ERV-Ls, primed with tRNA leucine are a diverse group of reiterated sequences related to foamy viruses and widely distributed among mammals. As shown in previous investigations, in many primates and rodents this class of elements has remained transpositionally active, as reflected by increased copy number and high sequence diversity within and among taxa. Results Here we examine whether proviral-like sequences may be suitable molecular probes for investigating the phylogeny of groups known to have high element diversity. As a test we characterized ERV-Ls occurring in a sample of extant members of superorder Uranotheria (Asian and African elephants, manatees, and hyraxes. The ERV-L complement in this group is even more diverse than previously suspected, and there is sequence evidence for active expansion, particularly in elephantids. Many of the elements characterized have protein coding potential suggestive of activity. Conclusions In general, the evidence supports the hypothesis that the complement had a single origin within basal Uranotheria.

Unexpected Diversity and Expression of Avian Endogenous Retroviruses

Science.gov (United States)

Bolisetty, Mohan; Blomberg, Jonas; Benachenhou, Farid; Sperber, Göran; Beemon, Karen

2012-01-01

ABSTRACT Endogenous retroviruses (ERVs) were identified and characterized in three avian genomes to gain insight into early retroviral evolution. Using the computer program RetroTector to detect relatively intact ERVs, we identified 500 ERVs in the chicken genome, 150 in the turkey genome, and 1,200 in the zebra finch genome. Previous studies suggested that endogenous alpharetroviruses were present in chicken genomes. In this analysis, a small number of alpharetroviruses were seen in the chicken and turkey genomes; however, these were greatly outnumbered by beta-like, gamma-like, and alphabeta proviruses. While the avian ERVs belonged to the same major groups as mammalian ERVs, they were more heterogeneous. In particular, the beta-like viruses revealed an evolutionary continuum with the gradual acquisition and loss of betaretroviral markers and a transition from beta to alphabeta and then to alpharetroviruses. Thus, it appears that birds may resemble a melting pot for early ERV evolution. Many of the ERVs were integrated in clusters on chromosomes, often near centromeres. About 25% of the chicken ERVs were in or near cellular transcription units; this is nearly random. The majority of these integrations were in the sense orientation in introns. A higher-than-random number of integrations were >100 kb from the nearest gene. Deep-sequencing studies of chicken embryo fibroblasts revealed that about 20% of the 500 ERVs were transcribed and translated. A subset of these were also transcribed in vivo in chickens, showing tissue-specific patterns of expression. PMID:23073767

Retrovirus XMRV Is Inhibited by Host Proteins and Anti-HIV Drugs AZT, Tenofovir, and Raltegravir | Center for Cancer Research

Science.gov (United States)

A newly discovered retrovirus, XMRV, isolated from prostate cancer tissues for the first time in 2006, has recently been reported in patients with this cancer, as well as in patients with chronic fatigue syndrome (CFS). However, five subsequent studies could not validate these reports. Since XMRV was isolated from the T and B cells of CFS patients, Vinay Pathak and his colleagues in the HIV Drug Resistance Program sought to determine how XMRV was countering intracellular defense mechanisms that inhibit retroviral replication in human cells.

Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

Science.gov (United States)

Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

2016-01-01

Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms

Induction of pluripotency by defined factors

International Nuclear Information System (INIS)

Okita, Keisuke; Yamanaka, Shinya

2010-01-01

Somatic cells can be reprogrammed into pluripotent stem cells by introducing a combination of several transcription factors. The induced pluripotent stem (iPS) cells from a patient's somatic cells could be useful source of cells for drug discovery and cell transplantation therapies. However, most human iPS cells are made by viral vectors, such as retrovirus and lentivirus, which integrate the reprogramming factors into host genomes and may increase the risk of tumor formation. Studies of the mechanisms underlying the reprogramming and establishment of non-integration methods contribute evidence to resolve the safety concerns associated with iPS cells. On the other hand, patient-specific iPS cells have already been established and used for recapitulating disease pathology.

Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

Science.gov (United States)

Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

2013-07-01

Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

(Some) Cellular Mechanisms Influencing the Transcription of Human Endogenous Retrovirus, HERV-Fc1

DEFF Research Database (Denmark)

Laska, Magdalena Janina; Nissen, Kari Konstantin; Nexø, Bjørn Andersen

2013-01-01

DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs) is not well...... investigated. The aim of this study was to investigate the transcriptional potential of HERV-Fc1 proviral 5'LTR in more detail, and examined the specific influence of CpG methylation on this LTR in number of cell lines. Specifically, the role of demethylating chemicals e.g. 5-aza-2' deoxycytidine...... and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza...

Susceptibility of Human Endogenous Retrovirus Type K to Reverse Transcriptase Inhibitors.

Science.gov (United States)

Contreras-Galindo, Rafael; Dube, Derek; Fujinaga, Koh; Kaplan, Mark H; Markovitz, David M

2017-12-01

Human endogenous retroviruses (HERVs) make up 8% of the human genome. The HERV type K (HERV-K) HML-2 (HK2) family contains proviruses that are the most recent entrants into the human germ line and are transcriptionally active. In HIV-1 infection and cancer, HK2 genes produce retroviral particles that appear to be infectious, yet the replication capacity of these viruses and potential pathogenicity has been difficult to ascertain. In this report, we screened the efficacy of commercially available reverse transcriptase inhibitors (RTIs) at inhibiting the enzymatic activity of HK2 RT and HK2 genomic replication. Interestingly, only one provirus, K103, was found to encode a functional RT among those examined. Several nucleoside analogue RTIs (NRTIs) blocked K103 RT activity and consistently inhibited the replication of HK2 genomes. The NRTIs zidovudine (AZT), stavudine (d4T), didanosine (ddI), and lamivudine (3TC), and the nucleotide RTI inhibitor tenofovir (TDF), show efficacy in blocking K103 RT. HIV-1-specific nonnucleoside RTIs (NNRTIs), protease inhibitors (PIs), and integrase inhibitors (IIs) did not affect HK2, except for the NNRTI etravirine (ETV). The inhibition of HK2 infectivity by NRTIs appears to take place at either the reverse transcription step of the viral genome prior to HK2 viral particle formation and/or in the infected cells. Inhibition of HK2 by these drugs will be useful in suppressing HK2 infectivity if these viruses prove to be pathogenic in cancer, neurological disorders, or other diseases associated with HK2. The present studies also elucidate a key aspect of the life cycle of HK2, specifically addressing how they do, and/or did, replicate. IMPORTANCE Endogenous retroviruses are relics of ancestral virus infections in the human genome. The most recent of these infections was caused by HK2. While HK2 often remains silent in the genome, this group of viruses is activated in HIV-1-infected and cancer cells. Recent evidence suggests that these

Infectious Entry Pathway Mediated by the Human Endogenous Retrovirus K Envelope Protein.

Science.gov (United States)

Robinson, Lindsey R; Whelan, Sean P J

2016-01-20

Endogenous retroviruses (ERVs), the majority of which exist as degraded remnants of ancient viruses, comprise approximately 8% of the human genome. The youngest human ERVs (HERVs) belong to the HERV-K(HML-2) subgroup and were endogenized within the past 1 million years. The viral envelope protein (ENV) facilitates the earliest events of endogenization (cellular attachment and entry), and here, we characterize the requirements for HERV-K ENV to mediate infectious cell entry. Cell-cell fusion assays indicate that a minimum of two events are required for fusion, proteolytic processing by furin-like proteases and exposure to acidic pH. We generated an infectious autonomously replicating recombinant vesicular stomatitis virus (VSV) in which the glycoprotein was replaced by HERV-K ENV. HERV-K ENV imparts an endocytic entry pathway that requires dynamin-mediated membrane scission and endosomal acidification but is distinct from clathrin-dependent or macropinocytic uptake pathways. The lack of impediments to the replication of the VSV core in eukaryotic cells allowed us to broadly survey the HERV-K ENV-dictated tropism. Unlike extant betaretroviral envelopes, which impart a narrow species tropism, we found that HERV-K ENV mediates broad tropism encompassing cells from multiple mammalian and nonmammalian species. We conclude that HERV-K ENV dictates an evolutionarily conserved entry pathway and that the restriction of HERV-K to primate genomes reflects downstream stages of the viral replication cycle. Approximately 8% of the human genome is of retroviral origin. While many of those viral genomes have become inactivated, some copies of the most recently endogenized human retrovirus, HERV-K, can encode individual functional proteins. Here, we characterize the envelope protein (ENV) of the virus to define how it mediates infection of cells. We demonstrate that HERV-K ENV undergoes a proteolytic processing step and triggers membrane fusion in response to acidic pH--a strategy

Human Retroviruses and AIDS. A compilation and analysis of nucleic acid and amino acid sequences: I--II; III--V

Energy Technology Data Exchange (ETDEWEB)

Myers, G.; Korber, B. [eds.] [Los Alamos National Lab., NM (United States); Wain-Hobson, S. [ed.] [Laboratory of Molecular Retrovirology, Pasteur Inst.; Smith, R.F. [ed.] [Baylor Coll. of Medicine, Houston, TX (United States). Dept. of Pharmacology; Pavlakis, G.N. [ed.] [National Cancer Inst., Frederick, MD (United States). Cancer Research Facility

1993-12-31

This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts that it comprises: (I) HIV and SIV Nucleotide Sequences; (II) Amino Acid Sequences; (III) Analyses; (IV) Related Sequences; and (V) Database Communications. Information within all the parts is updated at least twice in each year, which accounts for the modes of binding and pagination in the compendium.

Reply to comment on 'Model calculation of the scanned field enhancement factor of CNTs'

International Nuclear Information System (INIS)

Ahmad, Amir; Tripathi, V K

2010-01-01

In the paper (Ahmad and Tripathi 2006 Nanotechnology 17 3798), we derived an expression to compute the field enhancement factor of CNTs under any positional distribution of CNTs by using the model of a floating sphere between parallel anode and cathode plates. Using this expression we can compute the field enhancement factor of a CNT in a cluster (non-uniformly distributed CNTs). This expression was used to compute the field enhancement factor of a CNT in an array (uniformly distributed CNTs). We used an approximation to calculate the field enhancement factor. Hence, our expressions are correct in that assumption only. Zhbanov et al (2010 Nanotechnology 21 358001) suggest a correction that can calculate the field enhancement factor without using the approximation. Hence, this correction can improve the applicability of this model. (reply)

Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

DEFF Research Database (Denmark)

Brudek, T; Christensen, T; Hansen, H J

2008-01-01

Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...... effect on cell-mediated immune responses, which tend to be higher in MS patients in comparison with healthy individuals. Here, we investigate whether these synergistic immune responses are reflected in changes in the production of proinflammatory cytokines. Using enzyme-linked immunosorbent assays...

Susceptibility of recombinant porcine endogenous retrovirus reverse transcriptase to nucleoside and non-nucleoside inhibitors.

Science.gov (United States)

Wilhelm, M; Fishman, J A; Pontikis, R; Aubertin, A M; Wilhelm, F X

2002-12-01

Transplantation of organs, tissues or cells from pigs to humans could be a potential solution to the shortage of human organs for transplantation. Porcine endogenous retroviruses (PERVs) remain a major safety concern for porcine xenotransplantation. Thus, finding drugs that could be used as virological prophylaxis (or therapy) against PERV replication would be desirable. One of the most effective ways to block retroviral multiplication is to inhibit the enzyme reverse transcriptase (RT) which catalyzes the reverse transcription of viral RNA to proviral double-stranded DNA. We report here the cloning and expression of PERV RT and its susceptibility to several inhibitors. Our data demonstrate PERV susceptibility in vitro to the triphosphorylated nucleoside analog of zidovudine (AZT) and to ddGTP and to a lesser extent to ddTTP but almost no susceptibility to the non-nucleoside RT inhibitors tested.

Detection of porcine endogenous retrovirus (PERV) using highly specific antisera against Gag and Env

International Nuclear Information System (INIS)

Fischer, Nicole; Krach, Ulrich; Niebert, Marcus; Toenjes, Ralf R.

2003-01-01

Porcine endogenous retroviruses (PERV) are considered an obstacle to the safe use of cells, tissues, and organs from pigs in the course of xenotransplantation. Thus, the detection of viral proteins and of a potential PERV infection is of major interest. Recently, we have published the generation of a highly specific antiserum directed against the nucleocapsid (p10) of PERV (Xenotransplantation 7 (2000), 221). Here we present new peptide-antisera specific to the capsid protein (p30) and the surface molecule of PERV class B (SU, gp70(B)) as well as the transmembrane moiety of the envelope protein (TM, p15E) of PERV which showed functionality in several immunological assays, such as immunoblots, immunofluorescence, and immunogold staining. Thus, these antisera can be used as tools for the identification of viral proteins in basic research as well as clinical trials

Effective Factors in Enhancing School Managers' Job Motivation

Directory of Open Access Journals (Sweden)

S. Mahmoud Mirzamani

2011-10-01

Full Text Available "nObjective: This study examines the effective factors in enhancing school managers' job motivation from viewpoint of school mangers, teachers, education department managerial and staff experts in teaching, and also identifies and prioritizes each of these factors and indicators. "nMethod: For selecting a representative sample and increasing measurement precision, 587 people were selected using classified random sampling. The measurement tool was a 79-questionnaire made by the researcher. The questionnaire was collected using motivation theories and observing the findings of previous researches. Then, according to the three-stage Delphi technique, the questionnaire was sent to experts in education. The reliability of instruments was measured by calculating Cronbach's Alpha coefficient, and total reliability of the test was 0.99; the validity of the instrument was assessed by factor analysis (Construct Validity and its load factor was 0.4 which was high. "nResults: The results from factor analysis shows that the effective factors in enhancing managers' job motivation are as follows: self- actualization (51% including 28 indices; social factor (7/9% including 22 indices; self-esteem (3.2% including 17 indices; job desirable features (2.2% including 4 indices; physiologic (1.8% including 4 indices; and job richness (1.6% including 4 indices. "nConclusions: The results show that the six mentioned factors determine 68% of the total variance of managers' motivation.

Enhancing China’s energy security: Determining influential factors and effective strategic measures

International Nuclear Information System (INIS)

Ren, Jingzheng; Sovacool, Benjamin K.

2014-01-01

Highlights: • The most influential factors affecting China’s energy security are identified. • Fuzzy AHP is used to quantify the importance of influential factors. • Strategic measures for enhancing China’s energy security are prioritized. • Fuzzy AHP is used to determine the priorities of the strategic measures. - Abstract: This study investigates the most influential factors affecting China’s energy security. It also identifies the most effective strategic measures for enhancing it. Fuzzy AHP has been used to determine weights for ranking the importance of Chinese energy security factors, and it has also been used to determine the priorities of the strategic measures with respect to enhancing those same factors. The study argues that a low proportion of renewable energy penetration is the most severe factor threatening China’s energy security, and that conducting research and development on energy technologies and improving energy efficiency is the most salient, positive, and necessary strategic measure

The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses.

Science.gov (United States)

Hummel, Barbara; Hansen, Erik C; Yoveva, Aneliya; Aprile-Garcia, Fernando; Hussong, Rebecca; Sawarkar, Ritwick

2017-03-01

Understanding how genotypes are linked to phenotypes is important in biomedical and evolutionary studies. The chaperone heat-shock protein 90 (HSP90) buffers genetic variation by stabilizing proteins with variant sequences, thereby uncoupling phenotypes from genotypes. Here we report an unexpected role of HSP90 in buffering cis-regulatory variation affecting gene expression. By using the tripartite-motif-containing 28 (TRIM28; also known as KAP1)-mediated epigenetic pathway, HSP90 represses the regulatory influence of endogenous retroviruses (ERVs) on neighboring genes that are critical for mouse development. Our data based on natural variations in the mouse genome show that genes respond to HSP90 inhibition in a manner dependent on their genomic location with regard to strain-specific ERV-insertion sites. The evolutionary-capacitor function of HSP90 may thus have facilitated the exaptation of ERVs as key modifiers of gene expression and morphological diversification. Our findings add a new regulatory layer through which HSP90 uncouples phenotypic outcomes from individual genotypes.

The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases.

Science.gov (United States)

Brodziak, Andrzej; Ziółko, Ewa; Muc-Wierzgoń, Małgorzata; Nowakowska-Zajdel, Ewa; Kokot, Teresa; Klakla, Katarzyna

2012-06-01

This paper presents a new, recently formulated theory, which concerns the etiopathological process of autoimmune diseases. This theory takes into account the existence in the human genome, since approximately 40 million years, of so-called human endogenous retroviruses (HERVs), which are transmitted to descendants "vertically" by the germ cells. It was recently established that these generally silent sequences perform some physiological roles, but occasionally become active and influence the development of some chronic diseases like diabetes, some neoplasms, chronic diseases of the nervous system (eg, sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short synopsis of immunological processes involved in the pathogenesis of autoimmune diseases, such as molecular mimicry, epitope spreading and activation of the superantigen. We then focus on experimental findings related to systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and some diseases of hepar and otorhinal tissues. We conclude the outline of this new model of the development of chronic diseases and indicate the conclusions important for the teaching of the basis of pathology.

Lymphoma, Koala Retrovirus Infection and Reproductive Chlamydiosis in a Koala (Phascolarctos cinereus).

Science.gov (United States)

Fabijan, J; Woolford, L; Lathe, S; Simmons, G; Hemmatzadeh, F; Trott, D J; Speight, N

Koala retrovirus (KoRV) infection, thought to be associated with lymphoid neoplasia, and Chlamydia pecorum-related ocular and urogenital disease are both highly prevalent in eastern Australian koala (Phascolarctos cinereus) populations. However, in South Australian koalas, little is known about KoRV infection and C. pecorum-associated disease. We report the first South Australian case of lymphoma in a KoRV-A-positive female koala also affected by severe reproductive chlamydiosis. The koala was from the Mount Lofty Ranges population and was presented with hindlimb lameness. Clinical examination identified right stifle crepitus, enlarged superficial lymph nodes and paraovarian cysts. Necropsy examination revealed extensive cartilage degeneration and loss over the medial femoral condyle, solid femoral bone marrow, mesenteric and ovarian tumours, paraovarian cysts and purulent metritis. Histopathology confirmed lymphoma in the bone marrow, mesenteric lymph nodes and ovary, with infiltration and parenchymal effacement in the pancreas, adrenal glands and other tissues. Lymphoma, KoRV and chlamydiosis are being investigated further in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reassessing SERS enhancement factors: using thermodynamics to drive substrate design.

Science.gov (United States)

Guicheteau, J A; Tripathi, A; Emmons, E D; Christesen, S D; Fountain, Augustus W

2017-12-04

Over the past 40 years fundamental and application research into Surface-Enhanced Raman Scattering (SERS) has been explored by academia, industry, and government laboratories. To date however, SERS has achieved little commercial success as an analytical technique. Researchers are tackling a variety of paths to help break through the commercial barrier by addressing the reproducibility in both the SERS substrates and SERS signals as well as continuing to explore the underlying mechanisms. To this end, investigators use a variety of methodologies, typically studying strongly binding analytes such as aromatic thiols and azarenes, and report SERS enhancement factor calculations. However a drawback of the traditional SERS enhancement factor calculation is that it does not yield enough information to understand substrate reproducibility, application potential with another analyte, or the driving factors behind the molecule-metal interaction. Our work at the US Army Edgewood Chemical Biological Center has focused on these questions and we have shown that thermodynamic principles play a key role in the SERS response and are an essential factor in future designs of substrates and applications. This work will discuss the advantages and disadvantages of various experimental techniques used to report SERS enhancement with planar SERS substrates and present our alternative SERS enhancement value. We will report on three types of analysis scenarios that all yield different information concerning the effectiveness of the SERS substrate, practical application of the substrate, and finally the thermodynamic properties of the substrate. We believe that through this work a greater understanding for designing substrates will be achieved, one that is based on both thermodynamic and plasmonic properties as opposed to just plasmonic properties. This new understanding and potential change in substrate design will enable more applications for SERS based methodologies including targeting

Enhancing China’s Energy Security: Determining Influential Factors and Effective Strategic Measures

DEFF Research Database (Denmark)

Ren, Jingzheng; Sovacool, Benjamin

2014-01-01

This study investigates the most influential factors affecting China’s energy security. It also identifies the most effective strategic measures for enhancing it. Fuzzy AHP has been used to determine weights for ranking the importance of Chinese energy security factors, and it has also been used...... to determine the priorities of the strategic measures with respect to enhancing those same factors. The study argues that a low proportion of renewable energy penetration is the most severe factor threatening China’s energy security, and that conducting research and development on energy technologies...

Induction of pluripotency by defined factors

Energy Technology Data Exchange (ETDEWEB)

Okita, Keisuke, E-mail: okita@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507 (Japan); Yamanaka, Shinya [Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507 (Japan); Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507 (Japan); Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi 332-0012 (Japan); Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158 (United States)

2010-10-01

Somatic cells can be reprogrammed into pluripotent stem cells by introducing a combination of several transcription factors. The induced pluripotent stem (iPS) cells from a patient's somatic cells could be useful source of cells for drug discovery and cell transplantation therapies. However, most human iPS cells are made by viral vectors, such as retrovirus and lentivirus, which integrate the reprogramming factors into host genomes and may increase the risk of tumor formation. Studies of the mechanisms underlying the reprogramming and establishment of non-integration methods contribute evidence to resolve the safety concerns associated with iPS cells. On the other hand, patient-specific iPS cells have already been established and used for recapitulating disease pathology.

Expression patterns of endogenous avian retrovirus ALVE1 and its response to infection with exogenous avian tumour viruses.

Science.gov (United States)

Hu, Xuming; Zhu, Wenqi; Chen, Shihao; Liu, Yangyang; Sun, Zhen; Geng, Tuoyu; Song, Chengyi; Gao, Bo; Wang, Xiaoyan; Qin, Aijian; Cui, Hengmi

2017-01-01

Endogenous retroviruses (ERVs) are genomic elements that are present in a wide range of vertebrates and have been implicated in a variety of human diseases, including cancer. However, the characteristic expression patterns of ERVs, particularly in virus-induced tumours, is not fully clear. DNA methylation was analysed by bisulfite pyrosequencing, and gene expression was analysed by RT-qPCR. In this study, we first found that the endogenous avian retrovirus ALVE1 was highly expressed in some chicken tissues (including the heart, bursa, thymus, and spleen) at 2 days of age, but its expression was markedly decreased at 35 days of age. In contrast, the CpG methylation level of ALVE1 was significantly lower in heart and bursa at 2 days than at 35 days of age. Moreover, we found that the expression of ALVE1 was significantly inhibited in chicken embryo fibroblast cells (CEFs) and MSB1 cells infected with avian leukosis virus subgroup J (ALVJ) and reticuloendotheliosis virus (REV) at the early stages of infection. In contrast, the expression of the ALVE1 env gene was significantly induced in CEFs and MSB1 cells infected with Marek's disease virus (MDV). However, the methylation and expression levels of the ALVE1 long terminal repeat (LTR) did not show obvious alterations in response to viral infection. The present study revealed the expression patterns of ALVE1 in a variety of chicken organs and tissues and in chicken cells in response to avian tumour virus infection. These findings may be of significance for understanding the role and function of ERVs that are present in the host genome.

Human cytomegalovirus (HCMV) induces human endogenous retrovirus (HERV) transcription.

Science.gov (United States)

Assinger, Alice; Yaiw, Koon-Chu; Göttesdorfer, Ingmar; Leib-Mösch, Christine; Söderberg-Nauclér, Cecilia

2013-11-12

Emerging evidence suggests that human cytomegalovirus (HCMV) is highly prevalent in tumours of different origin. This virus is implied to have oncogenic and oncomodulatory functions, through its ability to control host gene expression. Human endogenous retroviruses (HERV) are also frequently active in tumours of different origin, and are supposed to contribute as cofactors to cancer development. Due to the high prevalence of HCMV in several different tumours, and its ability to control host cell gene expression, we sought to define whether HCMV may affect HERV transcription. Infection of 3 established cancer cell lines, 2 primary glioblastoma cells, endothelial cells from 3 donors and monocytes from 4 donors with HCMV (strains VR 1814 or TB40/F) induced reverse transcriptase (RT) activity in all cells tested, but the response varied between donors. Both, gammaretrovirus-related class I elements HERV-T, HERV-W, HERV-F and ERV-9, and betaretrovirus-related class II elements HML-2 - 4 and HML-7 - 8, as well as spuma-virus related class III elements of the HERV-L group were up-regulated in response to HCMV infection in GliNS1 cells. Up-regulation of HERV activity was more pronounced in cells harbouring active HCMV infection, but was also induced by UV-inactivated virus. The effect was only slightly affected by ganciclovir treatment and was not controlled by the IE72 or IE86 HCMV genes. Within this brief report we show that HCMV infection induces HERV transcriptional activity in different cell types.

An effective method for the quantitative detection of porcine endogenous retrovirus in pig tissues.

Science.gov (United States)

Zhang, Peng; Yu, Ping; Wang, Wei; Zhang, Li; Li, Shengfu; Bu, Hong

2010-05-01

Xenotransplantation shows great promise for providing a virtually limitless supply of cells, tissues, and organs for a variety of therapeutical procedures. However, the potential of porcine endogenous retrovirus (PERV) as a human-tropic pathogen, particularly as a public health risk, is a major concern for xenotransplantation. This study focus on the detection of copy number in various tissues and organs in Banna Minipig Inbreed (BMI) from 2006 to 2007 in West China Hospital, Sichuan University. Real-time quantitative polymerase chain reaction (SYBR Green I) was performed in this study. The results showed that the pol gene had the most copy number in tissues compared with gag, envA, and envB. Our experiment will offer a rapid and accurate method for the detection of the copy number in various tissues and was especially suitable for the selection of tissues or organs in future clinical xenotransplantation.

Identification of an algal carbon fixation-enhancing factor extracted from Paramecium bursaria.

Science.gov (United States)

Kato, Yutaka; Imamura, Nobutaka

2011-01-01

The green ciliate Paramecium bursaria contains several hundred symbiotic Chlorella species. We previously reported that symbiotic algal carbon fixation is enhanced by P. bursaria extracts and that the enhancing factor is a heat-stable, low-molecular-weight, water-soluble compound. To identify the factor, further experiments were carried out. The enhancing activity remained even when organic compounds in the extract were completely combusted at 700 degrees C, suggesting that the factor is an inorganic substance. Measurement of the major cations, K+, Ca2+, and Mg2+, by an electrode and titration of the extract resulted in concentrations of 0.90 mM, 0.55 mM, and 0.21 mM, respectively. To evaluate the effect of these cations, a mixture of the cations at the measured concentrations was prepared, and symbiotic algal carbon fixation was measured in the solution. The results demonstrated that the fixation was enhanced to the same extent as with the P. bursaria extract, and thus this mixture of K+, Ca2+, and Mg2+ was concluded to be the carbon fixation-enhancing factor. There was no effect of the cation mixture on free-living C. vulgaris. Comparison of the cation concentrations of nonsymbiotic and symbiotic Paramecium extracts revealed that the concentrations of K+ and Mg2+ in nonsymbiotic Paramecium extracts were too low to enhance symbiotic algal carbon fixation, suggesting that symbiotic P. bursaria provide suitable cation conditions for photosynthesis to its symbiotic Chlorella.

Control of RFM strain endogenous retrovirus in RFM mouse cells

International Nuclear Information System (INIS)

Tennant, R.W.; Otten, J.A.; Wang, T.W.; Liou, R.S.; Brown, A.; Yang, W.K.

1983-01-01

RFM/Un mice express an endogenous type C retrovirus throughout their life span in many tissues; primary or established embryo fibroblast cell cultures do not express a virus but can be induced by exposure to 5-iodo-2'-deoxyuridine. All of our sources yielded a single ecotropic virus (RFV) which appeared to be related more closely to the endogenous N-tropic virus (WN1802N) of BALB/c mice than to Gross leukemia virus on the basis of two-dimensional gel electropherograms of virion proteins. No xenotropic or recombinant viruses were isolated by cocultivation techniques. RFV is N-tropic, and RFM/Un cells possess the Fv-1/sup n/ allele, as indicated by restriction of B-tropic virus and susceptibility to Gross strain N-tropic virus. However, RFM cells are highly resistant to RFV and other endogenous N-tropic viruses. This resistance is expressed by two-hit titration kinetics and by inhibition of viral linear duplex DNA formation. This is similar to the effects of the Fv-1 locus, but preliminary work has shown no apparent genetic linkage between the two restrictions. The relative strength of the restriction, the presence of a single class of ecotropic virus, and the absence of recombinant viruses suggest that in RFM mice virus is expressed only in cells in which it is induced and not by cell-to-cell transmission

Diminished humoral responses against and reduced gene expression levels of human endogenous retrovirus-K (HERV-K) in psoriasis.

Science.gov (United States)

Gupta, Rashmi; Michaud, Henri-Alexandre; Zeng, Xue; Debbaneh, Maya; Arron, Sarah T; Jones, R Brad; Ormsby, Christopher E; Nixon, Douglas F; Liao, Wilson

2014-09-16

Psoriasis is a multifactorial, chronic disease of skin affecting 2-3% of the world's population. Genetic studies of psoriasis have identified a number of susceptibility genes that are involved in anti-viral immunity. Furthermore, physiological studies have also found an increase in anti-viral proteins in psoriatic skin. These findings suggest the presence of an anti-viral state in psoriatic skin. However, the triggers for this anti-viral cascade and its consequences for host immunity are not known. Endogenous retroviruses have previously been described in many autoimmune diseases including psoriasis. In the present study we examined the humoral immune response against human endogenous retrovirus-K (HERV-K) proteins and the cutaneous expression levels of multiple HERV-K genes in psoriasis patients and healthy controls. In psoriatic sera we observed a significant decrease in IgM response against three HERV-K proteins: Env surface unit (SU), Env transmembrane protein (TM), and Gag capsid (CA) in comparison to sera obtained from blood bank healthy controls. A decrease in IgG response was also observed against CA. Furthermore, using quantitative RT-PCR we observed a decrease in the expression of HERV-K Env, Gag, Pol and Rec as well as ERV-9 genes in lesional psoriatic skin as compared to healthy skin. Together, our results suggest that the pro-inflammatory, anti-viral state in psoriasis is associated with diminished expression of HERV-K gene transcripts and a concomitant decrease in humoral responses to HERV-K. Our results indicate that a simple model where continuous, minimally changing HERV-K expression serves as an antigenic trigger in psoriasis might not be correct and further studies are needed to decipher the possible relationship between psoriasis and HERVs.

Natural killer cells recognize friend retrovirus-infected erythroid progenitor cells through NKG2D-RAE-1 interactions In Vivo.

Science.gov (United States)

Ogawa, Tatsuya; Tsuji-Kawahara, Sachiyo; Yuasa, Takae; Kinoshita, Saori; Chikaishi, Tomomi; Takamura, Shiki; Matsumura, Haruo; Seya, Tsukasa; Saga, Toshihiko; Miyazawa, Masaaki

2011-06-01

Natural killer (NK) cells function as early effector cells in the innate immune defense against viral infections and also participate in the regulation of normal and malignant hematopoiesis. NK cell activities have been associated with early clearance of viremia in experimental simian immunodeficiency virus and clinical human immunodeficiency virus type 1 (HIV-1) infections. We have previously shown that NK cells function as major cytotoxic effector cells in vaccine-induced immune protection against Friend virus (FV)-induced leukemia, and NK cell depletion totally abrogates the above protective immunity. However, how NK cells recognize retrovirus-infected cells remains largely unclear. The present study demonstrates a correlation between the expression of the products of retinoic acid early transcript-1 (RAE-1) genes in target cells and their susceptibility to killing by NK cells isolated from FV-infected animals. This killing was abrogated by antibodies blocking the NKG2D receptor in vitro. Further, the expression of RAE-1 proteins on erythroblast surfaces increased early after FV inoculation, and administration of an RAE-1-blocking antibody resulted in increased spleen infectious centers and exaggerated pathology, indicating that FV-infected erythroid cells are recognized by NK cells mainly through the NKG2D-RAE-1 interactions in vivo. Enhanced retroviral replication due to host gene-targeting resulted in markedly increased RAE-1 expression in the absence of massive erythroid cell proliferation, indicating a direct role of retroviral replication in RAE-1 upregulation.

12th international conference on human retrovirology: HTLV and related retroviruses

Directory of Open Access Journals (Sweden)

Lairmore Michael D

2005-10-01

Full Text Available Abstract The 12th International Conference on Human Retrovirology: HTLV and Related Retroviruses, was held at the Half Moon Hotel in Montego Bay, Jamaica, from June 22nd to June 25th 2005. The scientific conference, sponsored by the International Retrovirology Association, is held biennially at rotating international venues around the world. The meeting brings together basic scientists, epidemiologists and clinical researchers to discuss findings to prevent HTLV infection or develop new therapies against HTLV-mediated diseases. The Association fosters the education and training of young scientists to bring new approaches to the complex problems of HTLV research, such as translational research to bring findings from the laboratory into clinical trials that benefit HTLV-infected patients. The breadth and quality of research presentations and workshops at the 12th International Conference indicate that these goals are being accomplished. As HTLV research enters its third decade a new generation of scientists face many challenges. However, HTLV scientists and clinicians displayed exciting new approaches and discoveries during plenary talks and poster sessions. The conference encouraged research in HTLV infections and disease, fostered collaborations, and stimulated new partnerships between clinicians and scientists to encourage clinical trials and novel therapeutic interventions.

Epigenetic interplay between mouse endogenous retroviruses and host genes.

Science.gov (United States)

Rebollo, Rita; Miceli-Royer, Katharine; Zhang, Ying; Farivar, Sharareh; Gagnier, Liane; Mager, Dixie L

2012-10-03

Transposable elements are often the targets of repressive epigenetic modifications such as DNA methylation that, in theory, have the potential to spread toward nearby genes and induce epigenetic silencing. To better understand the role of DNA methylation in the relationship between transposable elements and genes, we assessed the methylation state of mouse endogenous retroviruses (ERVs) located near genes. We found that ERVs of the ETn/MusD family show decreased DNA methylation when near transcription start sites in tissues where the nearby gene is expressed. ERVs belonging to the IAP family, however, are generally heavily methylated, regardless of the genomic environment and the tissue studied. Furthermore, we found full-length ETn and IAP copies that display differential DNA methylation between their two long terminal repeats (LTRs), suggesting that the environment surrounding gene promoters can prevent methylation of the nearby LTR. Spreading from methylated ERV copies to nearby genes was rarely observed, with the regions between the ERVs and genes apparently acting as a boundary, enriched in H3K4me3 and CTCF, which possibly protects the unmethylated gene promoter. Furthermore, the flanking regions of unmethylated ERV copies harbor H3K4me3, consistent with spreading of euchromatin from the host gene toward ERV insertions. We have shown that spreading of DNA methylation from ERV copies toward active gene promoters is rare. We provide evidence that genes can be protected from ERV-induced heterochromatin spreading by either blocking the invasion of repressive marks or by spreading euchromatin toward the ERV copy.

A universal formula for the field enhancement factor

Science.gov (United States)

Biswas, Debabrata

2018-04-01

The field enhancement factor (FEF) is an important quantity in field emission calculations since the tunneling electron current depends very sensitively on its magnitude. The exact dependence of FEF on the emitter height h, the radius of curvature at the apex Ra, as well as the shape of the emitter base are still largely unknown. In this work, a universal formula for the field enhancement factor is derived for a single emitter. It depends on the ratio h/Ra and has the form γ a = ( 2 h / R a ) / [ α 1 ln ( 4 h / R a ) - α 2 ] , where α1 and α2 depend on the charge distribution on the emitter. Numerical results show that a simpler form γ a = ( 2 h / R a ) / [ ln ( 4 h / R a ) - α ] is equally valid with α depending on the emitter-base. Thus, for the hyperboloid, conical, and ellipsoid emitters, the value of α is 0, 0.88, and 2, while for the cylindrical base, α ≃ 2.6.

Infection with koala retrovirus subgroup B (KoRV-B), but not KoRV-A, is associated with chlamydial disease in free-ranging koalas (Phascolarctos cinereus).

Science.gov (United States)

Waugh, Courtney A; Hanger, Jonathan; Loader, Joanne; King, Andrew; Hobbs, Matthew; Johnson, Rebecca; Timms, Peter

2017-03-09

The virulence of chlamydial infection in wild koalas is highly variable between individuals. Some koalas can be infected (PCR positive) with Chlamydia for long periods but remain asymptomatic, whereas others develop clinical disease. Chlamydia in the koala has traditionally been studied without regard to coinfection with other pathogens, although koalas are usually subject to infection with koala retrovirus (KoRV). Retroviruses can be immunosuppressive, and there is evidence of an immunosuppressive effect of KoRV in vitro. Originally thought to be a single endogenous strain, a new, potentially more virulent exogenous variant (KoRV-B) was recently reported. We hypothesized that KoRV-B might significantly alter chlamydial disease outcomes in koalas, presumably via immunosuppression. By studying sub-groups of Chlamydia and KoRV infected koalas in the wild, we found that neither total KoRV load (either viraemia or proviral copies per genome), nor chlamydial infection level or strain type, was significantly associated with chlamydial disease risk. However, PCR positivity with KoRV-B was significantly associated with chlamydial disease in koalas (p = 0.02961). This represents an example of a recently evolved virus variant that may be predisposing its host (the koala) to overt clinical disease when co-infected with an otherwise asymptomatic bacterial pathogen (Chlamydia).

Measurement of the linewidth enhancement factor based on nonlinear polarization rotation of semiconductor optical amplifier.

Science.gov (United States)

Liu, Guodong; Wu, Chongqing; Wang, Fu; Zhang, Tianyong; Shang, Chao; Gao, Kaiqiang

2015-06-01

A simple measurement scheme of the linewidth enhancement factor based on the nonlinear polarization rotation of a semiconductor optical amplifier is proposed. Considering the polarization dependent gain, the relationship between the linewidth enhancement factor and the Stokes vector was derived theoretically. It is proven that the linewidth enhancement factor can be calculated directly from the Stokes parameters without any other assistant measurement system. The results demonstrate that the linewidth enhancement factor varies in a small range from 10.5 to 8.5 for TE mode and from 8.2 to 5.8 for TM mode, respectively, when the input optical power varies from 50 μW to 1 mW and the bias current varies from 90 to 170 mA.

Enhanced/Synthetic Vision Systems - Human factors research and implications for future systems

Science.gov (United States)

Foyle, David C.; Ahumada, Albert J.; Larimer, James; Sweet, Barbara T.

1992-01-01

This paper reviews recent human factors research studies conducted in the Aerospace Human Factors Research Division at NASA Ames Research Center related to the development and usage of Enhanced or Synthetic Vision Systems. Research discussed includes studies of field of view (FOV), representational differences of infrared (IR) imagery, head-up display (HUD) symbology, HUD advanced concept designs, sensor fusion, and sensor/database fusion and evaluation. Implications for the design and usage of Enhanced or Synthetic Vision Systems are discussed.

B-lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus

DEFF Research Database (Denmark)

Munch, M; Møller-Larsen, A; Christensen, T

1995-01-01

with MS who had a reactivated Epstein-Barr virus (EBV) infection. Both LCLs were found by EM to produce RVLP and EBV particles. Reverse transcriptase (RT) assays were positive in purified viral material from both LCLs. To substantiate these findings we initiated an intensified culturing procedure and were......On several occasions we have observed retrovirus-like particles (RVLPs) by transmission electron microscopy (EM) of cultured T cells from a patient with MS. Later we established spontaneously formed B-lymphoblastoid cell lines (LCLs) from a patient with an MS-like disease and from another patient...

