WorldWideScience

Sample records for identify bona fide

  1. 19 CFR 10.152 - Bona-fide gifts.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Bona-fide gifts. 10.152 Section 10.152 Customs... and Bona Fide Gifts § 10.152 Bona-fide gifts. Subject to the conditions in § 10.153 of this part, the port director shall pass free of duty and tax any article sent as a bona-fide gift from a person in a...

  2. 19 CFR 145.32 - Bona-fide gifts.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Bona-fide gifts. 145.32 Section 145.32 Customs... (CONTINUED) MAIL IMPORTATIONS Special Classes of Merchandise § 145.32 Bona-fide gifts. The port director... as bona-fide gifts from persons in foreign countries to persons in the United States having an...

  3. 42 CFR 433.54 - Bona fide donations.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Bona fide donations. 433.54 Section 433.54 Public... Financial Participation § 433.54 Bona fide donations. (a) A bona fide donation means a provider-related donation, as defined in § 433.52, made to the State or unit of local government, that has no direct or...

  4. Exploring key considerations when determining bona fide inadvertent errors resulting in understatements

    Directory of Open Access Journals (Sweden)

    Chrizanne de Villiers

    2016-03-01

    Full Text Available Chapter 16 of the Tax Administration Act (28 of 2011 (the TA Act deals with understatement penalties. In the event of an ‘understatement’, in terms of Section 222 of the TA Act, a taxpayer must pay an understatement penalty, unless the understatement results from a bona fide inadvertent error. The determining of a bona fide inadvertent error on taxpayers’ returns is a totally new concept in the tax fraternity. It is of utmost importance that this section is applied correctly based on sound evaluation principles and not on professional judgement when determining if the error was indeed the result of a bona fide inadvertent error. This research study focuses on exploring key considerations when determining bona fide inadvertent errors resulting in understatements. The role and importance of tax penalty provisions is explored and the meaning of the different components in the term ‘bona fide inadvertent error’ critically analysed with the purpose to find a possible definition for the term ‘bona fide inadvertent error’. The study also compares the provisions of other tax jurisdictions with regards to errors made resulting in tax understatements in order to find possible guidelines on the application of bona fide inadvertent errors as contained in Section 222 of the TA Act. The findings of the research study revealed that the term ‘bona fide inadvertent error’ contained in Section 222 of the TA Act should be defined urgently and that guidelines must be provided by SARS on the application of the new amendment. SARS should also clarify the application of a bona fide inadvertent error in light of the behaviours contained in Section 223 of the TA Act to avoid any confusion.

  5. Fiat or bona fide boundary--a matter of granular perspective.

    Directory of Open Access Journals (Sweden)

    Lars Vogt

    Full Text Available Distinguishing bona fide (i.e. natural and fiat (i.e. artificial physical boundaries plays a key role for distinguishing natural from artificial material entities and is thus relevant to any scientific formal foundational top-level ontology, as for instance the Basic Formal Ontology (BFO. In BFO, the distinction is essential for demarcating two foundational categories of material entity: object and fiat object part. The commonly used basis for demarcating bona fide from fiat boundary refers to two criteria: (i intrinsic qualities of the boundary bearers (i.e. spatial/physical discontinuity, qualitative heterogeneity and (ii mind-independent existence of the boundary. The resulting distinction of bona fide and fiat boundaries is considered to be categorial and exhaustive.By Referring to various examples from biology, we demonstrate that the hitherto used distinction of boundaries is not categorial: (i spatial/physical discontinuity is a matter of scale and the differentiation of bona fide and fiat boundaries is thus granularity-dependent, and (ii this differentiation is not absolute, but comes in degrees. By reducing the demarcation criteria to mind-independence and by also considering dispositions and historical relations of the bearers of boundaries, instead of only considering their spatio-structural properties, we demonstrate with various examples that spatio-structurally fiat boundaries can nevertheless be mind-independent and in this sense bona fide.We argue that the ontological status of a given boundary is perspective-dependent and that the strictly spatio-structural demarcation criteria follow a static perspective that is ignorant of causality and the dynamics of reality. Based on a distinction of several ontologically independent perspectives, we suggest different types of boundaries and corresponding material entities, including boundaries based on function (locomotion, physiology, ecology, development, reproduction and common history

  6. 7 CFR 27.96 - Quotations in bona fide spot markets.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Quotations in bona fide spot markets. 27.96 Section 27... Differences § 27.96 Quotations in bona fide spot markets. The price or value and differences between the price... determined by the sale of spot cotton in such spot market. Quotations shall be determined and maintained in...

  7. DMPD: NOD-like receptors (NLRs): bona fide intracellular microbial sensors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18585455 NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Shaw...tml) (.csml) Show NOD-like receptors (NLRs): bona fide intracellular microbial sensors. PubmedID 18585455 Ti...tle NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Authors

  8. 78 FR 9330 - Revision of Regulations Defining Bona Fide Cotton Spot Markets

    Science.gov (United States)

    2013-02-08

    ... Cotton Spot Markets AGENCY: Agricultural Marketing Service, USDA. ACTION: Proposed rule. SUMMARY: The... bona fide cotton spot markets in order to assure consistency with the revised Cotton Research and Promotion Act. Updated bona fide spot market definitions will allow for published spot quotes to consider...

  9. 7 CFR 15a.61 - Sex as a bona-fide occupational qualification.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Sex as a bona-fide occupational qualification. 15a.61... RECEIVING OR BENEFITTING FROM FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs and Activities Prohibited § 15a.61 Sex as a bona-fide occupational...