HIV-1 Infection of Primary CD4+ T Cells Regulates the Expression of Specific Human Endogenous Retrovirus HERV-K (HML-2) Elements.

Science.gov (United States)

Young, George R; Terry, Sandra N; Manganaro, Lara; Cuesta-Dominguez, Alvaro; Deikus, Gintaras; Bernal-Rubio, Dabeiba; Campisi, Laura; Fernandez-Sesma, Ana; Sebra, Robert; Simon, Viviana; Mulder, Lubbertus C F

2018-01-01

Endogenous retroviruses (ERVs) occupy extensive regions of the human genome. Although many of these retroviral elements have lost their ability to replicate, those whose insertion took place more recently, such as the HML-2 group of HERV-K elements, still retain intact open reading frames and the capacity to produce certain viral RNA and/or proteins. Transcription of these ERVs is, however, tightly regulated by dedicated epigenetic control mechanisms. Nonetheless, it has been reported that some pathological states, such as viral infections and certain cancers, coincide with ERV expression, suggesting that transcriptional reawakening is possible. HML-2 elements are reportedly induced during HIV-1 infection, but the conserved nature of these elements has, until recently, rendered their expression profiling problematic. Here, we provide comprehensive HERV-K HML-2 expression profiles specific for productively HIV-1-infected primary human CD4 + T cells. We combined enrichment of HIV-1 infected cells using a reporter virus expressing a surface reporter for gentle and efficient purification with long-read single-molecule real-time sequencing. We show that three HML-2 proviruses-6q25.1, 8q24.3, and 19q13.42-are upregulated on average between 3- and 5-fold in HIV-1-infected CD4 + T cells. One provirus, HML-2 12q24.33, in contrast, was repressed in the presence of active HIV replication. In conclusion, this report identifies the HERV-K HML-2 loci whose expression profiles differ upon HIV-1 infection in primary human CD4 + T cells. These data will help pave the way for further studies on the influence of endogenous retroviruses on HIV-1 replication. IMPORTANCE Endogenous retroviruses inhabit big portions of our genome. Moreover, although they are mainly inert, some of the evolutionarily younger members maintain the ability to express both RNA and proteins. We have developed an approach using long-read single-molecule real-time (SMRT) sequencing that produces long reads that

The Related Transcriptional Enhancer Factor-1 Isoform, TEAD4216, Can Repress Vascular Endothelial Growth Factor Expression in Mammalian Cells

Science.gov (United States)

Appukuttan, Binoy; McFarland, Trevor J.; Stempel, Andrew; Kassem, Jean B.; Hartzell, Matthew; Zhang, Yi; Bond, Derek; West, Kelsey; Wilson, Reid; Stout, Andrew; Pan, Yuzhen; Ilias, Hoda; Robertson, Kathryn; Klein, Michael L.; Wilson, David; Smith, Justine R.; Stout, J. Timothy

2012-01-01

Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4216, which represses VEGF promoter activity. The TEAD4216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4216 isoform can competitively repress the stimulatory activity of the TEAD4434 and TEAD4148 enhancers. Synthesis of the native VEGF165 protein and cellular proliferation is suppressed by the TEAD4216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases. PMID:22761647

Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers

Science.gov (United States)

Sérandour, Aurélien A.; Avner, Stéphane; Percevault, Frédéric; Demay, Florence; Bizot, Maud; Lucchetti-Miganeh, Céline; Barloy-Hubler, Frédérique; Brown, Myles; Lupien, Mathieu; Métivier, Raphaël; Salbert, Gilles; Eeckhoute, Jérôme

2011-01-01

Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established. Here, we have analyzed on a genomic-scale enhancers that recruit FOXA1, a pioneer transcription factor that triggers transcriptional competency of these cis-regulatory sites. Importantly, we found that FOXA1 binds to genomic regions showing local DNA hypomethylation and that its cell-type-specific recruitment to chromatin is linked to differential DNA methylation levels of its binding sites. Using neural differentiation as a model, we showed that induction of FOXA1 expression and its subsequent recruitment to enhancers is associated with DNA demethylation. Concomitantly, histone H3 lysine 4 methylation is induced at these enhancers. These epigenetic changes may both stabilize FOXA1 binding and allow for subsequent recruitment of transcriptional regulatory effectors. Interestingly, when cloned into reporter constructs, FOXA1-dependent enhancers were able to recapitulate their cell type specificity. However, their activities were inhibited by DNA methylation. Hence, these enhancers are intrinsic cell-type-specific regulatory regions of which activities have to be potentiated by FOXA1 through induction of an epigenetic switch that includes notably DNA demethylation. PMID:21233399

Contribution of the Retrovirus Epidemiology Donor Study (REDS to research on blood transfusion safety in Brazil

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Paula Loureiro

2014-04-01

Full Text Available The Retrovirus Epidemiology Donor Study (REDS program was established in the United States in 1989 with the purpose of increasing blood transfusion safety in the context of the HIV/AIDS and human T-lymphotropic virus epidemics. REDS and its successor, REDS-II were at first conducted in the US, then expanded in 2006 to include international partnerships with Brazil and China. In 2011, a third wave of REDS renamed the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III was launched. This seven-year research program focuses on both blood banking and transfusion medicine research in the United States of America, Brazil, China, and South Africa. The main goal of the international programs is to reduce and prevent the transmission of HIV/AIDS and other known and emerging infectious agents through transfusion, and to address research questions aimed at understanding global issues related to the availability of safe blood. This article describes the contribution of REDS-II to transfusion safety in Brazil. Articles published from 2010 to 2013 are summarized, including database analyses to characterize blood donors, deferral rates, and prevalence, incidence and residual risk of the main blood-borne infections. Specific studies were developed to understand donor motivation, the impact of the deferral questions, risk factors and molecular surveillance among HIV-positive donors, and the natural history of Chagas disease. The purpose of this review is to disseminate the acquired knowledge and briefly summarize the findings of the REDS-II studies conducted in Brazil as well as to introduce the scope of the REDS-III program that is now in progress and will continue through 2018.

Enhancing the NCSU PULSTAR reactor control room with human factors considerations

International Nuclear Information System (INIS)

Glover, B.L.; Pupons, D.E.; Perez, P.B.

1993-01-01

The North Carolina PULSTAR research reactor was constructed to support teaching, training, and research. The training provided is not limited to academic students but encompasses plant operators, managers, engineers, designers, and supporting organizations in the nuclear industry. Our facility is under-going design changes to maximize teaching effectiveness and continued safe operation by providing current technology in the control room. The opportunity for the enhancements is a result of the generosity of neighboring utilities and the US Department of Energy instrumentation upgrade funds. Our objective, to provide a control room environment that conforms to selected industry practices, required human factors input. A human factors course, offered jointly between the industrial engineering and the psychology departments, included the PULSTAR control room enhancement as a case study

Induction and characterization of a replication competent cervid endogenous gammaretrovirus (CrERV) from mule deer cells

Czech Academy of Sciences Publication Activity Database

Fábryová, Helena; Hron, Tomáš; Kabickova, H.; Poss, M.; Elleder, Daniel

2015-01-01

Roč. 485, November (2015), s. 96-103 ISSN 0042-6822 R&D Projects: GA MŠk(CZ) LK11215 Institutional support: RVO:68378050 Keywords : Endogenous retrovirus * Retrovirus interference * Xenotropism Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.200, year: 2015

Human endogenous retrovirus expression is inversely related with the up-regulation of interferon-inducible genes in the skin of patients with lichen planus.

Science.gov (United States)

Nogueira, Marcelle Almeida de Sousa; Gavioli, Camila Fátima Biancardi; Pereira, Nátalli Zanete; de Carvalho, Gabriel Costa; Domingues, Rosana; Aoki, Valéria; Sato, Maria Notomi

2015-04-01

Lichen planus (LP) is a common inflammatory skin disease of unknown etiology. Reports of a common transactivation of quiescent human endogenous retroviruses (HERVs) support the connection of viruses to the disease. HERVs are ancient retroviral sequences in the human genome and their transcription is often deregulated in cancer and autoimmune diseases. We explored the transcriptional activity of HERV sequences as well as the antiviral restriction factor and interferon-inducible genes in the skin from LP patients and healthy control (HC) donors. The study included 13 skin biopsies from patients with LP and 12 controls. Real-time PCR assay identified significant decrease in the HERV-K gag and env mRNA expression levels in LP subjects, when compared to control group. The expressions of HERV-K18 and HERV-W env were also inhibited in the skin of LP patients. We observed a strong correlation between HERV-K gag with other HERV sequences, regardless the down-modulation of transcripts levels in LP group. In contrast, a significant up-regulation of the cytidine deaminase APOBEC 3G (apolipoprotein B mRNA-editing), and the GTPase MxA (Myxovirus resistance A) mRNA expression level was identified in the LP skin specimens. Other transcript expressions, such as the master regulator of type I interferon-dependent immune responses, STING (stimulator of interferon genes) and IRF-7 (interferon regulatory factor 7), IFN-β and the inflammassome NALP3, had increased levels in LP, when compared to HC group. Our study suggests that interferon-inducible factors, in addition to their role in innate immunity against exogenous pathogens, contribute to the immune control of HERVs. Evaluation of the balance between HERV and interferon-inducible factor expression could possibly contribute to surveillance of inflammatory/malignant status of skin diseases.

Sludge pretreatment chemistry evaluation: Enhanced sludge washing separation factors

International Nuclear Information System (INIS)

Colton, N.G.

1995-03-01

This report presents the work conducted in Fiscal Year 1994 by the Sludge Pretreatment Chemistry Evaluation Subtask for the Tank Waste Remediation System (TWRS) Tank Waste Treatment Science Task. The main purpose of this task, is to provide the technical basis and scientific understanding to support TWRS baseline decisions and actions, such as the development of an enhanced sludge washing process to reduce the volume of waste that will require high-level waste (HLW) vitrification. One objective within the Sludge Pretreatment Chemistry Evaluation Subtask was to establish wash factors for various SST (single-shell tank) sludges. First, analytical data were compiled from existing tank waste characterization reports. These data were summarized on tank-specific worksheets that provided a uniform format for reviewing and comparing data, as well as the means to verify whether the data set for each tank was complete. Worksheets were completed for 27 SST wastes. The analytical water wash data provided tank-specific information about the fraction of each component that dissolves with water, i.e., an estimate of tank-specific wash factors for evaluating tank-by-tank processing. These wash data were then used collectively to evaluate some of the wash factors that are assumed for the overall SST waste inventory; specifically, wash factors for elements that would be found primarily in sludges. The final step in this study was to incorporate the characterization and wash factor data into a spreadsheet that provides insight into the effect of enhanced sludge washing on individual tank sludges as well as for groups of sludges that may be representative of different waste types. Spreadsheet results include the estimated mass and percentage of each element that would be removed with washing and leaching. Furthermore, estimated compositions are given of the final wash and leach streams and residual solids, in terms of both concentration and dry weight percent

Factors enhancing learning possibilities in digital workshops

Directory of Open Access Journals (Sweden)

Christian Kobbernagel

2014-05-01

Full Text Available This article presents a study of processes supporting student learning possibilities in digital workshops planned and held at art museums in Denmark. The investigation aims to provide insights into factors enhancing learning possibilities, including the educator’s dialogic performance, experiences of art, and perceived qualities of digital content creation processes in art museum education workshops. To address the research question of what conditional and processual factors can be said to support learning possibilities, a model was developed on the basis of fieldwork and theories of media education, art pedagogy and motivation. The model was then analyzed using structural equation modelling (SEM on data collected (N= 502 after workshops in two museums. The results suggest that the dialogic performance of museum educators, a positive art experience and positive perceptions of working with digital media are factors that strongly support student participation and reflection – although to various degrees. The findings also show that, in cases in which students are disinterested and see little value in participating during the workshop, this amotivation is likely to be lower when their art experiences and their perceptions of the media production process are positive. 

Factors enhancing learning possibilities in digital workshops

Directory of Open Access Journals (Sweden)

Christian Kobbernagel

2014-06-01

Full Text Available This article presents a study of processes supporting student learning possibilities in digital workshops planned and held at art museums in Denmark. The investigation aims to provide insights into factors enhancing learning possibilities, including the educator’s dialogic performance, experiences of art, and perceived qualities of digital content creation processes in art museum education workshops. To address the research question of what conditional and processual factors can be said to support learning possibilities, a model was developed on the basis of fieldwork and theories of media education, art pedagogy and motivation. The model was then analyzed using structural equation modelling (SEM on data collected (N= 502 after workshops in two museums. The results suggest that the dialogic performance of museum educators, a positive art experience and positive perceptions of working with digital media are factors that strongly support student participation and reflection – although to various degrees. The findings also show that, in cases in which students are disinterested and see little value in participating during the workshop, this amotivation is likely to be lower when their art experiences and their perceptions of the media production process are positive.

Cross- and Co-Packaging of Retroviral RNAs and Their Consequences

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Lizna M. Ali

2016-10-01

Full Text Available Retroviruses belong to the family Retroviridae and are ribonucleoprotein (RNP particles that contain a dimeric RNA genome. Retroviral particle assembly is a complex process, and how the virus is able to recognize and specifically capture the genomic RNA (gRNA among millions of other cellular and spliced retroviral RNAs has been the subject of extensive investigation over the last two decades. The specificity towards RNA packaging requires higher order interactions of the retroviral gRNA with the structural Gag proteins. Moreover, several retroviruses have been shown to have the ability to cross-/co-package gRNA from other retroviruses, despite little sequence homology. This review will compare the determinants of gRNA encapsidation among different retroviruses, followed by an examination of our current understanding of the interaction between diverse viral genomes and heterologous proteins, leading to their cross-/co-packaging. Retroviruses are well-known serious animal and human pathogens, and such a cross-/co-packaging phenomenon could result in the generation of novel viral variants with unknown pathogenic potential. At the same time, however, an enhanced understanding of the molecular mechanisms involved in these specific interactions makes retroviruses an attractive target for anti-viral drugs, vaccines, and vectors for human gene therapy.

Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder.

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Yoshihisa Yamano

Full Text Available BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1 is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL. The pathogenesis of HAM/TSP is known to be as follows: HTLV-1-infected T cells trigger a hyperimmune response leading to neuroinflammation. However, the HTLV-1-infected T cell subset that plays a major role in the accelerated immune response has not yet been identified. PRINCIPAL FINDINGS: Here, we demonstrate that CD4(+CD25(+CCR4(+ T cells are the predominant viral reservoir, and their levels are increased in HAM/TSP patients. While CCR4 is known to be selectively expressed on T helper type 2 (Th2, Th17, and regulatory T (Treg cells in healthy individuals, we demonstrate that IFN-gamma production is extraordinarily increased and IL-4, IL-10, IL-17, and Foxp3 expression is decreased in the CD4(+CD25(+CCR4(+ T cells of HAM/TSP patients as compared to those in healthy individuals, and the alteration in function is specific to this cell subtype. Notably, the frequency of IFN-gamma-producing CD4(+CD25(+CCR4(+Foxp3(- T cells is dramatically increased in HAM/TSP patients, and this was found to be correlated with disease activity and severity. CONCLUSIONS: We have defined a unique T cell subset--IFN-gamma(+CCR4(+CD4(+CD25(+ T cells--that is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system.

Induction of complex immune responses and strong protection against retrovirus challenge by adenovirus-based immunization depends on the order of vaccine delivery.

Science.gov (United States)

Kaulfuß, Meike; Wensing, Ina; Windmann, Sonja; Hrycak, Camilla Patrizia; Bayer, Wibke

2017-02-06

In the Friend retrovirus mouse model we developed potent adenovirus-based vaccines that were designed to induce either strong Friend virus GagL 85-93 -specific CD8 + T cell or antibody responses, respectively. To optimize the immunization outcome we evaluated vaccination strategies using combinations of these vaccines. While the vaccines on their own confer strong protection from a subsequent Friend virus challenge, the simple combination of the vaccines for the establishment of an optimized immunization protocol did not result in a further improvement of vaccine effectivity. We demonstrate that the co-immunization with GagL 85-93 /leader-gag encoding vectors together with envelope-encoding vectors abrogates the induction of GagL 85-93 -specific CD8 + T cells, and in successive immunization protocols the immunization with the GagL 85-93 /leader-gag encoding vector had to precede the immunization with an envelope encoding vector for the efficient induction of GagL 85-93 -specific CD8 + T cells. Importantly, the antibody response to envelope was in fact enhanced when the mice were adenovirus-experienced from a prior immunization, highlighting the expedience of this approach. To circumvent the immunosuppressive effect of envelope on immune responses to simultaneously or subsequently administered immunogens, we developed a two immunizations-based vaccination protocol that induces strong immune responses and confers robust protection of highly Friend virus-susceptible mice from a lethal Friend virus challenge.

Assessing Input Enhancement as Positive Factor and Its Impact on L2 Vocabulary Learning

Science.gov (United States)

Motlagh, Seyyed Fariborz Pishdadi; Nasab, Mahdiyeh Seyed Beheshti

2015-01-01

Input enhancement's role to promote learners' awareness in L2 contexts has caused a tremendous amount of research. Conspicuously, by regarding all aspects of input enhancement, the study aimed to find out how differently many kinds of input enhancement factors such as bolding, underlining, and capitalizing impact on L2 learners' vocabulary…

Impact of Contextual Factors and Substance Characteristics on Perspectives toward Cognitive Enhancement

OpenAIRE

Sattler, Sebastian; Forlini, Cynthia; Racine, ?ric; Sauer, Carsten

2013-01-01

Enhancing cognitive performance with substances--especially prescription drugs--is a fiercely debated topic among scholars and in the media. The empirical basis for these discussions is limited, given that the actual nature of factors that influence the acceptability of and willingness to use cognitive enhancement substances remains unclear. In an online factorial survey, contextual and substance-specific characteristics of substances that improve academic performance were varied experimental...

Impact of contextual factors and substance characteristics on perspectives toward cognitive enhancement.

Directory of Open Access Journals (Sweden)

Sebastian Sattler

Full Text Available Enhancing cognitive performance with substances--especially prescription drugs--is a fiercely debated topic among scholars and in the media. The empirical basis for these discussions is limited, given that the actual nature of factors that influence the acceptability of and willingness to use cognitive enhancement substances remains unclear. In an online factorial survey, contextual and substance-specific characteristics of substances that improve academic performance were varied experimentally and presented to respondents. Students in four German universities rated their willingness to use and moral acceptance of different substances for cognitive enhancement. We found that the overall willingness to use performance enhancing substances is low. Most respondents considered the use of these substances as morally unacceptable. Situational influences such as peer pressure, policies concerning substance use, relative performance level of peers, but also characteristics of the substance, such as perceptions of substance safety, shape the willingness and acceptability of using a substance to enhance academic performance. Among the findings is evidence of a contagion effect meaning that the willingness was higher when the respondents have more CE drug users in their social network. We also found deterrence effects from strong side effects of using the substance, as well as from policy regulations and sanctions. Regulations might activate social norms against usage and sanctions can be seen as costly to users. Moreover, enhancement substances seem to be most tempting to low performers to catch up with others compared to high performers. By identifying contextual factors and substance characteristics influencing the willingness and acceptability of cognitive enhancers, policy approaches could consider these insights to better manage the use of such substances.

Impact of contextual factors and substance characteristics on perspectives toward cognitive enhancement.

Science.gov (United States)

Sattler, Sebastian; Forlini, Cynthia; Racine, Eric; Sauer, Carsten

2013-01-01

Enhancing cognitive performance with substances--especially prescription drugs--is a fiercely debated topic among scholars and in the media. The empirical basis for these discussions is limited, given that the actual nature of factors that influence the acceptability of and willingness to use cognitive enhancement substances remains unclear. In an online factorial survey, contextual and substance-specific characteristics of substances that improve academic performance were varied experimentally and presented to respondents. Students in four German universities rated their willingness to use and moral acceptance of different substances for cognitive enhancement. We found that the overall willingness to use performance enhancing substances is low. Most respondents considered the use of these substances as morally unacceptable. Situational influences such as peer pressure, policies concerning substance use, relative performance level of peers, but also characteristics of the substance, such as perceptions of substance safety, shape the willingness and acceptability of using a substance to enhance academic performance. Among the findings is evidence of a contagion effect meaning that the willingness was higher when the respondents have more CE drug users in their social network. We also found deterrence effects from strong side effects of using the substance, as well as from policy regulations and sanctions. Regulations might activate social norms against usage and sanctions can be seen as costly to users. Moreover, enhancement substances seem to be most tempting to low performers to catch up with others compared to high performers. By identifying contextual factors and substance characteristics influencing the willingness and acceptability of cognitive enhancers, policy approaches could consider these insights to better manage the use of such substances.

Ultrasound-enhanced bioscouring of greige cotton: regression analysis of process factors

Science.gov (United States)

Ultrasound-enhanced bioscouring process factors for greige cotton fabric are examined using custom experimental design utilizing statistical principles. An equation is presented which predicts bioscouring performance based upon percent reflectance values obtained from UV-Vis measurements of rutheniu...

Gain-dependent linewidth enhancement factor in the quantum dot structures

Energy Technology Data Exchange (ETDEWEB)

Kim, Kyoung Chan; Han, Il Ki; Lee, Jung Il [Nano Device Research Center, Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of); Kim, Tae Geun, E-mail: hikoel@kist.re.kr, E-mail: tgkim1@korea.ac.kr [School of Electrical Engineering, Korea University, Seoul 136-701 (Korea, Republic of)

2010-04-02

We measured the linewidth enhancement factor ({alpha} factor) of InAs quantum dot (QD) laser diodes (LDs) with two different QD structures. One is a normal QD LD with the same energy bandgap for each active QD layer, while the other is chirped with different energy bandgaps. The differential gain of the chirped InAs QD LDs is found to be about five times smaller than that of normal InAs QD LDs, whereas no overall wavelength shift with injection currents is observed in both QD LDs. The {alpha} factor is approximately five times higher in the chirped InAs QD LDs than in the normal InAs QD LDs. This relatively large {alpha} factor in the chirped InAs QD LDs is attributed to the asymmetrical, wide inhomogeneous gain profile.

Transcription factor and bone marrow stromal cells in osseointegration of dental implants

Directory of Open Access Journals (Sweden)

SG Yan

2018-05-01

Full Text Available Titanium implants are widely used in dental clinics and orthopaedic surgery. However, bone formation surrounding the implant is relatively slow after inserting the implant. The current study assessed the effects of bone marrow stromal cells (BMSCs with forced expression of special AT-rich sequence-binding protein 2 (SATB2 on the osseointegration of titanium implants. To determine whether SATB2 overexpression in BMSCs can enhance the osseointegration of implants, BMSCs were infected with the retrovirus encoding Satb2 (pBABE-Satb2 and were locally applied to bone defects before implanting the titanium implants in the mouse femur. Seven and twenty-one days after implantation, the femora were isolated for immunohistochemical (IHC staining, haematoxylin eosin (H&E staining, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR, and micro-computed tomography (μCT analysis. IHC staining analysis revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone tissue surrounding the implant. Histological analysis showed that SATB2-overexpressing BMSCs significantly enhanced new bone formation and bone-to-implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins in the implantation sites. μCT analysis demonstrated that SATB2-overexpressing BMSCs significantly increased the density of the newly formed bone surrounding the implant 3 weeks post-operatively. These results conclude that local delivery of SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium implants. These results provide support for future pharmacological and clinical applications of SATB2, which accelerates bone regeneration around titanium implants.

The related transcriptional enhancer factor-1 isoform, TEAD4(216, can repress vascular endothelial growth factor expression in mammalian cells.

Directory of Open Access Journals (Sweden)

Binoy Appukuttan

Full Text Available Increased cellular production of vascular endothelial growth factor (VEGF is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4 protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4(216, which represses VEGF promoter activity. The TEAD4(216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE, which is the sequence critical to hypoxia inducible factor (HIF-mediated effects. The TEAD4(216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4(216 isoform can competitively repress the stimulatory activity of the TEAD4(434 and TEAD4(148 enhancers. Synthesis of the native VEGF(165 protein and cellular proliferation is suppressed by the TEAD4(216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4(216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases.

Suministro de antirretrovirales en Argentina: Programa Nacional de Lucha contra los Retrovirus del Humano, SIDA y ETS Antiretroviral drug supply in Argentina: National Program to Combat Human Retroviruses, AIDS, and STDs

Directory of Open Access Journals (Sweden)

Marisel Colautti

2009-01-01

Full Text Available OBJETIVOS: Evaluar el circuito de suministro de antirretrovirales (ARV dentro del Programa Nacional de Lucha contra los Retrovirus del Humano, SIDA y ETS, mediante indicadores de desempeño, y recuperar la perspectiva de actores involucrados en el circuito de provisión. Se busca mejorar las acciones programáticas satisfaciendo las necesidades de los pacientes. MÉTODOS: En el servicio de farmacia de dos hospitales de Rosario, Argentina, de abril a septiembre de 2005 se llevó a cabo una investigación evaluativa con un abordaje cuantitativo, mediante indicadores y basado en fuentes secundarias, y otro cualitativo, con entrevistas semiestructuradas. RESULTADOS: Los indicadores revelan el impacto de las interrupciones en la provisión de ARV desde el Programa (nivel central y la acumulación de stock en el nivel local para paliar esas faltas. Los cambios de tratamiento con ARV representan más de 50% de las prescripciones. El cumplimiento en el retiro de ARV se aleja del valor de referencia. Los entrevistados describieron estrategias alternativas para superar dificultades de comunicación entre niveles, acumular stock, garantizar disponibilidad y acortar tiempos de espera; se establecieron acuerdos informales ante la falta de normativas y la escasez de recursos humanos; las instancias jurisdiccionales (central, intermedia y local o municipal suman dificultades, y se reconocen esfuerzos del nivel local para mejorar la gestión. CONCLUSIONES: Estos hallazgos pueden ser el punto de partida para la construcción de propuestas que involucren equipos de trabajo afectados en el circuito de provisión en su totalidad, a fin de lograr una descentralización efectiva, en congruencia con el papel rector que le corresponde necesariamente al Programa.OBJECTIVES: To evaluate the supply cycle of antiretroviral (ARV drugs, overseen by the National Program to Combat Human Retroviruses, AIDS, and STDs, through its order fulfillment indicators, and to obtain input

Domestic Wood Products Manufacturing Trends and Factors to Enhance Competitiveness

Science.gov (United States)

Urs Buehlmann; Matthew Bumgardner; Albert Schuler; Rich Christianson; Rich Christianson

2003-01-01

There is little question that imports have captured a substantial portion of the domestic furniture market. However, there is much speculation and concern as to the future of this and related industries. This study sought to obtain industry perspectives of trends in domestic manufacturing and importing, and to identify factors that can enhance domestic competitiveness...

Low-temperature thermoelectric power factor enhancement by controlling nanoparticle size distribution.

Science.gov (United States)

Zebarjadi, Mona; Esfarjani, Keivan; Bian, Zhixi; Shakouri, Ali

2011-01-12

Coherent potential approximation is used to study the effect of adding doped spherical nanoparticles inside a host matrix on the thermoelectric properties. This takes into account electron multiple scatterings that are important in samples with relatively high volume fraction of nanoparticles (>1%). We show that with large fraction of uniform small size nanoparticles (∼1 nm), the power factor can be enhanced significantly. The improvement could be large (up to 450% for GaAs) especially at low temperatures when the mobility is limited by impurity or nanoparticle scattering. The advantage of doping via embedded nanoparticles compared to the conventional shallow impurities is quantified. At the optimum thermoelectric power factor, the electrical conductivity of the nanoparticle-doped material is larger than that of impurity-doped one at the studied temperature range (50-500 K) whereas the Seebeck coefficient of the nanoparticle doped material is enhanced only at low temperatures (∼50 K).

Use of polyethyleneimine polymer in cell culture as attachment factor and lipofection enhancer.

Science.gov (United States)

Vancha, Ajith R; Govindaraju, Suman; Parsa, Kishore V L; Jasti, Madhuri; González-García, Maribel; Ballestero, Rafael P

2004-10-15

Several cell lines and primary cultures benefit from the use of positively charged extracellular matrix proteins or polymers that enhance their ability to attach to culture plates. Polyethyleneimine is a positively charged polymer that has gained recent attention as a transfection reagent. A less known use of this cationic polymer as an attachment factor was explored with several cell lines. Polyethyleneimine compared favorably to traditional attachment factors such as collagen and polylysine. PC-12 and HEK-293 cells plated on dishes coated with polyethyleneimine showed a homogeneous distribution of cells in the plate, demonstrating strong cell adhesion that survived washing procedures. The polymer could also be used to enhance the adherence and allow axonal outgrowth from zebrafish retinal explants. The effects of this coating agent on the transfection of loosely attaching cell lines were studied. Pre-coating with polyethyleneimine had the effect of enhancing the transfection yield in procedures using lipofection reagents. Polyethyleneimine is an effective attachment factor for weakly anchoring cell lines and primary cells. Its use in lipofection protocols makes the procedures more reliable and increases the yield of expressed products with commonly used cell lines such as PC-12 and HEK-293 cells.

Common cause failure: enhancing defenses against root cause and coupling factor

Energy Technology Data Exchange (ETDEWEB)

Kaushik, Poorva; Kim, Sok Chul [KINS, Daejeon (Korea, Republic of)

2016-10-15

A Common Cause Failure(CCF) event refers to a specific class of dependent events that result from co-existence of two main factors: Susceptibility of components to fail or become unavailable due to particular root cause of failure, and coupling factor coupling mechanism) that creates the condition for multiple components getting affected. PSA (Probabilistic Safety Assessment) operating experience of Nuclear Power Plants have demonstrated that dependent events such as CCF events are major contributor to risk during operation. From cost-benefit consideration, putting significant design modifications in place to prevent CCF would not be desirable in terms of risk management regulatory effectiveness and efficiency. The aim of this study was to propose feasible defenses against CCF from cost benefit consideration to enhance the safety. This study provides the CDM and CFDM of EDG. Defenses employed against cause and coupling factor can be easily employed in operation and maintenance programme of NPP and are not an additional cost burden. Such enhancement of defense against the CCF can give a modest improvement in CDF. This approach is specifically helpful in plants that are already under operation and significant modifications are not economically feasible.

Structural characterization of the fusion core in syncytin, envelope protein of human endogenous retrovirus family W

International Nuclear Information System (INIS)

Gong Rui; Peng Xiaoxue; Kang Shuli; Feng Huixing; Huang Jianying; Zhang Wentao; Lin Donghai; Tien Po; Xiao Gengfu

2005-01-01

Syncytin is a captive retroviral envelope protein, possibly involved in the formation of the placental syncytiotrophoblast layer generated by trophoblast cell fusion at the maternal-fetal interface. We found that syncytin and type I viral envelope proteins shared similar structural profiling, especially in the regions of N- and C-terminal heptad repeats (NHR and CHR). We expressed the predicted regions of NHR (41 aa) and CHR (34 aa) in syncytin as a native single chain (named 2-helix protein) to characterize it. 2-helix protein exists as a trimer and is highly α-helix, thermo-stable, and denatured by low pH. NHR and CHR could form a protease-resistant complex. The complex structure built by the molecular docking demonstrated that NHR and CHR associated in an antiparallel manner. Overall, the 2-helix protein could form a thermo-stable coiled coil trimer. The fusion core structure of syncytin was first demonstrated in endogenous retrovirus. These results support the explanation how syncytin mediates cytotrophoblast cell fusion involved in placental morphogenesis

Human retroviruses and AIDS 1996. A compilation and analysis of nucleic acid and amino acid sequences

Energy Technology Data Exchange (ETDEWEB)

Myers, G.; Foley, B.; Korber, B. [eds.] [Los Alamos National Lab., NM (United States). Theoretical Div.; Mellors, J.W. [ed.] [Univ. of Pittsburgh, PA (United States); Jeang, K.T. [ed.] [National Institutes of Health, Bethesda, MD (United States). Molecular Virology Section; Wain-Hobson, S. [Pasteur Inst., Paris (France)] [ed.

1997-04-01

This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts that it comprises: (1) Nuclear Acid Alignments and Sequences; (2) Amino Acid Alignments; (3) Analysis; (4) Related Sequences; and (5) Database Communications. Information within all the parts is updated throughout the year on the Web site, http://hiv-web.lanl.gov. While this publication could take the form of a review or sequence monograph, it is not so conceived. Instead, the literature from which the database is derived has simply been summarized and some elementary computational analyses have been performed upon the data. Interpretation and commentary have been avoided insofar as possible so that the reader can form his or her own judgments concerning the complex information. In addition to the general descriptions of the parts of the compendium, the user should read the individual introductions for each part.

Validation for a new apparatus measuring water vapour enhancement factors up to 6 MPa

International Nuclear Information System (INIS)

Sairanen, H; Heinonen, M

2014-01-01

High accuracy dew-point measurements require a water vapour enhancement factor to correct the effects of pressure drop in a sampling line. The enhancement factor is also needed when a humidity quantity value is converted to another. In this paper a new apparatus for traceable measurements of the enhancement factor is presented along with the results of validation measurements with air and methane. The apparatus is designed for dew-point temperatures from −50 to +15 °C and the pressure range from atmospheric pressure up to 6 MPa. The performance of the apparatus was investigated by comparing measurement results to the literature data for air and the data calculated from published thermodynamic measurement results for methane. It is shown that the experimental results agree with the reference data within the estimated uncertainties. (paper)

Fluorescence Enhancement Factors on Optical Antennas: Enlarging the Experimental Values without Changing the Antenna Design

Directory of Open Access Journals (Sweden)

Jérôme Wenger

2012-01-01

Full Text Available Plasmonic antennas offer promising opportunities to control the emission of quantum objects. As a consequence, the fluorescence enhancement factor is widely used as a figure of merit for a practical antenna realization. However, the fluorescence enhancement factor is not an intrinsic property of the antenna. It critically depends on several parameters, some of which are often disregarded. In this contribution, I explore the influence of the setup collection efficiency, emitter's quantum yield, and excitation intensity. Improperly setting these parameters may significantly alter the enhancement values, leading to potential misinterpretations. The discussion is illustrated by an antenna example of a nanoaperture surrounded by plasmonic corrugations.

Epidemiological aspects of retrovirus (HTLV infection among Indian populations in the Amazon Region of Brazil

Directory of Open Access Journals (Sweden)

Ricardo Ishak

Full Text Available HTLV was initially described in association with a form of leukemia in Japan and a neurological disease in the Caribbean. It was soon shown that HTLV-II was endemic among Amerindians and particularly among Brazilian Indians. The Amazon Region of Brazil is presently the largest endemic area for this virus and has allowed several studies concerning virus biology, the search for overt disease, epidemiological data including detailed demographic data on infected individuals, clear-cut geographic distribution, definition of modes of transmission and maintenance within small, epidemiologically-closed groups, and advances in laboratory diagnosis of the infection. A new molecular subtype named HTLV-IIc was further described on the basis of genome sequencing and phylogenetic analysis. This subtype is present in other areas of Brazil, indicating that the virus is additionally both a valuable marker for tracing past human migration routes in the Americas and a probable marker for social habits of the present human population. HIV, the other human retrovirus, is still not prevalent among indigenous communities in the Brazilian Amazon, but these groups are also easy targets for the virus.

[Antiretroviral drug supply in Argentina: National Program to Combat Human Retroviruses, AIDS, and STDs].

Science.gov (United States)

Colautti, Marisel; Luppi, Irene; Salamano, Mercedes; Traverso, María Luz; Botta, Carina; Palchik, Valeria

2009-01-01

To evaluate the supply cycle of antiretroviral (ARV) drugs, overseen by the National Program to Combat Human Retroviruses, AIDS, and STDs, through its order fulfillment indicators, and to obtain input from supply chain stakeholders. A study was carried out from April-September 2005 in the pharmacies of two hospitals in Rosario, Argentina, involving both a quantitative analysis of indicators and secondary sources and a qualitative evaluation using semistructured interviews. The indicators reveal the impact that interruptions in ARV supply stream from the Program (central level) have and the overstocking that takes place at the pharmacies (local level) to manage the shortages. Changes in ARV treatment account for over 50% of the prescriptions. Fulfillments fall short of the reference value. The interviewees shared possible strategies for overcoming the communication gaps between levels, for building-up stock, for guaranteeing availability, and for shortening waiting times; reached informal agreements to deal with the lack of policies and the shortage of staff; acknowledged the challenges facing the jurisdictions (central, intermediate, and local/community); and recognized local efforts to improve management. These challenges could be the starting point for building teams to work on effectively decentralizing the entire supply chain and allowing the Program to fulfill its much-needed oversight role.

Vaccination directed against the human endogenous retrovirus-K (HERV-K) gag protein slows HERV-K gag expressing cell growth in a murine model system.

Science.gov (United States)

Kraus, Benjamin; Fischer, Katrin; Sliva, Katja; Schnierle, Barbara S

2014-03-26

Human endogenous retroviruses (HERVs) are remnants of ancestral infections and chromosomally integrated in all cells of an individual, are transmitted only vertically and are defective in viral replication. However enhanced expression of HERV-K accompanied by the emergence of anti-HERV-K-directed immune responses has been observed inter-alia in HIV-infected individuals and tumor patients. Therefore HERV-K might serve as a tumor-specific antigen or even as a constant target for the development of an HIV vaccine. To verify our hypothesis, we tested the immunogenicity of HERV-K Gag by using a recombinant vaccinia virus (MVA-HKcon) expressing the HERV-K Gag protein and established an animal model to test its vaccination efficacy. Murine renal carcinoma cells (Renca) were genetically altered to express E. coli beta-galactosidase (RLZ cells) and the HERV-K Gag protein (RLZ-HKGag cells). Subcutaneous application of RLZ-HKGag cells into syngenic BALB/c mice resulted in the formation of local tumors in MVA vaccinated mice. MVA-HKcon vaccination reduced the tumor growth. Furthermore, intravenous injection of RLZ-HKGag cells led to the formation of pulmonary metastases. Vaccination of tumor-bearing mice with MVA-HKcon drastically reduced the number of pulmonary RLZ-HKGag tumor nodules compared to vaccination with wild-type MVA. The data demonstrate that HERV-K Gag is a useful target for vaccine development and might offer new treatment opportunities for cancer patients.

‘There and back again’: revisiting the pathophysiological roles of human endogenous retroviruses in the post-genomic era

Science.gov (United States)

Magiorkinis, Gkikas; Belshaw, Robert; Katzourakis, Aris

2013-01-01

Almost 8% of the human genome comprises endogenous retroviruses (ERVs). While they have been shown to cause specific pathologies in animals, such as cancer, their association with disease in humans remains controversial. The limited evidence is partly due to the physical and bioethical restrictions surrounding the study of transposons in humans, coupled with the major experimental and bioinformatics challenges surrounding the association of ERVs with disease in general. Two biotechnological landmarks of the past decade provide us with unprecedented research artillery: (i) the ultra-fine sequencing of the human genome and (ii) the emergence of high-throughput sequencing technologies. Here, we critically assemble research about potential pathologies of ERVs in humans. We argue that the time is right to revisit the long-standing questions of human ERV pathogenesis within a robust and carefully structured framework that makes full use of genomic sequence data. We also pose two thought-provoking research questions on potential pathophysiological roles of ERVs with respect to immune escape and regulation. PMID:23938753

Identification and detection of a novel human endogenous retrovirus-related gene, and structural characterization of its related elements

Directory of Open Access Journals (Sweden)

Qiaoyi Liang

2009-01-01

Full Text Available Up-regulation of human endogenous retroviruses (HERVs is associated with many diseases, including cancer. In this study, an H family HERV (HERV-H-related gene was identified and characterized. Its spliced transcript lacks protein-coding capacity and may belong to the emerging class of noncoding RNAs (ncRNAs. The 1.3-kb RNA consisting of four exons is transcribed from an Alu element upstream of a 5.0-kb structurally incomplete HERV-H element. RT-PCR and quantitative RT-PCR results indicated that expression of this HERV-related transcript was negatively associated with colon, stomach, and kidney cancers. Its expression was induced upon treatment with DNA methylation and histone deacetylation inhibitors. A BLAT search using long terminal repeats (LTRs identified 50 other LTR homogenous HERV-H elements. Further analysis of these elements revealed that all are structurally incomplete and only five exert transcriptional activity. The results presented here recommend further investigation into a potentially functional HERV-H-related ncRNA.

Use of polyethyleneimine polymer in cell culture as attachment factor and lipofection enhancer

Directory of Open Access Journals (Sweden)

González-García Maribel

2004-10-01

Full Text Available Abstract Background Several cell lines and primary cultures benefit from the use of positively charged extracellular matrix proteins or polymers that enhance their ability to attach to culture plates. Polyethyleneimine is a positively charged polymer that has gained recent attention as a transfection reagent. A less known use of this cationic polymer as an attachment factor was explored with several cell lines. Results Polyethyleneimine compared favorably to traditional attachment factors such as collagen and polylysine. PC-12 and HEK-293 cells plated on dishes coated with polyethyleneimine showed a homogeneous distribution of cells in the plate, demonstrating strong cell adhesion that survived washing procedures. The polymer could also be used to enhance the adherence and allow axonal outgrowth from zebrafish retinal explants. The effects of this coating agent on the transfection of loosely attaching cell lines were studied. Pre-coating with polyethyleneimine had the effect of enhancing the transfection yield in procedures using lipofection reagents. Conclusion Polyethyleneimine is an effective attachment factor for weakly anchoring cell lines and primary cells. Its use in lipofection protocols makes the procedures more reliable and increases the yield of expressed products with commonly used cell lines such as PC-12 and HEK-293 cells.

Hypoxia-Inducible Factor-1α: A Potential Factor for the Enhancement of Osseointegration between Dental Implants and Tissue-Engineered Bone

Directory of Open Access Journals (Sweden)

Duohong Zou

2011-07-01

Full Text Available Introduction: Tissue-engineered bones are widely utilized to protect healthy tissue, reduce pain, and increase the success rate of dental implants. one of the most challenging obstacles lies in obtaining effective os-seointegration between dental implants and tissue-engineered structures. Deficiencies in vascularization, osteogenic factors, oxygen, and other nutrients inside the tissue-engineered bone during the early stages following implantation all inhibit effective osseointe-gration. Oxygen is required for aerobic metabolism in bone and blood vessel tissues, but oxygen levels inside tissue-engineered bone are not suf-ficient for cell proliferation. HIF-1α is a pivotal regulator of hypoxic and ischemic vascular responses, driving transcriptional activation of hundreds of genes involved in vascular reactivity, angiogenesis, arteriogenesis, and osteogenesis.The hypothesis: Hypoxia-Inducible Factor-1α seems a potential factor for the enhancement of osseointegration between dental implants and tissue-engineered bone.Evaluation of the hypothesis: Enhancement of HIF-1α protein expression is recognized as the most promising approach for angiogenesis, because it can induce multiple angiogenic targets in a coordinated manner. Therefore, it will be a novel potential therapeutic methods targeting HIF-1α expression to enhance osseointegration be-tween dental implants and tissue-engineered bone.

National plan to enhance aviation safety through human factors improvements

Science.gov (United States)

Foushee, Clay

1990-01-01

The purpose of this section of the plan is to establish a development and implementation strategy plan for improving safety and efficiency in the Air Traffic Control (ATC) system. These improvements will be achieved through the proper applications of human factors considerations to the present and future systems. The program will have four basic goals: (1) prepare for the future system through proper hiring and training; (2) develop a controller work station team concept (managing human errors); (3) understand and address the human factors implications of negative system results; and (4) define the proper division of responsibilities and interactions between the human and the machine in ATC systems. This plan addresses six program elements which together address the overall purpose. The six program elements are: (1) determine principles of human-centered automation that will enhance aviation safety and the efficiency of the air traffic controller; (2) provide new and/or enhanced methods and techniques to measure, assess, and improve human performance in the ATC environment; (3) determine system needs and methods for information transfer between and within controller teams and between controller teams and the cockpit; (4) determine how new controller work station technology can optimally be applied and integrated to enhance safety and efficiency; (5) assess training needs and develop improved techniques and strategies for selection, training, and evaluation of controllers; and (6) develop standards, methods, and procedures for the certification and validation of human engineering in the design, testing, and implementation of any hardware or software system element which affects information flow to or from the human.

Suppressive effect on polyclonal B-cell activation of a synthetic peptide homologous to a transmembrane component of oncogenic retroviruses

Energy Technology Data Exchange (ETDEWEB)

Mitani, M.; Cianciolo, G.J.; Snyderman, R.; Yasuda, M.; Good, R.A.; Day, N.K.

1987-01-01

Purified feline leukemia virus, UV light-inactivated feline leukemia virus, and a synthetic peptide (CKS-17) homologous to a well-conserved region of the transmembrane components of several human and animal retroviruses were each studied for their effect on IgG production by feline peripheral blood lymphocytes. Using a reverse hemolytic plaque assay, both the viable virus and the UV-inactivated feline leukemia virus, but not the CKS-17, activated B lymphocytes to secrete IgG. When staphylococcal protein A, a polyclonal B-cell activator, was used to stimulate IgG synthesis by feline lymphocytes, the viable virus, the UV-inactivated virus, and the CKS-17 peptide each strongly suppressed IgG secretion without compromising viability of the lymphocytes. These finding suggest that the immunosuppressive influences of feline leukemia virus on immunoglobulin synthesis may reside in a conserved portion of the envelope glycoprotein that includes the region homologous to CKS-17.

Suppressive effect on polyclonal B-cell activation of a synthetic peptide homologous to a transmembrane component of oncogenic retroviruses

International Nuclear Information System (INIS)

Mitani, M.; Cianciolo, G.J.; Snyderman, R.; Yasuda, M.; Good, R.A.; Day, N.K.

1987-01-01

Purified feline leukemia virus, UV light-inactivated feline leukemia virus, and a synthetic peptide (CKS-17) homologous to a well-conserved region of the transmembrane components of several human and animal retroviruses were each studied for their effect on IgG production by feline peripheral blood lymphocytes. Using a reverse hemolytic plaque assay, both the viable virus and the UV-inactivated feline leukemia virus, but not the CKS-17, activated B lymphocytes to secrete IgG. When staphylococcal protein A, a polyclonal B-cell activator, was used to stimulate IgG synthesis by feline lymphocytes, the viable virus, the UV-inactivated virus, and the CKS-17 peptide each strongly suppressed IgG secretion without compromising viability of the lymphocytes. These finding suggest that the immunosuppressive influences of feline leukemia virus on immunoglobulin synthesis may reside in a conserved portion of the envelope glycoprotein that includes the region homologous to CKS-17

Quantitative investigation of physical factors contributing to gold nanoparticle-mediated proton dose enhancement

International Nuclear Information System (INIS)

Cho, Jongmin; Manohar, Nivedh; Kerr, Matthew; Cho, Sang Hyun; Gonzalez-Lepera, Carlos; Krishnan, Sunil

2016-01-01

Some investigators have shown tumor cell killing enhancement in vitro and tumor regression in mice associated with the loading of gold nanoparticles (GNPs) before proton treatments. Several Monte Carlo (MC) investigations have also demonstrated GNP-mediated proton dose enhancement. However, further studies need to be done to quantify the individual physical factors that contribute to the dose enhancement or cell-kill enhancement (or radiosensitization). Thus, the current study investigated the contributions of particle-induced x-ray emission (PIXE), particle-induced gamma-ray emission (PIGE), Auger and secondary electrons, and activation products towards the total dose enhancement. Specifically, GNP-mediated dose enhancement was measured using strips of radiochromic film that were inserted into vials of cylindrical GNPs, i.e. gold nanorods (GNRs), dispersed in a saline solution (0.3 mg of GNRs/g or 0.03% of GNRs by weight), as well as vials containing water only, before proton irradiation. MC simulations were also performed with the tool for particle simulation code using the film measurement setup. Additionally, a high-purity germanium detector system was used to measure the photon spectrum originating from activation products created from the interaction of protons and spherical GNPs present in a saline solution (20 mg of GNPs/g or 2% of GNPs by weight). The dose enhancement due to PIXE/PIGE recorded on the films in the GNR-loaded saline solution was less than the experimental uncertainty of the film dosimetry (<2%). MC simulations showed highly localized dose enhancement (up to a factor 17) in the immediate vicinity (<100 nm) of GNRs, compared with hypothetical water nanorods (WNRs), mostly due to GNR-originated Auger/secondary electrons; however, the average dose enhancement over the entire GNR-loaded vial was found to be minimal (0.1%). The dose enhancement due to the activation products from GNPs was minimal (<0.1%) as well. In conclusion, under the

The beneficial effect of genetically engineered Schwann cells with enhanced motility in peripheral nerve regeneration: review.

Science.gov (United States)

Gravvanis, A I; Lavdas, A A; Papalois, A; Tsoutsos, D A; Matsas, R

2007-01-01

The importance of Schwann cells in promoting nerve regeneration across a conduit has been extensively reported in the literature, and Schwann cell motility has been acknowledged as a prerequisite for myelination of the peripheral nervous system during regeneration after injury. Review of recent literature and retrospective analysis of our studies with genetically modified Schwann Cells with increased motility in order to identify the underlying mechanism of action and outline the future trends in peripheral nerve repair. Schwann cell transduction with the pREV-retrovirus, for expression of Sialyl-Transferase-X, resulting in conferring Polysialyl-residues (PSA) on NCAM, increases their motility in-vitro and ensures nerve regeneration through silicone tubes after end-to-side neurorraphy in the rat sciatic nerve model, thus significantly promoting fiber maturation and functional outcome. An artificial nerve graft consisting of a type I collagen tube lined with the genetically modified Schwann cells with increased motility, used to bridge a defect in end-to-end fashion in the rat sciatic nerve model, was shown to promote nerve regeneration to a level equal to that of a nerve autograft. The use of genetically engineered Schwann cells with enhanced motility for grafting endoneural tubes promotes axonal regeneration, by virtue of the interaction of the transplanted cells with regenerating axonal growth cones as well as via the recruitment of endogenous Schwann cells. It is envisaged that mixed populations of Schwann cells, expressing PSA and one or more trophic factors, might further enhance the regenerating and remyelinating potential of the lesioned nerves.

Brain-derived neurotrophic factor enhances conditioned taste aversion retention.

Science.gov (United States)

Castillo, Diana V; Figueroa-Guzmán, Yazmín; Escobar, Martha L

2006-01-05

Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that induction of long-term potentiation (LTP) in the projection from the basolateral nucleus of the amygdala (Bla) to the IC, previous to CTA training, enhances the retention of this task. Recently, we found that intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the Bla-IC projection of adult rats in vivo. In this work, we present experimental data showing that intracortical microinfusion of BDNF previous to CTA training enhances the retention of this task. These findings support the concept that BDNF may contribute to memory-related functions performed by a neocortical area, playing a critical role in long-term synaptic plasticity.

Profile correction to electron temperature and enhancement factor in soft-x-ray pulse-height-analysis measurements in tokamaks

International Nuclear Information System (INIS)

Sesnic, S.; Diesso, M.; Hill, K.; Holland, A.; Pohl, F.

1988-01-01

Because soft-x-ray pulse-height-analysis spectra contain chordal information, the electron temperature and the radiation intensity (enhancement factor) measurements do not represent the local values. The correction factors for the electron temperature and the enhancement factor as a function of the temperature and density profile parameters and the energy are obtained. The spectrum distortion due to pulse pileup effects is also evaluated. A set of curves is given from which the distortion of the spectrum can be obtained if the electron temperature, the Be filter thickness, and the electronic parameters of the acquisition system are known. PG 1810,1812 ID 131801CON N X-ray diagnostics TT Profile correction to electron temperature and enhancement factor in soft-x-ray pulse-height-analysis measurements in tokamaks AU S. Sesnic, M. Diesso, K. Hill, and A. Holland LO Princeton University, Plasma Physics Laboratory, P.O. Box 451, Princeton, New Jersey 08543 AU F. Pohl LO Max-Planck Institut fuer Plasmaphysik, 8046-Garching, Federal Republic of Germany SD (Presented on 16 March 1988) AB Because soft-x-ray pulse-height-analysis spectra contain chordal information, the electron temperature and the radiation intensity (enhancement factor) measurements do not represent the local values. The correction factors for the electron temperature and the enhancement factor as a function of the temperature and density profile parameters and the energy are obtained. The spectrum distortion due to pulse pileup effects is also evaluated. A set of curves is given from which the distortion of the spectrum can be obtained if the electron tempe

Characterization of Insertional Variation of Porcine Endogenous Retroviruses in Six Different Pig Breeds

Directory of Open Access Journals (Sweden)

W. Y. Jung

2012-10-01

Full Text Available Pigs may need to be exploited as xenotransplantation donors due to the shortage of human organs, tissues and cells. Porcine endogenous retroviruses (PERVs are a significant obstacle to xenotransplantation because they can infect human cells in vitro and have the potential for transmission of unexpected pathogens to humans. In this research, 101 pigs, including four commercial breeds (23 Berkshire, 13 Duroc, 22 Landrace and 14 Yorkshire pigs, one native breed (19 Korean native pigs and one miniature breed (10 NIH miniature pigs were used to investigate insertional variations for 11 PERV loci (three PERV-A, six PERV-B and two PERV-C. Over 60% of the pigs harbored one PERV-A (907F8 integration and five PERV-B (B3-3G, B3-7G, 742H1, 1155D9 and 465D1 integrations. However, two PERV-A loci (A1-6C and 1347C1 and one PERV-B locus (B3-7F were absent in Duroc pigs. Moreover, two PERV-C loci (C2-6C and C4-2G only existed in Korean native pigs and NIH miniature pigs. The results suggest that PERV insertional variations differ among pig breeds as well as among individuals within a breed. Also, the results presented here can be used for the selection of animals that do not have specific PERV integration for xenotransplantation research.

Mechanisms and factors that influence high frequency retroviral recombination

DEFF Research Database (Denmark)

Delviks-Frankenberry, Krista; Galli, Andrea; Nikolaitchik, Olga

2011-01-01

With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic diversity, which improves the chances for the survival of their population. Recombination occurs during DNA synthesis, whereby reverse...... transcriptase undergoes template switching events between the two copackaged RNAs, resulting in a viral recombinant with portions of the genetic information from each parental RNA. This review summarizes our current understanding of the factors and mechanisms influencing retroviral recombination, fidelity...... of the recombination process, and evaluates the subsequent viral diversity and fitness of the progeny recombinant. Specifically, the high mutation rates and high recombination frequencies of HIV-1 will be analyzed for their roles in influencing HIV-1 global diversity, as well as HIV-1 diagnosis, drug treatment...

Multivariable analysis of clinical influence factors on liver enhancement of Gd-EOB-DTPA-enhanced 3T MRI; Multivariable Analyse klinischer Einflussfaktoren auf die Signalintensitaet bei Gd-EOB-DTPA 3T-MRT der Leber

Energy Technology Data Exchange (ETDEWEB)

Verloh, N.; Haimerl, M.; Stroszczynski, C.; Fellner, C.; Wiggermann, P. [University Hospital Regensburg (Germany). Dept. of Radiology; Zeman, F. [University Hospital Regensburg (Germany). Center for Clinical Trials; Teufel, A. [University Hospital Regensburg (Germany). Dept. of Gastroenterology; Lang, S. [University Hospital Regensburg (Germany). Dept. of Surgery

2015-01-15

The purpose of this study was to identify clinical factors influencing Gd-EOB-DTPA liver uptake in patients with healthy liver parenchyma. A total of 124 patients underwent contrast-enhanced MRI with a hepatocyte-specific contrast agent at 3T. T1-weighted volume interpolated breath-hold examination (VIBE) sequences with fat suppression were acquired before and 20 minutes after contrast injection. The relative enhancement (RE) between plain and contrast-enhanced signal intensity was calculated. Simple and multiple linear regression analyses were performed to evaluate clinical factors influencing the relative enhancement. Patients were subdivided into three groups according to their relative liver enhancement (HRE, RE ≥ 100 %; MRE, 100 % > RE > 50 %; NRE, RE ≤ 50 %) and were analyzed according to the relevant risk factors. Simple regression analyses revealed patient age, transaminases (AST, ALT, GGT), liver, spleen and delta-liver volume (the difference between the volumetrically measured liver volume and the estimated liver volume based on body weight) as significant factors influencing relative enhancement. In the multiple analysis the transaminase AST, spleen and delta liver volume remained significant factors influencing relative enhancement. Delta liver volume showed a significant difference between all analyzed groups. Liver enhancement in the hepatobiliary phase depends on a variety of factors. Body weight-adapted administration of Gd-EOB-DTPA may lead to inadequate liver enhancement after 20 minutes especially when the actual liver volume differs from the expected volume.

E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.

Science.gov (United States)

Na, Ha-Na; Hegde, Vijay; Dubuisson, Olga; Dhurandhar, Nikhil V

2016-01-01

Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR), and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown) with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling.

E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.

Directory of Open Access Journals (Sweden)

Ha-Na Na

Full Text Available Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR, and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1. In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling.

Not so bad after all: retroviruses and long terminal repeat retrotransposons as a source of new genes in vertebrates.

Science.gov (United States)

Naville, M; Warren, I A; Haftek-Terreau, Z; Chalopin, D; Brunet, F; Levin, P; Galiana, D; Volff, J-N

2016-04-01

Viruses and transposable elements, once considered as purely junk and selfish sequences, have repeatedly been used as a source of novel protein-coding genes during the evolution of most eukaryotic lineages, a phenomenon called 'molecular domestication'. This is exemplified perfectly in mammals and other vertebrates, where many genes derived from long terminal repeat (LTR) retroelements (retroviruses and LTR retrotransposons) have been identified through comparative genomics and functional analyses. In particular, genes derived from gag structural protein and envelope (env) genes, as well as from the integrase-coding and protease-coding sequences, have been identified in humans and other vertebrates. Retroelement-derived genes are involved in many important biological processes including placenta formation, cognitive functions in the brain and immunity against retroelements, as well as in cell proliferation, apoptosis and cancer. These observations support an important role of retroelement-derived genes in the evolution and diversification of the vertebrate lineage. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Changes in lymphocyte and macrophage subsets due to morphine and ethanol treatment during a retrovirus infection causing murine AIDS

Energy Technology Data Exchange (ETDEWEB)

Watson, R.R.; Prabhala, R.H.; Darban, H.R.; Yahya, M.D.; Smith, T.L.

1988-01-01

The number of lymphocytes of various subsets were not significantly changed by the ethanol exposure except those showing activation markers which were reduced. The percentage of peripheral blood cells showing markers for macrophage functions and their activation were significantly reduced after binge use of ethanol. Ethanol retarded suppression of cells by retroviral infection. However by 25 weeks of infection there was a 8.6% survival in the ethanol fed mice infected with retrovirus which was much less than virally infected controls. Morphine treatment also increased the percentage of cells with markers for macrophages and activated macrophages in virally infected mice, while suppressing them in uninfected mice. The second and third morphine injection series suppressed lymphocyte T-helper and T-suppressor cells, but not total T cells. However, suppression by morphine was significantly less during retroviral disease than suppression caused by the virus only. At 25 weeks of infection 44.8% of morphine treated, infected mice survived.

Human endogenous retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods.

Science.gov (United States)

Jones, R Brad; Leal, Fabio E; Hasenkrug, Aaron M; Segurado, Aluisio C; Nixon, Douglas F; Ostrowski, Mario A; Kallas, Esper G

2013-01-10

An estimated 10-20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

The Epithelial-Mesenchymal Transition Factor SNAIL Paradoxically Enhances Reprogramming

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Juli J. Unternaehrer

2014-11-01

Full Text Available Reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs entails a mesenchymal to epithelial transition (MET. While attempting to dissect the mechanism of MET during reprogramming, we observed that knockdown (KD of the epithelial-to-mesenchymal transition (EMT factor SNAI1 (SNAIL paradoxically reduced, while overexpression enhanced, reprogramming efficiency in human cells and in mouse cells, depending on strain. We observed nuclear localization of SNAI1 at an early stage of fibroblast reprogramming and using mouse fibroblasts expressing a knockin SNAI1-YFP reporter found cells expressing SNAI1 reprogrammed at higher efficiency. We further demonstrated that SNAI1 binds the let-7 promoter, which may play a role in reduced expression of let-7 microRNAs, enforced expression of which, early in the reprogramming process, compromises efficiency. Our data reveal an unexpected role for the EMT factor SNAI1 in reprogramming somatic cells to pluripotency.

Use of polyethyleneimine polymer in cell culture as attachment factor and lipofection enhancer

OpenAIRE

Vancha, Ajith R; Govindaraju, Suman; Parsa, Kishore VL; Jasti, Madhuri; González-García, Maribel; Ballestero, Rafael P

2004-01-01

Abstract Background Several cell lines and primary cultures benefit from the use of positively charged extracellular matrix proteins or polymers that enhance their ability to attach to culture plates. Polyethyleneimine is a positively charged polymer that has gained recent attention as a transfection reagent. A less known use of this cationic polymer as an attachment factor was explored with several cell lines. Results Polyethyleneimine compared favorably to traditional attachment factors suc...

Supersymmetric enhancement factor for the 1-jet cross-section in p-anti p reactions

International Nuclear Information System (INIS)

Antoniadis, I.; Baulieu, L.; Delduc, F.

1984-01-01

We compare the 1-jet inclusive cross-section at high psub(perpendicular to) in proton-antiproton reaction at SPS collider predicted by standard QCD and by its simplest supersymmetric extension (SQCD). We first compute the total enhancement factor K between QCD and SQCD jets as a function of psub(perpendicular to). Then we compute the observable enhancement factor which is smaller than K since the transverse momentum of supersymmetric particles is not fully observable. We have analyzed two cases (i) psub(perpendicular to) is small compared to the masses of squarks and only light gluinos (2 GeV) are considered (ii) psub(perpendicular to) is large compared to the masses of squarks (17 GeV in our analysis) and both gluinos and squarks are taken into account. The observable enhancement factor between QCD and SQCD is found to be small (of order 1.3 to 1.5 for psub(perpendicular to)=100 GeV). Missing psub(perpendicular to) events with one ordinary jet and one jet due to the production of a supersymmetric particle are found to be non negligible with respect to those with two supersymmetric jets. We also display some interesting supersymmetric relations among parton cross-sections. (orig.)

A review of protective factors and causal mechanisms that enhance the mental health of Indigenous Circumpolar youth

OpenAIRE

Petrasek MacDonald, Joanna; Ford, James D.; Cunsolo Willox, Ashlee; Ross, Nancy A.

2013-01-01

Objectives To review the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. Study design A systematic literature review of peer-reviewed English-language research was conducted to systematically examine the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta-An...

Novel NAC transcription factor TaNAC67 confers enhanced multi-abiotic stress tolerances in Arabidopsis.

Directory of Open Access Journals (Sweden)

Xinguo Mao

Full Text Available Abiotic stresses are major environmental factors that affect agricultural productivity worldwide. NAC transcription factors play pivotal roles in abiotic stress signaling in plants. As a staple crop, wheat production is severely constrained by abiotic stresses whereas only a few NAC transcription factors have been characterized functionally. To promote the application of NAC genes in wheat improvement by biotechnology, a novel NAC gene designated TaNAC67 was characterized in common wheat. To determine its role, transgenic Arabidopsis overexpressing TaNAC67-GFP controlled by the CaMV-35S promoter was generated and subjected to various abiotic stresses for morphological and physiological assays. Gene expression showed that TaNAC67 was involved in response to drought, salt, cold and ABA treatments. Localization assays revealed that TaNAC67 localized in the nucleus. Morphological analysis indicated the transgenics had enhanced tolerances to drought, salt and freezing stresses, simultaneously supported by enhanced expression of multiple abiotic stress responsive genes and improved physiological traits, including strengthened cell membrane stability, retention of higher chlorophyll contents and Na(+ efflux rates, improved photosynthetic potential, and enhanced water retention capability. Overexpression of TaNAC67 resulted in pronounced enhanced tolerances to drought, salt and freezing stresses, therefore it has potential for utilization in transgenic breeding to improve abiotic stress tolerance in crops.

Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis.

Science.gov (United States)

Triviai, Ioanna; Ziegler, Marion; Bergholz, Ulla; Oler, Andrew J; Stübig, Thomas; Prassolov, Vladimir; Fehse, Boris; Kozak, Christine A; Kröger, Nicolaus; Stocking, Carol

2014-06-10

The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation.

Experimental study on condensation heat transfer enhancement and pressure drop penalty factors in four microfin tubes

Energy Technology Data Exchange (ETDEWEB)

Han, D [Korea University, Seoul (Korea). Institute of Advanced Machinery Design; Lee, Kyu-Jung [Korea University, Seoul (Korea). Dept. of Mechanical Engineering

2005-08-01

Heat transfer and pressure drop characteristics of four microfin tubes were experimentally investigated for condensation of refrigerants R134a, R22, and R410A in four different test sections. The microfin tubes examined during this study consisted of 8.92, 6.46, 5.1, and 4 mm maximum inside diameter. The effect of mass flux, vapor quality, and refrigerants on condensation was investigated in terms of the heat transfer enhancement factor and the pressure drop penalty factor. The pressure drop penalty factor and the heat transfer enhancement factor showed a similar tendency for each tube at given vapor quality and mass flux. Based on the experimental data and the heat-momentum analogy, correlations for the condensation heat transfer coefficients in an annular flow regime and the frictional pressure drops are proposed. (author)

Transcription factor assisted loading and enhancer dynamics dictate the hepatic fasting response

Science.gov (United States)

Goldstein, Ido; Baek, Songjoon; Presman, Diego M.; Paakinaho, Ville; Swinstead, Erin E.; Hager, Gordon L.

2017-01-01

Fasting elicits transcriptional programs in hepatocytes leading to glucose and ketone production. This transcriptional program is regulated by many transcription factors (TFs). To understand how this complex network regulates the metabolic response to fasting, we aimed at isolating the enhancers and TFs dictating it. Measuring chromatin accessibility revealed that fasting massively reorganizes liver chromatin, exposing numerous fasting-induced enhancers. By utilizing computational methods in combination with dissecting enhancer features and TF cistromes, we implicated four key TFs regulating the fasting response: glucocorticoid receptor (GR), cAMP responsive element binding protein 1 (CREB1), peroxisome proliferator activated receptor alpha (PPARA), and CCAAT/enhancer binding protein beta (CEBPB). These TFs regulate fuel production by two distinctly operating modules, each controlling a separate metabolic pathway. The gluconeogenic module operates through assisted loading, whereby GR doubles the number of sites occupied by CREB1 as well as enhances CREB1 binding intensity and increases accessibility of CREB1 binding sites. Importantly, this GR-assisted CREB1 binding was enhancer-selective and did not affect all CREB1-bound enhancers. Single-molecule tracking revealed that GR increases the number and DNA residence time of a portion of chromatin-bound CREB1 molecules. These events collectively result in rapid synergistic gene expression and higher hepatic glucose production. Conversely, the ketogenic module operates via a GR-induced TF cascade, whereby PPARA levels are increased following GR activation, facilitating gradual enhancer maturation next to PPARA target genes and delayed ketogenic gene expression. Our findings reveal a complex network of enhancers and TFs that dynamically cooperate to restore homeostasis upon fasting. PMID:28031249

Effects of computed tomography contrast medium factors on contrast enhancement

International Nuclear Information System (INIS)

Terasawa, Kazuaki; Hatcho, Atsushi; Okuda, Itsuko

2011-01-01

The various nonionic iodinated contrast media used in contrast computed tomography (CT) studies differ in terms of their composition, characteristics, and iodine concentration (mgI/ml), as well as the volume injected (ml). Compared with ionic iodinated contrast media, nonionic iodinated contrast media are low-osmolar agents, with different agents having different osmotic pressures. Using a custom-made phantom incorporating a semipermeable membrane, the osmotic flow rate (hounsfield unit (HU)/s) could easily be measured based on the observed increase in CT numbers, and the relationship between the osmotic pressure and the osmotic flow rate could be obtained (r 2 =0.84). In addition, taking the effects of patient size into consideration, the levels of contrast enhancement in the abdominal aorta (AA) and inferior vena cava (IVC) were compared among four types of CT contrast medium. The results showed differences in contrast enhancement in the IVC during the equilibrium phase depending on the type of contrast medium used. It was found that the factors responsible for the differences observed in enhancement in the IVC were the osmotic flow rate and the volume of the blood flow pathways in the circulatory system. It is therefore considered that the reproducibility of contrast enhancement is likely to be reduced in the examination of parenchymal organs, in which scanning must be performed during the equilibrium phase, even if the amount of iodine injected per unit body weight (mgI/kg) is maintained at a specified level. (author)

A single-amino-acid substitution in the TvbS1 receptor results in decreased susceptibility to infection by avian sarcoma and leukosis virus subgroups B and D and resistance to infection by subgroup E in vitro and in vivo

Czech Academy of Sciences Publication Activity Database

Reinišová, Markéta; Šenigl, Filip; Yin, X.; Plachý, Jiří; Geryk, Josef; Elleder, Daniel; Svoboda, Jan; Federspiel, M. J.; Hejnar, Jiří

2008-01-01

Roč. 82, č. 5 (2008), s. 2097-2105 ISSN 0022-538X R&D Projects: GA ČR GA523/07/1171; GA ČR GA523/07/1282 Grant - others:NIH(US) AI48682 Institutional research plan: CEZ:AV0Z50520514 Keywords : retrovirus receptors * avian sarcoma and leukosis virus * resistance to retrovirus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.308, year: 2008

Enhanced somatic embryogenesis in Theobroma cacao using the homologous BABY BOOM transcription factor.

Science.gov (United States)

Florez, Sergio L; Erwin, Rachel L; Maximova, Siela N; Guiltinan, Mark J; Curtis, Wayne R

2015-05-16

Theobroma cacao, the chocolate tree, is an important economic crop in East Africa, South East Asia, and South and Central America. Propagation of elite varieties has been achieved through somatic embryogenesis (SE) but low efficiencies and genotype dependence still presents a significant limitation for its propagation at commercial scales. Manipulation of transcription factors has been used to enhance the formation of SEs in several other plant species. This work describes the use of the transcription factor Baby Boom (BBM) to promote the transition of somatic cacao cells from the vegetative to embryonic state. An ortholog of the Arabidopsis thaliana BBM gene (AtBBM) was characterized in T. cacao (TcBBM). TcBBM expression was observed throughout embryo development and was expressed at higher levels during SE as compared to zygotic embryogenesis (ZE). TcBBM overexpression in A. thaliana and T. cacao led to phenotypes associated with SE that did not require exogenous hormones. While transient ectopic expression of TcBBM provided only moderate enhancements in embryogenic potential, constitutive overexpression dramatically increased SE proliferation but also appeared to inhibit subsequent development. Our work provides validation that TcBBM is an ortholog to AtBBM and has a specific role in both somatic and zygotic embryogenesis. Furthermore, our studies revealed that TcBBM transcript levels could serve as a biomarker for embryogenesis in cacao tissue. Results from transient expression of TcBBM provide confirmation that transcription factors can be used to enhance SE without compromising plant development and avoiding GMO plant production. This strategy could compliment a hormone-based method of reprogramming somatic cells and lead to more precise manipulation of SE at the regulatory level of transcription factors. The technology would benefit the propagation of elite varieties with low regeneration potential as well as the production of transgenic plants, which

Studying wedge factors and beam profiles for physical and enhanced dynamic wedges

Directory of Open Access Journals (Sweden)

Ahmad Misbah

2010-01-01

Full Text Available This study was designed to investigate variation in Varian′s Physical and Enhanced Dynamic Wedge Factors (WF as a function of depth and field size. The profiles for physical wedges (PWs and enhanced dynamic wedges (EDWs were also measured using LDA-99 array and compared for confirmation of EDW angles at different depths and field sizes. WF measurements were performed in water phantom using cylindrical 0.66 cc ionization chamber. WF was measured by taking the ratio of wedge and open field ionization data. A normalized wedge factor (NWF was introduced to circumvent large differences between wedge factors for different wedge angles. A strong linear dependence of PW Factor (PWF with depth was observed. Maximum variation of 8.9% and 4.1% was observed for 60° PW with depth at 6 and 15 MV beams respectively. The variation in EDW Factor (EDWF with depth was almost negligible and less than two per cent. The highest variation in PWF as a function of field size was 4.1% and 3.4% for thicker wedge (60° at 6 and 15 MV beams respectively and decreases with decreasing wedge angle. EDWF shows strong field size dependence and significant variation was observed for all wedges at both photon energies. Differences in profiles between PW and EDW were observed on toe and heel sides. These differences were dominant for larger fields, shallow depths, thicker wedges and low energy beam. The study indicated that ignoring depth and field size dependence of WF may result in under/over dose to the patient especially doing manual point dose calculation.

Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3.

Science.gov (United States)

Chen, M; Hieng, S; Qian, X; Costa, R; Ou, J H

1994-11-15

Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.

A review of protective factors and causal mechanisms that enhance the mental health of Indigenous Circumpolar youth.

Science.gov (United States)

MacDonald, Joanna Petrasek; Ford, James D; Willox, Ashlee Cunsolo; Ross, Nancy A

2013-12-09

To review the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. A systematic literature review of peer-reviewed English-language research was conducted to systematically examine the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with elements of a realist review. From 160 records identified in the initial search of 3 databases, 15 met the inclusion criteria and were retained for full review. Data were extracted using a codebook to organize and synthesize relevant information from the articles. More than 40 protective factors at the individual, family, and community levels were identified as enhancing Indigenous youth mental health. These included practicing and holding traditional knowledge and skills, the desire to be useful and to contribute meaningfully to one's community, having positive role models, and believing in one's self. Broadly, protective factors at the family and community levels were identified as positively creating and impacting one's social environment, which interacts with factors at the individual level to enhance resilience. An emphasis on the roles of cultural and land-based activities, history, and language, as well as on the importance of social and family supports, also emerged throughout the literature. More than 40 protective factors at the individual, family, and community levels were identified as enhancing Indigenous youth mental health. These included practicing and holding traditional knowledge and skills, the desire to be useful and to contribute meaningfully to one's community, having positive role models, and believing in one's self. Broadly, protective factors at the family and community levels were identified as positively creating and impacting one's social

Mechanisms and Factors that Influence High Frequency Retroviral Recombination

Science.gov (United States)

Delviks-Frankenberry, Krista; Galli, Andrea; Nikolaitchik, Olga; Mens, Helene; Pathak, Vinay K.; Hu, Wei-Shau

2011-01-01

With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic diversity, which improves the chances for the survival of their population. Recombination occurs during DNA synthesis, whereby reverse transcriptase undergoes template switching events between the two copackaged RNAs, resulting in a viral recombinant with portions of the genetic information from each parental RNA. This review summarizes our current understanding of the factors and mechanisms influencing retroviral recombination, fidelity of the recombination process, and evaluates the subsequent viral diversity and fitness of the progeny recombinant. Specifically, the high mutation rates and high recombination frequencies of HIV-1 will be analyzed for their roles in influencing HIV-1 global diversity, as well as HIV-1 diagnosis, drug treatment, and vaccine development. PMID:21994801

Hypoxia-induced mitogenic factor enhances angiogenesis by promoting proliferation and migration of endothelial cells

International Nuclear Information System (INIS)

Tong Qiangsong; Zheng Liduan; Li Bo; Wang Danming; Huang Chuanshu; Matuschak, George M.; Li Dechun

2006-01-01

Our previous studies have indicated that hypoxia-induced mitogenic factor (HIMF) has angiogenic properties in an in vivo matrigel plug model and HIMF upregulates expression of vascular endothelial growth factor (VEGF) in mouse lungs and cultured lung epithelial cells. However, whether HIMF exerts angiogenic effects through modulating endothelial cell function remains unknown. In this study, mouse aortic rings cultured with recombinant HIMF protein resulted in enhanced vascular sprouting and increased endothelial cell spreading as confirmed by Dil-Ac-LDL uptake, von Willebrand factor and CD31 staining. In cultured mouse endothelial cell line SVEC 4-10, HIMF dose-dependently enhanced cell proliferation, in vitro migration and tubulogenesis, which was not attenuated by SU1498, a VEGFR2/Flk-1 receptor tyrosine kinase inhibitor. Moreover, HIMF stimulation resulted in phosphorylation of Akt, p38 and ERK1/2 kinases in SVEC 4-10 cells. Treatment of mouse aortic rings and SVEC 4-10 cells with LY294002, but not SB203580, PD098059 or U0126, abolished HIMF-induced vascular sprouting and angiogenic responses. In addition, transfection of a dominant-negative mutant of phosphatidylinositol 3-kinase (PI-3K), Δp85, blocked HIMF-induced phosphorylation of Akt, endothelial activation and tubulogenesis. These results indicate that HIMF enhances angiogenesis by promoting proliferation and migration of endothelial cells via activation of the PI-3K/Akt pathways

Transformation and scattering activities of the receptor tyrosine kinase RON/Stk in rodent fibroblasts and lack of regulation by the jaagsiekte sheep retrovirus receptor, Hyal2

International Nuclear Information System (INIS)

Miller, A Dusty; Van Hoeven, Neal S; Liu, Shan-Lu

2004-01-01

The envelope (Env) protein of jaagsiekte sheep retrovirus (JSRV) can transform cells in culture and is likely to be the main factor responsible for lung cancer induction by JSRV in animals. A recent report indicates that the epithelial-cell transforming activity of JSRV Env depends on activation of the cell-surface receptor tyrosine kinase Mst1r (called RON for the human and Stk for the rodent orthologs). In the immortalized line of human epithelial cells used (BEAS-2B cells), the virus receptor Hyal2 was found to bind to and suppress the activity of RON. When Env was expressed it bound to Hyal2 causing its degradation, release of RON activity from Hyal2 suppression, and activation of pathways resulting in cell transformation. Due to difficulty with reproducibility of the transformation assay in BEAS-2B cells, we have used more tractable rodent fibroblast models to further study Hyal2 modulation of RON/Stk transforming activity and potential effects of Hyal2 on RON/Stk activation by its natural ligand, macrophage stimulating protein (MSP). We did not detect transformation of NIH 3T3 cells by plasmids expressing RON or Stk, but did detect transformation of 208F rat fibroblasts by these plasmids at a very low rate. We were able to isolate 208F cell clones that expressed RON or Stk and that showed changes in morphology indicative of transformation. The parental 208F cells did not respond to MSP but 208F cells expressing RON or Stk showed obvious increases in scattering/transformation in response to MSP. Human Hyal2 had no effect on the basal or MSP-induced phenotypes of RON-expressing 208F cells, and human, mouse or rat Hyal2 had no effect on the basal or MSP-induced phenotypes of Stk-expressing 208F cells. We have shown that RON or Stk expression in 208F rat fibroblasts results in a transformed phenotype that is enhanced by addition of the natural ligand for these proteins, MSP. Hyal2 does not directly modulate the basal or MSP-induced RON/Stk activity, although it

S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.