  10. Oportere ex fide bona. Una construcción decisiva de la jurisprudencia romana

    Directory of Open Access Journals (Sweden)

    Javier Humberto Facco

    2013-07-01

    Full Text Available Verificada la secularización de la antigua fides, asistimos al surgimiento de una construcción cuya valencia técnica parece concretarse en el específico ámbito del proceso. La fides resulta adjetivada con el calificativo de bona. A partir de entonces el sintagma bona fides significará una característica procesal, una cualidad de ciertas acciones que en la intentio de su fórmula se estructuraban en base al oportere ex fide bona. El núcleo de estas acciones estaba representado por los contratos sinalagmáticos, cuya fuerza obligatoria se fundaba en el consentimiento y pertenecían a la órbita del comercio internacional (ius gentium. Con todo, al margen de su aplicación pretoriana, la cláusula quidquid dare facere oportet ex fide bona fue una elaboración eminentemente jurisprudencial, producto del ingenio de los juristas romanos. Fueron ellos quienes idearon buena parte de las soluciones sobre cuestiones ligadas a la eficacia de los contratos consensuales que todavía hoy se consideran emanaciones de la buena fe-lealtad. Recuperar la trascendencia del rol de los juristas en la tarea de hacer que el derecho sea adherente a la realidad constituye la principal invitación que nace de este escrito.

  11. 7 CFR 27.93 - Bona fide spot markets.

    Science.gov (United States)

    2010-01-01

    ... Southwest Markets and the New Mexico counties of Union, Quay, Curry, Roosevelt and Lea. Desert Southwest The..., Hudspeth and El Paso, all New Mexico counties except those included in the West Texas market, all counties... 7 Agriculture 2 2010-01-01 2010-01-01 false Bona fide spot markets. 27.93 Section 27.93...

  12. 24 CFR 3.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Sex as a bona fide occupational... and Urban Development NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education...

  13. 38 CFR 23.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Sex as a bona fide... VETERANS AFFAIRS (CONTINUED) NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education...

  14. 45 CFR 2555.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Sex as a bona fide occupational qualification. 2555.550 Section 2555.550 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION... to such action is essential to successful operation of the employment function concerned. A recipient...

  15. 44 CFR 19.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Sex as a bona fide... MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in...

  16. 10 CFR 5.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Sex as a bona fide occupational qualification. 5.550 Section 5.550 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in...

  17. 45 CFR 618.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Sex as a bona fide occupational qualification. 618.550 Section 618.550 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE... successful operation of the employment function concerned. A recipient shall not take action pursuant to this...

  18. 34 CFR 106.61 - Sex as a bona-fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Sex as a bona-fide occupational qualification. 106.61..., DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or...

  19. Comparing bona fide psychotherapies of depression in adults with two meta-analytical approaches.

    Directory of Open Access Journals (Sweden)

    Sarah R Braun

    Full Text Available OBJECTIVE: Despite numerous investigations, the question whether all bona fide treatments of depression are equally efficacious in adults has not been sufficiently answered. METHOD: We applied two different meta-analytical techniques (conventional meta-analysis and mixed treatment comparisons. Overall, 53 studies with 3,965 patients, which directly compared two or more bona fide psychotherapies in a randomized trial, were included. Meta-analyses were conducted regarding five different types of outcome measures. Additionally, the influence of possible moderators was examined. RESULTS: Direct comparisons of cognitive behavior therapy, behavior activation therapy, psychodynamic therapy, interpersonal therapy, and supportive therapies versus all other respective treatments indicated that at the end of treatment all treatments but supportive therapies were equally efficacious whereas there was some evidence that supportive therapies were somewhat less efficacious than all other treatments according to patient self-ratings and clinical significance. At follow-up no significant differences were present. Age, gender, comorbid mental disorders, and length of therapy session were found to moderate efficacy. Cognitive behavior therapy was superior in studies where therapy sessions lasted 90 minutes or longer, behavior activation therapy was more efficacious when therapy sessions lasted less than 90 minutes. Mixed treatment comparisons indicated no statistically significant differences in treatment efficacy but some interesting trends. CONCLUSIONS: This study suggests that there might be differential effects of bona fide psychotherapies which should be examined in detail.

  20. 17 CFR 240.16b-5 - Bona fide gifts and inheritance.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Bona fide gifts and inheritance. 240.16b-5 Section 240.16b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... gifts and inheritance. Both the acquisition and the disposition of equity securities shall be exempt...

  1. 49 CFR 25.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Sex as a bona fide occupational qualification. 25... BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 25.550 Sex as a...

  2. 29 CFR 36.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Sex as a bona fide occupational qualification. 36.550 Section 36.550 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in...

  3. 28 CFR 54.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Sex as a bona fide occupational... ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 54.550 Sex as a...

  4. 40 CFR 5.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Sex as a bona fide occupational... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 5.550 Sex as a...

  5. 6 CFR 17.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Sex as a bona fide occupational qualification... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 17.550 Sex as a...

  6. 43 CFR 41.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Sex as a bona fide occupational... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 41.550 Sex as a...

  7. 45 CFR 86.61 - Sex as a bona-fide occupational qualification.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Sex as a bona-fide occupational qualification. 86... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 86.61 Sex as a...

  8. 31 CFR 28.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Sex as a bona fide occupational... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 28.550 Sex as a...

  9. 15 CFR 8a.550 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Sex as a bona fide occupational... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 8a.550 Sex as a...

  10. 29 CFR 1625.12 - Exemption for bona fide executive or high policymaking employees.

    Science.gov (United States)

    2010-07-01

    ... corporations [or other business organizations] are usually located at corporate or regional headquarters. With respect to employees whose duties are associated with corporate headquarters operations, such as finance..., would be covered by the term “bona fide executive.” Individuals at higher levels in the corporate...

  11. 29 CFR 516.3 - Bona fide executive, administrative, and professional employees (including academic...