Science.gov (United States)

Bektik, Emre; Dennis, Adrienne; Pawlowski, Gary; Zhou, Chen; Maleski, Danielle; Takahashi, Satoru; Laurita, Kenneth R; Deschênes, Isabelle; Fu, Ji-Dong

2018-05-04

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of 5-ethynyl-20-deoxyuridine (EdU)⁺/α-myosin heavy chain (αMHC)-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP low cells. However, S-phase synchronization did not enhance the reprogramming with a polycistronic-viral vector, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

Expression and regulation of the endogenous retrovirus 3 (ERV3 in Hodgkin’s lymphoma cells

Directory of Open Access Journals (Sweden)

Stefanie eKewitz

2013-07-01

Full Text Available Human endogenous retroviruses (ERV are an integral part of our genome. Expression of ERV is usually switched off but reactivation of ERV has been observed in varying human diseases including cancer. Recently, reactivation of ERV associated promoters in Hodgkin’s lymphoma (HL cells has been described. Despite relatively good prognosis, not all patients with HL can be cured with the established therapy and this therapy is associated with severe late side effects. Therefore, new targets are required for the development of future treatment strategies. Reactivated ERV might represent such target structures. Therefore, we asked which ERV loci are expressed in HL cells. Using DNA microarray analysis, we found no evidence for a general activation of ERV transcription in HL cells. In contrast, we observed down-regulation of ERV3, an ERV with potential tumor suppressor function, in HL cells in comparison to normal blood cells. Interestingly, ERV3 was also differentially expressed in published DNA microarray data from resting versus cycling B cells. Treatment of HL cells with the histone deacetylase inhibitor vorinostat strongly up-regulated ERV3 expression. In addition, we observed up-regulation in HL cells after treatment with hypoxia-mimetic cobalt(II chloride. Like vorinostat, cobalt(II chloride inhibited cell growth of HL cells. Our results suggest that cell cycle inhibition of HL cells is accompanied by up-regulation of ERV3.

Human endogenous retrovirus HERV-K(HML-2) activity in prostate cancer is dominated by a few loci.

Science.gov (United States)

Goering, Wolfgang; Schmitt, Katja; Dostert, Melanie; Schaal, Heiner; Deenen, René; Mayer, Jens; Schulz, Wolfgang A

2015-12-01

Increased expression of human endogenous retroviruses, especially HERV-K(HML-2) proviruses, has recently been associated with prostate carcinoma progression. In particular, a HML-2 locus in chromosome 22q11.23 (H22q) is upregulated in many cases. We therefore aimed at delineating the extent and repertoire of HML-2 transcription in prostate cancer tissues and cell lines and to define the transcription pattern and biological effects of H22q. Sanger and high throughput amplicon sequencing was used to define the repertoire of expressed HML-2 in a selected set of samples. qRT-PCR was used to quantify expression of selected proviruses in an extended set of prostate cancer tissues. Transcription factor binding sites (TFBS) were compared bioinformatically using the Transfac database. Expression of H22q was further characterized by siRNA-mediated knockdown, 5' RACE mapping of transcriptional start sites (TSS) and identification of splice sites. Functional effects of H22q knockdown were investigated by viability and apoptosis assays. In addition to H22q, a limited number of other proviruses were found expressed by sequencing. Of these, provirus ERVK-5 and to a lesser degree ERVK-15 were frequently upregulated in prostate cancer. In contrast, expression of ERVK-24, predominant in germ cell tumors, was not detectable in prostatic tissues. While HML-2 LTRs contain binding sites for the androgen receptor and cofactors, no consistent differences in transcription factor binding sites were found between expressed and non-expressed proviruses. The H22q locus contains two 5'-LTRs of which the upstream LTR is predominantly used in prostatic cells, with an imprecise TSS. Splicing of H22q transcripts is complex, generating, among others, a transcript with an Np9-like ORF. Knockdown of H22q did not significantly affect proliferation or apoptosis of prostate cancer cells. Our findings further underline that HML-2 expression is commonly highly tissue-specific. In prostate cancer, a limited

Human-factors methods for assessing and enhancing power-plant maintainability

International Nuclear Information System (INIS)

Seminara, J.L.

1982-05-01

EPRI Final Report NP-1567, dated February 1981, presented the results of a human factors review of plant maintainability at nine power plants (five nuclear and four fossil). This investigation revealed a wide range of plant and equipment design features that can potentially compromise the effectiveness, safety, and productivity of maintenance personnel. The present study is an extension of the earlier work. It provides those utilities that did not participate in the original study with the methodological tools to conduct a review of maintenance provisions, facilities, and practices. This report describes and provides a self-review checklist; a structured interview; a task analysis approach; methods for reviewing maintenance errors or accidents; and recommended survey techniques for evaluating such factors as noise, illumination, and communications. Application of the human factors methods described in this report should reveal avenues for enhancing existing power plants from the maintainability and availability standpoints. This document may also serve a useful purpose for designers or reviewers of new plant designs or near-operational plants presently being constructed

Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice

Science.gov (United States)

Adam, Rene C.; Yang, Hanseul; Rockowitz, Shira; Larsen, Samantha B.; Nikolova, Maria; Oristian, Daniel S.; Polak, Lisa; Kadaja, Meelis; Asare, Amma; Zheng, Deyou; Fuchs, Elaine

2015-01-01

Adult stem cells (SCs) reside in niches which balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, SCs outside their niche often display fate flexibility1-4. Here we show that super-enhancers5 underlie the identity, lineage commitment and plasticity of adult SCs in vivo. Using hair follicle (HF) as model, we map the global chromatin domains of HFSCs and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters (‘epicenters’) of transcription factor (TF) binding sites change upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicenters, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, HFSCs dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicenters, enabling them to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of HFSC super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense TF-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status, but also stemness, plasticity in transitional states and differentiation. PMID:25799994

Exchange enhancement of the electron g-factor in a two-dimensional semimetal in HgTe quantum wells

Energy Technology Data Exchange (ETDEWEB)

Bovkun, L. S., E-mail: bovkun@ipmras.ru; Krishtopenko, S. S.; Zholudev, M. S.; Ikonnikov, A. V.; Spirin, K. E. [Russian Academy of Sciences, Institute for Physics of Microstructures (Russian Federation); Dvoretsky, S. A.; Mikhailov, N. N. [Russian Academy of Sciences, Rzhanov Institute of Semiconductor Physics, Siberian Branch (Russian Federation); Teppe, F.; Knap, W. [Universite Montpellier II, Laboratoire Charles Coulomb (L2C), UMR CNRS 5221, GIS-TERALAB (France); Gavrilenko, V. I. [Russian Academy of Sciences, Institute for Physics of Microstructures (Russian Federation)

2015-12-15

The exchange enhancement of the electron g-factor in perpendicular magnetic fields to 12 T in HgTe/CdHgTe quantum wells 20 nm wide with a semimetal band structure is studied. The electron effective mass and g-factor at the Fermi level are determined by analyzing the temperature dependence of the amplitude of Shubnikov–de Haas oscillation in weak fields and near odd Landau-level filling factors ν ≤ 9. The experimental values are compared with theoretical calculations performed in the one-electron approximation using the eight-band kp Hamiltonian. The found dependence of g-factor enhancement on the electron concentration is explained by changes in the contributions of hole- and electron-like states to exchange corrections to the Landau-level energies in the conduction band.

Measurements of Coster-Kronig enhancement factors for Yb, Lu, Os and Pt elements

International Nuclear Information System (INIS)

Yilmaz, R.; Oz, E.; Tan, M.; Durak, R.; Demirel, A.I.; Sahin, Y.

2009-01-01

In this work X-ray production cross-sections' measurements, L ι , L α , L β and L γ , of Yb, Lu, Os and Pt elements have been studied at energies in the range 9.572-14.384 keV and the effect of Coster-Kronig transitions on fluorescence cross-sections for L X-ray line has been obtained. From these studies absolute values of L X-ray cross-sections have been calculated with incorporation of the enhancement due to the Coster-Kronig effect. The experimental enhancement factors tend to be smaller than those predicted by theory.

Measurements of Coster-Kronig enhancement factors for Yb, Lu, Os and Pt elements

Energy Technology Data Exchange (ETDEWEB)

Yilmaz, R. [Department of Physics, Faculty of Sciences and Arts, Yuezuencue Yil University, 65080 Van (Turkey)], E-mail: ryilmaz@yyu.edu.tr; Oz, E. [Department of Physics, Faculty of Sciences and Arts, 25240 Erzurum (Turkey); Tan, M. [Department of Physics, Faculty of Education, Gazi University, 06500 Ankara (Turkey); Durak, R. [Department of Physics, Faculty of Sciences and Arts, 25240 Erzurum (Turkey); Demirel, A.I. [Department of Physics, Faculty of Sciences and Arts, Yuezuencue Yil University, 65080 Van (Turkey); Sahin, Y. [Department of Physics, Faculty of Sciences and Arts, 25240 Erzurum (Turkey)

2009-05-15

In this work X-ray production cross-sections' measurements, L{sub {iota}}, L{sub {alpha}}, L{sub {beta}} and L{sub {gamma}}, of Yb, Lu, Os and Pt elements have been studied at energies in the range 9.572-14.384 keV and the effect of Coster-Kronig transitions on fluorescence cross-sections for L X-ray line has been obtained. From these studies absolute values of L X-ray cross-sections have been calculated with incorporation of the enhancement due to the Coster-Kronig effect. The experimental enhancement factors tend to be smaller than those predicted by theory.

A broader consideration of human factor to enhance sustainable building design.

Science.gov (United States)

Attaianese, Erminia

2012-01-01

The link between ergonomic/human factor and sustainability seems to be clearly evidenced mainly in relation to social dimension of sustainability, in order to contribute to assure corporate social responsibility and global value creation. But the will to establish an equilibrated connection among used resources in human activities, supported by the sustainability perspective, evidences that the contribution of ergonomics/human factors can be effectively enlarged to other aspects, especially in relation to building design. In fact a sustainable building is meant to be a building that contributes, through its characteristics and attribute, to a sustainable development by assuring, in the same time, a decrease of resources use and environmental impact and an increase of health, safety and comfort of the occupants. The purpose of this paper is to analyze in a broader sense the contribution of ergonomic/human factor to design of sustainable building, focusing how ergonomics principles, methodology and techniques can improve building design, enhancing its sustainability performance during all phases of building lifecycle.

An Enhanced Factor Analysis of Performance Degradation Assessment on Slurry Pump Impellers

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Shilong Sun

2017-01-01

Full Text Available Slurry pumps, such as oil sand pumps, are widely used in industry to convert electrical energy to slurry potential and kinetic energy. Because of adverse working conditions, slurry pump impellers are prone to suffer wear, which may result in slurry pump breakdowns. To prevent any unexpected breakdowns, slurry pump impeller performance degradation assessment should be immediately conducted to monitor the current health condition and to ensure the safety and reliability of slurry pumps. In this paper, to provide an alternative to the impeller health indicator, an enhanced factor analysis based impeller indicator (EFABII is proposed. Firstly, a low-pass filter is employed to improve the signal to noise ratios of slurry pump vibration signals. Secondly, redundant statistical features are extracted from the filtered vibration signals. To reduce the redundancy of the statistic features, the enhanced factor analysis is performed to generate new statistical features. Moreover, the statistic features can be automatically grouped and developed a new indicator called EFABII. Data collected from industrial oil sand pumps are used to validate the effectiveness of the proposed method. The results show that the proposed method is able to track the current health condition of slurry pump impellers.

Knock-in of Enhanced Green Fluorescent Protein or/and Human Fibroblast Growth Factor 2 Gene into β-Casein Gene Locus in the Porcine Fibroblasts to Produce Therapeutic Protein.

Science.gov (United States)

Lee, Sang Mi; Kim, Ji Woo; Jeong, Young-Hee; Kim, Se Eun; Kim, Yeong Ji; Moon, Seung Ju; Lee, Ji-Hye; Kim, Keun-Jung; Kim, Min-Kyu; Kang, Man-Jong

2014-11-01

Transgenic animals have become important tools for the production of therapeutic proteins in the domestic animal. Production efficiencies of transgenic animals by conventional methods as microinjection and retrovirus vector methods are low, and the foreign gene expression levels are also low because of their random integration in the host genome. In this study, we investigated the homologous recombination on the porcine β-casein gene locus using a knock-in vector for the β-casein gene locus. We developed the knock-in vector on the porcine β-casein gene locus and isolated knock-in fibroblast for nuclear transfer. The knock-in vector consisted of the neomycin resistance gene (neo) as a positive selectable marker gene, diphtheria toxin-A gene as negative selection marker, and 5' arm and 3' arm from the porcine β-casein gene. The secretion of enhanced green fluorescent protein (EGFP) was more easily detected in the cell culture media than it was by western blot analysis of cell extract of the HC11 mouse mammary epithelial cells transfected with EGFP knock-in vector. These results indicated that a knock-in system using β-casein gene induced high expression of transgene by the gene regulatory sequence of endogenous β-casein gene. These fibroblasts may be used to produce transgenic pigs for the production of therapeutic proteins via the mammary glands.

A review of protective factors and causal mechanisms that enhance the mental health of Indigenous Circumpolar youth

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Joanna Petrasek MacDonald

2013-12-01

Full Text Available Objectives . To review the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. Study design . A systematic literature review of peer-reviewed English-language research was conducted to systematically examine the protective factors and causal mechanisms which promote and enhance Indigenous youth mental health in the Circumpolar North. Methods . This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines, with elements of a realist review. From 160 records identified in the initial search of 3 databases, 15 met the inclusion criteria and were retained for full review. Data were extracted using a codebook to organize and synthesize relevant information from the articles. Results . More than 40 protective factors at the individual, family, and community levels were identified as enhancing Indigenous youth mental health. These included practicing and holding traditional knowledge and skills, the desire to be useful and to contribute meaningfully to one's community, having positive role models, and believing in one's self. Broadly, protective factors at the family and community levels were identified as positively creating and impacting one's social environment, which interacts with factors at the individual level to enhance resilience. An emphasis on the roles of cultural and land-based activities, history, and language, as well as on the importance of social and family supports, also emerged throughout the literature. Conclusions . Healthy communities and families foster and support youth who are resilient to mental health challenges and able to adapt and cope with multiple stressors, be they social, economic, or environmental. Creating opportunities and environments where youth can successfully navigate challenges and enhance their resilience can in turn contribute to fostering healthy Circumpolar communities. Looking at the

Enhancement of crop photosynthesis by diffuse light: quantifying the contributing factors.

Science.gov (United States)

Li, T; Heuvelink, E; Dueck, T A; Janse, J; Gort, G; Marcelis, L F M

2014-07-01

Plants use diffuse light more efficiently than direct light. However, experimental comparisons between diffuse and direct light have been obscured by co-occurring differences in environmental conditions (e.g. light intensity). This study aims to analyse the factors that contribute to an increase in crop photosynthesis in diffuse light and to quantify their relative contribution under different levels of diffuseness at similar light intensities. The hypothesis is that the enhancement of crop photosynthesis in diffuse light results not only from the direct effects of more uniform vertical and horizontal light distribution in the crop canopy, but also from crop physiological and morphological acclimation. Tomato (Solanum lycopersicum) crops were grown in three greenhouse compartments that were covered by glass with different degrees of light diffuseness (0, 45 and 71 % of the direct light being converted into diffuse light) while maintaining similar light transmission. Measurements of horizontal and vertical photosynthetic photon flux density (PPFD) distribution in the crop, leaf photosynthesis light response curves and leaf area index (LAI) were used to quantify each factor's contribution to an increase in crop photosynthesis in diffuse light. In addition, leaf temperature, photoinhibition, and leaf biochemical and anatomical properties were studied. The highest degree of light diffuseness (71 %) increased the calculated crop photosynthesis by 7·2 %. This effect was mainly attributed to a more uniform horizontal (33 % of the total effect) and vertical PPFD distribution (21 %) in the crop. In addition, plants acclimated to the high level of diffuseness by gaining a higher photosynthetic capacity of leaves in the middle of the crop and a higher LAI, which contributed 23 and 13 %, respectively, to the total increase in crop photosynthesis in diffuse light. Moreover, diffuse light resulted in lower leaf temperatures and less photoinhibition at the top of the canopy when

Icaritin enhances mESC self-renewal through upregulating core pluripotency transcription factors mediated by ER?

OpenAIRE

Tsang, Wing Pui; Zhang, Fengjie; He, Qiling; Cai, Waijiao; Huang, Jianhua; Chan, Wai Yee; Shen, Ziyin; Wan, Chao

2017-01-01

Utilization of small molecules in modulation of stem cell self-renewal is a promising approach to expand stem cells for regenerative therapy. Here, we identify Icaritin, a phytoestrogen molecule enhances self-renewal of mouse embryonic stem cells (mESCs). Icaritin increases mESCs proliferation while maintains their self-renewal capacity in vitro and pluripotency in vivo. This coincides with upregulation of key pluripotency transcription factors OCT4, NANOG, KLF4 and SOX2. The enhancement of m...

Activation of MSRV-Type Endogenous Retroviruses during Infectious Mononucleosis and Epstein-Barr Virus Latency: The Missing Link with Multiple Sclerosis?

Science.gov (United States)

Mameli, Giuseppe; Madeddu, Giordano; Mei, Alessandra; Uleri, Elena; Poddighe, Luciana; Delogu, Lucia G.; Maida, Ivana; Babudieri, Sergio; Serra, Caterina; Manetti, Roberto; Mura, Maria S.; Dolei, Antonina

2013-01-01

The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral?) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA-1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These

Activation of MSRV-type endogenous retroviruses during infectious mononucleosis and Epstein-Barr virus latency: the missing link with multiple sclerosis?

Science.gov (United States)

Mameli, Giuseppe; Madeddu, Giordano; Mei, Alessandra; Uleri, Elena; Poddighe, Luciana; Delogu, Lucia G; Maida, Ivana; Babudieri, Sergio; Serra, Caterina; Manetti, Roberto; Mura, Maria S; Dolei, Antonina

2013-01-01

The etiology of multiple sclerosis (MS) is still unclear. The immuno-pathogenic phenomena leading to neurodegeneration are thought to be triggered by environmental (viral?) factors operating on predisposing genetic backgrounds. Among the proposed co-factors are the Epstein Barr virus (EBV), and the potentially neuropathogenic HERV-W/MSRV/Syncytin-1 endogenous retroviruses. The ascertained links between EBV and MS are history of late primary infection, possibly leading to infectious mononucleosis (IM), and high titers of pre-onset IgG against EBV nuclear antigens (anti-EBNA IgG). During MS, there is no evidence of MS-specific EBV expression, while a continuous expression of HERV-Ws occurs, paralleling disease behaviour. We found repeatedly extracellular HERV-W/MSRV and MSRV-specific mRNA sequences in MS patients (in blood, spinal fluid, and brain samples), and MRSV presence/load strikingly paralleled MS stages and active/remission phases. Aim of the study was to verify whether HERV-W might be activated in vivo, in hospitalized young adults with IM symptoms, that were analyzed with respect to expression of HERV-W/MSRV transcripts and proteins. Healthy controls were either EBV-negative or latently EBV-infected with/without high titers of anti-EBNA-1 IgG. The results show that activation of HERV-W/MSRV occurs in blood mononuclear cells of IM patients (2Log10 increase of MSRV-type env mRNA accumulation with respect to EBV-negative controls). When healthy controls are stratified for previous EBV infection (high and low, or no anti-EBNA-1 IgG titers), a direct correlation occurs with MSRV mRNA accumulation. Flow cytometry data show increased percentages of cells exposing surface HERV-Wenv protein, that occur differently in specific cell subsets, and in acute disease and past infection. Thus, the data indicate that the two main links between EBV and MS (IM and high anti-EBNA-1-IgG titers) are paralleled by activation of the potentially neuropathogenic HERV-W/MSRV. These

Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain.

Science.gov (United States)

Ou, Wu; Delisle, Josie; Jacques, Jerome; Shih, Joanna; Price, Graeme; Kuhn, Jens H; Wang, Vivian; Verthelyi, Daniela; Kaplan, Gerardo; Wilson, Carolyn A

2012-01-25

The genus Ebolavirus includes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2) is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD). We hypothesized that immunization with MLD-deleted GP1,2 (GPΔMLD) would induce cross-species immunity by making more conserved regions accessible to the immune system. To test this hypothesis, mice were immunized with retrovirus-like particles (retroVLPs) bearing Ebola virus GPΔMLD, DNA plasmids (plasmo-retroVLP) that can produce such retroVLPs in vivo, or plasmo-retroVLP followed by retroVLPs. Cross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced. Our findings suggest that GPΔMLD presented through retroVLPs may provide a strategy for development of a vaccine against multiple ebolaviruses. Similar vaccination strategies may be adopted for other viruses whose envelope proteins contain highly variable regions that may mask more conserved domains from the immune system.

Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV closely resembles lung cancer in sheep infected with JSRV

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York Denis

2006-12-01

Full Text Available Abstract Background Jaagsiekte sheep retrovirus (JSRV causes a lethal lung cancer in sheep and goats. Expression of the JSRV envelope (Env protein in mouse lung, by using a replication-defective adeno-associated virus type 6 (AAV6 vector, induces tumors resembling those seen in sheep. However, the mouse and sheep tumors have not been carefully compared to determine if Env expression alone in mice can account for the disease features observed in sheep, or whether additional aspects of virus replication in sheep are important, such as oncogene activation following retrovirus integration into the host cell genome. Results We have generated mouse monoclonal antibodies (Mab against JSRV Env and have used these to study mouse and sheep lung tumor histology. These Mab detect Env expression in tumors in sheep infected with JSRV from around the world with high sensitivity and specificity. Mouse and sheep tumors consisted mainly of well-differentiated adenomatous foci with little histological evidence of anaplasia, but at long times after vector exposure some mouse tumors did have a more malignant appearance typical of adenocarcinoma. In addition to epithelial cell tumors, lungs of three of 29 sheep examined contained fibroblastic cell masses that expressed Env and appeared to be separate neoplasms. The Mab also stained nasal adenocarcinoma tissue from one United States sheep, which we show was due to expression of Env from ovine enzootic nasal tumor virus (ENTV, a virus closely related to JSRV. Systemic administration of the AAV6 vector encoding JSRV Env to mice produced numerous hepatocellular tumors, and some hemangiomas and hemangiosarcomas, showing that the Env protein can induce tumors in multiple cell types. Conclusion Lung cancers induced by JSRV infection in sheep and by JSRV Env expression in mice have similar histologic features and are primarily characterized by adenomatous proliferation of peripheral lung epithelial cells. Thus it is

Epidermal Growth Factor Enhances Cellular Uptake of Polystyrene Nanoparticles by Clathrin-Mediated Endocytosis.

Science.gov (United States)

Phuc, Le Thi Minh; Taniguchi, Akiyoshi

2017-06-19

The interaction between nanoparticles and cells has been studied extensively, but most research has focused on the effect of various nanoparticle characteristics, such as size, morphology, and surface charge, on the cellular uptake of nanoparticles. In contrast, there have been very few studies to assess the influence of cellular factors, such as growth factor responses, on the cellular uptake efficiency of nanoparticles. The aim of this study was to clarify the effects of epidermal growth factor (EGF) on the uptake efficiency of polystyrene nanoparticles (PS NPs) by A431 cells, a human carcinoma epithelial cell line. The results showed that EGF enhanced the uptake efficiency of A431 cells for PS NPs. In addition, inhibition and localization studies of PS NPs and EGF receptors (EGFRs) indicated that cellular uptake of PS NPs is related to the binding of EGF-EGFR complex and PS NPs. Different pathways are used to enter the cells depending on the presence or absence of EGF. In the presence of EGF, cellular uptake of PS NPs is via clathrin-mediated endocytosis, whereas, in the absence of EGF, uptake of PS NPs does not involve clathrin-mediated endocytosis. Our findings indicate that EGF enhances cellular uptake of PS NPs by clathrin-mediated endocytosis. This result could be important for developing safe nanoparticles and their safe use in medical applications.

Epidermal Growth Factor Enhances Cellular Uptake of Polystyrene Nanoparticles by Clathrin-Mediated Endocytosis

Directory of Open Access Journals (Sweden)

Le Thi Minh Phuc

2017-06-01

Full Text Available The interaction between nanoparticles and cells has been studied extensively, but most research has focused on the effect of various nanoparticle characteristics, such as size, morphology, and surface charge, on the cellular uptake of nanoparticles. In contrast, there have been very few studies to assess the influence of cellular factors, such as growth factor responses, on the cellular uptake efficiency of nanoparticles. The aim of this study was to clarify the effects of epidermal growth factor (EGF on the uptake efficiency of polystyrene nanoparticles (PS NPs by A431 cells, a human carcinoma epithelial cell line. The results showed that EGF enhanced the uptake efficiency of A431 cells for PS NPs. In addition, inhibition and localization studies of PS NPs and EGF receptors (EGFRs indicated that cellular uptake of PS NPs is related to the binding of EGF–EGFR complex and PS NPs. Different pathways are used to enter the cells depending on the presence or absence of EGF. In the presence of EGF, cellular uptake of PS NPs is via clathrin-mediated endocytosis, whereas, in the absence of EGF, uptake of PS NPs does not involve clathrin-mediated endocytosis. Our findings indicate that EGF enhances cellular uptake of PS NPs by clathrin-mediated endocytosis. This result could be important for developing safe nanoparticles and their safe use in medical applications.

Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds.

Science.gov (United States)

Hlavaty, K A; Gibly, R F; Zhang, X; Rives, C B; Graham, J G; Lowe, W L; Luo, X; Shea, L D

2014-07-01

Islet transplantation represents a potential cure for type 1 diabetes, yet the clinical approach of intrahepatic delivery is limited by the microenvironment. Microporous scaffolds enable extrahepatic transplantation, and the microenvironment can be designed to enhance islet engraftment and function. We investigated localized trophic factor delivery in a xenogeneic human islet to mouse model of islet transplantation. Double emulsion microspheres containing exendin-4 (Ex4) or insulin-like growth factor-1 (IGF-1) were incorporated into a layered scaffold design consisting of porous outer layers for islet transplantation and a center layer for sustained factor release. Protein encapsulation and release were dependent on both the polymer concentration and the identity of the protein. Proteins retained bioactivity upon release from scaffolds in vitro. A minimal human islet mass transplanted on Ex4-releasing scaffolds demonstrated significant improvement and prolongation of graft function relative to blank scaffolds carrying no protein, and the release profile significantly impacted the duration over which the graft functioned. Ex4-releasing scaffolds enabled better glycemic control in animals subjected to an intraperitoneal glucose tolerance test. Scaffolds releasing IGF-1 lowered blood glucose levels, yet the reduction was insufficient to achieve euglycemia. Ex4-delivering scaffolds provide an extrahepatic transplantation site for modulating the islet microenvironment to enhance islet function posttransplant. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5

International Nuclear Information System (INIS)

Li, Yang; Fan, Xing; Goodwin, C Rory; Laterra, John; Xia, Shuli

2008-01-01

Hepatocyte growth factor (HGF) and its receptor c-MET are commonly expressed in malignant gliomas and embryonic neuroectodermal tumors including medulloblastoma and appear to play an important role in the growth and dissemination of these malignancies. Dependent on cell context and the involvement of specific downstream effectors, both pro- and anti-apoptotic effects of HGF have been reported. Human medulloblastoma cells were treated with HGF for 24–72 hours followed by death receptor ligand TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) for 24 hours. Cell death was measured by MTT and Annexin-V/PI flow cytometric analysis. Changes in expression levels of targets of interest were measured by Northern blot analysis, quantitative reverse transcription-PCR, Western blot analysis as well as immunoprecipitation. In this study, we show that HGF promotes medulloblastoma cell death induced by TRAIL. TRAIL alone triggered apoptosis in DAOY cells and death was enhanced by pre-treating the cells with HGF for 24–72 h prior to the addition of TRAIL. HGF (100 ng/ml) enhanced TRAIL (10 ng/ml) induced cell death by 36% (P < 0.001). No cell death was associated with HGF alone. Treating cells with PHA-665752, a specific c-Met receptor tyrosine kinase inhibitor, significantly abrogated the enhancement of TRAIL-induced cell death by HGF, indicating that its death promoting effect requires activation of its canonical receptor tyrosine kinase. Cell death induced by TRAIL+HGF was predominately apoptotic involving both extrinsic and intrinsic pathways as evidenced by the increased activation of caspase-3, 8, 9. Promotion of apoptosis by HGF occurred via the increased expression of the death receptor DR5 and enhanced formation of death-inducing signal complexes (DISC). Taken together, these and previous findings indicate that HGF:c-Met pathway either promotes or inhibits medulloblastoma cell death via pathway and context specific mechanisms

Enhancement of intestinal growth in neonatal rats by epidermal growth factor in milk

International Nuclear Information System (INIS)

Berseth, C.L.

1987-01-01

Breast milk has been shown to enhance neonatal intestinal growth. Because epidermal growth factor (EGF) is present in the milk of various mammalian species, the hypothesis was tested that EGF in rodent milk mediates, in part, the breast milk-enhanced intestinal growth in neonatal rat. Fifty-eight rat pups fed artificial formal that contained 1.2, 3.0, and 6.0 μg/ml EGF for 39 h had greater incorporation of [ 3 H]thymidine into DNA and DNA content of intestine than 29 pups fed unsupplemented formula. Pups fed EGF for 5 days had significantly greater body weight, intestinal weight, length, and DNA content than control pups. Conversely, pups fed pooled rat milk containing rabbit-derived antibody to EGF for 39 h had intestines of lower weight that contained less DNA than animals fed rat milk containing normal rabbit serum. EGF appears to mediate, in part, breast milk-enhanced neonatal intestinal growth

Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

International Nuclear Information System (INIS)

Nakajima, Hideaki; Shibata, Fumi; Fukuchi, Yumi; Goto-Koshino, Yuko; Ito, Miyuki; Urano, Atsushi; Nakahata, Tatsutoshi; Aburatani, Hiroyuki; Kitamura, Toshio

2006-01-01

Immune suppressor factor (ISF) is a subunit of the vacuolar ATPase proton pump. We earlier identified a short form of ISF (ShIF) as a stroma-derived factor that supports cytokine-independent growth of mutant Ba/F3 cells. Here, we report that ISF/ShIF supports self-renewal and expansion of primary hematopoietic stem cells (HSCs). Co-culture of murine bone marrow cells with a stromal cell line overexpressing ISF or ShIF (MS10/ISF or MS10/ShIF) not only enhanced their colony-forming activity and the numbers of long-term culture initiating cells, but also maintained the competitive repopulating activity of HSC. This stem cell supporting activity depended on the proton-transfer function of ISF/ShIF. Gene expression analysis of ISF/ShIF-transfected cell lines revealed down-regulation of secreted frizzled-related protein-1 and tissue inhibitor of metalloproteinase-3, and the restoration of their expressions in MS10/ISF cells partially reversed its enhanced LTC-IC supporting activity to a normal level. These results suggest that ISF/ShIF confers stromal cells with enhanced supporting activities for HSCs by modulating Wnt-activity and the extracellular matrix

Calculating the momentum enhancement factor for asteroid deflection studies

International Nuclear Information System (INIS)

Heberling, Tamra; Gisler, Galen; Plesko, Catherine; Weaver, Robert

2017-01-01

The possibility of kinetic-impact deflection of threatening near-Earth asteroids will be tested for the first time in the proposed AIDA (Asteroid Impact Deflection Assessment) mission, involving NASAs DART (Double Asteroid Redirection Test). The impact of the DART spacecraft onto the secondary of the binary asteroid 65803 Didymos at a speed of 5 to 7 km/s is expected to alter the mutual orbit by an observable amount. Furthermore, the velocity transferred to the secondary depends largely on the momentum enhancement factor, typically referred to as beta. Here, we use two hydrocodes developed at Los Alamos, RAGE and PAGOSA, to calculate an approximate value for beta in laboratory-scale benchmark experiments. Convergence studies comparing the two codes show the importance of mesh size in estimating this crucial parameter.

Influencing Factors for Adopting Technology Enhanced Learning in the Medical Schools of Punjab, Pakistan

Science.gov (United States)

Iqbal, Shazia; Ahmad, Shahzad; Willis, Ian

2017-01-01

As the successful establishment of technology supported educational systems requires wide investment in terms of finances and faculty time, this study explores the influencing factors in the adoption of Technology Enhanced Learning (TEL) and the main barriers encountered during the use of TEL in Punjab, Pakistan. Semi-structured interviews were…

Genetic Engineering of T Cells to Target HERV-K, an Ancient Retrovirus on Melanoma.

Science.gov (United States)

Krishnamurthy, Janani; Rabinovich, Brian A; Mi, Tiejuan; Switzer, Kirsten C; Olivares, Simon; Maiti, Sourindra N; Plummer, Joshua B; Singh, Harjeet; Kumaresan, Pappanaicken R; Huls, Helen M; Wang-Johanning, Feng; Cooper, Laurence J N

2015-07-15

The human endogenous retrovirus (HERV-K) envelope (env) protein is a tumor-associated antigen (TAA) expressed on melanoma but not normal cells. This study was designed to engineer a chimeric antigen receptor (CAR) on T-cell surface, such that they target tumors in advanced stages of melanoma. Expression of HERV-K protein was analyzed in 220 melanoma samples (with various stages of disease) and 139 normal organ donor tissues using immunohistochemical (IHC) analysis. HERV-K env-specific CAR derived from mouse monoclonal antibody was introduced into T cells using the transposon-based Sleeping Beauty (SB) system. HERV-K env-specific CAR(+) T cells were expanded ex vivo on activating and propagating cells (AaPC) and characterized for CAR expression and specificity. This includes evaluating the HERV-K-specific CAR(+) T cells for their ability to kill A375-SM metastasized tumors in a mouse xenograft model. We detected HERV-K env protein on melanoma but not in normal tissues. After electroporation of T cells and selection on HERV-K(+) AaPC, more than 95% of genetically modified T cells expressed the CAR with an effector memory phenotype and lysed HERV-K env(+) tumor targets in an antigen-specific manner. Even though there is apparent shedding of this TAA from tumor cells that can be recognized by HERV-K env-specific CAR(+) T cells, we observed a significant antitumor effect. Adoptive cellular immunotherapy with HERV-K env-specific CAR(+) T cells represents a clinically appealing treatment strategy for advanced-stage melanoma and provides an approach for targeting this TAA on other solid tumors. ©2015 American Association for Cancer Research.

Review on porcine endogenous retrovirus detection assays—impact on quality and safety of xenotransplants

Science.gov (United States)

Godehardt, Antonia W; Rodrigues Costa, Michael; Tönjes, Ralf R

2015-01-01

Xenotransplantation of porcine organs, tissues, and cells inherits a risk for xenozoonotic infections. Viable tissues and cells intended for transplantation have to be considered as potentially contaminated non-sterile products. The demands on microbial testing, based on the regulatory requirements, are often challenging due to a restricted shelf life or the complexity of the product itself. In Europe, the regulatory framework for xenogeneic cell therapy is based on the advanced therapy medicinal products (ATMP) regulation (2007), the EMA CHMP Guideline on xenogeneic cell-based medicinal products (2009), as well as the WHO and Council of Europe recommendations. In the USA, FDA guidance for industry (2003) regulates the use of xenotransplants. To comply with the regulations, validated test methods need to be established that reveal the microbial status of a transplant within its given shelf life, complemented by strictly defined action alert limits and supported by breeding in specific pathogen-free (SPF) facilities. In this review, we focus on assays for the detection of the porcine endogenous retroviruses PERV-A/-B/-C, which exhibit highly polymorphic proviral loci in pig genomes. PERVs are transmitted vertically and cannot be completely eliminated by breeding or gene knock out technology. PERVs entail a public health concern that will persist even if no evidence of PERV infection of xenotransplant recipients in vivo has been revealed yet. Nevertheless, infectious risks must be minimized by full assessment of pigs as donors by combining different molecular screening assays for sensitive and specific detection as well as a functional analysis of the infectivity of PERV including an adequate monitoring of recipients. PMID:25641488

Factors Associated with Enhanced Gross Motor Progress in Children with Cerebral Palsy: A Register-Based Study.

Science.gov (United States)

Størvold, Gunfrid V; Jahnsen, Reidun B; Evensen, Kari Anne I; Romild, Ulla K; Bratberg, Grete H

2018-05-01

To examine associations between interventions and child characteristics; and enhanced gross motor progress in children with cerebral palsy (CP). Prospective cohort study based on 2048 assessments of 442 children (256 boys, 186 girls) aged 2-12 years registered in the Cerebral Palsy Follow-up Program and the Cerebral Palsy Register of Norway. Gross motor progress estimates were based on repeated measures of reference percentiles for the Gross Motor Function Measure (GMFM-66) in a linear mixed model. Mean follow-up time: 2.9 years. Intensive training was the only intervention factor associated with enhanced gross motor progress (mean 3.3 percentiles, 95% CI: 1.0, 5.5 per period of ≥3 sessions per week and/or participation in an intensive program). Gross motor function was on average 24.2 percentiles (95% CI: 15.2, 33.2) lower in children with intellectual disability compared with others. Except for eating problems (-10.5 percentiles 95% CI: -18.5, -2.4) and ankle contractures by age (-1.9 percentiles 95% CI: -3.6, -0.2) no other factors examined were associated with long-term gross motor progress. Intensive training was associated with enhanced gross motor progress over an average of 2.9 years in children with CP. Intellectual disability was a strong negative prognostic factor. Preventing ankle contractures appears important for gross motor progress.

Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents

Science.gov (United States)

Sharma, Sanjai; Murai, Fukashi; Miyanohara, Atsushi; Friedmann, Theodore

1997-01-01

Retrovirus packaging cell lines expressing the Moloney murine leukemia virus gag and pol genes but lacking virus envelope genes produce virus-like particles constitutively, whether or not they express a transcript from an integrated retroviral provirus. In the absence of a proviral transcript, the assembled particles contain processed gag and reverse transcriptase, and particles made by cells expressing an integrated lacZ provirus also contain viral RNA. The virus-like particles from both cell types are enveloped and are secreted/budded into the extracellular space but are noninfectious. Their physicochemical properties are similar to those of mature retroviral particles. The noninfectious gag pol RNA particles can readily be made infectious by the addition of lipofection reagents to produce preparations with titers of up to 105 colony-forming units per ml. PMID:9380714

Noninfectious virus-like particles produced by Moloney murine leukemia virus-based retrovirus packaging cells deficient in viral envelope become infectious in the presence of lipofection reagents.