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Bona fide executive, administrative, and professional... outside sales employees employed pursuant to section 13(a)(1) of the Act. 516.3 Section 516.3 Labor... professional employees (including academic administrative personnel and teachers in elementary or secondary...

  12. Law and culture: a theory of comparative variation in bona fide purchase rules

    NARCIS (Netherlands)

    Dari-Mattiacci, G.; Guerriero, C.

    2015-01-01

    A key question in comparative law is why different legal systems provide different legal solutions for the same problem. To answer this question, we use novel comparative evidence on how the conflict between the dispossessed original owner and the bona fide purchaser of a stolen good is resolved in

  13. On Improving Density Estimators which are not Bona Fide Functions

    OpenAIRE

    Gajek, Leslaw

    1986-01-01

    In order to improve the rate of decrease of the IMSE for nonparametric kernel density estimators with nonrandom bandwidth beyond $O(n^{-4/5})$ all current methods must relax the constraint that the density estimate be a bona fide function, that is, be nonnegative and integrate to one. In this paper we show how to achieve similar improvement without relaxing any of these constraints. The method can also be applied for orthogonal series, adaptive orthogonal series, spline, jackknife, and other ...

  14. Generating Bona Fide Mammalian Prions with Internal Deletions.

    Science.gov (United States)

    Munoz-Montesino, Carola; Sizun, Christina; Moudjou, Mohammed; Herzog, Laetitia; Reine, Fabienne; Chapuis, Jérôme; Ciric, Danica; Igel-Egalon, Angelique; Laude, Hubert; Béringue, Vincent; Rezaei, Human; Dron, Michel

    2016-08-01

    Mammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and de novo infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions. Prions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative

  15. Discovery of a new Galactic bona fide luminous blue variable with Spitzer★

    Science.gov (United States)

    Gvaramadze, V. V.; Kniazev, A. Y.; Berdnikov, L. N.; Langer, N.; Grebel, E. K.; Bestenlehner, J. M.

    2014-11-01

    We report the discovery of a circular mid-infrared shell around the emission-line star Wray 16-137 using archival data of the Spitzer Space Telescope. Follow-up optical spectroscopy of Wray 16-137 with the Southern African Large Telescope revealed a rich emission spectrum typical of the classical luminous blue variables (LBVs) like P Cygni. Subsequent spectroscopic and photometric observations showed drastic changes in the spectrum and brightness during the last three years, meaning that Wray 16-137 currently undergoes an S Dor-like outburst. Namely, we found that the star has brightened by ≈1 mag in the V and Ic bands, while its spectrum became dominated by Fe II lines. Taken together, our observations unambiguously show that Wray 16-137 is a new member of the family of Galactic bona fide LBVs.

  16. WS1: one more new Galactic bona fide luminous blue variable★

    Science.gov (United States)

    Kniazev, A. Y.; Gvaramadze, V. V.; Berdnikov, L. N.

    2015-04-01

    In this Letter, we report the results of spectroscopic and photometric monitoring of the candidate luminous blue variable (LBV) WS1, which was discovered in 2011 through the detection of a mid-infrared circular shell and follow-up optical spectroscopy of its central star. Our monitoring showed that WS1 brightened in the B, V and I bands by more than 1 mag during the last three years, while its spectrum revealed dramatic changes during the same time period, indicating that the star became much cooler. The light curve of WS1 demonstrates that the brightness of this star has reached maximum in 2013 December and then starts to decline. These findings unambiguously proved the LBV nature of WS1 and added one more member to the class of Galactic bona fide LBVs, bringing their number to sixteen (an updated census of these objects is provided).

  17. A Resource for the Transcriptional Signature of Bona Fide Trophoblast Stem Cells and Analysis of Their Embryonic Persistence

    Directory of Open Access Journals (Sweden)

    Georg Kuales

    2015-01-01

    Full Text Available Trophoblast stem cells (TSCs represent the multipotent progenitors that give rise to the different cells of the embryonic portion of the placenta. Here, we analysed the expression of key TSC transcription factors Cdx2, Eomes, and Elf5 in the early developing placenta of mouse embryos and in cultured TSCs and reveal surprising heterogeneity in protein levels. We analysed persistence of TSCs in the early placenta and find that TSCs remain in the chorionic hinge until E9.5 and are lost shortly afterwards. To define the transcriptional signature of bona fide TSCs, we used inducible gain- and loss-of-function alleles of Eomes or Cdx2, and EomesGFP, to manipulate and monitor the core maintenance factors of TSCs, followed by genome-wide expression profiling. Combinatorial analysis of resulting expression profiles allowed for defining novel TSC marker genes that might functionally contribute to the maintenance of the TSC state. Analyses by qRT-PCR and in situ hybridisation validated novel TSC- and chorion-specific marker genes, such as Bok/Mtd, Cldn26, Duox2, Duoxa2, Nr0b1, and Sox21. Thus, these expression data provide a valuable resource for the transcriptional signature of bona fide and early differentiating TSCs and may contribute to an increased understanding of the transcriptional circuitries that maintain and/or establish stemness of TSCs.

  18. Discrimination-pregnancy leave-Pregnancy Discrimination Act not retroactive-bona fide seniority system. AT&T Corp. v. Hulteen, 2009 U.S. LEXIS 3470 (U.S. 5/18/2009).

    Science.gov (United States)

    2009-01-01

    A pension plan whose terms are those of a bona fide seniority system and which treats pregnancy leave, taken before the addition of the Pregnancy Discrimination Act (PDA) to Title VII, differently than other kinds of medical leave, does not amount to sex and pregnancy discrimination under Title VII because PDA does not apply retroactively.

  19. Discovery of a new bona fide luminous blue variable in Norma

    Science.gov (United States)

    Gvaramadze, V. V.; Kniazev, A. Y.; Berdnikov, L. N.

    2015-12-01

    We report the results of optical spectroscopy of the candidate evolved massive star MN44 revealed via detection of a circular shell with the Spitzer Space Telescope. First spectra taken in 2009 May-June showed the Balmer lines in emission as well as numerous emission lines of iron, which is typical of luminous blue variables (LBVs) near the visual maximum. New observations carried out in 2015 May-September detected significant changes in the spectrum, indicating that the star became hotter. We found that these changes are accompanied by significant brightness variability of MN44. In particular, the Ic-band brightness decreased by ≈ 1.6 mag during the last six years and after reaching its minimum in 2015 June has started to increase. Using archival data, we also found that the Ic-band brightness increased by ≈3 mag in ≈30 yr preceding our observations. MN44 therefore represents the 17th known example of the Galactic bona fide LBVs. We detected a nitrogen-rich knot to the north-west of the star, which might represent an interstellar cloudlet interacting with the circumstellar shell. We discuss a possible association between MN44 and the INTEGRAL transient source of hard X-ray emission IGR J16327-4940, implying that MN44 might be either a colliding-wind binary or a high-mass X-ray binary.

  20. Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators.

    Science.gov (United States)

    Poganik, Jesse R; Long, Marcus J C; Aye, Yimon

    2018-05-01

    Precision cell signaling activities of reactive electrophilic species (RES) are arguably among the most poorly-understood means to transmit biological messages. Latest research implicates native RES to be a chemically-distinct subset of endogenous redox signals that influence cell decision making through non-enzyme-assisted modifications of specific proteins. Yet, fundamental questions remain regarding the role of RES as bona fide second messengers. Here, we lay out three sets of criteria we feel need to be met for RES to be considered as true cellular signals that directly mediate information transfer by modifying "first-responding" sensor proteins. We critically assess the available evidence and define the extent to which each criterion has been fulfilled. Finally, we offer some ideas on the future trajectories of the electrophile signaling field taking inspiration from work that has been done to understand canonical signaling mediators. Also see the video abstract here: https://youtu.be/rG7o0clVP0c. © 2018 WILEY Periodicals, Inc.

  1. MN48: a new Galactic bona fide luminous blue variable revealed by Spitzer and SALT

    Science.gov (United States)

    Kniazev, A. Y.; Gvaramadze, V. V.; Berdnikov, L. N.

    2016-07-01

    In this paper, we report the results of spectroscopic and photometric observations of the candidate evolved massive star MN48 disclosed via detection of a mid-infrared circular shell around it with the Spitzer Space Telescope. Follow-up optical spectroscopy of MN48 with the Southern African Large Telescope (SALT) carried out in 2011-2015 revealed significant changes in the spectrum of this star, which are typical of luminous blue variables (LBVs). The LBV status of MN48 was further supported by photometric monitoring which shows that in 2009-2011 this star has brightened by ≈0.9 and 1 mag in the V and Ic bands, respectively, then faded by ≈1.1 and 1.6 mag during the next four years, and apparently started to brighten again recently. The detected changes in the spectrum and brightness of MN48 make this star the 18th known Galactic bona fide LBV and increase the percentage of LBVs associated with circumstellar nebulae to more than 70 per cent. We discuss the possible birth place of MN48 and suggest that this star might have been ejected either from a putative star cluster embedded in the H II region IRAS 16455-4531 or the young massive star cluster Westerlund 1.

  2. IC 3639 - A New Bona Fide Compton-Thick AGN Unveiled By NuSTAR

    Science.gov (United States)

    Boorman, Peter G.; Gandhi, P.; Alexander, D. M.; Annuar, A.; Ballantyne, D. R.; Bauer, F.; Boggs, S. E.; Brandt, W. N.; Brightman, M.; Christensen, F. E.; hide

    2016-01-01

    We analyze high-quality NuSTAR observations of the local (z = 0.011) Seyfert 2 active galactic nucleus (AGN) IC 3639, in conjunction with archival Suzaku and Chandra data. This provides the first broadband X-ray spectral analysis of the source, spanning nearly two decades in energy (0.5-30 keV). Previous X-ray observations of the source below 10 keV indicated strong reflection/obscuration on the basis of a pronounced iron fluorescence line at 6.4 keV. The hard X-ray energy coverage of NuSTAR, together with self-consistent toroidal reprocessing models, enables direct broadband constraints on the obscuring column density of the source. We find the source to be heavily Compton-thick (CTK) with an obscuring column in excess of 3.6 x 10(exp 24) cm(exp -2), unconstrained at the upper end. We further find an intrinsic 2-10 keV luminosity of log(sub 10) (L(sub 2-10 keV) [erg s(exp -1)])= 43.4(+0.6/-1.1) to 90% confidence, almost 400 times the observed flux, and consistent with various multiwavelength diagnostics. Such a high ratio of intrinsic to observed flux, in addition to an Fe-K(alpha) fluorescence line equivalent width exceeding 2 keV, is extreme among known bona fide CTK AGNs, which we suggest are both due to the high level of obscuration present around IC 3639. Our study demonstrates that broadband spectroscopic modeling with NuSTAR enables large corrections for obscuration to be carried out robustly and emphasizes the need for improved modeling of AGN tori showing intense iron fluorescence.