Science.gov (United States)

Sharma, S; Murai, F; Miyanohara, A; Friedmann, T

1997-09-30

Retrovirus packaging cell lines expressing the Moloney murine leukemia virus gag and pol genes but lacking virus envelope genes produce virus-like particles constitutively, whether or not they express a transcript from an integrated retroviral provirus. In the absence of a proviral transcript, the assembled particles contain processed gag and reverse transcriptase, and particles made by cells expressing an integrated lacZ provirus also contain viral RNA. The virus-like particles from both cell types are enveloped and are secreted/budded into the extracellular space but are noninfectious. Their physicochemical properties are similar to those of mature retroviral particles. The noninfectious gag pol RNA particles can readily be made infectious by the addition of lipofection reagents to produce preparations with titers of up to 10(5) colony-forming units per ml.

p8 inhibits the growth of human pancreatic cancer cells and its expression is induced through pathways involved in growth inhibition and repressed by factors promoting cell growth

Directory of Open Access Journals (Sweden)

Vasseur Sophie

2003-11-01

Full Text Available Abstract Background p8 is a stress-induced protein with multiple functions and biochemically related to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in pancreatic cancer-derived cells. Methods Expression of p8 was silenced in the human pancreatic cancer cell lines Panc-1 and BxPc-3 by infection with a retrovirus expressing p8 RNA in the antisense orientation. Cell growth was measured in control and p8-silenced cells. Influence on p8 expression of the induction of intracellular pathways promoting cellular growth or growth arrest was monitored. Results p8-silenced cells grew more rapidly than control cells transfected with the empty retrovirus. Activation of the Ras→Raf→MEK→ERK and JNK intracellular pathways down-regulated p8 expression. In addition, the MEK1/2 inhibitor U0126 and the JNK inhibitor SP600125 up-regulates expression of p8. Conversely, p38 or TGFβ-1 induced p8 expression whereas the specific p38 inhibitor SB203580 down-regulated p8 expression. Finally, TGFβ-1 induction was in part mediated through p38. Conclusions p8 inhibits the growth of human pancreatic cancer cells. p8 expression is induced through pathways involved in growth inhibition and repressed by factors that promote cell growth. These results suggest that p8 belongs to a pathway regulating the growth of pancreatic cancer cells.

Endogenous retrovirus insertion in the KIT oncogene determines white and white spotting in domestic cats.

Science.gov (United States)

David, Victor A; Menotti-Raymond, Marilyn; Wallace, Andrea Coots; Roelke, Melody; Kehler, James; Leighty, Robert; Eizirik, Eduardo; Hannah, Steven S; Nelson, George; Schäffer, Alejandro A; Connelly, Catherine J; O'Brien, Stephen J; Ryugo, David K

2014-08-01

The Dominant White locus (W) in the domestic cat demonstrates pleiotropic effects exhibiting complete penetrance for absence of coat pigmentation and incomplete penetrance for deafness and iris hypopigmentation. We performed linkage analysis using a pedigree segregating White to identify KIT (Chr. B1) as the feline W locus. Segregation and sequence analysis of the KIT gene in two pedigrees (P1 and P2) revealed the remarkable retrotransposition and evolution of a feline endogenous retrovirus (FERV1) as responsible for two distinct phenotypes of the W locus, Dominant White, and white spotting. A full-length (7125 bp) FERV1 element is associated with white spotting, whereas a FERV1 long terminal repeat (LTR) is associated with all Dominant White individuals. For purposes of statistical analysis, the alternatives of wild-type sequence, FERV1 element, and LTR-only define a triallelic marker. Taking into account pedigree relationships, deafness is genetically linked and associated with this marker; estimated P values for association are in the range of 0.007 to 0.10. The retrotransposition interrupts a DNAase I hypersensitive site in KIT intron 1 that is highly conserved across mammals and was previously demonstrated to regulate temporal and tissue-specific expression of KIT in murine hematopoietic and melanocytic cells. A large-population genetic survey of cats (n = 270), representing 30 cat breeds, supports our findings and demonstrates statistical significance of the FERV1 LTR and full-length element with Dominant White/blue iris (P < 0.0001) and white spotting (P < 0.0001), respectively. Copyright © 2014 David et al.

Felis Catus Gammaherpesvirus 1 DNAemia in Whole Blood from Therapeutically Immunosuppressed or Retrovirus-Infected Cats

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Alicia J. McLuckie

2017-03-01

Full Text Available Gammaherpesviruses are major co-pathogens of human immunodeficiency virus (HIV infection, making the interactions between feline immunodeficiency virus (FIV and Felis catus gammaherpesvirus 1 (FcaGHV1 pertinent to both human and veterinary medical research. FIV-infected cats are at increased risk of FcaGHV1 DNAemia and consistently harbor higher FcaGHV1 loads than FIV-uninfected cats. Whether immune deficiencies unrelated to FIV are associated with similar risks is unknown. Using whole blood FcaGHV1 qPCR, we found no difference in the frequency of DNAemia or DNA load in therapeutically immunosuppressed (P1, n = 18 or feline leukemia virus (FeLV-infected (P2, n = 57 patients compared with age- and sex-matched controls (C1, n = 58; C2, n = 57. In contrast, FIV/FeLV-co-infected cats (P3, n = 5 were at increased risk of FcaGHV1 DNAemia compared to retrovirus uninfected controls (C3, n = 39; p = 0.0068, and had a higher median FcaGHV1 DNA load, although the latter was not significant. FIV/FeLV-co-infected cats (P3 had a similar frequency of FcaGHV1 DNAemia reported compared to FIV-infected controls (C4. In conclusion, we found no evidence that cats with therapeutic immunosuppression or FeLV infection were at greater risk of FcaGHV1 DNAemia or had higher FcaGHV1 DNA load in whole blood. The risk of DNAemia in FIV/FeLV-co-infected cats was similar to that documented previously in cats infected with FIV alone.

Comparison of the convergent receptor utilization of a retargeted feline leukemia virus envelope with a naturally-occurring porcine endogenous retrovirus A.

Science.gov (United States)

Mazari, Peter M; Argaw, Takele; Valdivieso, Leonardo; Zhang, Xia; Marcucci, Katherine T; Salomon, Daniel R; Wilson, Carolyn A; Roth, Monica J

2012-06-05

In vitro screening of randomized FeLV Envelope libraries identified the CP isolate, which enters cells through HuPAR-1, one of two human receptors utilized by porcine endogenous retrovirus-A (PERV-A), a distantly related gammaretrovirus. The CP and PERV-A Envs however, share little amino acid homology. Their receptor utilization was examined to define the common receptor usage of these disparate viral Envs. We demonstrate that the receptor usage of CP extends to HuPAR-2 but not to the porcine receptor PoPAR, the cognate receptor for PERV-A. Reciprocal interference between virus expressing CP and PERV-A Envs was observed on human cells. Amino acid residues localized to within the putative second extracellular loop (ECL-2) of PAR-1 and PAR-2 are found to be critical for CP envelope function. Through a panel of receptor chimeras and point mutations, this area was also found to be responsible for the differential usage of the PoPAR receptor between CP and PERV-A. Copyright © 2012 Elsevier Inc. All rights reserved.

Analyses of prevalence and polymorphisms of six replication-competent and chromosomally assigned porcine endogenous retroviruses in individual pigs and pig subspecies

International Nuclear Information System (INIS)

Niebert, Marcus; Toenjes, Ralf R.

2003-01-01

As porcine endogenous retroviruses (PERV) productively infect human cells in vitro, they pose a serious risk in xenotransplantation and xenogeneic cell therapies. We have analyzed the prevalence of six well-characterized full-length PERV, five of them being replication-competent and four of them being chromosomally assigned (J. Virol. 75 (2001) 5465; J. Virol. 76 (2002) 2714). These analyses revealed a heterogeneous distribution of PERV among individuals and, as no PERV is present in every pig, it seems feasible to generate pigs free of functional PERV by conventional breeding. Conversely, as PERV are polymorphic, single proviruses may have escaped detection and this kind of assay must be performed for every herd used in xenotransplantation or xenogeneic cell therapies. In addition, specific proviruses show internal point mutations which significantly affect their replicational capacities. As there are two different types of PERV LTR structures showing varying levels of transcriptional capacity (J. Virol. 75 (2001) 6933), an analysis of 21 distinct chromosomal locations revealed that PERV which harbor highly active LTRs with repeat elements in U3 are dominant

An experimental method to determine the electrostatic field enhancement factor of a practical conductor surface

DEFF Research Database (Denmark)

McAllister, Iain Wilson; Crichton, George C

1989-01-01

A method of determining the field enhancement factor of a practical conductor is presented. The method is developed from a modified theory of discharge onset in a gaseous medium. This modification incorporates the influence of conductor surface roughness. Onset data from an experimental study...

SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV

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Gracia Viviana Gonzalez-Enriquez

2017-01-01

Full Text Available The serine incorporator 5 (SERINC5 is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef, S2, and glycosylated Gag (glycoGag. These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy.

The Study on Properties and Application of Enhanced Dynamic Wedge Factor

International Nuclear Information System (INIS)

Kim, Dae Sup; Ban, Tae Joon; Yeom, Mi Suk; Yoo, Soon Mi; Lee, Woo Seok; Back, Geum Mun; Kwon, Kyung Tae

2010-01-01

We try to calculate EDW-factor easily with the formula applies essential data of EDW-factor and evaluate the validity through a measurement. We used the given value of GSTT (Golden Segmented Treatment Table) for the calculation of the EDW-factor. As to the experimental device, 0.6 cc farmer-type ion-chamber, an electrometer and water- phantom were used. A measurement was made at the maximum dose depth of the photon beam energy 6 MV and 15 MV under the condition that SSD (Source to Surface Distance) was 100 cm. The angle of the EDW (Enhanced Dynamic Wedge) which we use in an experiment was 60 degree, 30 degree, 20 degree in the Y1-OUT direction. We used Eclipse planning system (Varian, USA) as RTP system and the EDW-factor was calculated about all fields and EDW direction. In order to show the EDW-factor feature, a measurement was made at the selected field that verify the influence of the dependability about X, Y jaw and off-axis field. When we change the Y1 field, it influence on the EDW-Factor and measured value. But the error between measured values and calculated values was less than 1%. The experimental result indicated the tendency that the error of the result of calculation and measured value becomes smaller as the EDW angle become smaller whether the calculation point (measurement point) and iso-center are same or not. The influence of the field size and energy did not show up. We simulated with the same condition using the RTP system. And we found that it makes no difference between the MU which is calculated manually by applying the EDW-Factor obtained from the commercial program and the value which is calculated by using RTP system. We excluded fitting value from well-known EDW-Factor formula and calculated EDW-factor with the formula applies essential data of EDW-factor only. As a result, there are no significant difference between the measured value and calculated value and it showed errors less than 1%. Also, we implemented the commercial program to

Elastic enhancement factor in the 11B(p,n0)11C reaction at Ep=14.3 MeV

International Nuclear Information System (INIS)

Hussein, M.S.; Pessoa, E.F.; Schelin, H.R.; Carlson, B.V.; Douglas, R.A.

1985-01-01

The elastic enhancement factor in charge exchange reactions proceeding via the compound nucleus, predicted to attain the value of 2 in the weak isospin mixing regime by Harney, Weidenmuller and Richter five years ago, is tested here in the system 11 B(p,n) 11 C at = 14.3 MeV. Both the DWBA and Hauser-Feshbach calculations employed in the analysis are used in a way which physically simulates a two coupled-channels model. Our results show an enhancement factor larger than 1 indicating that isospin is mainly conserved in this reaction. (Author) [pt

Compressive strain induced enhancement in thermoelectric-power-factor in monolayer MoS2 nanosheet

International Nuclear Information System (INIS)

Dimple; Jena, Nityasagar; De Sarkar, Abir

2017-01-01

Strain and temperature induced tunability in the thermoelectric properties in monolayer MoS 2 (ML-MoS 2 ) has been demonstrated using density functional theory coupled to semi-classical Boltzmann transport theory. Compressive strain, in general and uniaxial compressive strain (along the zig-zag direction), in particular, is found to be most effective in enhancing the thermoelectric power factor, owing to the higher electronic mobility and its sensitivity to lattice compression along this direction. Variation in the Seebeck coefficient and electronic band gap with strain is found to follow the Goldsmid–Sharp relation. n-type doping is found to raise the relaxation time-scaled thermoelectric power factor higher than p-type doping and this divide widens with increasing temperature. The relaxation time-scaled thermoelectric power factor in optimally n-doped ML-MoS 2 is found to undergo maximal enhancement under the application of 3% uniaxial compressive strain along the zig-zag direction, when both the ( direct ) electronic band gap and the Seebeck coefficient reach their maximum, while the electron mobility drops down drastically from 73.08 to 44.15 cm 2 V −1 s −1 . Such strain sensitive thermoelectric responses in ML-MoS 2 could open doorways for a variety of applications in emerging areas in 2D-thermoelectrics, such as on-chip thermoelectric power generation and waste thermal energy harvesting. (paper)

Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain

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Ou Wu

2012-01-01

Full Text Available Abstract Background The genus Ebolavirus includes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2 is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD. We hypothesized that immunization with MLD-deleted GP1,2 (GPΔMLD would induce cross-species immunity by making more conserved regions accessible to the immune system. Methods To test this hypothesis, mice were immunized with retrovirus-like particles (retroVLPs bearing Ebola virus GPΔMLD, DNA plasmids (plasmo-retroVLP that can produce such retroVLPs in vivo, or plasmo-retroVLP followed by retroVLPs. Results Cross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced. Conclusion Our findings suggest that GPΔMLD presented through retroVLPs may provide a strategy for development of a vaccine against multiple ebolaviruses. Similar vaccination strategies may be adopted for other viruses whose envelope proteins contain highly variable regions that may mask more conserved domains from the immune system.

Characterization of retrovirus-based reporter viruses pseudotyped with the precursor membrane and envelope glycoproteins of four serotypes of dengue viruses

International Nuclear Information System (INIS)

Hu, H.-P.; Hsieh, S.-C.; King, C.-C.; Wang, W.-K.

2007-01-01

In this study, we successfully established retrovirus-based reporter viruses pseudotyped with the precursor membrane and envelope (PrM/E) proteins of each of the four serotypes of dengue viruses, which caused the most important arboviral diseases in this century. Co-sedimentation of the dengue E protein and HIV-1 core proteins by sucrose gradient analysis of the pseudotype reporter virus of dengue virus type 2, D2(HIVluc), and detection of HIV-1 core proteins by immunoprecipitation with anti-E monoclonal antibody suggested that dengue viral proteins were incorporated into the pseudotype viral particles. The infectivity in target cells, as assessed by the luciferase activity, can be inhibited by the lysosomotropic agents, suggesting a pH-dependent mechanism of entry. Amino acid substitutions of the leucine at position 107, a critical residue at the fusion loop of E protein, with lysine resulted in severe impairment in infectivity, suggesting that entry of the pseudotype reporter virus is mediated through the fusogenic properties of E protein. With more and more dengue viral sequences available from different outbreaks worldwide, this sensitive and convenient tool has the potential to facilitate molecular characterization of the PrM/E proteins of dengue field isolates

Inherently variable responses to glucocorticoid stress among endogenous retroviruses isolated from 23 mouse strains.

Science.gov (United States)

Hsu, Karen; Lee, Young-Kwan; Chew, Alex; Chiu, Sophia; Lim, Debora; Greenhalgh, David G; Cho, Kiho

2017-10-01

Active participation of endogenous retroviruses (ERVs) in disease processes has been exemplified by the finding that the HERV (human ERV)-W envelope protein is involved in the pathogenesis of multiple sclerosis, an autoimmune disease. We also demonstrated that injury-elicited stressors alter the expression of murine ERVs (MuERVs), both murine leukemia virus-type and mouse mammary tumor virus (MMTV)-type (MMTV-MuERV). In this study, to evaluate MMTV-MuERVs' responses to stress (e.g., injury, infection)-elicited systemic glucocorticoid (GC) levels, we examined the GC-stress response of 64 MMTV-MuERV promoters isolated from the genomes of 23 mouse strains. All 64 promoters responded to treatment with a synthetic GC, dexamethasone (DEX), at a wide range from a 0.6- to 85.7-fold increase in reporter activity compared to no treatment. An analysis of the 10 lowest and 10 highest DEX responders revealed specific promoter elements exclusively present in either the three lowest or the two highest responders. Each promoter had a unique profile of transcription regulatory elements and the glucocorticoid response element (GRE) was identified in all promoters with the number of GREs ranging from 2 to 7. The three lowest DEX responders were the only promoters with two GREs. The findings from this study suggest that certain MMTV-MuERVs are more responsive to stress-elicited systemic GC elevation compared to the others. The mouse strain-specific genomic MMTV-MuERV profiles and individual MMTV-MuERVs' differential responses to GC-stress might explain, at least in part, the variable inflammatory responses to injury and/or infection, often observed among different mouse strains. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis edited by Dr. Raghavan Raju. Copyright © 2016 Elsevier B.V. All rights reserved.

Cerebellum-specific and age-dependent expression of an endogenous retrovirus with intact coding potential

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Itoh Takayuki

2011-10-01

Full Text Available Abstract Background Endogenous retroviruses (ERVs, including murine leukemia virus (MuLV type-ERVs (MuLV-ERVs, are presumed to occupy ~10% of the mouse genome. In this study, following the identification of a full-length MuLV-ERV by in silico survey of the C57BL/6J mouse genome, its distribution in different mouse strains and expression characteristics were investigated. Results Application of a set of ERV mining protocols identified a MuLV-ERV locus with full coding potential on chromosome 8 (named ERVmch8. It appears that ERVmch8 shares the same genomic locus with a replication-incompetent MuLV-ERV, called Emv2; however, it was not confirmed due to a lack of relevant annotation and Emv2 sequence information. The ERVmch8 sequence was more prevalent in laboratory strains compared to wild-derived strains. Among 16 different tissues of ~12 week-old female C57BL/6J mice, brain homogenate was the only tissue with evident expression of ERVmch8. Further ERVmch8 expression analysis in six different brain compartments and four peripheral neuronal tissues of C57BL/6J mice revealed no significant expression except for the cerebellum in which the ERVmch8 locus' low methylation status was unique compared to the other brain compartments. The ERVmch8 locus was found to be surrounded by genes associated with neuronal development and/or inflammation. Interestingly, cerebellum-specific ERVmch8 expression was age-dependent with almost no expression at 2 weeks and a plateau at 6 weeks. Conclusions The ecotropic ERVmch8 locus on the C57BL/6J mouse genome was relatively undermethylated in the cerebellum, and its expression was cerebellum-specific and age-dependent.

Dual infections with HIV-1, HIV-2 and HTLV-I are more common in older women than in men in Guinea-Bissau

DEFF Research Database (Denmark)

Holmgren, B; da Silva, Z; Larsen, Olav Ditlevsen

2003-01-01

OBJECTIVES: To investigate the association between the three human retroviruses, HIV-1, HIV-2 and HTLV-I. DESIGN: Community-based follow-up studies of retrovirus infections in two cohorts. METHODS: A total of 2057 individuals aged 35 years and over were eligible for inclusion. Participants were...... interviewed and had a blood sample drawn. Samples were analysed for HIV-1, HIV-2 and HTLV infections. Uni- and multivariate analyses that included behavioural and socio-economic factors were performed using logistic regression and Poisson regression models. RESULTS: A total of 1686 individuals participated...... increased with age for all three retroviruses. Dual infections were more common in women than in men. Assuming independent distribution of the viruses, the observed prevalence of dual infections in women was significantly higher than expected, while the prevalence was not increased in men. The prevalence...

Manipulation of the membrane binding site of vitamin K-dependent proteins: Enhanced biological function of human factor VII

OpenAIRE

Shah, Amit M.; Kisiel, Walter; Foster, Donald C.; Nelsestuen, Gary L.

1998-01-01

Recent studies suggested that modification of the membrane contact site of vitamin K-dependent proteins may enhance the membrane affinity and function of members of this protein family. The properties of a factor VII mutant, factor VII-Q10E32, relative to wild-type factor VII (VII, containing P10K32), have been compared. Membrane affinity of VII-Q10E32 was about 20-fold higher than that of wild-type factor VII. The rate of autoactivation VII-Q10E32 with soluble tissue factor was 100-fold fast...

Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells

Science.gov (United States)

Benson, Don M.; Yu, Jianhua; Becknell, Brian; Wei, Min; Freud, Aharon G.; Ferketich, Amy K.; Trotta, Rossana; Perrotti, Danilo; Briesewitz, Roger

2009-01-01

Stem cell factor (SCF) promotes synergistic cellular proliferation in combination with several growth factors, and appears important for normal natural killer (NK)–cell development. CD34+ hematopoietic precursor cells (HPCs) require interleukin-15 (IL-15) for differentiation into human NK cells, and this effect can be mimicked by IL-2. Culture of CD34+ HPCs or some primary human NK cells in IL-2/15 and SCF results in enhanced growth compared with either cytokine alone. The molecular mechanisms responsible for this are unknown and were investigated in the present work. Activation of NK cells by IL-2/15 increases expression of c-kit whose kinase activity is required for synergy with IL-2/15 signaling. Mitogen-activated protein kinase (MAPK) signaling intermediaries that are activated both by SCF and IL-2/15 are enhanced in combination to facilitate earlier cell-cycle entry. The effect results at least in part via enhanced MAPK-mediated modulation of p27 and CDK4. Collectively the data reveal a novel mechanism by which SCF enhances cellular proliferation in combination with IL-2/15 in primary human NK cells. PMID:19060242

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

Science.gov (United States)

Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

2017-08-01

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

Seroprevalence of feline leukemia virus and feline immunodeficiency virus infection among cats in Canada.

Science.gov (United States)

Little, Susan; Sears, William; Lachtara, Jessica; Bienzle, Dorothee

2009-06-01

The purposes of this study were to determine the seroprevalence of feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infection among cats in Canada and to identify risk factors for seropositivity. Signalment, lifestyle factors, and test results for FeLV antigen and FIV antibody were analyzed for 11 144 cats from the 10 Canadian provinces. Seroprevalence for FIV antibody was 4.3% and seroprevalence for FeLV antigen was 3.4%. Fifty-eight cats (0.5%) were seropositive for both viruses. Seroprevalence varied geographically. Factors such as age, gender, health status, and lifestyle were significantly associated with risk of FeLV and FIV seropositivity. The results suggest that cats in Canada are at risk of retrovirus infection and support current recommendations that the retrovirus status of all cats should be known.

Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation

International Nuclear Information System (INIS)

Leigh, B.R.; Khan, W.; Hancock, S.L.

1995-01-01

Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 μ/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 ± 0.7 per duodenal cross section for controls to 30.0 ± 1.7 after treatment with SCF (P=0.03). The TBI dose producing 50% mortality of 6 days (LD 50/6 ) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine. 29 refs., 4 figs

Theoretical studies of surface enhanced hyper-Raman spectroscopy: The chemical enhancement mechanism

Science.gov (United States)

Valley, Nicholas; Jensen, Lasse; Autschbach, Jochen; Schatz, George C.

2010-08-01

Hyper-Raman spectra for pyridine and pyridine on the surface of a tetrahedral 20 silver atom cluster are calculated using static hyperpolarizability derivatives obtained from time dependent density functional theory. The stability of the results with respect to choice of exchange-correlation functional and basis set is verified by comparison with experiment and with Raman spectra calculated for the same systems using the same methods. Calculated Raman spectra were found to match well with experiment and previous theoretical calculations. The calculated normal and surface enhanced hyper-Raman spectra closely match experimental results. The chemical enhancement factors for hyper-Raman are generally larger than for Raman (102-104 versus 101-102). Integrated hyper-Raman chemical enhancement factors are presented for a set of substituted pyridines. A two-state model is developed to predict these chemical enhancement factors and this was found to work well for the majority of the molecules considered, providing a rationalization for the difference between hyper-Raman and Raman enhancement factors.

The dynamic characteristics and linewidth enhancement factor of quasi-supercontinuum self-assembled quantum dot lasers

KAUST Repository

Tan, Cheeloon

2009-09-01

The theoretical analysis of optical gain and chirp characteristics of a semiconductor quantum dot (Qdot) broadband laser is presented. The model based on population rate equations, has been developed to investigate the multiple states lasing or quasi-supercontinuum lasing in InGaAs/GaAs Qdot laser. The model takes into account factors such as Qdot size fluctuation, finite carrier lifetime in each confined energy states, wetting layer induced nonconfined states and the presence of continuum states. Hence, calculation of the linewidth enhancement factor together with the variation of optical gain and index change across the spectrum of interest becomes critical to yield a basic understanding on the limitation of this new class of lasers. Such findings are important for the design of a practical single broadband laser diode for applications in low coherence interferometry sensing and optical fiber communications. Calculation results show that the linewidth enhancement factor from the ground state of broadband Qdot lasers (α ∼ 3) is slightly larger but in the same order of magnitude as compared to that of conventional Qdot lasers. The gain spectrum of the quasi-supercontinuum lasing system exhibits almost twice the bandwidth than conventional lasers but with comparable material differential gain (∼ 10-16 cm2) and material differential refractive index (∼ 10sup>-20 cm3 ) near current threshold. © 2009 IEEE.

The dynamic characteristics and linewidth enhancement factor of quasi-supercontinuum self-assembled quantum dot lasers

KAUST Repository

Tan, Cheeloon; Wang, Yang; Djie, Hery Susanto; Ooi, Boon S.

2009-01-01

The theoretical analysis of optical gain and chirp characteristics of a semiconductor quantum dot (Qdot) broadband laser is presented. The model based on population rate equations, has been developed to investigate the multiple states lasing or quasi-supercontinuum lasing in InGaAs/GaAs Qdot laser. The model takes into account factors such as Qdot size fluctuation, finite carrier lifetime in each confined energy states, wetting layer induced nonconfined states and the presence of continuum states. Hence, calculation of the linewidth enhancement factor together with the variation of optical gain and index change across the spectrum of interest becomes critical to yield a basic understanding on the limitation of this new class of lasers. Such findings are important for the design of a practical single broadband laser diode for applications in low coherence interferometry sensing and optical fiber communications. Calculation results show that the linewidth enhancement factor from the ground state of broadband Qdot lasers (α ∼ 3) is slightly larger but in the same order of magnitude as compared to that of conventional Qdot lasers. The gain spectrum of the quasi-supercontinuum lasing system exhibits almost twice the bandwidth than conventional lasers but with comparable material differential gain (∼ 10-16 cm2) and material differential refractive index (∼ 10sup>-20 cm3 ) near current threshold. © 2009 IEEE.

Icaritin enhances mESC self-renewal through upregulating core pluripotency transcription factors mediated by ERα.

Science.gov (United States)

Tsang, Wing Pui; Zhang, Fengjie; He, Qiling; Cai, Waijiao; Huang, Jianhua; Chan, Wai Yee; Shen, Ziyin; Wan, Chao

2017-01-16

Utilization of small molecules in modulation of stem cell self-renewal is a promising approach to expand stem cells for regenerative therapy. Here, we identify Icaritin, a phytoestrogen molecule enhances self-renewal of mouse embryonic stem cells (mESCs). Icaritin increases mESCs proliferation while maintains their self-renewal capacity in vitro and pluripotency in vivo. This coincides with upregulation of key pluripotency transcription factors OCT4, NANOG, KLF4 and SOX2. The enhancement of mESCs self-renewal is characterized by increased population in S-phase of cell cycle, elevation of Cylin E and Cyclin-dependent kinase 2 (CDK2) and downregulation of p21, p27 and p57. PCR array screening reveals that caudal-related homeobox 2 (Cdx2) and Rbl2/p130 are remarkably suppressed in mESCs treated with Icaritin. siRNA knockdown of Cdx2 or Rbl2/p130 upregulates the expression of Cyclin E, OCT4 and SOX2, and subsequently increases cell proliferation and colony forming efficiency of mESCs. We then demonstrate that Icaritin co-localizes with estrogen receptor alpha (ERα) and activates its nuclear translocation in mESCs. The promotive effect of Icaritin on cell cycle and pluripotency regulators are eliminated by siRNA knockdown of ERα in mESCs. The results suggest that Icaritin enhances mESCs self-renewal by regulating cell cycle machinery and core pluripotency transcription factors mediated by ERα.

Tropism, Cytotoxicity, and Inflammatory Properties of Two Envelope Genes of Murine Leukemia Virus Type-Endogenous Retroviruses of C57BL/6J Mice

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Young-Kwan Lee

2011-01-01

Full Text Available Envelope (env proteins of certain endogenous retroviruses (ERVs participate in various pathophysiological processes. In this study, we characterized pathophysiologic properties of two murine leukemia virus-type ERV (MuLV-ERV env genes cloned from the ovary of C57BL/6J mice. The two env genes (named ENVOV1 and ENVOV2, with 1,926\\,bp coding region, originated from two MuLV-ERV loci on chromosomes 8 and 18, respectively. ENVOV1 and ENVOV2 were ~75 kDa and predominantly expressed on the cell membrane. They were capable of producing pseudotype murine leukemia virus virions. Tropism trait and infectivity of ENVOV2 were similar to the polytropic env; however, ENVOV1 had very low level of infectivity. Overexpression of ENVOV2, but not ENVOV1, exerted cytotoxic effects and induced expression of COX-2, IL-1β, IL-6, and iNOS. These findings suggest that the ENVOV1 and ENVOV2 are capable of serving as an env protein for virion assembly, and they exert differential cytotoxicity and modulation of inflammatory mediators.

Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2

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Jung-Seok Lee

2018-04-01

Full Text Available This study aimed to determine the cellular characteristics and behaviors of human bone marrow stromal cells (hBMSCs expanded in media in a hypoxic or normoxic condition and with or without fibroblast growth factor-2 (FGF-2 treatment. hBMSCs isolated from the vertebral body and expanded in these four groups were evaluated for cellular proliferation/migration, colony-forming units, cell-surface characterization, in vitro differentiation, in vivo transplantation, and gene expression. Culturing hBMSCs using a particular environmental factor (hypoxia and with the addition of FGF-2 increased the cellular proliferation rate while enhancing the regenerative potential, modulated the multipotency-related processes (enhanced chondrogenesis-related processes/osteogenesis, but reduced adipogenesis, and increased cellular migration and collagen formation. The gene expression levels in the experimental samples showed activation of the hypoxia-inducible factor-1 pathway and glycolysis in the hypoxic condition, with this not being affected by the addition of FGF-2. The concurrent application of hypoxia and FGF-2 could provide a favorable condition for culturing hBMSCs to be used in clinical applications associated with bone tissue engineering, due to the enhancement of cellular proliferation and regenerative potential. Keywords: Bone marrow stromal cells, Hypoxia, Fibroblast growth factor, Tissue regeneration, Microenvironment interactions

Measurement of carrier lifetime and linewidth enhancement factor for 1.5- mu m ridge-waveguide laser amplifier

DEFF Research Database (Denmark)

Storkfelt, Niels; Mikkelsen, B.; Olesen, D. S.

1991-01-01

Semiconductor optical amplifiers are used for investigation of the effective carrier lifetime and the linewidth enhancement factor. Contrary to semiconductor lasers, semiconductor optical amplifiers allow measurement at high levels of injected carrier density. The carrier lifetime and the linewid...

Improving the robustness of Surface Enhanced Raman Spectroscopy based sensors by Bayesian Non-negative Matrix Factorization

DEFF Research Database (Denmark)

Alstrøm, Tommy Sonne; Frøhling, Kasper Bayer; Larsen, Jan

2014-01-01

a Bayesian Non-negative Matrix Factorization (NMF) approach to identify locations of target molecules. The proposed method is able to successfully analyze the spectra and extract the target spectrum. A visualization of the loadings of the basis vector is created and the results show a clear SNR enhancement...

Meningococcal factor H-binding protein vaccines with decreased binding to human complement factor H have enhanced immunogenicity in human factor H transgenic mice.

Science.gov (United States)

Rossi, Raffaella; Granoff, Dan M; Beernink, Peter T

2013-11-04

Factor H-binding protein (fHbp) is a component of a meningococcal vaccine recently licensed in Europe for prevention of serogroup B disease, and a second vaccine in clinical development. The protein specifically binds human factor H (fH), which down-regulates complement activation and enhances resistance to bactericidal activity. There are conflicting data from studies in human fH transgenic mice on whether binding of human fH to fHbp vaccines decreases immunogenicity, and whether mutant fHbp vaccines with decreased fH binding have enhanced immunogenicity. fHbp can be classified into two sub-families based on sequence divergence and immunologic cross-reactivity. Previous studies of mutant fHbp vaccines with low fH binding were from sub-family B, which account for approximately 60% of serogroup B case isolates. In the present study, we evaluated the immunogenicity of two mutant sub-family A fHbp vaccines containing single substitutions, T221A or D211A, which resulted in 15- or 30-fold lower affinity for human fH, respectively, than the corresponding control wild-type fHbp vaccine. In transgenic mice with high serum concentrations of human fH, both mutant vaccines elicited significantly higher IgG titers and higher serum bactericidal antibody responses than the control fHbp vaccine that bound human fH. Thus, mutations introduced into a sub-family A fHbp antigen to decrease fH binding can increase protective antibody responses in human fH transgenic mice. Collectively the data suggest that mutant fHbp antigens with decreased fH binding will result in superior vaccines in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Contrast-enhanced Spectral Mammography: Modality-Specific Artifacts and Other Factors Which May Interfere with Image Quality.

Science.gov (United States)

Bhimani, Chandni; Li, Luna; Liao, Lydia; Roth, Robyn G; Tinney, Elizabeth; Germaine, Pauline

2017-01-01

Contrast-enhanced spectral mammography (CESM) uses full field digital mammography with the added benefit of intravenous contrast administration to significantly reduce false-positive and false-negative results and improve specificity while maintaining high sensitivity. For CESM to fulfill its purpose, one should be aware of possible artifacts and other factors which may interfere with image quality, and attention should be taken to minimize these factors. This pictorial demonstration will depict types of artifacts detected and other factors that interfere with image acquisition in our practice since CESM implementation. Many of the artifacts and other factors we have encountered while using CESM have simple solutions to resolve them. The illustrated artifacts and other factors interfering with image quality will serve as a useful reference to anyone using CESM. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis

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Michael G. Poulos

2015-11-01

Full Text Available Hematopoietic stem cells (HSCs inhabit distinct microenvironments within the adult bone marrow (BM, which govern the delicate balance between HSC quiescence, self-renewal, and differentiation. Previous reports have proposed that HSCs localize to the vascular niche, comprised of endothelium and tightly associated perivascular cells. Herein, we examine the capacity of BM endothelial cells (BMECs to support ex vivo and in vivo hematopoiesis. We demonstrate that AKT1-activated BMECs (BMEC-Akt1 have a unique transcription factor/cytokine profile that supports functional HSCs in lieu of complex serum and cytokine supplementation. Additionally, transplantation of BMEC-Akt1 cells enhanced regenerative hematopoiesis following myeloablative irradiation. These data demonstrate that BMEC-Akt1 cultures can be used as a platform for the discovery of pro-HSC factors and justify the utility of BMECs as a cellular therapy. This technical advance may lead to the development of therapies designed to decrease pancytopenias associated with myeloablative regimens used to treat a wide array of disease states.

The HaDREB2 transcription factor enhances basal thermotolerance and longevity of seeds through functional interaction with HaHSFA9

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Carranco Raúl

2009-06-01

Full Text Available Abstract Background Transcription factor HaDREB2 was identified in sunflower (Helianthus annuus L. as a drought-responsive element-binding factor 2 (DREB2 with unique properties. HaDREB2 and the sunflower Heat Shock Factor A9 (HaHSFA9 co-activated the Hahsp17.6G1 promoter in sunflower embryos. Both factors could be involved in transcriptional co-activation of additional small heat stress protein (sHSP promoters, and thus contribute to the HaHSFA9-mediated enhancement of longevity and basal thermotolerance of seeds. Results We found that overexpression of HaDREB2 in seeds did not enhance longevity. This was deduced from assays of basal thermotolerance and controlled seed-deterioration, which were performed with transgenic tobacco. Furthermore, the constitutive overexpression of HaDREB2 did not increase thermotolerance in seedlings or result in the accumulation of HSPs at normal growth temperatures. In contrast, when HaDREB2 and HaHSFA9 were conjointly overexpressed in seeds, we observed positive effects on seed longevity, beyond those observed with overexpression of HaHSFA9 alone. Such additional effects are accompanied by a subtle enhancement of the accumulation of subsets of sHSPs belonging to the CI and CII cytosolic classes. Conclusion Our results reveal the functional interdependency of HaDREB2 and HaHSFA9 in seeds. HaDREB2 differs from other previously characterized DREB2 factors in plants in terms of its unique functional interaction with the seed-specific HaHSFA9 factor. No functional interaction between HaDREB2 and HaHSFA9 was observed when both factors were conjointly overexpressed in vegetative tissues. We therefore suggest that additional, seed-specific factors, or protein modifications, could be required for the functional interaction between HaDREB2 and HaHSFA9.

Radiation-induced leukemogenesis in RFM/UN strain mice: a potential model for retrovirus sequence transposition

International Nuclear Information System (INIS)

Tennant, R.W.; Hand, R.E. Jr.; Otten, J.A.; Liou, R.; Kiggans, J.O. Jr.; Yang, W.K.; Wang, T.W.

1982-01-01

Analysis of various tissues from normal and tumor-bearing mice, including bone marrow, spleen, thymus, and embryonic cells, showed low-level expression of viral p 30 protein or an infectious type C virus. However, It was possible to cultivate and establish cell lines from embryonic tissues and adult thymuses that were virus-negative but which could be chemically induced to express retrovirus. In all cases, only ecotropic virus with N-tropic host range was detected, and the production of a similar virus was detected in transplantable myeloid leukemia cells. Virus isolates of RFM/Un endogenous origin showed good infectivity in most Fv-1/sup n/ cells such as NIH Swiss mouse embryo cells but were severely restricted in Fv-1/sub f/ cells, confirming the N-tropic host range; in addition, the replication of this RFM/Un endogenous N-tropic virus (RFV) was preferentially restricted in RFM/Un cells which are of the Fv-1/sup n/ genotype. The restriction of RFM/Un cells for RFV was analyzed at the stage of viral DNA formation by means of a modified Hirt extraction procedure and the electrophoresis/diazobenzyloxymethyl-paper transfer/molecular hybridization method; it was found that synthesis of both linear and covalently closed circular forms of viral DNA, either by RFV or by WN1802B B-tropic virus, was markedly inhibited in RFM/Un cells relative to that of Gross virus. Analysis by restriction endonuclease EcoR1 digestion demonstration that nuclear DNA of RFM/Un cells contained multiple copies of endogenous type C retroviral genes, including distinct retroviral sequence not found in NIH Swiss cells which never express endogenous ecotropic viruses. These results suggest that the RFM/Un mouse may possess only one inducible ecotropic host-range class of inducible virus and a unique gene, possibly an allele of the Fv-1 locus, which specifically restricts endogenous virus

Extrinsic factors promoting insulin producing cell-differentiation and insulin expression enhancement-hope for diabetics.

Science.gov (United States)

Dave, Shruti

2013-11-01

Diabetes mellitus (DM) is considered to be an autoimmune disorder leading to destruction of beta-cells resulting in to a loss of blood sugar control. Attempts using many pharmacological compositions including exogenous insulin have failed to show tight control of glycemia and associated manifestations. Stem cells are considered a potential tool for the supply of insulin-producing cells (IPC) generation in vitro. Stem cell differentiation in to pancreatic lineages requires influence of both intrinsic and extrinsic factors. Application of islet growth factors is considered to be potential for enhancement of beta-cell replication, function and survival. Use of certain extrinsic factors is known to facilitate expression of transcription factors known to be important for beta-cell differentiation and production of insulin enabling IPC generation. Hierarchies of secreted signals and transcription factors have been identified by studies from several laboratories that guide cell differentiation in to IPC. This knowledge provides insights for in vitro IPC differentiation from stem cells. Current advancement in medical knowledge promises an insulin independency for DM patients. The review sheds light on few specific extrinsic factors which facilitate differentiation of stem cells in to IPC in vitro have been discussed; which can be proven as a potential therapeutic option for treatment of DM and associated diseases.