  3. SCFJFK is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer

    Science.gov (United States)

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng

    2015-01-01

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1–Cul1–F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCFJFK as a bona fide E3 ligase for ING4 and unraveled the JFK–ING4–NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. PMID:25792601

  4. IC 3639—a New Bona Fide Compton-Thick AGN Unveiled by NuSTAR

    Science.gov (United States)

    Boorman, Peter G.; Gandhi, P.; Alexander, D. M.; Annuar, A.; Ballantyne, D. R.; Bauer, F.; Boggs, S. E.; Brandt, W. N.; Brightman, M.; Christensen, F. E.; Craig, W. W.; Farrah, D.; Hailey, C. J.; Harrison, F. A.; Hönig, S. F.; Koss, M.; LaMassa, S. M.; Masini, A.; Ricci, C.; Risaliti, G.; Stern, D.; Zhang, W. W.

    2016-12-01

    We analyze high-quality NuSTAR observations of the local (z = 0.011) Seyfert 2 active galactic nucleus (AGN) IC 3639, in conjunction with archival Suzaku and Chandra data. This provides the first broadband X-ray spectral analysis of the source, spanning nearly two decades in energy (0.5-30 keV). Previous X-ray observations of the source below 10 keV indicated strong reflection/obscuration on the basis of a pronounced iron fluorescence line at 6.4 keV. The hard X-ray energy coverage of NuSTAR, together with self-consistent toroidal reprocessing models, enables direct broadband constraints on the obscuring column density of the source. We find the source to be heavily Compton-thick (CTK) with an obscuring column in excess of 3.6× {10}24 cm-2, unconstrained at the upper end. We further find an intrinsic 2-10 keV luminosity of {{log}}10({L}2{--10{keV}} [{erg} {{{s}}}-1])={43.4}-1.1+0.6 to 90% confidence, almost 400 times the observed flux, and consistent with various multiwavelength diagnostics. Such a high ratio of intrinsic to observed flux, in addition to an Fe-Kα fluorescence line equivalent width exceeding 2 keV, is extreme among known bona fide CTK AGNs, which we suggest are both due to the high level of obscuration present around IC 3639. Our study demonstrates that broadband spectroscopic modeling with NuSTAR enables large corrections for obscuration to be carried out robustly and emphasizes the need for improved modeling of AGN tori showing intense iron fluorescence.

  5. SCF(JFK) is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer.

    Science.gov (United States)

    Yan, Ruorong; He, Lin; Li, Zhongwu; Han, Xiao; Liang, Jing; Si, Wenzhe; Chen, Zhe; Li, Lei; Xie, Guojia; Li, Wanjin; Wang, Peiyan; Lei, Liandi; Zhang, Hongquan; Pei, Fei; Cao, Dengfeng; Sun, Luyang; Shang, Yongfeng

    2015-03-15

    Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1-Cul1-F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCF(JFK) as a bona fide E3 ligase for ING4 and unraveled the JFK-ING4-NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention. © 2015 Yan et al.; Published by Cold Spring Harbor Laboratory Press.

  6. The LAMOST spectroscopic survey of globular clusters in M31 and M33. I. catalog and new identifications

    International Nuclear Information System (INIS)

    Chen, Bing-Qiu; Liu, Xiao-Wei; Xiang, Mao-Sheng; Huang, Yang; Sun, Ning-Chen; Wang, Chun; Ren, Juan-Juan; Zhang, Hua-Wei; Yuan, Hai-Bo; Rebassa-Mansergas, Alberto; Huo, Zhi-Ying; Yang, Ming; Zhang, Yong; Hou, Yong-Hui; Wang, Yue-Fei

    2015-01-01

    We present a catalog of 908 objects observed with the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) in fields in the vicinity of M31 and M33, targeted as globular clusters (GCs) and candidates. The targets include known GCs and candidates selected from the literature, as well as new candidates selected from the Sloan Digital Sky Survey (SDSS). Analysis shows that 356 of them are likely GCs with various confidence levels, while the remaining ones turn out to be background galaxies and quasars, stars and H ii regions in M31 or foreground Galactic stars. The 356 likely GCs include 298 bona fide GCs and 26 candidates known in the literature. Three candidates, selected from the Revised Bologna Catalog of M31 GCs and candidates (RBC) and one possible cluster from Johnson et al., are confirmed to be bona fide clusters. We search for new GCs in the halo of the M31 among the new candidates selected from the SDSS photometry. Based on radial velocities yielded by LAMOST spectra and visual examination of the SDSS images, we find 28 objects, 5 bona fide and 23 likely GCs. Among the five bona fide GCs, three have been recently discovered independently by others, and the remaining 25 are our new identifications, including two bona fide ones. The newly identified objects fall at projected distances ranging from 13 to 265kpc from M31. Of the two newly discovered bona fide GCs, one is located near M33, probably a GC belonging to M33. The other bona fide GC falls on the Giant Stream with a projected distance of 78 kpc from M31. Of the 23 newly identified likely GCs, one has a projected distance of about 265 kpc from M31 and could be an intergalactic cluster. (paper)

  7. CRISPR/Cas9 Mediated GFP Knock-in at the MAP1LC3B Locus in 293FT Cells Is Better for Bona Fide Monitoring Cellular Autophagy.

    Science.gov (United States)

    Wu, Zhiqiang; Zhao, Jinlin; Qiu, Minghan; Mi, Zeyun; Meng, Maobin; Guo, Yu; Wang, Hui; Yuan, Zhiyong

    2018-04-19

    Accurately identifying and quantifying cellular autophagy is very important as the significance of autophagy in physiological and pathological processes becomes increasingly evident. Ectopically expressed fluorescent-tagged microtubule-associated protein light chain 3B (MAP1LC3B, LC3) is the most widely used reporter for monitoring autophagy activity thus far. However, this approach ignores the influence of constitutively overexpressed LC3 on autophagy itself and autophagy-related processes and its accuracy in indicating autophagy is questionable. Here, we generated a knock-in GFP-LC3 reporter via the CRISPR/Cas9 system in 293FT cells to add GFP to the N-terminal of and in frame with endogenous LC3. We proved that this knock-in GFP-LC3 was expressed at biological level driven by the endogenous transcriptional regulatory elements as the wild type alleles. Compared with the ectopically expressed GFP-LC3, the endogenous knock-in reporter exhibited much higher sensitivity and signal-to-noise ratio of GFP-LC3 puncta upon the induction or inhibition of autophagy at certain step for monitoring autophagy activity. Thus, according to the previous reported concerning and the results presented here, we suggest that this knock-in GFP-LC3 reporter is better for bona fide monitoring cellular autophagy and should be employed for further study of autophagy in vitro and in vivo. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Functional validation of putative toxin-antitoxin genes from the Gram-positive pathogen Streptococcus pneumoniae: phd-doc is the fourth bona-fide operon.

    Science.gov (United States)

    Chan, Wai Ting; Yeo, Chew Chieng; Sadowy, Ewa; Espinosa, Manuel

    2014-01-01

    Bacterial toxin-antitoxin (TAs) loci usually consist of two genes organized as an operon, where their products are bound together and inert under normal conditions. However, under stressful circumstances the antitoxin, which is more labile, will be degraded more rapidly, thereby unleashing its cognate toxin to act on the cell. This, in turn, causes cell stasis or cell death, depending on the type of TAs and/or time of toxin exposure. Previously based on in silico analyses, we proposed that Streptococcus pneumoniae, a pathogenic Gram-positive bacterium, may harbor between 4 and 10 putative TA loci depending on the strains. Here we have chosen the pneumococcal strain Hungary(19A)-6 which contains all possible 10 TA loci. In addition to the three well-characterized operons, namely relBE2, yefM-yoeB, and pezAT, we show here the functionality of a fourth operon that encodes the pneumococcal equivalent of the phd-doc TA. Transcriptional fusions with gene encoding Green Fluorescent Protein showed that the promoter was slightly repressed by the Phd antitoxin, and exhibited almost background values when both Phd-Doc were expressed together. These findings demonstrate that phd-doc shows the negative self-regulatory features typical for an authentic TA. Further, we also show that the previously proposed TAs XreA-Ant and Bro-XreB, although they exhibit a genetic organization resembling those of typical TAs, did not appear to confer a functional behavior corresponding to bona fide TAs. In addition, we have also discovered new interesting bioinformatics results for the known pneumococcal TAs RelBE2 and PezAT. A global analysis of the four identified toxins-antitoxins in the pneumococcal genomes (PezAT, RelBE2, YefM-YoeB, and Phd-Doc) showed that RelBE2 and Phd-Doc are the most conserved ones. Further, there was good correlation among TA types, clonal complexes and sequence types in the 48 pneumococcal strains analyzed.

  9. 26 CFR 1.132-5T - Working condition fringe-1985 through 1988 (temporary).

    Science.gov (United States)

    2010-04-01

    ... United States, a factor indicating a bona fide business-oriented security concern is threats on the life... is primarily personal. If, however, for bona fide business-oriented security concerns, the employee... have paid for the same mode of transportation absent the bona fide business-oriented security concerns...

  10. 76 FR 48884 - Stacey J. Webb, M.D.; Denial of Application

    Science.gov (United States)

    2011-08-09

    ... and maintain a bona fide doctor-patient relationship in order to act ``in the usual course of... whom they did not establish a bona-fide doctor-patient relationship, DEA has denied pending... prescriptions outside bona fide doctor-patient relationship with customers of a website); see also Ronald Lynch...

  11. 7 CFR 905.23 - Selection.

    Science.gov (United States)

    2010-01-01

    ... affiliated with bona fide cooperative marketing organizations. (b) From the nominations made pursuant to... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... alternates to represent bona fide cooperative marketing organizations which are handlers, and the remaining...

  12. 39 CFR 320.4 - Suspension for certain letters of college and university organizations.

    Science.gov (United States)

    2010-07-01

    ... universities to carry in their internal mail systems the letters of their bona fide student or faculty... university. Colleges and universities choosing to provide their student or faculty organizations access to their internal mail systems are responsible for assuring that only letters of bona fide student or...

  13. 76 FR 24523 - Sun & Lake Pharmacy, Inc.; D/B/A the Medicine Shoppe; Revocation of Registration

    Science.gov (United States)

    2011-05-02

    ... fundamental that a physician practitioner must have established a bona fide doctor-patient relationship in... state law to determine whether a bona fide doctor patient relationship existed.'' Id. at 33-34... issued pursuant to a valid doctor-patient relationship. The ALJ noted that a DEA Diversion Investigator...

  14. 42 CFR 433.67 - Limitations on level of FFP for permissible provider-related donations.

    Science.gov (United States)

    2010-10-01

    ... provider-related donations. 433.67 Section 433.67 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... permissible provider-related donations. (a)(1) Limitations on bona fide donations. There are no limitations on the amount of bona fide provider-related donations that a State may receive without a reduction in FFP...