The distressed (Type D) personality factor of social inhibition, but not negative affectivity, enhances eyeblink conditioning.

Science.gov (United States)

Allen, M T; Handy, J D; Blankenship, M R; Servatius, R J

2018-06-01

Recent work has focused on a learning diathesis model in which specific personality factors such as behavioral inhibition (BI) may influence associative learning and in turn increase risk for the development of anxiety disorders. We have found in a series of studies that individuals self-reporting high levels of BI exhibit enhanced acquisition of conditioned eyeblinks. In the study reported here, hypotheses were extended to include distressed (Type D) personality which has been found to be related to BI. Type D personality is measured with the DS-14 scale which includes two subscales measuring negative affectivity (NA) and social inhibition (SI). We hypothesized that SI, which is similar to BI, would result in enhanced acquisition while the effect of NA is unclear. Eighty nine participants completed personality inventories including the Adult Measure of Behavioral Inhibition (AMBI) and DS-14. All participants received 60 acquisition trials with a 500 ms, 1000 Hz, tone CS and a co-terminating 50 ms, 5 psi corneal airpuff US. Participants received either 100% CS-US paired trials or a schedule of partial reinforcement where 50% US alone trials were intermixed into CS-US training. Acquisition of CRs did not differ between the two training protocols. Whereas BI was significantly related to Type D, SI, and NA, only BI and SI individuals exhibited enhanced acquisition of conditioned eyeblinks as compared to non-inhibited individuals. Personality factors now including social inhibition can be used to identify individuals who express enhanced associative learning which lends further support to a learning diathesis model of anxiety disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Akv murine leukemia virus enhances bone tumorigenesis in hMT-c-fos-LTR transgenic mice

DEFF Research Database (Denmark)

Schmidt, Jörg; Krump-Konvalinkova, Vera; Luz, Arne

1995-01-01

hMt-c-fos-LTR transgenic mice (U. Rüther, D. Komitowski, F. R. Schubert, and E. F. Wagner. Oncogene 4, 861–865, 1989) developed bone sarcomas in 20% (3/15) of females at 448 ± 25 days and in 8% (1/12) of males at 523 days. After infection of newborns with Akv, an infectious retrovirus derived from...

Security enhanced multi-factor biometric authentication scheme using bio-hash function.

Directory of Open Access Journals (Sweden)

Younsung Choi

Full Text Available With the rapid development of personal information and wireless communication technology, user authentication schemes have been crucial to ensure that wireless communications are secure. As such, various authentication schemes with multi-factor authentication have been proposed to improve the security of electronic communications. Multi-factor authentication involves the use of passwords, smart cards, and various biometrics to provide users with the utmost privacy and data protection. Cao and Ge analyzed various authentication schemes and found that Younghwa An's scheme was susceptible to a replay attack where an adversary masquerades as a legal server and a user masquerading attack where user anonymity is not provided, allowing an adversary to execute a password change process by intercepting the user's ID during login. Cao and Ge improved upon Younghwa An's scheme, but various security problems remained. This study demonstrates that Cao and Ge's scheme is susceptible to a biometric recognition error, slow wrong password detection, off-line password attack, user impersonation attack, ID guessing attack, a DoS attack, and that their scheme cannot provide session key agreement. Then, to address all weaknesses identified in Cao and Ge's scheme, this study proposes a security enhanced multi-factor biometric authentication scheme and provides a security analysis and formal analysis using Burrows-Abadi-Needham logic. Finally, the efficiency analysis reveals that the proposed scheme can protect against several possible types of attacks with only a slightly high computational cost.

Security enhanced multi-factor biometric authentication scheme using bio-hash function.

Science.gov (United States)

Choi, Younsung; Lee, Youngsook; Moon, Jongho; Won, Dongho

2017-01-01

With the rapid development of personal information and wireless communication technology, user authentication schemes have been crucial to ensure that wireless communications are secure. As such, various authentication schemes with multi-factor authentication have been proposed to improve the security of electronic communications. Multi-factor authentication involves the use of passwords, smart cards, and various biometrics to provide users with the utmost privacy and data protection. Cao and Ge analyzed various authentication schemes and found that Younghwa An's scheme was susceptible to a replay attack where an adversary masquerades as a legal server and a user masquerading attack where user anonymity is not provided, allowing an adversary to execute a password change process by intercepting the user's ID during login. Cao and Ge improved upon Younghwa An's scheme, but various security problems remained. This study demonstrates that Cao and Ge's scheme is susceptible to a biometric recognition error, slow wrong password detection, off-line password attack, user impersonation attack, ID guessing attack, a DoS attack, and that their scheme cannot provide session key agreement. Then, to address all weaknesses identified in Cao and Ge's scheme, this study proposes a security enhanced multi-factor biometric authentication scheme and provides a security analysis and formal analysis using Burrows-Abadi-Needham logic. Finally, the efficiency analysis reveals that the proposed scheme can protect against several possible types of attacks with only a slightly high computational cost.

Security enhanced multi-factor biometric authentication scheme using bio-hash function

Science.gov (United States)

Lee, Youngsook; Moon, Jongho

2017-01-01

With the rapid development of personal information and wireless communication technology, user authentication schemes have been crucial to ensure that wireless communications are secure. As such, various authentication schemes with multi-factor authentication have been proposed to improve the security of electronic communications. Multi-factor authentication involves the use of passwords, smart cards, and various biometrics to provide users with the utmost privacy and data protection. Cao and Ge analyzed various authentication schemes and found that Younghwa An’s scheme was susceptible to a replay attack where an adversary masquerades as a legal server and a user masquerading attack where user anonymity is not provided, allowing an adversary to execute a password change process by intercepting the user’s ID during login. Cao and Ge improved upon Younghwa An’s scheme, but various security problems remained. This study demonstrates that Cao and Ge’s scheme is susceptible to a biometric recognition error, slow wrong password detection, off-line password attack, user impersonation attack, ID guessing attack, a DoS attack, and that their scheme cannot provide session key agreement. Then, to address all weaknesses identified in Cao and Ge’s scheme, this study proposes a security enhanced multi-factor biometric authentication scheme and provides a security analysis and formal analysis using Burrows-Abadi-Needham logic. Finally, the efficiency analysis reveals that the proposed scheme can protect against several possible types of attacks with only a slightly high computational cost. PMID:28459867

Gata4 expression in lateral mesoderm is downstream of BMP4 and isactivated directly by Forkhead and GATA transcription factors through adistal enhancer element

Energy Technology Data Exchange (ETDEWEB)

Rojas, Anabel; De Val, Sarah; Heidt, Analeah B.; Xu, Shan-Mei; Bristow, James; Black, Brian L.

2005-05-20

The GATA family of zinc-finger transcription factors plays key roles in the specification and differentiation of multiple cell types during development. GATA4 is an early regulator of gene expression during the development of endoderm and mesoderm, and genetic studies in mice have demonstrated that GATA4 is required for embryonic development.Despite the importance of GATA4 in tissue specification and differentiation, the mechanisms by which Gata4 expression is activated and the transcription factor pathways upstream of GATA4 remain largely undefined. To identify transcriptional regulators of Gata4 in the mouse,we screened conserved noncoding sequences from the mouse Gata4 gene for enhancer activity in transgenic embryos. Here, we define the regulation of a distal enhancer element from Gata4 that is sufficient to direct expression throughout the lateral mesoderm, beginning at 7.5 days of mouse embryonic development. The activity of this enhancer is initially broad but eventually becomes restricted to the mesenchyme surrounding the liver. We demonstrate that the function of this enhancer in transgenic embryos is dependent upon highly conserved Forkhead and GATA transcription factor binding sites, which are bound by FOXF1 and GATA4,respectively. Furthermore, the activity of the Gata4 lateral mesoderm enhancer is attenuated by the BMP antagonist Noggin, and the enhancer is not activated in Bmp4-null embryos. Thus, these studies establish that Gata4 is a direct transcriptional target of Forkhead and GATA transcription factors in the lateral mesoderm, and demonstrate that Gata4lateral mesoderm enhancer activation requires BMP4, supporting a model in which GATA4 serves as a downstream effector of BMP signaling in the lateral mesoderm.

Activated Integrin-Linked Kinase Negatively Regulates Muscle Cell Enhancement Factor 2C in C2C12 Cells

Directory of Open Access Journals (Sweden)

Zhenguo Dong

2015-01-01

Full Text Available Our previous study reported that muscle cell enhancement factor 2C (MEF2C was fully activated after inhibition of the phosphorylation activity of integrin-linked kinase (ILK in the skeletal muscle cells of goats. It enhanced the binding of promoter or enhancer of transcription factor related to proliferation of muscle cells and then regulated the expression of these genes. In the present investigation, we explored whether ILK activation depended on PI3K to regulate the phosphorylation and transcriptional activity of MEF2C during C2C12 cell proliferation. We inhibited PI3K activity in C2C12 with LY294002 and then found that ILK phosphorylation levels and MEF2C phosphorylation were decreased and that MCK mRNA expression was suppressed significantly. After inhibiting ILK phosphorylation activity with Cpd22 and ILK-shRNA, we found MEF2C phosphorylation activity and MCK mRNA expression were increased extremely significantly. In the presence of Cpd22, PI3K activity inhibition increased MEF2C phosphorylation and MCK mRNA expression indistinctively. We conclude that ILK negatively and independently of PI3K regulated MEF2C phosphorylation activity and MCK mRNA expression in C2C12 cells. The results provide new ideas for the study of classical signaling pathway of PI3K-ILK-related proteins and transcription factors.

Diversity in Board of Directors: Review of Diversity as a Factor to Enhance Board Performance

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Pechersky Alexander

2016-06-01

Full Text Available In light of growing corporate influence in the business world and thus increasing further need to improve framework of corporate governance for shareholders’ protection, diversity is examined as a necessary factor to enhance monitoring and leadership functions of board of directors. This article analyses empirical studies with samples on various countries in order to examine effect of board composition and diversity on primary responsibilities of Board of Directors. Author is providing theoretical overview of diversity benefits and practical perspective of gender, qualifications, and background diversity in board performance. Our results show an added value of gender diversity to company performance in social and healthcare industries. Furthermore, author shows a rather negative effect of gender quotas. This study sheds a light on empirical researches and a need to include additional cultural factors called country readiness factors.

Multivalent conjugates of basic fibroblast growth factor enhance in vitro proliferation and migration of endothelial cells.

Science.gov (United States)

Zbinden, Aline; Browne, Shane; Altiok, Eda I; Svedlund, Felicia L; Jackson, Wesley M; Healy, Kevin E

2018-05-01

Growth factors hold great promise for regenerative therapies. However, their clinical use has been halted by poor efficacy and rapid clearance from tissue, necessitating the delivery of extremely high doses to achieve clinical effectiveness which has raised safety concerns. Thus, strategies to either enhance growth factor activity at low doses or to increase their residence time within target tissues are necessary for clinical success. In this study, we generated multivalent conjugates (MVCs) of basic fibroblast growth factor (bFGF), a key growth factor involved in angiogenesis and wound healing, to hyaluronic acid (HyA) polymer chains. Multivalent bFGF conjugates (mvbFGF) were fabricated with minimal non-specific interaction observed between bFGF and the HyA chain. The hydrodynamic radii of mvbFGF ranged from ∼50 to ∼75 nm for conjugation ratios of bFGF to HyA chains at low (10 : 1) and high (30 : 1) feed ratios, respectively. The mvbFGF demonstrated enhanced bioactivity compared to unconjugated bFGF in assays of cell proliferation and migration, processes critical to angiogenesis and tissue regeneration. The 30 : 1 mvbFGF outperformed the 10 : 1 conjugate, which could be due to either FGF receptor clustering or interference with receptor mediated internalization and signal deactivation. This study simultaneously investigated the role of both protein to polymer ratio and multivalent conjugate size on their bioactivity, and determined that increasing the protein-to-polymer ratio and conjugate size resulted in greater cell bioactivity.

Estimating effective wedge factor for enhanced dynamic wedge 2100CD a Varian Clinac; Calculo De factor cuna efectiva para cuna dinamica mejorada de un Clinac 2100CD de Varian

Energy Technology Data Exchange (ETDEWEB)

Pizarro Trigo, F.; Morillas Ruiz, J.; Nunuz Martinez, L.; Sanchez Jimenez, J.

2011-07-01

The purpose of this paper is to compare different methods of calculating the effective factor enhanced dynamic wedge (EDWF) with the values ??obtained in measurements of symmetric and asymmetric fields.

Histone deacetylase inhibitor trichostatin A enhances myogenesis by coordinating muscle regulatory factors and myogenic repressors

International Nuclear Information System (INIS)

Hagiwara, Hiroki; Saito, Fumiaki; Masaki, Toshihiro; Ikeda, Miki; Nakamura-Ohkuma, Ayami; Shimizu, Teruo; Matsumura, Kiichiro

2011-01-01

Highlights: ► We investigated the effect of TSA, one of most potent HDACIs, on myogenesis using the C2C12 skeletal muscle cell line. ► TSA enhances the expression of myosin heavy chain without affecting DAPC expression. ► TSA enhances the expression of the early MRFs, Myf5 and MEF2, and suppresses the late MRF, myogenin, after 24 h treatment. ► TSA enhances the expression of the myogenic repressors, Ids, which inhibit myogenic differentiation. ► TSA promotes myogenesis by coordinating the expression of MRFs and myogenic repressors. -- Abstract: Histone deacetylase inhibitors (HDACIs) are known to promote skeletal muscle formation. However, their mechanisms that include effects on the expression of major muscle components such as the dystrophin-associated proteins complex (DAPC) or myogenic regulatory factors (MRFs) remain unknown. In this study, we investigated the effects of HDACIs on skeletal muscle formation using the C2C12 cell culture system. C2C12 myoblasts were exposed to trichostatin A (TSA), one of the most potent HDACIs, and differentiation was subsequently induced. We found that TSA enhances the expression of myosin heavy chain without affecting DAPC expression. In addition, TSA increases the expression of the early MRFs, Myf5 and MEF2, whereas it suppresses the expression of the late MRF, myogenin. Interestingly, TSA also enhances the expression of Id1, Id2, and Id3 (Ids). Ids are myogenic repressors that inhibit myogenic differentiation. These findings suggest that TSA promotes gene expression in proliferation and suppresses it in the differentiation stage of muscle formation. Taken together, our data demonstrate that TSA enhances myogenesis by coordinating the expression of MRFs and myogenic repressors.

NAC transcription factor JUNGBRUNNEN1 enhances drought tolerance in tomato

KAUST Repository

Thirumalaikumar, Venkatesh P.

2017-06-22

Water deficit (drought stress) massively restricts plant growth and the yield of crops; reducing the deleterious effects of drought is therefore of high agricultural relevance. Drought triggers diverse cellular processes including the inhibition of photosynthesis, the accumulation of cell-damaging reactive oxygen species, and gene expression reprogramming, besides others. Transcription factors (TF) are central regulators of transcriptional reprogramming and expression of many TF genes is affected by drought, including members of the NAC family. Here, we identify the NAC factor JUNGBRUNNEN1 (JUB1) as a regulator of drought tolerance in tomato (Solanum lycopersicum). Expression of tomato JUB1 (SlJUB1) is enhanced by various abiotic stresses, including drought. Inhibiting SlJUB1 by virus-induced gene silencing drastically lowers drought tolerance concomitant with an increase in ion leakage, an elevation of hydrogen peroxide (H2 O2 ) levels, and a decrease of the expression of various drought-responsive genes. In contrast, overexpression of AtJUB1 from Arabidopsis thaliana increases drought tolerance in tomato, alongside with a higher relative leaf water content during drought and reduced H2 O2 levels. AtJUB1 was previously shown to stimulate expression of DREB2A, a TF involved in drought responses, and of the DELLA genes GAI and RGL1. We show here that SlJUB1 similarly controls the expression of the tomato orthologs SlDREB1, SlDREB2, and SlDELLA. Furthermore, AtJUB1 directly binds to the promoters of SlDREB1, SlDREB2 and SlDELLA in tomato. Our study highlights JUB1 as a transcriptional regulator of drought tolerance and suggests considerable conservation of the abiotic stress-related gene regulatory networks controlled by this NAC factor between Arabidopsis and tomato. This article is protected by copyright. All rights reserved.

Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype.

Science.gov (United States)

Yuldasheva, Nadira Y; Rashid, Sheikh Tawqeer; Haywood, Natalie J; Cordell, Paul; Mughal, Romana; Viswambharan, Hema; Imrie, Helen; Sukumar, Piruthivi; Cubbon, Richard M; Aziz, Amir; Gage, Matthew; Mbonye, Kamatamu Amanda; Smith, Jessica; Galloway, Stacey; Skromna, Anna; Scott, D Julian A; Kearney, Mark T; Wheatcroft, Stephen B

2014-09-01

Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R(+/-)). Endothelial regeneration after arterial injury was accelerated in IGF1R(+/-) mice. Although the yield of angiogenic progenitor cells was lower in IGF1R(+/-) mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R(+/-) bone marrow-derived CD117(+) cells into wild-type mice. IGF1R(+/-) cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117(+) cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury. © 2014 American Heart Association, Inc.

The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

Science.gov (United States)

Diccianni, M B; Imagawa, M; Muramatsu, M

1992-10-11

Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

International Nuclear Information System (INIS)

Wang Wei-dong; Chen Zheng-tang; Li De-zhi; Duan Yu-zhong; Cao Zheng-huai; Li Rong

2005-01-01

The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O 2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

Rapidity dependence of strangeness enhancement factor at FAIR energies

International Nuclear Information System (INIS)

Dey, Kalyan; Bhattacharjee, B.

2014-01-01

Strange particles are produced only at the time of collisions and thus expected to carry important information of collision dynamics. Strangeness enhancement is considered to be one of the traditional signatures of formation of Quark Gluon Plasma (QGP). Due to the limitation of the detector acceptance, the past and ongoing heavy ion experiments could measure the strangeness enhancement at midrapidity only. But the future heavy ion experiment CBM at FAIR will have the access to the entire forward rapidity hemisphere and thus the experimental determination of rapidity dependent strangeness enhancement is a possibility. In this work, an attempt has therefore been made to study the rapidity dependent strangeness enhancement at FAIR energies with the help of a string based hadronic model (UrQMD). A sum of 93 million minimum biased UrQMD events have been used for the present analysis

HERVd: database of human endogenous retroviruses

Czech Academy of Sciences Publication Activity Database

Pačes, Jan; Pavlíček, Adam; Pačes, Václav

2002-01-01

Roč. 30, č. 1 (2002), s. 205-206 ISSN 0305-1048 R&D Projects: GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5052915 Keywords : elements * repeats Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.051, year: 2002

Endogenous retrovirus EAV-HP linked to blue egg phenotype in Mapuche fowl.

Science.gov (United States)

Wragg, David; Mwacharo, Joram M; Alcalde, José A; Wang, Chen; Han, Jian-Lin; Gongora, Jaime; Gourichon, David; Tixier-Boichard, Michèle; Hanotte, Olivier

2013-01-01

Oocyan or blue/green eggshell colour is an autosomal dominant trait found in native chickens (Mapuche fowl) of Chile and in some of their descendants in European and North American modern breeds. We report here the identification of an endogenous avian retroviral (EAV-HP) insertion in oocyan Mapuche fowl and European breeds. Sequencing data reveals 100% retroviral identity between the Mapuche and European insertions. Quantitative real-time PCR analysis of European oocyan chicken indicates over-expression of the SLCO1B3 gene (P<0.05) in the shell gland and oviduct. Predicted transcription factor binding sites in the long terminal repeats (LTR) indicate AhR/Ar, a modulator of oestrogen, as a possible promoter/enhancer leading to reproductive tissue-specific over-expression of the SLCO1B3 gene. Analysis of all jungle fowl species Gallus sp. supports the retroviral insertion to be a post-domestication event, while identical LTR sequences within domestic chickens are in agreement with a recent de novo mutation.

Factors on Enhancing the Competitive Edge and Attributes of Graduates as Inputs to the Development of Teacher Education Enhancement Program

Directory of Open Access Journals (Sweden)

Susan S. Janer

2015-11-01

Full Text Available In response to the CHED’s Higher Education Development Project and the need to track the status of Sorsogon State College (SSC teacher education graduates, this research was conceptualized. The study aims to gauge the teacher education program’s thrust of providing a quality and relevant education that could ensure worthwhile and appropriate employment opportunity to its graduates. Descriptive research design was employed in this study. Surveys, unstructured interviews, and documentary analysis were undertaken to gather pertinent data among the respondents. The study consists of 427 teacher education graduates who were selected through stratified random technique. This tracer study determined the employability of Teacher Education graduates in SSC, Sorsogon Campus from 2009 to 2013 with an end-view of proposing a Teacher Education Enhancement Program (TEEP to enhance the competitive edge of SSC Teacher Education graduates in all teaching job opportunities. The intellectual, social and linguistic attributes of the SSC graduates were likewise identified in this study. Some of the factors identified by the respondents that could help improve their competitive edge are the pre-service trainings, job placement program, teacher education curriculum enrichment, and Licensure Examination for Teachers (LET review program.

The origins of enhanced activity in factor VIIa analogs and the interplay between key allosteric sites revealed by hydrogen exchange mass spectrometry

DEFF Research Database (Denmark)

Rand, Kasper D; Andersen, Mette D; Olsen, Ole H

2008-01-01

Factor VIIa (FVIIa) circulates in the blood in a zymogen-like state. Only upon association with membrane-bound tissue factor (TF) at the site of vascular injury does FVIIa become active and able to initiate blood coagulation. Here we used hydrogen exchange monitored by mass spectrometry to invest......Factor VIIa (FVIIa) circulates in the blood in a zymogen-like state. Only upon association with membrane-bound tissue factor (TF) at the site of vascular injury does FVIIa become active and able to initiate blood coagulation. Here we used hydrogen exchange monitored by mass spectrometry...... to investigate the conformational effects of site-directed mutagenesis at key positions in FVIIa and the origins of enhanced intrinsic activity of FVIIa analogs. The differences in hydrogen exchange of two highly active variants, FVIIa(DVQ) and FVIIa(VEAY), imply that enhanced catalytic efficiency was attained...

HERVd: database of human endogenous retroviruses

Czech Academy of Sciences Publication Activity Database

Pačes, Jan; Pavlíček, Adam; Pačes, Václav

2002-01-01

Roč. 30, č. 1 (2002), s. 205-206 ISSN 0305-1048 R&D Projects: GA MŠk LN00A079; GA ČR GA301/99/M023 Keywords : HERV * database * human genome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.051, year: 2002

Survival time and effect of selected predictor variables on survival in owned pet cats seropositive for feline immunodeficiency and leukemia virus attending a referral clinic in northern Italy.

Science.gov (United States)

Spada, Eva; Perego, Roberta; Sgamma, Elena Assunta; Proverbio, Daniela

2018-02-01

Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are among the most important feline infectious diseases worldwide. This retrospective study investigated survival times and effects of selected predictor factors on survival time in a population of owned pet cats in Northern Italy testing positive for the presence of FIV antibodies and FeLV antigen. One hundred and three retrovirus-seropositive cats, 53 FIV-seropositive cats, 40 FeLV-seropositive cats, and 10 FIV+FeLV-seropositive cats were included in the study. A population of 103 retrovirus-seronegative age and sex-matched cats was selected. Survival time was calculated and compared between retrovirus-seronegative, FIV, FeLV and FIV+FeLV-seropositive cats using Kaplan-Meier survival analysis. Cox proportional-hazards regression analysis was used to study the effect of selected predictor factors (male gender, peripheral blood cytopenia as reduced red blood cells - RBC- count, leukopenia, neutropenia and lymphopenia, hypercreatininemia and reduced albumin to globulin ratio) on survival time in retrovirus-seropositive populations. Median survival times for seronegative cats, FIV, FeLV and FIV+FeLV-seropositive cats were 3960, 2040, 714 and 77days, respectively. Compared to retrovirus-seronegative cats median survival time was significantly lower (P<0.000) in FeLV and FIV+FeLV-seropositive cats. Median survival time in FeLV and FIV+FeLV-seropositive cats was also significant lower (P<0.000) when compared to FIV-seropositive cats. Hazard ratio of death in FeLV and FIV+FeLV-seropositive cats being respectively 3.4 and 7.4 times higher, in comparison to seronegative cats and 2.3 and 4.8 times higher in FeLV and FIV+FeLV-seropositive cats as compared to FIV-seropositive cats. A Cox proportional-hazards regression analysis showed that FIV and FeLV-seropositive cats with reduced RBC counts at time of diagnosis of seropositivity had significantly shorter survival times when compared to FIV and Fe

Manipulation of factors affecting phytate hydrolysis in enhancing phytase efficacy in poultry: A review

Directory of Open Access Journals (Sweden)

Noraini*, S.

2017-06-01

Full Text Available Phosphorus in phytate is largely unavailable to chickens unless they are provided with dietary phytase. Phytase was shown to increase phytate degradation in the crop and proventriculus-gizzard and very little phytate degradation occurred in the duodenum-jejunum or ileum. These previous investigations were conducted on chickens fed corn based diet but not with wheat based diet. Increase in digesta passage or mean retention time (MRT along the gastrointestinal tract could enhance phytase efficacy as the prolonged reaction time between substrates and phytase may further facilitate phytate dephosphorylation. Dietary fat and fibre supplementation have been shown to influence intestinal MRT in chickens therefore it is expected that inclusion of both dietary fat and fibre could be manipulated to further improve phytase efficacy in broiler chickens. This paper provides a brief review of in vitro phytate hydrolysis, phytate hydrolysis in the gastrointestinal tract of broilers and factors that affect phytate hydrolysis that can be manipulated to enhance the efficacy of phytase in poultry diets.

Enhanced intestinal anastomotic healing with gelatin hydrogel incorporating basic fibroblast growth factor.

Science.gov (United States)

Hirai, Kenjiro; Tabata, Yasuhiko; Hasegawa, Suguru; Sakai, Yoshiharu

2016-10-01

Anastomotic leakage is a common complication of intestinal surgery. In an attempt to resolve this issue, a promising approach is enhancement of anastomotic wound healing. A method for controlled release of basic fibroblast growth factor (bFGF) using a gelatin hydrogel was developed with the objective of investigating the effects of this technology on intestinal anastomotic healing. The small intestine of Wistar rats was cut, end-to-end anastomosis was performed and rats were divided into three groups: bFGF group (anastomosis wrapped with a hydrogel sheet incorporating bFGF), PBS group (wrapped with a sheet incorporating phosphate-buffered saline solution) and NT group (no additional treatment). Degradation profiles of gelatin hydrogels in vivo and histological examinations were performed using gelatin hydrogels with various water contents and bFGF concentrations to define the optimal bFGF dose and hydrogel biodegradability. The anastomotic wound healing process was evaluated by histological examinations, adhesion-related score and bursting pressure. The optimal water content of the hydrogel and bFGF dose was determined as 96% and 30 µg per sheet, respectively. Application of bFGF significantly enhanced neovascularization, fibroblast infiltration and collagen production around the anastomotic site when compared with the other groups. Bursting pressure was significantly increased in the bFGF group. No significant difference was observed in the adhesion-related score among the groups and no anastomotic obstruction and leakage were observed. Therefore controlled release of bFGF enhanced healing of an intestinal anastomosis during the early postoperative period and is a promising method to suppress anastomotic leakage. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Subendometrial enhancement and peritumoral enhancement for assessing endometrial cancer on dynamic contrast enhanced MR imaging

International Nuclear Information System (INIS)

Fujii, Shinya; Kido, Aki; Baba, Tsukasa; Fujimoto, Koji; Daido, Sayaka; Matsumura, Noriomi; Konishi, Ikuo; Togashi, Kaori

2015-01-01

Highlights: •We have assessed the peritumoral enhancement (PTE), which mimics SEE on DCE. •We evaluated the diagnostic accuracy of SEE for the myometrial invasion and the frequency of PTE. •We assessed the relationship between these enhancements and important pathologic factors. •PTE Type 1 is the main factor causing the overestimation of myometrial invasion using SEE on DCE. •PTE Type 2 correlates the myometrial invasion and may play an important role in the diagnosis of LVSI. -- Abstract: Objectives: To evaluate the diagnostic accuracy of subendometrial enhancement (SEE) in assessing the myometrial invasion in endometrial cancer, the frequency and clinical significance of peritumoral enhancement (PTE) on dynamic contrast enhanced (DCE) imaging. Materials and methods: MR images of 147 patients with endometrial cancer were retrospectively analyzed for intact SEE and PTEs: Type 1, a focal early enhancement peritumorally, and Type 2, an irregular thin-layered early intense enhancement peritumorally. Two radiologists independently assessed intact SEE and PTEs on DCE imaging and compared the lesions by the presence and depth of myometrial invasion, grade, lymphovascular space involvement (LVSI), and lymph node metastasis. The relationship between SEE, PTEs, and each factor was analyzed using univariate and multivariate analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for SEE. Results: The sensitivity, specificity, PPV, NPV and diagnostic accuracy for myometrial invasion based on SEE disruption on DCE were 96.6%, 32.1–46.4%, 85.8–88.5%, 69.2–76.5%, and 84.4–87.1%. According to multivariate analysis, SEE significantly predicted myometrial invasion (p < 0.0001). PTE Type 2 significantly predicted myometrial invasion presence (p < 0.05) and depth (p < 0.01). Conclusion: Diagnosis of myometrial invasion only by using SEE might be difficult on DCE-MRI due to the

Subendometrial enhancement and peritumoral enhancement for assessing endometrial cancer on dynamic contrast enhanced MR imaging

Energy Technology Data Exchange (ETDEWEB)

Fujii, Shinya [Division of Radiology, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, Yonago (Japan); Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Kido, Aki, E-mail: akikido@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Baba, Tsukasa [Departments of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Fujimoto, Koji; Daido, Sayaka [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Matsumura, Noriomi; Konishi, Ikuo [Departments of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Togashi, Kaori [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan)

2015-04-15

Highlights: •We have assessed the peritumoral enhancement (PTE), which mimics SEE on DCE. •We evaluated the diagnostic accuracy of SEE for the myometrial invasion and the frequency of PTE. •We assessed the relationship between these enhancements and important pathologic factors. •PTE Type 1 is the main factor causing the overestimation of myometrial invasion using SEE on DCE. •PTE Type 2 correlates the myometrial invasion and may play an important role in the diagnosis of LVSI. -- Abstract: Objectives: To evaluate the diagnostic accuracy of subendometrial enhancement (SEE) in assessing the myometrial invasion in endometrial cancer, the frequency and clinical significance of peritumoral enhancement (PTE) on dynamic contrast enhanced (DCE) imaging. Materials and methods: MR images of 147 patients with endometrial cancer were retrospectively analyzed for intact SEE and PTEs: Type 1, a focal early enhancement peritumorally, and Type 2, an irregular thin-layered early intense enhancement peritumorally. Two radiologists independently assessed intact SEE and PTEs on DCE imaging and compared the lesions by the presence and depth of myometrial invasion, grade, lymphovascular space involvement (LVSI), and lymph node metastasis. The relationship between SEE, PTEs, and each factor was analyzed using univariate and multivariate analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for SEE. Results: The sensitivity, specificity, PPV, NPV and diagnostic accuracy for myometrial invasion based on SEE disruption on DCE were 96.6%, 32.1–46.4%, 85.8–88.5%, 69.2–76.5%, and 84.4–87.1%. According to multivariate analysis, SEE significantly predicted myometrial invasion (p < 0.0001). PTE Type 2 significantly predicted myometrial invasion presence (p < 0.05) and depth (p < 0.01). Conclusion: Diagnosis of myometrial invasion only by using SEE might be difficult on DCE-MRI due to the

SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state.

Directory of Open Access Journals (Sweden)

Michael A Lodato

Full Text Available SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs and multipotent neural progenitor cells (NPCs; however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal enhancer elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1 in ESCs, the related POU family member BRN2 (Pou3f2 co-occupied a large set of putative distal enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors.

Contrast-enhanced breast MRI: factors affecting sensitivity and specificity

Energy Technology Data Exchange (ETDEWEB)

Piccoli, C.W. [Department of Radiology, Jefferson Medical College, Thomas Jefferson University Hospital, 132 South 10th Street, 7th floor, Philadelphia, PA 19107-5244 (United States)

1997-12-31

Contrast-enhanced MRI (CE-MRI) of the breast has been investigated for over 10 years. The reports of sensitivity for cancer detection have generally been greater than 90 %. However, estimates of specificity have varied greatly. Differing results are due to differences in study populations, technical methods and criteria for interpretation. Early and marked signal rise, detected using dynamic imaging technique following contrast administration, is the MRI hallmark of cancer. However, some malignant lesions may enhance slowly or minimally, and a variety of benign lesions may enhance rapidly with marked signal intensity. High resolution techniques generally requiring longer acquisition times are more likely to depict the slowly enhancing malignancies at the cost of a decrease in specificity due to lack of temporal resolution. This disadvantage may be offset by the improved visualization of lesion morphology with high resolution images. This report reviews the methods and results of the leading investigators of breast MRI. (orig.) With 3 figs., 70 refs.

Contrast-enhanced breast MRI: factors affecting sensitivity and specificity

International Nuclear Information System (INIS)

Piccoli, C.W.

1997-01-01

Contrast-enhanced MRI (CE-MRI) of the breast has been investigated for over 10 years. The reports of sensitivity for cancer detection have generally been greater than 90 %. However, estimates of specificity have varied greatly. Differing results are due to differences in study populations, technical methods and criteria for interpretation. Early and marked signal rise, detected using dynamic imaging technique following contrast administration, is the MRI hallmark of cancer. However, some malignant lesions may enhance slowly or minimally, and a variety of benign lesions may enhance rapidly with marked signal intensity. High resolution techniques generally requiring longer acquisition times are more likely to depict the slowly enhancing malignancies at the cost of a decrease in specificity due to lack of temporal resolution. This disadvantage may be offset by the improved visualization of lesion morphology with high resolution images. This report reviews the methods and results of the leading investigators of breast MRI. (orig.)

Measuring the surface-enhanced Raman scattering enhancement factors of hot spots formed between an individual Ag nanowire and a single Ag nanocube

International Nuclear Information System (INIS)

Camargo, Pedro H C; Cobley, Claire M; Rycenga, Matthew; Xia Younan

2009-01-01

This paper describes a systematic study of the surface-enhanced Raman scattering (SERS) activity of hot spots formed between a Ag nanowire and a Ag nanocube with sharp corners. We investigated two distinct dimer structures: (i) a nanocube having one side face nearly touching the side face of a nanowire, and (ii) a nanocube having one edge nearly touching the side face of a nanowire. The field enhancements for the dimers displayed a strong dependence on laser polarization, and the strongest SERS intensities were observed for polarization along the hot-spot axis. Moreover, the detected SERS intensities were dependent on the hot-spot structure, i.e., the relative orientation of the Ag nanocube with respect to the nanowire's side face. When the dimer had a face-to-face configuration, the enhancement factor EF dimer was 1.4 x 10 7 . This corresponds to 22-fold and 24-fold increases compared to those for individual Ag nanowires and nanocubes, respectively. Conversely, when the dimer had an edge-to-face configuration, EF dimer was 4.3 x 10 6 . These results demonstrated that the number of probe molecules adsorbed at the hot spot played an important role in determining the detected SERS intensities. EF dimer was maximized when the dimer configuration allowed for a larger number of probe molecules to be trapped within the hot-spot region.

Enhanced quality factors and force sensitivity by attaching magnetic beads to cantilevers for atomic force microscopy in liquid

Science.gov (United States)

Hoof, Sebastian; Nand Gosvami, Nitya; Hoogenboom, Bart W.

2012-12-01

Dynamic-mode atomic force microscopy (AFM) in liquid remains complicated due to the strong viscous damping of the cantilever resonance. Here, we show that a high-quality resonance (Q >20) can be achieved in aqueous solution by attaching a microgram-bead at the end of the nanogram-cantilever. The resulting increase in cantilever mass causes the resonance frequency to drop significantly. However, the force sensitivity—as expressed via the minimum detectable force gradient—is hardly affected, because of the enhanced quality factor. Through the enhancement of the quality factor, the attached bead also reduces the relative importance of noise in the deflection detector. It can thus yield an improved signal-to-noise ratio when this detector noise is significant. We describe and analyze these effects for a set-up that includes magnetic actuation of the cantilevers and that can be easily implemented in any AFM system that is compatible with an inverted optical microscope.

Q-factor enhancement for self-actuated self-sensing piezoelectric MEMS resonators applying a lock-in driven feedback loop

International Nuclear Information System (INIS)

Kucera, M; Bittner, A; Schmid, U; Manzaneque, T; Sánchez-Rojas, J L

2013-01-01

This paper presents a robust Q-control approach based on an all-electrical feedback loop enhancing the quality factor of a resonant microstructure by using the self-sensing capability of a piezoelectric thin film actuator made of aluminium nitride. A lock-in amplifier is used to extract the feedback signal which is proportional to the piezoelectric current. The measured real part is used to replace the originally low-quality and noisy feedback signal to modulate the driving voltage of the piezoelectric thin-film actuator. Since the lock-in amplifier reduces the noise in the feedback signal substantially, the proposed enhancement loop avoids the disadvantage of a constant signal-to-noise ratio, which an analogue feedback circuit usually suffers from. The quality factor was increased from the intrinsic value of 1766 to a maximum of 34 840 in air. These promising results facilitate precise measurements for self-actuated and self-sensing MEMS cantilevers even when operated in static viscous media. (paper)

A biomimetic growth factor delivery strategy for enhanced regeneration of iliac crest defects

International Nuclear Information System (INIS)

Yilgor Huri, Pinar; Huri, Gazi; Yasar, Umit; Dikmen, Nurten; Ucar, Yurdanur; Hasirci, Nesrin; Hasirci, Vasif

2013-01-01

The importance of provision of growth factors in the engineering of tissues has long been shown to control the behavior of the cells within the construct and several approaches were applied toward this end. In nature, more than one type of growth factor is known to be effective during the healing of tissue defects and their peak concentrations are not always simultaneous. One of the most recent strategies includes the delivery of a combination of growth factors with the dose and timing to mimic the natural regeneration cascade. The sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 which are early and late appearing factors during bone regeneration, respectively, was shown in vitro to enhance osteoblastic differentiation of bone marrow derived mesenchymal stem cells. In the present study, the aim was to study the effectiveness of this delivery strategy in a rabbit iliac crest model. 3D plotted poly(ε-caprolactone) scaffolds were loaded with BMP carrying nanoparticles to achieve: (a) single BMP-2 or BMP-7 delivery, and (b) their combined delivery in a simultaneous or (c) sequential (biomimetic) fashion. After eight weeks of implantation, computed tomography and biomechanical tests showed better mineralized matrix formation and bone-implant union strength at the defect site in the case of sequential delivery compared to single or simultaneous delivery modes. Bone mineral density (BMD) and push-out stress were: 33.65±2.25 g cm −3 and 14.5±2.28 MPa, respectively, and almost 2.5 fold higher in comparison to those without growth factors (BMD: 14.14±1.21 g cm −3 ; PS: 6.59±0.65 MPa). This study, therefore, supports those obtained in vitro and emphasizes the importance of mimicking the natural timing of bioavailability of osteogenic factors in improving the regeneration of critical-sized bone defects. (paper)

Overexpression of Pax5 is not sufficient for neoplastic transformation of mouse neuroectoderm

Czech Academy of Sciences Publication Activity Database

Steinbach, P. J.; Kozmik, Zbyněk; Pfeffer, P.; Aguzzi, A.