  15. SLoWPoKES-II: 100,000 WIDE BINARIES IDENTIFIED IN SDSS WITHOUT PROPER MOTIONS

    Energy Technology Data Exchange (ETDEWEB)

    Dhital, Saurav [Department of Physical Sciences, Embry-Riddle Aeronautical University, 600 South Clyde Morris Blvd., Daytona Beach, FL 32114 (United States); West, Andrew A.; Schluns, Kyle J.; Massey, Angela P. [Department of Astronomy, Boston University, 725 Commonwealth Avenue, Boston, MA 02215 (United States); Stassun, Keivan G., E-mail: dhitals@erau.edu [Department of Physics and Astronomy, Vanderbilt University, 6301 Stevenson Center, Nashville, TN, 37235 (United States)

    2015-08-15

    We present the Sloan Low-mass Wide Pairs of Kinematically Equivalent Stars (SLoWPoKES)-II catalog of low-mass visual binaries identified from the Sloan Digital Sky Survey (SDSS) by matching photometric distances. The candidate pairs are vetted by comparing the stellar information. The candidate pairs are vetted by comparing the stellar density at their respective Galactic positions to Monte Carlo realizations of a simulated Milky Way. In this way, we are able to identify large numbers of bona fide wide binaries without the need for proper motions. Here, 105,537 visual binaries with angular separations of ∼1–20″ were identified, each with a probability of chance alignment of ≤5%. This is the largest catalog of bona fide wide binaries to date, and it contains a diversity of systems—in mass, mass ratios, binary separations, metallicity, and evolutionary states—that should facilitate follow-up studies to characterize the properties of M dwarfs and white dwarfs. There is a subtle but definitive suggestion of multiple populations in the physical separation distribution, supporting earlier findings. We suggest that wide binaries are composed of multiple populations, most likely representing different formation modes. There are 141 M7 or later wide binary candidates, representing a seven-fold increase over the number currently known. These binaries are too wide to have been formed via the ejection mechanism. Finally, we found that 6% of spectroscopically confirmed M dwarfs are not included in the SDSS STAR catalog; they are misclassified as extended sources due to the presence of a nearby or partially resolved companion. The SLoWPoKES-II catalog is publicly available to the entire community on the World Wide Web via the Filtergraph data visualization portal.

  16. Comparison of Sprint Fidelis and Riata defibrillator lead failure rates.

    Science.gov (United States)

    Fazal, Iftikhar A; Shepherd, Ewen J; Tynan, Margaret; Plummer, Christopher J; McComb, Janet M

    2013-09-30

    Sprint Fidelis and Riata defibrillator leads are prone to early failure. Few data exist on the comparative failure rates and mortality related to lead failure. The aims of this study were to determine the failure rate of Sprint Fidelis and Riata leads, and to compare failure rates and mortality rates in both groups. Patients implanted with Sprint Fidelis leads and Riata leads at a single centre were identified and in July 2012, records were reviewed to ascertain lead failures, deaths, and relationship to device/lead problems. 113 patients had Sprint Fidelis leads implanted between June 2005 and September 2007; Riata leads were implanted in 106 patients between January 2003 and February 2008. During 53.0 ± 22.3 months of follow-up there were 13 Sprint Fidelis lead failures (11.5%, 2.60% per year) and 25 deaths. Mean time to failure was 45.1 ± 15.5 months. In the Riata lead cohort there were 32 deaths, and 13 lead failures (11.3%, 2.71% per year) over 54.8 ± 26.3 months follow-up with a mean time to failure of 53.5 ± 24.5 months. There were no significant differences in the lead failure-free Kaplan-Meier survival curve (p=0.77), deaths overall (p=0.17), or deaths categorised as sudden/cause unknown (p=0.54). Sprint Fidelis and Riata leads have a significant but comparable failure rate at 2.60% per year and 2.71% per year of follow-up respectively. The number of deaths in both groups is similar and no deaths have been identified as being related to lead failure in either cohort. Copyright © 2012. Published by Elsevier Ireland Ltd.

  17. 26 CFR 31.3401(a)(6)-1A - Remuneration for services of certain nonresident alien individuals paid before January 1, 1967.

    Science.gov (United States)

    2010-04-01

    ... follows: Sec. 101. Definitions. [Immigration and Nationality Act (66 Stat. 166)] (a) As used in this... has no intention of abandoning, who is a bona fide student qualified to pursue a full course of study... intention of abandoning who is a bona fide student, scholar, trainee, teacher, professor, research assistant...

  18. Office of International Affairs | NSU

    Science.gov (United States)

    Undergraduate Studies Overview Central Administration Administrative Services and Marketing Student Activity Fee valid advance parole and those with a bona fide relationship to a person or entity in the United States foreign nationals who have a credible claim of a bona fide relationship to an entity or person in the

  19. 76 FR 4289 - Honey From the People's Republic of China: Final Results and Rescission of Antidumping Duty New...

    Science.gov (United States)

    2011-01-25

    ... Fenglian Co., Ltd. (``Fenglian''), the Department finds that that sales under review are not bona fide... Shipper Reviews, 75 FR 55307 (September 10, 2010). Because the sales under review were made during the POR... Republic of China: Bona Fide Analysis of the Sale Under Review for Suzhou Shanding Honey Product Co., Ltd...

  20. 75 FR 55307 - Honey From the People's Republic of China: Preliminary Intent To Rescind New Shipper Reviews

    Science.gov (United States)

    2010-09-10

    ... Shipper Review, 75 FR 38980 (July 7, 2010). Expansion of the POR When the sale of the subject merchandise... review is based on a single sale, exclusion of that sale as non-bona fide necessarily must end the review... Shipper Review of Honey from the People's Republic of China: Bona Fide Analysis of the Sale Under Review...

  1. Experiment list: SRX190196 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNA mismatch repair, and MBD4 gene meets 4 of 5 criteria of a bona fide MIS targe...h repair, and MBD4 gene meets 4 of 5 criteria of a bona fide MIS target gene. (provided by RefSeq) || antibo...rimary microsatellite-instability (MSI), a form of genomic instability associated with defective DNA mismatc

  2. 19 CFR 10.153 - Conditions for exemption.

    Science.gov (United States)

    2010-04-01

    ... over $200 and Bona Fide Gifts § 10.153 Conditions for exemption. Customs officers shall be further... § 10.151 or § 10.152: (a) A “bona fide gift” for purposes of § 10.152 is an article formerly owned by a... promise of compensation. It does not include articles acquired by purchase, barter, promissory exchange...