2001-01-01

Roč. 93, č. 4 (2001), s. 459-467 ISSN 0020-7136 Institutional research plan: CEZ:AV0Z5052915 Keywords : Pax5 * retrovirus * transgenic mice Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.233, year: 2001

Double tube heat exchanger with novel enhancement: Part I - flow development length and adiabatic friction factor

Energy Technology Data Exchange (ETDEWEB)

Tiruselvam, R.; Raghavan, Vijay R. [Universiti Teknologi PETRONAS, Faculty of Mechanical Engineering, Tronoh (Malaysia)

2012-04-15

The study is conducted to evaluate the flow characteristics in a double tube heat exchanger using two new and versatile enhancement configurations. The novelty is that they are usable in single phase forced convection, evaporation and condensation. Correlations are proposed for flow development length and friction factor for use in predicting fluid pumping power in thermal equipment as well as in subsequent heat transfer characterization of the surface. (orig.)

Suppression of the stellar enhancement factor and the reaction 85Rb(p,n)85Sr

International Nuclear Information System (INIS)

Rauscher, T.; Kiss, G. G.; Gyuerky, Gy.; Simon, A.; Fueloep, Zs.; Somorjai, E.

2009-01-01

It is shown that a Coulomb suppression of the stellar enhancement factor occurs in many endothermic reactions at and far from stability. Contrary to common assumptions, reaction measurements for astrophysics with minimal impact of stellar enhancement should be preferably performed for those reactions instead of their reverses, despite of their negative Q value. As a demonstration, the cross section of the astrophysically relevant 85 Rb(p,n) 85 Sr reaction has been measured by activation between 2.16≤E c.m. ≤3.96 MeV and the astrophysical reaction rates at p process temperatures for (p,n) as well as (n,p) are directly inferred from the data. Additionally, our results confirm a previously derived modification of a global optical proton potential. The presented arguments are also relevant for other α- and proton-induced reactions in the p, rp, and νp processes.

Submonolayer InGaAs/GaAs quantum-dot lasers with high modal gain and zero-linewidth enhancement factor

DEFF Research Database (Denmark)

Xu, Zhangcheng; Birkedal, Dan; Juhl, Michael

2004-01-01

.1 nm. When the injection current is about 0.98 times the threshold, the gain spectrum becomes symmetric with respect to the lasing wavelength, and zero-linewidth enhancement factor is observed. These properties are attributed to the high density and the high uniformity of SML QDs in our laser diode....

Malaysian adolescent students' needs for enhancing thinking skills, counteracting risk factors and demonstrating academic resilience

Science.gov (United States)

Kuldas, Seffetullah; Hashim, Shahabuddin; Ismail, Hairul Nizam

2015-01-01

The adolescence period of life comes along with changes and challenges in terms of physical and cognitive development. In this hectic period, many adolescents may suffer more from various risk factors such as low socioeconomic status, substance abuse, sexual abuse and teenage pregnancy. Findings indicate that such disadvantaged backgrounds of Malaysian adolescent students lead to failure or underachievement in their academic performance. This narrative review scrutinises how some of these students are able to demonstrate academic resilience, which is satisfactory performance in cognitive or academic tasks in spite of their disadvantaged backgrounds. The review stresses the need for developing a caregiving relationship model for at-risk adolescent students in Malaysia. Such a model would allow educators to meet the students' needs for enhancing thinking skills, counteracting risk factors and demonstrating academic resilience. PMID:25663734

Optimized method for isolation of immature intracytoplasmic retroviral particles from mammalian cells

Czech Academy of Sciences Publication Activity Database

Langerová, Hana; Ruml, T.; Rumlová, M.

2017-01-01

Roč. 248, Oct (2017), s. 19-25 ISSN 0166-0934 Institutional support: RVO:61388963 Keywords : intracytoplasmic particles (ICAPs) * retrovirus * assembly * Mason-Pfizer monkey virus Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 1.693, year: 2016

Isolation, characterization, and genetic complementation of a cellular mutant resistant to retroviral infection

Science.gov (United States)

Agarwal, Sumit; Harada, Josephine; Schreifels, Jeffrey; Lech, Patrycja; Nikolai, Bryan; Yamaguchi, Tomoyuki; Chanda, Sumit K.; Somia, Nikunj V.

2006-01-01

By using a genetic screen, we have isolated a mammalian cell line that is resistant to infection by retroviruses that are derived from the murine leukemia virus, human immunodeficiency virus type 1, and feline immunodeficiency virus. We demonstrate that the cell line is genetically recessive for the resistance, and hence it is lacking a factor enabling infection by retroviruses. The block to infection is early in the life cycle, at the poorly understood uncoating stage. We implicate the proteasome at uncoating by completely rescuing the resistant phenotype with the proteasomal inhibitor MG-132. We further report on the complementation cloning of a gene (MRI, modulator of retrovirus infection) that can also act to reverse the inhibition of infection in the mutant cell line. These data implicate a role for the proteasome during uncoating, and they suggest that MRI is a regulator of this activity. Finally, we reconcile our findings and other published data to suggest a model for the involvement of the proteasome in the early phase of the retroviral life cycle. PMID:17043244

Contribution of type W human endogenous retroviruses to the human genome: characterization of HERV-W proviral insertions and processed pseudogenes.

Science.gov (United States)

Grandi, Nicole; Cadeddu, Marta; Blomberg, Jonas; Tramontano, Enzo

2016-09-09

Human endogenous retroviruses (HERVs) are ancient sequences integrated in the germ line cells and vertically transmitted through the offspring constituting about 8 % of our genome. In time, HERVs accumulated mutations that compromised their coding capacity. A prominent exception is HERV-W locus 7q21.2, producing a functional Env protein (Syncytin-1) coopted for placental syncytiotrophoblast formation. While expression of HERV-W sequences has been investigated for their correlation to disease, an exhaustive description of the group composition and characteristics is still not available and current HERV-W group information derive from studies published a few years ago that, of course, used the rough assemblies of the human genome available at that time. This hampers the comparison and correlation with current human genome assemblies. In the present work we identified and described in detail the distribution and genetic composition of 213 HERV-W elements. The bioinformatics analysis led to the characterization of several previously unreported features and provided a phylogenetic classification of two main subgroups with different age and structural characteristics. New facts on HERV-W genomic context of insertion and co-localization with sequences putatively involved in disease development are also reported. The present work is a detailed overview of the HERV-W contribution to the human genome and provides a robust genetic background useful to clarify HERV-W role in pathologies with poorly understood etiology, representing, to our knowledge, the most complete and exhaustive HERV-W dataset up to date.

Enhanced sensitivity to near-infrared with high fill factor in small molecular organic solar cells

Science.gov (United States)

Shim, Hyun-Sub; Kim, Hyo Jung; Kim, Ji Whan; Kim, Sei-Yong; Jeong, Won-Ik; Kim, Tae-Min; Kim, Jang-Joo

2012-09-01

High efficiency near-infrared (NIR) absorbing solar cells based on lead phthalocyanine (PbPc) are reported using copper iodide (CuI) as a templating layer to control the crystal structure of PbPc. Devices with CuI inserted between the ITO and PbPc layers exhibit a two times enhancement of the JSC compared to the case in the absence of the CuI layer. This is due to the increase of crystallinity in the molecules grown on the CuI templating layer, which is investigated via an x-ray diffraction study. Moreover, fill factor is also enhanced to 0.63 from 0.57 due to low series resistance although the additional CuI layer is inserted between the ITO and the PbPc layer. As a result, the corrected power conversion efficiency of 2.5% was obtained, which is the highest one reported up to now among the PbPc based solar cells.

Computational identification of developmental enhancers:conservation and function of transcription factor binding-site clustersin drosophila melanogaster and drosophila psedoobscura

Energy Technology Data Exchange (ETDEWEB)

Berman, Benjamin P.; Pfeiffer, Barret D.; Laverty, Todd R.; Salzberg, Steven L.; Rubin, Gerald M.; Eisen, Michael B.; Celniker, SusanE.

2004-08-06

The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayed embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated to those of neighboring genes; the remaining 18 do not appear to have enhancer activity. We used the Drosophila pseudoobscura genome to compare patterns of evolution in and around the 15 positive and 18 false-positive predictions. Although conservation of primary sequence cannot distinguish true from false positives, conservation of binding-site clustering accurately discriminates functional binding-site clusters from those with no function. We incorporated conservation of binding-site clustering into a new genome-wide enhancer screen, and predict several hundred new regulatory sequences, including 85 adjacent to genes with embryonic patterns. Measuring conservation of sequence features closely linked to function--such as binding-site clustering--makes better use of comparative sequence data than commonly used methods that examine only sequence identity.

Optimization of critical factors to enhance polyhydroxyalkanoates (PHA) synthesis by mixed culture using Taguchi design of experimental methodology.

Science.gov (United States)

Venkata Mohan, S; Venkateswar Reddy, M

2013-01-01

Optimizing different factors is crucial for enhancement of mixed culture bioplastics (polyhydroxyalkanoates (PHA)) production. Design of experimental (DOE) methodology using Taguchi orthogonal array (OA) was applied to evaluate the influence and specific function of eight important factors (iron, glucose concentration, VFA concentration, VFA composition, nitrogen concentration, phosphorous concentration, pH, and microenvironment) on the bioplastics production. Three levels of factor (2(1) × 3(7)) variation were considered with symbolic arrays of experimental matrix [L(18)-18 experimental trails]. All the factors were assigned with three levels except iron concentration (2(1)). Among all the factors, microenvironment influenced bioplastics production substantially (contributing 81%), followed by pH (11%) and glucose concentration (2.5%). Validation experiments were performed with the obtained optimum conditions which resulted in improved PHA production. Good substrate degradation (as COD) of 68% was registered during PHA production. Dehydrogenase and phosphatase enzymatic activities were monitored during process operation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics.

Science.gov (United States)

Kulshreshtha, Parul; Tiwari, Ashutosh; Priyanka; Joon, Shikha; Sinha, Subrata; Bhatnagar, Rakesh

2015-12-01

Hybridomas were created using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor). Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immnized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H10 and H8) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). Single chain variable fragment (LETscFv) was derived from H10 hybridoma. H11 was found to have disease-enhancing property. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature. This in vitro abrogation of disease-enhancement provides the proof of concept that in polyclonal sera the disease enhancing character of a fraction of antibodies is overshadowed by the protective nature of the rest of the antibodies generated on active immunization. Copyright © 2015. Published by Elsevier Ltd.

Life History of the Oldest Lentivirus: Characterization of ELVgv Integrations in the Dermopteran Genome

Czech Academy of Sciences Publication Activity Database

Hron, Tomáš; Farkašová, Helena; Padhi, A.; Pačes, Jan; Elleder, Daniel

2016-01-01

Roč. 33, č. 10 (2016), s. 2659-2669 ISSN 0737-4038 R&D Projects: GA MŠk(CZ) LK11215 Institutional support: RVO:68378050 Keywords : endogenous retrovirus * dermoptera * TRIM5 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.202, year: 2016

Nucleosome mediated crosstalk between transcription factors at eukaryotic enhancers

International Nuclear Information System (INIS)

Teif, Vladimir B; Rippe, Karsten

2011-01-01

A recent study of transcription regulation in Drosophila embryonic development revealed a complex non-monotonic dependence of gene expression on the distance between binding sites of repressor and activator proteins at the corresponding enhancer cis-regulatory modules (Fakhouri et al 2010 Mol. Syst. Biol. 6 341). The repressor efficiency was high at small separations, low around 30 bp, reached a maximum at 50–60 bp, and decreased at larger distances to the activator binding sites. Here, we propose a straightforward explanation for the distance dependence of repressor activity by considering the effect of the presence of a nucleosome. Using a method that considers partial unwrapping of nucleosomal DNA from the histone octamer core, we calculated the dependence of activator binding on the repressor–activator distance and found a quantitative agreement with the distance dependence reported for the Drosophila enhancer element. In addition, the proposed model offers explanations for other distance-dependent effects at eukaryotic enhancers. (communication)

Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells

Directory of Open Access Journals (Sweden)

Manpreet S. Chahal

2010-07-01

Full Text Available Phospholipase D2 (PLD2 generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells.

Science.gov (United States)

Chahal, Manpreet S; Brauner, Daniel J; Meier, Kathryn E

2010-07-02

Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR) can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

DENdb: database of integrated human enhancers

KAUST Repository

Ashoor, Haitham

2015-09-05

Enhancers are cis-acting DNA regulatory regions that play a key role in distal control of transcriptional activities. Identification of enhancers, coupled with a comprehensive functional analysis of their properties, could improve our understanding of complex gene transcription mechanisms and gene regulation processes in general. We developed DENdb, a centralized on-line repository of predicted enhancers derived from multiple human cell-lines. DENdb integrates enhancers predicted by five different methods generating an enriched catalogue of putative enhancers for each of the analysed cell-lines. DENdb provides information about the overlap of enhancers with DNase I hypersensitive regions, ChIP-seq regions of a number of transcription factors and transcription factor binding motifs, means to explore enhancer interactions with DNA using several chromatin interaction assays and enhancer neighbouring genes. DENdb is designed as a relational database that facilitates fast and efficient searching, browsing and visualization of information.

DENdb: database of integrated human enhancers

KAUST Repository

Ashoor, Haitham; Kleftogiannis, Dimitrios A.; Radovanovic, Aleksandar; Bajic, Vladimir B.

2015-01-01

Enhancers are cis-acting DNA regulatory regions that play a key role in distal control of transcriptional activities. Identification of enhancers, coupled with a comprehensive functional analysis of their properties, could improve our understanding of complex gene transcription mechanisms and gene regulation processes in general. We developed DENdb, a centralized on-line repository of predicted enhancers derived from multiple human cell-lines. DENdb integrates enhancers predicted by five different methods generating an enriched catalogue of putative enhancers for each of the analysed cell-lines. DENdb provides information about the overlap of enhancers with DNase I hypersensitive regions, ChIP-seq regions of a number of transcription factors and transcription factor binding motifs, means to explore enhancer interactions with DNA using several chromatin interaction assays and enhancer neighbouring genes. DENdb is designed as a relational database that facilitates fast and efficient searching, browsing and visualization of information.

Contrast-enhanced CT and diffusion-weighted MR imaging: Performance as a prognostic factor in patients with pancreatic ductal adenocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Fukukura, Yoshihiko, E-mail: fukukura@m.kufm.kagoshima-u.ac.jp [Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City 890-8544 (Japan); Takumi, Koji [Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City 890-8544 (Japan); Higashi, Michiyo [Department of Human Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City 890-8544 (Japan); Shinchi, Hiroyuki [Department of Surgical Oncology and Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City 890-8544 (Japan); Kamimura, Kiyohisa; Yoneyama, Tomohide; Tateyama, Akihiro [Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City 890-8544 (Japan)

2014-04-15

Objective: To determine whether contrast enhancement of CT and apparent diffusion coefficient on diffusion-weighted MR imaging are important parameters that can predict outcomes for patients with pancreatic ductal adenocarcinoma. Materials and methods: Ninety-two patients with histologically confirmed pancreatic ductal adenocarcinoma who underwent quadriphasic CT (including unenhanced, pancreatic parenchymal, portal venous and delayed phases) and fat-suppressed single-shot echo-planar diffusion-weighted MR imaging at 3.0 T were retrospectively analyzed to investigate prognostic factors. Overall survival curves were drawn using the Kaplan–Meier method. Effects on survival of variables including age, sex, tumor location, tumor size, TNM stage, carbohydrate antigen 19-9, carcinoembryonic antigen, treatment, tumor contrast enhancement and apparent diffusion coefficient values were analyzed in univariate analysis using the log-rank test. Variables were analyzed in multivariate analyses using the Cox proportional hazards regression model. Results: Median survival for the entire patient population was 18.2 months. Higher contrast enhancement during all phases was associated with significantly longer overall survival (P < 0.001 for all phases). The difference in overall survival between groups divided by median apparent diffusion coefficient value was not significant (P = 0.672). TNM stage (P = 0.026) and tumor contrast enhancement on CT (P = 0.027) were significantly related to survival in multivariate analysis. Conclusions: Poor enhancement of pancreatic adenocarcinomas on enhanced CT is associated with reduced patient survival.

Contrast-enhanced CT and diffusion-weighted MR imaging: Performance as a prognostic factor in patients with pancreatic ductal adenocarcinoma

International Nuclear Information System (INIS)

Fukukura, Yoshihiko; Takumi, Koji; Higashi, Michiyo; Shinchi, Hiroyuki; Kamimura, Kiyohisa; Yoneyama, Tomohide; Tateyama, Akihiro

2014-01-01

Objective: To determine whether contrast enhancement of CT and apparent diffusion coefficient on diffusion-weighted MR imaging are important parameters that can predict outcomes for patients with pancreatic ductal adenocarcinoma. Materials and methods: Ninety-two patients with histologically confirmed pancreatic ductal adenocarcinoma who underwent quadriphasic CT (including unenhanced, pancreatic parenchymal, portal venous and delayed phases) and fat-suppressed single-shot echo-planar diffusion-weighted MR imaging at 3.0 T were retrospectively analyzed to investigate prognostic factors. Overall survival curves were drawn using the Kaplan–Meier method. Effects on survival of variables including age, sex, tumor location, tumor size, TNM stage, carbohydrate antigen 19-9, carcinoembryonic antigen, treatment, tumor contrast enhancement and apparent diffusion coefficient values were analyzed in univariate analysis using the log-rank test. Variables were analyzed in multivariate analyses using the Cox proportional hazards regression model. Results: Median survival for the entire patient population was 18.2 months. Higher contrast enhancement during all phases was associated with significantly longer overall survival (P < 0.001 for all phases). The difference in overall survival between groups divided by median apparent diffusion coefficient value was not significant (P = 0.672). TNM stage (P = 0.026) and tumor contrast enhancement on CT (P = 0.027) were significantly related to survival in multivariate analysis. Conclusions: Poor enhancement of pancreatic adenocarcinomas on enhanced CT is associated with reduced patient survival

Antenna-assisted enhanced transmission through subwavelength nanoholes

DEFF Research Database (Denmark)

Xiao, Sanshui; Peng, Liang; Mortensen, Asger

2010-01-01

By structural engineering of sub-wavelength apertures, we numerically demonstrate that transmission through apertures can be significantly enhanced. Based on equivalent circuit theory analysis, structured apertures are obtained with a 1900-fold transmission enhancement factor. We show that the en......By structural engineering of sub-wavelength apertures, we numerically demonstrate that transmission through apertures can be significantly enhanced. Based on equivalent circuit theory analysis, structured apertures are obtained with a 1900-fold transmission enhancement factor. We show...

Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

Science.gov (United States)

Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

Local Overexpression of V1a-Vasopressin Receptor Enhances Regeneration in Tumor Necrosis Factor-Induced Muscle Atrophy

Directory of Open Access Journals (Sweden)

Alessandra Costa

2014-01-01

Full Text Available Skeletal muscle atrophy occurs during disuse and aging, or as a consequence of chronic diseases such as cancer and diabetes. It is characterized by progressive loss of muscle tissue due to hypotrophic changes, degeneration, and an inability of the regeneration machinery to replace damaged myofibers. Tumor necrosis factor (TNF is a proinflammatory cytokine known to mediate muscle atrophy in many chronic diseases and to inhibit skeletal muscle regeneration. In this study, we investigated the role of Arg-vasopressin-(AVP-dependent pathways in muscles in which atrophy was induced by local overexpression of TNF. AVP is a potent myogenesis-promoting factor and is able to enhance skeletal muscle regeneration by stimulating Ca2+/calmodulin-dependent kinase and calcineurin signaling. We performed morphological and molecular analyses and demonstrated that local over-expression of the AVP receptor V1a enhances regeneration of atrophic muscle. By upregulating the regeneration/differentiation markers, modulating the inflammatory response, and attenuating fibrogenesis, the stimulation of AVP-dependent pathways creates a favourable environment for efficient and sustained muscle regeneration and repair even in the presence of elevated levels of TNF. This study highlights a novel in vivo role for AVP-dependent pathways, which may represent an interesting strategy to counteract muscle decline in aging or in muscular pathologies.

Molecular selectivity of graphene-enhanced Raman scattering.

Science.gov (United States)

Huang, Shengxi; Ling, Xi; Liang, Liangbo; Song, Yi; Fang, Wenjing; Zhang, Jin; Kong, Jing; Meunier, Vincent; Dresselhaus, Mildred S

2015-05-13

Graphene-enhanced Raman scattering (GERS) is a recently discovered Raman enhancement phenomenon that uses graphene as the substrate for Raman enhancement and can produce clean and reproducible Raman signals of molecules with increased signal intensity. Compared to conventional Raman enhancement techniques, such as surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS), in which the Raman enhancement is essentially due to the electromagnetic mechanism, GERS mainly relies on a chemical mechanism and therefore shows unique molecular selectivity. In this paper, we report graphene-enhanced Raman scattering of a variety of different molecules with different molecular properties. We report a strong molecular selectivity for the GERS effect with enhancement factors varying by as much as 2 orders of magnitude for different molecules. Selection rules are discussed with reference to two main features of the molecule, namely its molecular energy levels and molecular structures. In particular, the enhancement factor involving molecular energy levels requires the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies to be within a suitable range with respect to graphene's Fermi level, and this enhancement effect can be explained by the time-dependent perturbation theory of Raman scattering. The enhancement factor involving the choice of molecular structures indicates that molecular symmetry and substituents similar to that of the graphene structure are found to be favorable for GERS enhancement. The effectiveness of these factors can be explained by group theory and the charge-transfer interaction between molecules and graphene. Both factors, involving the molecular energy levels and structural symmetry of the molecules, suggest that a remarkable GERS enhancement requires strong molecule-graphene coupling and thus effective charge transfer between the molecules and graphene. These conclusions are further

Analysis of swine leukocyte antigen class I gene profiles and porcine endogenous retrovirus viremia level in a transgenic porcine herd inbred for xenotransplantation research

Science.gov (United States)

Sypniewski, Daniel; Gałka, Sabina; Sołtysik, Dagna; Loch, Tomasz; Nowak, Ewa; Smorąg, Zdzisław; Bednarek, Ilona

2018-01-01

Molecular characterization of swine leukocyte antigen (SLA) genes is important for elucidating the immune responses between swine-donor and human-recipient in xenotransplantation. Examination of associations between alleles of SLA class I genes, type of pig genetic modification, porcine endogenous retrovirus (PERV) viral titer, and PERV subtypes may shed light on the nature of xenograft acceptance or rejection and the safety of xenotransplantation. No significant difference in PERV gag RNA level between transgenic and non-transgenic pigs was noted; likewise, the type of applied transgene had no impact on PERV viremia. SLA-1 gene profile type may correspond with PERV level in blood and thereby influence infectiveness. Screening of pigs should provide selection of animals with low PERV expression and exclusion of specimens with PERV-C in the genome due to possible recombination between A and C subtypes, which may lead to autoinfection. Presence of PERV-C integrated in the genome was detected in 31.25% of specimens, but statistically significant increased viremia in specimens with PERV-C was not observed. There is a need for multidirectional molecular characterization (SLA typing, viremia estimation, and PERV subtype screening) of animals intended for xenotransplantation research in the interest of xeno-recipient safety. PMID:29366300

Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas

International Nuclear Information System (INIS)

Smith, F.E.; Rosen, K.M.; Villa-Komaroff, L.; Weir, G.C.; Bonner-Weir, S.

1991-01-01

Insulin-like growth factor I (IGF-I) mRNA expression was studied after 90% partial pancreatectomy in the rat to determine whether IGF-I was associated with pancreatic regeneration. The level of IGF-I mRNA was maximally increased (4-fold above control value) 3 days after pancreatectomy, but thereafter gradually decreased, returning to control levels by 14 days after surgery. By in situ hybridization, IGF-I mRNA in both pancreatectomized and sham-operated rats was localized to capillary endothelial cells, indicating that this is the site of IGF-I expression in the normal rat pancreas. However, enhanced IGF-I mRNA expression was localized to focal areas of regeneration unique to pancreatectomized rats. In these areas, epithelial cells of proliferating ductules and individual connective tissue cells expressed IGF-I, suggesting that IGF-I may play an important role in the growth or differentiation of pancreatic tissue

Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas

Energy Technology Data Exchange (ETDEWEB)

Smith, F.E.; Rosen, K.M.; Villa-Komaroff, L.; Weir, G.C.; Bonner-Weir, S. (E. P. Joslin Research Laboratory, Joslin Diabetes Center, Harvard Medical School, Boston, MA (USA))

1991-07-15

Insulin-like growth factor I (IGF-I) mRNA expression was studied after 90% partial pancreatectomy in the rat to determine whether IGF-I was associated with pancreatic regeneration. The level of IGF-I mRNA was maximally increased (4-fold above control value) 3 days after pancreatectomy, but thereafter gradually decreased, returning to control levels by 14 days after surgery. By in situ hybridization, IGF-I mRNA in both pancreatectomized and sham-operated rats was localized to capillary endothelial cells, indicating that this is the site of IGF-I expression in the normal rat pancreas. However, enhanced IGF-I mRNA expression was localized to focal areas of regeneration unique to pancreatectomized rats. In these areas, epithelial cells of proliferating ductules and individual connective tissue cells expressed IGF-I, suggesting that IGF-I may play an important role in the growth or differentiation of pancreatic tissue.

Three cysteine residues of SLC52A1, a receptor for the porcine endogenous retrovirus-A (PERV-A), play a critical role in cell surface expression and infectivity.

Science.gov (United States)

Colon-Moran, Winston; Argaw, Takele; Wilson, Carolyn A

2017-07-01

Porcine endogenous retrovirus-A (PERV-A), a gammaretrovirus, infects human cells in vitro, thus raising the potential risk of cross-species transmission in xenotransplantation. Two members of the solute carrier family 52 (SLC52A1 and SLC52A2) are PERV-A receptors. Site-directed mutagenesis of the cDNA encoding SLC52A1 identified that only one of two putative glycosylation signals is occupied by glycans. In addition, we showed that glycosylation of SLC52A1 is not necessary for PERV-A receptor function. We also identified that at a minimum, three cysteine residues are sufficient for SLC52A1 cell surface expression. Mutation of cysteine at position 365 and either of the two cysteine residues in the C-terminal tail at positions 442 or 446 reduced SLC52A1 surface expression and PERV-A infection suggesting that these residues may contribute to overall structural stability and receptor function. Understanding interactions between PERV-A and its cellular receptor may provide novel strategies to prevent zoonotic infection in the setting of xenotransplantation. Published by Elsevier Inc.

Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases.

Science.gov (United States)

Arru, G; Mameli, G; Deiana, G A; Rassu, A L; Piredda, R; Sechi, E; Caggiu, E; Bo, M; Nako, E; Urso, D; Mariotto, S; Ferrari, S; Zanusso, G; Monaco, S; Sechi, G; Sechi, L A

2018-03-31

Human endogenous retroviruses (HERV) K/W seem to play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) was investigated for ALS, multiple sclerosis (MS) and Alzheimer's disease patients and in healthy controls. Four antigenic peptides derived respectively from HERV-K and HERV-W env-su proteins were studied in 21 definite or probable ALS patients, 26 possible or definite relapsing-remitting MS patients, 18 patients with Alzheimer's disease and 39 healthy controls. An indirect enzyme-linked immunosorbent assay was set up to detect specific antibodies (Abs) against env-su peptides. Amongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su 19-37 was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, amongst the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su 93-108 and HERV-W env-su 248-262 were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su 19-37 Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. Increased circulating levels of Abs directed against the HERV-W env-su 93-108 and HERV-W env-su 248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su 19-37 peptide fragment could serve as a possible early novel biomarker in patients with ALS. © 2018 EAN.

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair.

Science.gov (United States)

Murgia, Claudio; Caporale, Marco; Ceesay, Ousman; Di Francesco, Gabriella; Ferri, Nicola; Varasano, Vincenzo; de las Heras, Marcelo; Palmarini, Massimo

2011-03-01

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer.

Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea

Directory of Open Access Journals (Sweden)

Bu M

2015-11-01

Full Text Available Meng Bu,1,2 Jingling Tang,3 Yinghui Wei,4 Yanhui Sun,1 Xinyu Wang,1 Linhua Wu,2 Hongzhuo Liu1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Department of Pharmacy, the Second Affiliated Hospital, 3School of Pharmacy, Harbin Medical University, Harbin, People’s Republic of China; 4College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China Purpose: Supplementation of exogenous nerve growth factor (NGF into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route.Methods: A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic® F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously.Results: Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane. Conclusion: Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants. Keywords: nerve growth factor, lipid-based crystalline nanoparticles, PC12 cells, inner ear drug

Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors

International Nuclear Information System (INIS)

Zhu Lingyan; Han Wei; Chen Shaopeng; Zhao Ye; Jiang Erkang; Bao Lingzhi; Pei Bei; Yang Gen; Zhao Guoping; Wang Jun; Xu An; Wu Lijun

2008-01-01

Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of α-particle irradiation, the fraction of γ-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy α-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2 h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H 2 O 2 ), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress

Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

Directory of Open Access Journals (Sweden)

Cristina Puy

Full Text Available Factor (F XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα, in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin.Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma.Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

Tenax extraction for exploring rate-limiting factors in methyl-β-cyclodextrin enhanced anaerobic biodegradation of PAHs under denitrifying conditions in a red paddy soil

Energy Technology Data Exchange (ETDEWEB)

Sun, Mingming, E-mail: sunmingming@njau.edu.cn [Soil Ecology Lab, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Key Laboratory of Soil Environmental and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Ye, Mao [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Hu, Feng, E-mail: fenghu@njau.edu.cn [Soil Ecology Lab, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Li, Huixin [Soil Ecology Lab, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Teng, Ying [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Luo, Yongming [Yantai Institute of Costal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China); Jiang, Xin [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Kengara, Fredrick Orori [Department of Chemistry, Maseno University, Private Bag, Maseno 40105 (Kenya)

2014-01-15

Highlights: • Enhanced anaerobic bioremediation of a red paddy soil polluted with PAHs. • 1% (w/w) methyl-β-cyclodextrin (MCD) and 20 mM nitrate addition acted as solubility-enhancing agent and electron acceptor respectively. • Tenax extraction and a first-three-compartment modeling were applicable to explore the rate-limiting factors in the biodegradation. • Lack of PAH-degraders hindered biodegradation in control and MCD addition treatments. • Inadequate bioaccessible PAHs was vital rate-limiting factor in nitrate addition treatments. -- Abstract: The effectiveness of anaerobic bioremediation systems for PAH-contaminated soil may be constrained by low contaminants bioaccessibility due to limited aqueous solubility and lack of suitable electron acceptors. Information on what is the rate-limiting factor in bioremediation process is of vital importance in the decision in what measures can be taken to assist the biodegradation efficacy. In the present study, four different microcosms were set to study the effect of methyl-β-cyclodextrin (MCD) and nitrate addition (N) on PAHs biodegradation under anaerobic conditions in a red paddy soil. Meanwhile, sequential Tenax extraction combined with a first-three-compartment model was employed to evaluate the rate-limiting factors in MCD enhanced anaerobic biodegradation of PAHs. Microcosms with both 1% (w/w) MCD and 20 mM N addition produced maximum biodegradation of total PAHs of up to 61.7%. It appears rate-limiting factors vary with microcosms: low activity of degrading microorganisms is the vital rate-limiting factor for control and MCD addition treatments (CK and M treatments); and lack of bioaccessible PAHs is the main rate-limiting factor for nitrate addition treatments (N and MN treatments). These results have practical implications for site risk assessment and cleanup strategies.

Tenax extraction for exploring rate-limiting factors in methyl-β-cyclodextrin enhanced anaerobic biodegradation of PAHs under denitrifying conditions in a red paddy soil

International Nuclear Information System (INIS)

Sun, Mingming; Ye, Mao; Hu, Feng; Li, Huixin; Teng, Ying; Luo, Yongming; Jiang, Xin; Kengara, Fredrick Orori

2014-01-01

Highlights: • Enhanced anaerobic bioremediation of a red paddy soil polluted with PAHs. • 1% (w/w) methyl-β-cyclodextrin (MCD) and 20 mM nitrate addition acted as solubility-enhancing agent and electron acceptor respectively. • Tenax extraction and a first-three-compartment modeling were applicable to explore the rate-limiting factors in the biodegradation. • Lack of PAH-degraders hindered biodegradation in control and MCD addition treatments. • Inadequate bioaccessible PAHs was vital rate-limiting factor in nitrate addition treatments. -- Abstract: The effectiveness of anaerobic bioremediation systems for PAH-contaminated soil may be constrained by low contaminants bioaccessibility due to limited aqueous solubility and lack of suitable electron acceptors. Information on what is the rate-limiting factor in bioremediation process is of vital importance in the decision in what measures can be taken to assist the biodegradation efficacy. In the present study, four different microcosms were set to study the effect of methyl-β-cyclodextrin (MCD) and nitrate addition (N) on PAHs biodegradation under anaerobic conditions in a red paddy soil. Meanwhile, sequential Tenax extraction combined with a first-three-compartment model was employed to evaluate the rate-limiting factors in MCD enhanced anaerobic biodegradation of PAHs. Microcosms with both 1% (w/w) MCD and 20 mM N addition produced maximum biodegradation of total PAHs of up to 61.7%. It appears rate-limiting factors vary with microcosms: low activity of degrading microorganisms is the vital rate-limiting factor for control and MCD addition treatments (CK and M treatments); and lack of bioaccessible PAHs is the main rate-limiting factor for nitrate addition treatments (N and MN treatments). These results have practical implications for site risk assessment and cleanup strategies

Target‐specific epigenetic silencing of endogenous retroviruses in mammals

DEFF Research Database (Denmark)

Wolf, Gernot

factors, have evolved to recognise and restrict ERVs in a target-specific manner. During his studies, Gernot Wolf investigated evolutionary and mechanistic aspects of epigenetic ERV restriction in various mammalian species. The studies included genome-wide transcription factor binding analysis using next...

Enhancing the estimation of blood pressure using pulse arrival time and two confounding factors

International Nuclear Information System (INIS)

Baek, Hyun Jae; Kim, Ko Keun; Kim, Jung Soo; Lee, Boreom; Park, Kwang Suk

2010-01-01

A new method of blood pressure (BP) estimation using multiple regression with pulse arrival time (PAT) and two confounding factors was evaluated in clinical and unconstrained monitoring situations. For the first analysis with clinical data, electrocardiogram (ECG), photoplethysmogram (PPG) and invasive BP signals were obtained by a conventional patient monitoring device during surgery. In the second analysis, ECG, PPG and non-invasive BP were measured using systems developed to obtain data under conditions in which the subject was not constrained. To enhance the performance of BP estimation methods, heart rate (HR) and arterial stiffness were considered as confounding factors in regression analysis. The PAT and HR were easily extracted from ECG and PPG signals. For arterial stiffness, the duration from the maximum derivative point to the maximum of the dicrotic notch in the PPG signal, a parameter called TDB, was employed. In two experiments that normally cause BP variation, the correlation between measured BP and the estimated BP was investigated. Multiple-regression analysis with the two confounding factors improved correlation coefficients for diastolic blood pressure and systolic blood pressure to acceptable confidence levels, compared to existing methods that consider PAT only. In addition, reproducibility for the proposed method was determined using constructed test sets. Our results demonstrate that non-invasive, non-intrusive BP estimation can be obtained using methods that can be applied in both clinical and daily healthcare situations

Enhancing the estimation of blood pressure using pulse arrival time and two confounding factors.

Science.gov (United States)

Baek, Hyun Jae; Kim, Ko Keun; Kim, Jung Soo; Lee, Boreom; Park, Kwang Suk

2010-02-01

A new method of blood pressure (BP) estimation using multiple regression with pulse arrival time (PAT) and two confounding factors was evaluated in clinical and unconstrained monitoring situations. For the first analysis with clinical data, electrocardiogram (ECG), photoplethysmogram (PPG) and invasive BP signals were obtained by a conventional patient monitoring device during surgery. In the second analysis, ECG, PPG and non-invasive BP were measured using systems developed to obtain data under conditions in which the subject was not constrained. To enhance the performance of BP estimation methods, heart rate (HR) and arterial stiffness were considered as confounding factors in regression analysis. The PAT and HR were easily extracted from ECG and PPG signals. For arterial stiffness, the duration from the maximum derivative point to the maximum of the dicrotic notch in the PPG signal, a parameter called TDB, was employed. In two experiments that normally cause BP variation, the correlation between measured BP and the estimated BP was investigated. Multiple-regression analysis with the two confounding factors improved correlation coefficients for diastolic blood pressure and systolic blood pressure to acceptable confidence levels, compared to existing methods that consider PAT only. In addition, reproducibility for the proposed method was determined using constructed test sets. Our results demonstrate that non-invasive, non-intrusive BP estimation can be obtained using methods that can be applied in both clinical and daily healthcare situations.

Anthropogenic and climatic factors enhancing hypolimnetic anoxia in a temperate mountain lake

Science.gov (United States)

Sánchez-España, Javier; Mata, M. Pilar; Vegas, Juana; Morellón, Mario; Rodríguez, Juan Antonio; Salazar, Ángel; Yusta, Iñaki; Chaos, Aida; Pérez-Martínez, Carmen; Navas, Ana

2017-12-01

Oxygen depletion (temporal or permanent) in freshwater ecosystems is a widespread and globally important environmental problem. However, the factors behind increased hypolimnetic anoxia in lakes and reservoirs are often diverse and may involve processes at different spatial and temporal scales. Here, we evaluate the combined effects of different anthropogenic pressures on the oxygen dynamics and water chemistry of Lake Enol, an emblematic mountain lake in Picos de Europa National Park (NW Spain). A multidisciplinary study conducted over a period of four years (2013-2016) indicates that the extent and duration of hypolimnetic anoxia has increased dramatically in recent years. The extent and duration of hypolimnetic anoxia is typical of meso-eutrophic systems, in contrast with the internal productivity of the lake, which remains oligo-mesotrophic and phosphorus-limited. This apparent contradiction is ascribed to the combination of different external pressures in the catchment, which have increased the input of allochthonous organic matter in recent times through enhanced erosion and sediment transport. The most important among these pressures appears to be cattle grazing, which affects not only the import of carbon and nutrients, but also the lake microbiology. The contribution of clear-cutting, runoff channelling, and tourism is comparatively less significant. The cumulative effects of these local human impacts are not only affecting the lake metabolism, but also the import of sulfate, nitrate- and ammonium-nitrogen, and metals (Zn). However, these local factors alone cannot explain entirely the observed oxygen deficit. Climatic factors (e.g., warmer and drier spring and autumn seasons) are also reducing oxygen levels in deep waters through a longer and increasingly steep thermal stratification. Global warming may indirectly increase anoxia in many other mountain lakes in the near future.

Genotyping of feline leukemia virus in Mexican housecats.

Science.gov (United States)

Ramírez, Hugo; Autran, Marcela; García, M Martha; Carmona, M Ángel; Rodríguez, Cecilia; Martínez, H Alejandro

2016-04-01

Feline leukemia virus (FeLV) is a retrovirus with variable rates of infection globally. DNA was obtained from cats' peripheral blood mononuclear cells, and proviral DNA of pol and env genes was detected using PCR. Seventy-six percent of cats scored positive for FeLV using env-PCR; and 54 %, by pol-PCR. Phylogenetic analysis of both regions identified sequences that correspond to a group that includes endogenous retroviruses. They form an independent branch and, therefore, a new group of endogenous viruses. Cat gender, age, outdoor access, and cohabitation with other cats were found to be significant risk factors associated with the disease. This strongly suggests that these FeLV genotypes are widely distributed in the studied feline population in Mexico.

The inhibitory effect of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members on the activity of cellular microRNAs.

Science.gov (United States)

Zhang, Hui

2010-01-01

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or APOBEC3G) and its fellow cytidine deaminase family members are potent restrictive factors for human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. However, the cellular function of APOBEC3G remains to be further clarified. It has been reported that APOBEC3s can restrict the mobility of endogenous retroviruses and LTR-retrotransposons, suggesting that they can maintain stability in host genomes. However, APOBEC3G is normally cytoplasmic. Further studies have demonstrated that it is associated with an RNase-sensitive high molecular mass (HMM) and located in processing bodies (P-bodies) of replicating T-cells, indicating that the major cellular function of APOBEC3G seems to be related to P-body-related RNA processing and metabolism. As the function of P-body is closely related to miRNA activity, APOBEC3G could affect the miRNA function. Recent studies have demonstrated that APOBEC3G and its family members counteract miRNA-mediated repression of protein translation. Further, APOBEC3G enhances the association of miRNA-targeted mRNA with polysomes, and facilitates the dissociation of miRNA-targeted mRNA from P-bodies. As such, APOBEC3G regulate the activity of cellular miRNAs. Whether this function is related to its potent antiviral activity remains to be further determined.

Three approaches for estimating recovery factors in carbon dioxide enhanced oil recovery

Science.gov (United States)

Verma, Mahendra K.

2017-07-17

PrefaceThe Energy Independence and Security Act of 2007 authorized the U.S. Geological Survey (USGS) to conduct a national assessment of geologic storage resources for carbon dioxide (CO2) and requested the USGS to estimate the “potential volumes of oil and gas recoverable by injection and sequestration of industrial carbon dioxide in potential sequestration formations” (42 U.S.C. 17271(b)(4)). Geologic CO2 sequestration associated with enhanced oil recovery (EOR) using CO2 in existing hydrocarbon reservoirs has the potential to increase the U.S. hydrocarbon recoverable resource. The objective of this report is to provide detailed information on three approaches that can be used to calculate the incremental recovery factors for CO2-EOR. Therefore, the contents of this report could form an integral part of an assessment methodology that can be used to assess the sedimentary basins of the United States for the hydrocarbon recovery potential using CO2-EOR methods in conventional oil reservoirs.

HOCOMOCO: expansion and enhancement of the collection of transcription factor binding sites models

KAUST Repository

Kulakovskiy, Ivan V.

2015-11-19

Models of transcription factor (TF) binding sites provide a basis for a wide spectrum of studies in regulatory genomics, from reconstruction of regulatory networks to functional annotation of transcripts and sequence variants. While TFs may recognize different sequence patterns in different conditions, it is pragmatic to have a single generic model for each particular TF as a baseline for practical applications. Here we present the expanded and enhanced version of HOCOMOCO (http://hocomoco.autosome.ru and http://www.cbrc.kaust.edu.sa/hocomoco10), the collection of models of DNA patterns, recognized by transcription factors. HOCOMOCO now provides position weight matrix (PWM) models for binding sites of 601 human TFs and, in addition, PWMs for 396 mouse TFs. Furthermore, we introduce the largest up to date collection of dinucleotide PWM models for 86 (52) human (mouse) TFs. The update is based on the analysis of massive ChIP-Seq and HT-SELEX datasets, with the validation of the resulting models on in vivo data. To facilitate a practical application, all HOCOMOCO models are linked to gene and protein databases (Entrez Gene, HGNC, UniProt) and accompanied by precomputed score thresholds. Finally, we provide command-line tools for PWM and diPWM threshold estimation and motif finding in nucleotide sequences.

Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.

OpenAIRE

Matsumoto, M; Imagawa, M; Aoki, Y

2000-01-01

Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did no...

Nerve growth factor enhances cough via a central mechanism of action.

Science.gov (United States)

El-Hashim, Ahmed Z; Jaffal, Sahar M; Al-Rashidi, Fatma T; Luqmani, Yunus A; Akhtar, Saghir

2013-08-01

The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by real-time PCR and immunoblotting. I.c.v. and inhaled NGF enhanced citric acid induced-cough and airway obstruction. Pretreatment (i.c.v.) with antagonists of TrkA (K252a) or TRPV1 (IRTX) significantly reduced both the NGF (i.c.v.) enhanced cough and airway obstruction whereas the NK1 antagonist (FK888) inhibited only cough. The H1 antagonist (cetirizine) did not affect either. Inhaled NGF increased phosphorylation of TrkA receptors in the bronchi but not the brainstem at 0.5h post-treatment. TrkA mRNA was elevated at 0.5h in the bronchi and at 24h in the brainstem while TRPV1 mRNA was elevated from 0.5h to 24h in brainstem and at 24h in the bronchi. Pretreatment (i.c.v.) with IRTX, but not K252a, significantly inhibited the inhaled NGF-enhanced cough. Central NGF administration enhances cough and airway obstruction by mechanisms dependent on central activation of TrkA, TRPV1 and NK1 receptors while inhaled NGF enhances cough via a mechanism dependent on central TRPV1 and not TrkA receptors. These data show that NGF, in addition to its effects on the airways, has an important central mechanism of action in the enhancement of cough. Therefore, therapeutic strategies targeting NGF signaling in both the airways and CNS may be more effective in the management of cough. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fibroblast Growth Factor-9 Activates c-Kit Progenitor Cells and Enhances Angiogenesis in the Infarcted Diabetic Heart

Directory of Open Access Journals (Sweden)

Dinender Singla

2016-01-01

Full Text Available We hypothesized that fibroblast growth factor-9 (FGF-9 would enhance angiogenesis via activating c-kit positive stem cells in the infarcted nondiabetic and diabetic heart. In brief, animals were divided into three groups: Sham, MI, and MI+FGF-9. Two weeks following MI or sham surgery, our data suggest that treatment with FGF-9 significantly diminished vascular apoptosis compared to the MI group in both C57BL/6 and db/db mice (p<0.05. Additionally, the number of c-kit+ve/SM α-actin+ve cells and c-kit+ve/CD31+ve cells were greatly enhanced in the MI+FGF-9 groups relative to the MI suggesting FGF-9 enhances c-Kit cell activation and their differentiation into vascular smooth muscle cells and endothelial cells, respectively (p<0.05. Histology shows that the total number of vessels were quantified for all groups and our data suggest that the FGF-9 treated groups had significantly more vessels than their MI counterparts (p<0.05. Finally, echocardiographic data suggests a significant improvement in left ventricular output, as indicated by fractional shortening and ejection fraction in both nondiabetic and diabetic animals treated with FGF-9 (p<0.05. Overall, our data suggests FGF-9 has the potential to attenuate vascular cell apoptosis, activate c-Kit progenitor cells, and enhance angiogenesis and neovascularization in C57BL/6 and db/db mice leading to improved cardiac function.

Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

Science.gov (United States)

Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

2010-11-01

Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

Characterization of the enhanced apoptotic response to azidothymidine by pharmacological inhibition of NF-kB.

Science.gov (United States)

Matteucci, Claudia; Minutolo, Antonella; Marino-Merlo, Francesca; Grelli, Sandro; Frezza, Caterina; Mastino, Antonio; Macchi, Beatrice

2015-04-15

The present study addresses the issue of enhanced apoptotic response to AZT following co-treatment with an NF-kB inhibitor. To investigate this issue, different cell lines were assayed for susceptibility to AZT-mediated apoptosis without or with the addition of the NF-kB inhibitor Bay-11-7085. For further investigation, U937 cells were selected as good-responder cells to the combination treatment with 32 or 128 μM AZT, and 1 μM Bay-11-7085. Inhibition of NF-kB activation by Bay-11-7085 in cells treated with AZT was assayed through Western blot analysis of p65 expression and by EMSA. Involvement of the mitochondrial pathway of apoptosis in mechanisms underlying the improved effect of AZT following Bay-11-7085 co-treatment, was evaluated by assaying the cytochrome c release and the mitochondrial membrane potential (MMP) status using the JC-1 dye. Moreover, the transcriptional activity of both anti- and pro-apoptotic genes in U937 cells after combination treatment was quantitatively evaluated through real-time PCR. We found that the combined treatment induced high levels of cytochrome c release and of MMP collapse in association with evident changes in the expression of both anti- and pro-apoptotic genes of the Bcl-2 family. Overexpression of Bcl-2 significantly suppressed the sensitization of U937 cells to an enhanced apoptotic response to AZT following co-treatment with the NF-kB inhibitor. The new findings suggest that a combination regimen based on AZT plus an NF-kB inhibitor could represent a new chemotherapeutic tool for retrovirus-related pathologies.

Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors

Energy Technology Data Exchange (ETDEWEB)

Zhu Lingyan; Han Wei; Chen Shaopeng; Zhao Ye; Jiang Erkang; Bao Lingzhi; Pei Bei; Yang Gen; Zhao Guoping; Wang Jun; Xu An [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China)], E-mail: ljw@ipp.ac.cn

2008-09-26

Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of {alpha}-particle irradiation, the fraction of {gamma}-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy {alpha}-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2 h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H{sub 2}O{sub 2}), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress.

Close linkage of genes encoding receptors for subgroups A and C of avian sarcoma/leucosis virus on chicken chromosome 28

Czech Academy of Sciences Publication Activity Database

Elleder, Daniel; Plachý, Jiří; Hejnar, Jiří; Geryk, Josef; Svoboda, Jan

2004-01-01

Roč. 35, č. 3 (2004), s. 176-181 ISSN 0268-9146 R&D Projects: GA ČR GA523/04/0489 Institutional research plan: CEZ:AV0Z5052915 Keywords : ASLV * retrovirus receptor * linkage analysis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.108, year: 2004

Microwave-assisted hydrolysis of phosphonate diesters: an efficient protocol for the preparation of phosphonic acids

Czech Academy of Sciences Publication Activity Database

Jansa, Petr; Baszczyňski, Ondřej; Procházková, Eliška; Dračínský, Martin; Janeba, Zlatko

2012-01-01

Roč. 14, č. 8 (2012), s. 2282-2288 ISSN 1463-9262 R&D Projects: GA MV VG20102015046 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * DNA virus * retrovirus infections * cidofovir * organic-synthesis Subject RIV: CC - Organic Chemistry Impact factor: 6.828, year: 2012

Structure of the immature HIV-1 capsid in intact virus particles at 8.8 angstrom resolution

Czech Academy of Sciences Publication Activity Database

Schur, F. K. M.; Hagen, W. J. H.; Rumlová, Michaela; Ruml, T.; Müller, B.; Kräusslich, H. G.; Briggs, J. A. G.

2015-01-01

Roč. 517, č. 7535 (2015), s. 505-508 ISSN 0028-0836 R&D Projects: GA ČR(CZ) GA14-15326S Institutional support: RVO:61388963 Keywords : retrovirus * HIV * M-PMV * capsid protein * CA * assembly * immature particles Subject RIV: CE - Biochemistry Impact factor: 38.138, year: 2015

Molecular aspects of the interaction between MasonPfizer monkey virus matrix protein and artificial phospholipid membrane

Czech Academy of Sciences Publication Activity Database

Junková, P.; Prchal, J.; Spiwok, V.; Pleskot, Roman; Kadlec, J.; Krásný, Libor; Hynek, R.; Hrabal, R.; Ruml, T.

2016-01-01

Roč. 84, č. 11 (2016), s. 1717-1727 ISSN 0887-3585 Institutional support: RVO:61389030 ; RVO:61388971 Keywords : d-type retrovirus * force-field * nucleotide-sequence * myristate exposure * plasma-membrane * rhesus monkey Subject RIV: EB - Genetics ; Molecular Biology; EE - Microbiology, Virology (MBU-M) Impact factor: 2.289, year: 2016

Effect of various enhancers on transdermal penetration of indomethacin and urea, and relationship between penetration parameters and enhancement factors.

Science.gov (United States)

Ogiso, T; Iwaki, M; Paku, T

1995-04-01

The enhancing capacity of various chemicals, which are widely recognized as enhancers, for the transdermal penetration into full-thickness rat skin of a model lipophilic drug [indomethacin (IND)] and a hydrophilic permeant (urea) was estimated by an in vitro technique. In addition, the fluidity of the stratum corneum lipids, the partitioning of IND into skin, the lipid (ceramides) extraction from the stratum corneum by enhancers, and the IND solubility in enhancer vehicle were measured and related to the enhancing capacity. In vitro permeation experiments with hairless rat skin unequivocally revealed that the enhancers varied in abilities to enhance the fluxes of both agents. Laurocapram, isopropylmyristate (IPM), sodium oleate, and cineol increased fluxes of both agents to a great extent, but N-methyl-2-pyrrolidone (NMP), N,N-diethyl-m-tolamide (DEET), and oleyl oleate were less effective acclerants. Many enhancers increased the fluidity of the lipids [with a threshold of approximately 0.6-0.8 ns at 37 degrees C in the rotational correlation time (tau c)], the skin partitioning of IND, the extraction of ceramides from the cornified cells, and the thermodynamic activity of IND in vehicle (calculated from the solubility) to varying extents. A good correlation was observed between the increase in the fluidity of stratum corneum lipids and the partitioning of IND into skin, between the increase in the fluidity and the flux or the decrease in lag time for IND, between the removal of ceramides and the skin partitioning of IND, and between the removal of ceramides and the flux of urea (p < 0.05 in all cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoxia enhances the interaction between pancreatic stellate cells and cancer cells via increased secretion of connective tissue growth factor.

Science.gov (United States)

Eguchi, Daiki; Ikenaga, Naoki; Ohuchida, Kenoki; Kozono, Shingo; Cui, Lin; Fujiwara, Kenji; Fujino, Minoru; Ohtsuka, Takao; Mizumoto, Kazuhiro; Tanaka, Masao

2013-05-01

Pancreatic cancer (PC), a hypovascular tumor, thrives under hypoxic conditions. Pancreatic stellate cells (PSCs) promote PC progression by secreting soluble factors, but their functions in hypoxia are poorly understood. This study aimed to clarify the effects of hypoxic conditions on the interaction between PC cells and PSCs. We isolated human PSCs from fresh pancreatic ductal adenocarcinomas and analyzed functional differences in PSCs between normoxia (21% O2) and hypoxia (1% O2), including expression of various factors related to tumor-stromal interactions. We particularly analyzed effects on PC invasiveness of an overexpressed molecule-connective tissue growth factor (CTGF)-in PSCs under hypoxic conditions, using RNA interference techniques. Conditioned media from hypoxic PSCs enhanced PC cell invasiveness more intensely than that from normoxic PSCs (P cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

[THE ORGANIZATIONAL TECHNOLOGIES OF INCREASING OF EFFECTIVENESS OF DISPENSARY MONITORING OF HIV-INFECTED PERSONS].

Science.gov (United States)

Moskvitcheva, M G; Yu, Kitmanova L

2015-01-01

The organizational technologies of increasing effectiveness ofdispensarization monitoring of HIV-infected persons are to targeted to development in patients commitment to get medical care. The cohort monitoring of registered patients receiving anti-retrovirus therapy permitted to evaluate effectiveness of organizational model of multi-professional team developing commitment ofpatients to anti-retrovirus therapy in conditions of center ofprevention and struggle with AIDS and infectious diseases. The criteria ofeffectiveness offunctioning ofmulti-professional team are developed and implemented The list of criteria include percentage of patients in cohort with optimal commitment (not lower than 95% of applied dosage of anti-retrovirus pharmaceuticals at 12th, 24th, 36th, 48th and 60th month), percentage ofpatients with achieved effect of anti-retrovirus therapy, percentage of patients proceeding anti-retrovirus therapy. The multi-professional team implemented motivational techniques of behavior alteration and patient-oriented care. The main strategy of development of of commitment to anti-retrovirus therapy under HIV-infection is determined as management of resources and risks capable decreasing commitment to dispensarization monitoring. The analysis of problems permitted to structure them in risks of commitment failure: medical (13.7%), medical biological under using psychoactive substances (43.1%), psychological (27.7%), social (15.5%). This listing determined the profile of specialists of multi-professional team. The ranking of risks lead out to the first ranking place medical risks, including diagnosed tuberculosis, combination of secondary and concomitant diseases inpatient, number of intaking pills more than 7 per day. The second ranking place took medical biological risks in users of psychoactive substances. Up to 60th month the anti-retrovirus therapy was proceeded by 61.5% of users of psychoactive substances with optimal commitment in 60%. The implementation

Identification of BC005512 as a DNA damage responsive murine endogenous retrovirus of GLN family involved in cell growth regulation.

Directory of Open Access Journals (Sweden)

Yuanfeng Wu

Full Text Available Genotoxicity assessment is of great significance in drug safety evaluation, and microarray is a useful tool widely used to identify genotoxic stress responsive genes. In the present work, by using oligonucleotide microarray in an in vivo model, we identified an unknown gene BC005512 (abbreviated as BC, official full name: cDNA sequence BC005512, whose expression in mouse liver was specifically induced by seven well-known genotoxins (GTXs, but not by non-genotoxins (NGTXs. Bioinformatics revealed that BC was a member of the GLN family of murine endogenous retrovirus (ERV. However, the relationship to genotoxicity and the cellular function of GLN are largely unknown. Using NIH/3T3 cells as an in vitro model system and quantitative real-time PCR, BC expression was specifically induced by another seven GTXs, covering diverse genotoxicity mechanisms. Additionally, dose-response and linear regression analysis showed that expression level of BC in NIH/3T3 cells strongly correlated with DNA damage, measured using the alkaline comet assay,. While in p53 deficient L5178Y cells, GTXs could not induce BC expression. Further functional studies using RNA interference revealed that down-regulation of BC expression induced G1/S phase arrest, inhibited cell proliferation and thus suppressed cell growth in NIH/3T3 cells. Together, our results provide the first evidence that BC005512, a member from GLN family of murine ERV, was responsive to DNA damage and involved in cell growth regulation. These findings could be of great value in genotoxicity predictions and contribute to a deeper understanding of GLN biological functions.

A Reference Viral Database (RVDB) To Enhance Bioinformatics Analysis of High-Throughput Sequencing for Novel Virus Detection.

Science.gov (United States)

Goodacre, Norman; Aljanahi, Aisha; Nandakumar, Subhiksha; Mikailov, Mike; Khan, Arifa S

2018-01-01

developed a new reference viral database (RVDB) that provides a broad representation of different virus species from eukaryotes by including all viral, virus-like, and virus-related sequences (excluding bacteriophages), regardless of their size. In particular, RVDB contains endogenous nonretroviral elements, endogenous retroviruses, and retrotransposons. Sequences were clustered to reduce redundancy while retaining high viral sequence diversity. A particularly useful feature of RVDB is the reduction of cellular sequences, which can enhance the run efficiency of large transcriptomic and genomic data analysis and increase the specificity of virus detection.

Enhanced glucose tolerance in pancreatic-derived factor (PANDER knockout C57BL/6 mice

Directory of Open Access Journals (Sweden)

Shari L. Moak

2014-11-01

Full Text Available Pancreatic-derived factor (PANDER; also known as FAM3B is a uniquely structured protein strongly expressed within and secreted from the endocrine pancreas. PANDER has been hypothesized to regulate fasting and fed glucose homeostasis, hepatic lipogenesis and insulin signaling, and to serve a potential role in the onset or progression of type 2 diabetes (T2D. Despite having potentially pivotal pleiotropic roles in glycemic regulation and T2D, there has been limited generation of stable animal models for the investigation of PANDER function, and there are no models on well-established genetic murine backgrounds for T2D. Our aim was to generate an enhanced murine model to further elucidate the biological function of PANDER. Therefore, a pure-bred PANDER knockout C57BL/6 (PANKO-C57 model was created and phenotypically characterized with respect to glycemic regulation and hepatic insulin signaling. The PANKO-C57 model exhibited an enhanced metabolic phenotype, particularly with regard to enhanced glucose tolerance. Male PANKO-C57 mice displayed decreased fasting plasma insulin and C-peptide levels, whereas leptin levels were increased as compared with matched C57BL/6J wild-type mice. Despite similar peripheral insulin sensitivity between both groups, hepatic insulin signaling was significantly increased during fasting conditions, as demonstrated by increased phosphorylation of hepatic PKB/Akt and AMPK, along with mature SREBP-1 expression. Insulin stimulation of PANKO-C57 mice resulted in increased hepatic triglyceride and glycogen content as compared with wild-type C57BL/6 mice. In summary, the PANKO-C57 mouse represents a suitable model for the investigation of PANDER in multiple metabolic states and provides an additional tool to elucidate the biological function and potential role in T2D.

Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

Science.gov (United States)

Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

2016-07-01

Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

Contrast induced nephropathy in patients undergoing intravenous (IV) contrast enhanced computed tomography (CECT) and the relationship with risk factors: a meta-analysis

NARCIS (Netherlands)

Moos, Shira I.; van Vemde, David N. H.; Stoker, Jaap; Bipat, Shandra

2013-01-01

To summarize the incidence of contrast-induced nephropathy (CIN) and associations between CIN incidence and risk factors in patients undergoing intravenous contrast-enhanced computed tomography (CECT) with low- or iso-osmolar iodinated contrast medium. This review is performed in accordance with the

One-step separation of myristoylated and nonmyristoylated retroviral matrix proteins

Czech Academy of Sciences Publication Activity Database

Doležal, Michal; Zábranský, Aleš; Hrabal, R.; Ruml, T.; Pichová, Iva; Rumlová, Michaela

2013-01-01

Roč. 92, č. 1 (2013), s. 94-99 ISSN 1046-5928 R&D Projects: GA ČR GA204/09/1388 Institutional support: RVO:61388963 Keywords : matrix protein * mouse mammary tumor virus * murine leukemia virus * myristoylation * N-myristoyltransferase * retrovirus Subject RIV: CE - Biochemistry Impact factor: 1.508, year: 2013

Retroviral proteases and their roles in virion maturation

Czech Academy of Sciences Publication Activity Database

Konvalinka, Jan; Kräusslich, H. G.; Müller, B.

2015-01-01

Roč. 479, SI (2015), s. 403-417 ISSN 0042-6822 R&D Projects: GA ČR GBP208/12/G016; GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : retrovirus * aspartic protease * maturation * human immunodeficiency virus * Gag Subject RIV: CE - Biochemistry Impact factor: 3.200, year: 2015

Discovery of an endogenous Deltaretrovirus in the genome of long-fingered bats (Chiroptera: Miniopteridae)

Czech Academy of Sciences Publication Activity Database

Farkašová, Helena; Hron, Tomáš; Pačes, Jan; Hulva, P.; Benda, P.; Gifford, R.J.; Elleder, Daniel

2017-01-01

Roč. 114, č. 12 (2017), s. 3145-3150 ISSN 0027-8424 R&D Projects: GA MŠk(CZ) LK11215; GA MŠk(CZ) LM2015047 Institutional support: RVO:68378050 Keywords : Deltaretroviruses * Endogenous retroviruses * Chiroptera Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Virology Impact factor: 9.661, year: 2016

Enhanced actions of insulin-like growth factor-I and interferon-alpha co-administration in experimental cirrhosis.

Science.gov (United States)

Tutau, Federico; Rodríguez-Ortigosa, Carlos; Puche, Juan Enrique; Juanarena, Nerea; Monreal, Iñigo; García Fernández, María; Clavijo, Encarna; Castilla, Alberto; Castilla-Cortázar, Inma

2009-01-01

Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation. The liver is the major source of circulating insulin-like growth factor-I (IGF-I) whose plasma levels are diminished in cirrhosis. IGF-I supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects. On other hand, interferon-alpha (IFN-alpha) therapy seems to suppress the progression of hepatic fibrosis. The aim of this study was to investigate the effect of the co-administration of IGF-I+IFN-alpha to Wistar rats with CCl(4)-induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology. The mechanisms underlying the effects of these agents were studied by reverse transcription-polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin, collagen, tissular inhibitor of metalloproteinases-1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection. Both IGF-I and IFN-alpha exerted significant effects on fibrogenesis. IGF-I significantly increased serum albumin and HGF whereas IFN-alpha-therapy did not. The inhibition of TGF-beta expression was only observed by the effect of IFN-alpha-therapy. In addition, only the co-administration of IGF-I and IFN-alpha was able to increase the PXR. The combined therapy with both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture. The co-administration IGF-I+IFN enhanced all the beneficial effects observed with each factor separately, showing an additive action on histopathology and PXR expression, which is involved in the inhibition of fibrogenesis.

Type W Human Endogenous Retrovirus (HERV-W) Integrations and Their Mobilization by L1 Machinery: Contribution to the Human Transcriptome and Impact on the Host Physiopathology.

Science.gov (United States)

Grandi, Nicole; Tramontano, Enzo

2017-06-27

Human Endogenous Retroviruses (HERVs) are ancient infection relics constituting ~8% of our DNA. While HERVs' genomic characterization is still ongoing, impressive amounts of data have been obtained regarding their general expression across tissues. Among HERVs, one of the most studied is the W group, which is the sole HERV group specifically mobilized by the long interspersed element-1 (LINE-1) machinery, providing a source of novel insertions by retrotransposition of HERV-W processed pseudogenes, and comprising a member encoding a functional envelope protein coopted for human placentation. The HERV-W group has been intensively investigated for its putative role in several diseases, such as cancer, inflammation, and autoimmunity. Despite major interest in the link between HERV-W expression and human pathogenesis, no conclusive correlation has been demonstrated so far. In general, (i) the absence of a proper identification of the specific HERV-W sequences expressed in a given condition, and (ii) the lack of studies attempting to connect the various observations in the same experimental conditions are the major problems preventing the definitive assessment of the HERV-W impact on human physiopathology. In this review, we summarize the current knowledge on the HERV-W group presence within the human genome and its expression in physiological tissues as well as in the main pathological contexts.

Enhancement of the Purcell factor in multiperiodic hyperboliclike metamaterials

DEFF Research Database (Denmark)

Chebykin, A. V.; Babicheva, V. E.; Iorsh, I. V.

2016-01-01

Spontaneous emission enhancement is theoretically investigated in multiperiodic metal-dielectric multilayers (multiperiodic hyperboliclike metamaterials or photonic hypercrystals) where the unit cell consists of two layers of different dielectrics alternating with identical metallic layers. It is...

DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors.

Science.gov (United States)

Narasimhan, Kamesh; Pillay, Shubhadra; Huang, Yong-Heng; Jayabal, Sriram; Udayasuryan, Barath; Veerapandian, Veeramohan; Kolatkar, Prasanna; Cojocaru, Vlad; Pervushin, Konstantin; Jauch, Ralf

2015-02-18

Sox2 and Pax6 are transcription factors that direct cell fate decision during neurogenesis, yet the mechanism behind how they cooperate on enhancer DNA elements and regulate gene expression is unclear. By systematically interrogating Sox2 and Pax6 interaction on minimal enhancer elements, we found that cooperative DNA recognition relies on combinatorial nucleotide switches and precisely spaced, but cryptic composite DNA motifs. Surprisingly, all tested Sox and Pax paralogs have the capacity to cooperate on such enhancer elements. NMR and molecular modeling reveal very few direct protein-protein interactions between Sox2 and Pax6, suggesting that cooperative binding is mediated by allosteric interactions propagating through DNA structure. Furthermore, we detected and validated several novel sites in the human genome targeted cooperatively by Sox2 and Pax6. Collectively, we demonstrate that Sox-Pax partnerships have the potential to substantially alter DNA target specificities and likely enable the pleiotropic and context-specific action of these cell-lineage specifiers. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Enhancement of insulin-like growth factor 2 receptors in glioblastoma

International Nuclear Information System (INIS)

Sara, V.; Prisell, Per; Sjoegren, Barbro; Enberg, Goesta

1986-01-01

The somatomedins (IGF-1/IGF-2) are a family of growth-promoting hormones which have been identified in the human central nervous system where their specific receptors are distributed. The present study identified somatomedin receptors in glioblastoma and compared them with those found in normal brain. A significant enhancement in the binding of 125 1-IGF-2 but not 125 1-IGF-1 to glioblastoma membranes was found. A fourfold increase in IGF-2 receptor concentration was observed. These findings indicate enhanced expression of the IGF-2 receptor in glioblastoma. (author)

Enhancement of insulin-like growth factor 2 receptors in glioblastoma

Energy Technology Data Exchange (ETDEWEB)

Sara, V; Prisell, P; Sjoegren, B; Persson, L; Boethius, J; Enberg, G

1986-09-01

The somatomedins (IGF-1/IGF-2) are a family of growth-promoting hormones which have been identified in the human central nervous system where their specific receptors are distributed. The present study identified somatomedin receptors in glioblastoma and compared them with those found in normal brain. A significant enhancement in the binding of /sup 125/1-IGF-2 but not /sup 125/1-IGF-1 to glioblastoma membranes was found. A fourfold increase in IGF-2 receptor concentration was observed. These findings indicate enhanced expression of the IGF-2 receptor in glioblastoma. 14 refs.

Dual infections with HIV-1, HIV-2 and HTLV-I are more common in older women than in men in Guinea-Bissau

DEFF Research Database (Denmark)

Holmgren, B; da Silva, Z; Larsen, Olav Ditlevsen

2003-01-01

OBJECTIVES: To investigate the association between the three human retroviruses, HIV-1, HIV-2 and HTLV-I. DESIGN: Community-based follow-up studies of retrovirus infections in two cohorts. METHODS: A total of 2057 individuals aged 35 years and over were eligible for inclusion. Participants were...... interviewed and had a blood sample drawn. Samples were analysed for HIV-1, HIV-2 and HTLV infections. Uni- and multivariate analyses that included behavioural and socio-economic factors were performed using logistic regression and Poisson regression models. RESULTS: A total of 1686 individuals participated...... with a blood sample in the HIV prevalence analyses and 1581 individuals participated in the HTLV-I prevalence analyses. The overall prevalence was 2.1% for HIV-1, 13.5% for HIV-2 and 7.1% for HTLV-I. Comparing the

Application of Live-Cell RNA Imaging Techniques to the Study of Retroviral RNA Trafficking

Directory of Open Access Journals (Sweden)

Darrin V. Bann

2012-06-01

Full Text Available Retroviruses produce full-length RNA that serves both as a genomic RNA (gRNA, which is encapsidated into virus particles, and as an mRNA, which directs the synthesis of viral structural proteins. However, we are only beginning to understand the cellular and viral factors that influence trafficking of retroviral RNA and the selection of the RNA for encapsidation or translation. Live cell imaging studies of retroviral RNA trafficking have provided important insight into many aspects of the retrovirus life cycle including transcription dynamics, nuclear export of viral RNA, translational regulation, membrane targeting, and condensation of the gRNA during virion assembly. Here, we review cutting-edge techniques to visualize single RNA molecules in live cells and discuss the application of these systems to studying retroviral RNA trafficking.

Enhancing Placebo Effects: Insights From Social Psychology

Science.gov (United States)

SLIWINSKI, JIM; ELKINS, GARY R.

2012-01-01

Placebo effects are widely recognized as having a potent impact upon treatment outcomes in both medical and psychological interventions, including hypnosis. In research utilizing randomized clinical trials, there is usually an effort to minimize or control placebo effects. However, in clinical practice there may be significant benefits in enhancing placebo effects. Prior research from the field of social psychology has identified three factors that may enhance placebo effects, namely: priming, client perceptions, and the theory of planned behavior. These factors are reviewed and illustrated via a case example. The consideration of social-psychological factors to enhance positive expectancies and beliefs has implications for clinical practice as well as future research into hypnotic interventions. PMID:23488251

MGMT DNA repair gene promoter/enhancer haplotypes alter transcription factor binding and gene expression.

Science.gov (United States)

Xu, Meixiang; Cross, Courtney E; Speidel, Jordan T; Abdel-Rahman, Sherif Z

2016-10-01

The O 6 -methylguanine-DNA methyltransferase (MGMT) protein removes O 6 -alkyl-guanine adducts from DNA. MGMT expression can thus alter the sensitivity of cells and tissues to environmental and chemotherapeutic alkylating agents. Previously, we defined the haplotype structure encompassing single nucleotide polymorphisms (SNPs) in the MGMT promoter/enhancer (P/E) region and found that haplotypes, rather than individual SNPs, alter MGMT promoter activity. The exact mechanism(s) by which these haplotypes exert their effect on MGMT promoter activity is currently unknown, but we noted that many of the SNPs comprising the MGMT P/E haplotypes are located within or in close proximity to putative transcription factor binding sites. Thus, these haplotypes could potentially affect transcription factor binding and, subsequently, alter MGMT promoter activity. In this study, we test the hypothesis that MGMT P/E haplotypes affect MGMT promoter activity by altering transcription factor (TF) binding to the P/E region. We used a promoter binding TF profiling array and a reporter assay to evaluate the effect of different P/E haplotypes on TF binding and MGMT expression, respectively. Our data revealed a significant difference in TF binding profiles between the different haplotypes evaluated. We identified TFs that consistently showed significant haplotype-dependent binding alterations (p ≤ 0.01) and revealed their role in regulating MGMT expression using siRNAs and a dual-luciferase reporter assay system. The data generated support our hypothesis that promoter haplotypes alter the binding of TFs to the MGMT P/E and, subsequently, affect their regulatory function on MGMT promoter activity and expression level.

Effects of mechanical stimulation on the reprogramming of somatic cells into human-induced pluripotent stem cells.

Science.gov (United States)

Kim, Young Mi; Kang, Yun Gyeong; Park, So Hee; Han, Myung-Kwan; Kim, Jae Ho; Shin, Ji Won; Shin, Jung-Woog

2017-06-08

Mechanical stimuli play important roles in the proliferation and differentiation of adult stem cells. However, few studies on their effects on induced pluripotent stem cells (iPSCs) have been published. Human dermal fibroblasts were seeded onto flexible membrane-bottom plates, and infected with retrovirus expressing the four reprogramming factors OCT4, SOX2, KLF, and c-MYC (OSKM). The cells were subjected to equiaxial stretching (3% or 8% for 2, 4, or 7 days) and seeded on feeder cells (STO). The reprogramming into iPSCs was evaluated by the expression of pluripotent markers, in vitro differentiation into three germ layers, and teratoma formation. Equiaxial stretching enhanced reprogramming efficiency without affecting the viral transduction rate. iPSCs induced by transduction of four reprogramming factors and application of equiaxial stretching had characteristics typical of iPSCs in terms of pluripotency and differentiation potentials. This is the first study to show that mechanical stimuli can increase reprogramming efficiency. However, it did not enhance the infection rate, indicating that mechanical stimuli, defined as stretching in this study, have positive effects on reprogramming rather than on infection. Additional studies should evaluate the mechanism underlying the modulation of reprogramming of somatic cells into iPSCs.

Two different molecular defects in the Tva receptor gene explain the resistance of two tvar lines of chickens to infection by subgroup A avian sarcoma and leukosis viruses

Czech Academy of Sciences Publication Activity Database

Elleder, Daniel; Melder, D. C.; Trejbalová, Kateřina; Svoboda, Jan; Federspiel, M.

2004-01-01

Roč. 78, č. 24 (2004), s. 13489-13500 ISSN 0022-538X R&D Projects: GA ČR GA523/04/0489; GA AV ČR KSK5011112 Institutional research plan: CEZ:AV0Z5052915 Keywords : ASLV * retrovirus receptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.398, year: 2004

The human factor: enhancing women's rights.

Science.gov (United States)

Steinzor, N

1995-01-01

The Universal Declaration of Human Rights, adopted by the UN in 1948, declares that all human beings are born free and equal in dignity and rights, and that everyone has the right to life, liberty, and security of person. In practice, however, far from everyone has these rights, especially women. Many women worldwide have neither the awareness of nor access to family planning methods with which they could regulate their fertility and childbearing. Thus deprived of their reproductive freedom, these women cannot pursue education, employment, and other life options which would otherwise be readily available to them were they not saddled with poor reproductive health and too many children. Expanded choices enhance the status of women, which in turn helps them to reduce fertility rates and stabilize population growth. The author discusses how the wide range of cultural and social norms, and economic and political systems worldwide make it very difficult and complex to actually implement universal human rights.

Growth/differentiation factor-5 significantly enhances periodontal wound healing/regeneration compared with platelet-derived growth factor-BB in dogs.

Science.gov (United States)

Kwon, Hyuk-Rak; Wikesjö, Ulf M E; Park, Jung-Chul; Kim, Young-Taek; Bastone, Patrizia; Pippig, Susanne D; Kim, Chong-Kwan

2010-08-01

Recombinant human growth/differentiation factor-5 (rhGDF-5) in a particulate beta-tricalcium phosphate (beta-TCP) carrier is being evaluated to support periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following an established clinical (benchmark) protocol including surgical implantation of rhGDF-5/beta-TCP in comparison with that following implantation of recombinant human platelet-derived growth factor-BB (rhPDGF) combined with a particulate beta-TCP biomaterial using an established canine defect model. Bilateral, 4 x 5 mm (width x depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in five adult Beagle dogs. Defect sites were randomized to receive rhGDF-5/beta-TCP or the rhPDGF construct followed by wound closure for primary intention healing. The animals were sacrificed following an 8-week healing interval for histological and histometric examination. Clinical healing was generally uneventful. Sites receiving rhGDF-5/beta-TCP exhibited a significantly enhanced cementum formation compared with sites receiving the rhPDGF construct, averaging (+/-SD) 4.49+/-0.48 versus 2.72+/-0.91 mm (palveolar bone. Both protocols displayed beta-TCP residues apparently undergoing resorption. Application of both materials appears safe, as they were associated with limited, if any, adverse events. rhGDF-5/beta-TCP shows a significant potential to support/accelerate periodontal wound healing/regeneration. Application of rhGDF-5/beta-TCP appears safe and should be further evaluated in human clinical trials.

Overhauser-enhanced MR imaging (OMRI)

DEFF Research Database (Denmark)

Golman, K; Leunbach, I; Ardenkjaer-Larsen, JH

1998-01-01

Purpose. To evaluate a new single-electron contrast agent for Overhauser-enhanced MR imaging. The contrast agents that are currently available give enhancement factors that are too low to make the technique a valid option for routine clinical use. Material and Methods. MR images were generated di...

The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer.

Science.gov (United States)

Brabletz, T; Pietrowski, I; Serfling, E

1991-01-11

Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. The block of II-2 synthesis occurs at the transcriptional level. At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Under the same conditions, the DNA binding of other II-2 enhancer factors remains unaffected by both compounds. These results support the view that FK 506 and CsA, which both inhibit the activity of peptidylprolyl cis/trans isomerases, suppress T cell activation by a similar, if not identical mechanism.

Derivation of a JC virus-resistant human glial cell line: implications for the identification of host cell factors that determine viral tropism