  3. Hate Speech Provisions and Provisos: A Response to Marais and ...

    African Journals Online (AJOL)

    MJM Venter

    2017-11-06

    Nov 6, 2017 ... right to freedom of expression and the hate speech limitation in section ... important to take into account that the Act was enacted as a legal means to ...... Films and Publications Act,91 both of which exclude bona fide forms of ..... Likewise, in the context of a bona fide stand-up comedy production, a rude.

  4. DZ Chamaeleontis: a bona fide photoevaporating disc

    Science.gov (United States)

    Canovas, H.; Montesinos, B.; Schreiber, M. R.; Cieza, L. A.; Eiroa, C.; Meeus, G.; de Boer, J.; Ménard, F.; Wahhaj, Z.; Riviere-Marichalar, P.; Olofsson, J.; Garufi, A.; Rebollido, I.; van Holstein, R. G.; Caceres, C.; Hardy, A.; Villaver, E.

    2018-02-01

    Context. DZ Cha is a weak-lined T Tauri star (WTTS) surrounded by a bright protoplanetary disc with evidence of inner disc clearing. Its narrow Hα line and infrared spectral energy distribution suggest that DZ Cha may be a photoevaporating disc. Aims: We aim to analyse the DZ Cha star + disc system to identify the mechanism driving the evolution of this object. Methods: We have analysed three epochs of high resolution optical spectroscopy, photometry from the UV up to the sub-mm regime, infrared spectroscopy, and J-band imaging polarimetry observations of DZ Cha. Results: Combining our analysis with previous studies we find no signatures of accretion in the Hα line profile in nine epochs covering a time baseline of 20 yr. The optical spectra are dominated by chromospheric emission lines, but they also show emission from the forbidden lines [SII] 4068 and [OI] 6300Å that indicate a disc outflow. The polarized images reveal a dust depleted cavity of 7 au in radius and two spiral-like features, and we derive a disc dust mass limit of Mdust 80 MJup) companions are detected down to 0.̋07 ( 8 au, projected). Conclusions: The negligible accretion rate, small cavity, and forbidden line emission strongly suggests that DZ Cha is currently at the initial stages of disc clearing by photoevaporation. At this point the inner disc has drained and the inner wall of the truncated outer disc is directly exposed to the stellar radiation. We argue that other mechanisms like planet formation or binarity cannot explain the observed properties of DZ Cha. The scarcity of objects like this one is in line with the dispersal timescale (≲105 yr) predicted by this theory. DZ Cha is therefore an ideal target to study the initial stages of photoevaporation. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programme 097.C-0536. Based on data obtained from the ESO Science Archive Facility under request number 250112.

  5. The CRAPome: a contaminant repository for affinity purification–mass spectrometry data

    NARCIS (Netherlands)

    Mellacheruvu, D.; Wright, Z.; Couzens, A.L.; Low, T.Y.|info:eu-repo/dai/nl/411298437; Halim, V.A.|info:eu-repo/dai/nl/326157441; Heck, A.J.R.|info:eu-repo/dai/nl/105189332; Mohammed, S.|info:eu-repo/dai/nl/30483632X; Nesvizhskii, A.

    2013-01-01

    Affinity purification coupled with mass spectrometry (AP-MS) is a widely used approach for the identification of protein-protein interactions. However, for any given protein of interest, determining which of the identified polypeptides represent bona fide interactors versus those that are background

  6. Identifying New Members of Nearby Moving Groups

    Science.gov (United States)

    Holmbeck, Erika; Vican, Laura

    2014-06-01

    Our group has assembled a sample of 14,000 stars of spectral types B9-M9 with measured UVW Galactic space velocities and lying within 125 pc of Earth. We have identified candidate members of three nearby young (less than 100 Myr) moving groups. For stars of spectral types G5 and later, we have used the Kast spectrometer on the Shane 3m telescope at Lick Observatory to measure lithium abundance in order to determine stellar ages. With the data we have obtained from this run, we will be able to establish whether our candidates are bona fide members of the moving groups in question. I will be presenting the preliminary results from this survey, including spectra of the ~50 stars observed thus far. These nearby young stars will make excellent targets for direct imaging followup surveys, since any giant planets around young stars will still be warm, and will therefore be bright enough to detect with instruments like GPI.

  7. BANYAN. XII. New Members of Nearby Young Associations from GAIA–Tycho Data

    Science.gov (United States)

    Gagné, Jonathan; Roy-Loubier, Olivier; Faherty, Jacqueline K.; Doyon, René; Malo, Lison

    2018-06-01

    We present a search for stellar members of young associations within 150 pc of the Sun, based on TGAS and an updated version of the BANYAN Σ software to determine Bayesian membership probabilities that includes Gaia–2MASS color-magnitude diagrams. We identify 32 new F0–M3-type bona fide members of the 10–200 Myr old Sco-Cen, Carina, Tucana-Horologium, Columba, and Octans associations and the AB Doradus, β Pictoris, and Carina-Near moving groups. These new bona fide members have measurements of their full kinematics and literature data consistent with a young age. We also confirm the membership of 66 previously known candidate members using their Gaia–Tycho trigonometric distances or new literature radial velocities, and identify 219 additional new candidate members, most of which do not yet have a radial velocity measurement. This work is the first step toward a completeness-corrected survey of young association members based on Gaia DR2 in the near future.

  8. Incorporation of unique molecular identifiers in TruSeq adapters improves the accuracy of quantitative sequencing.

    Science.gov (United States)

    Hong, Jungeui; Gresham, David

    2017-11-01

    Quantitative analysis of next-generation sequencing (NGS) data requires discriminating duplicate reads generated by PCR from identical molecules that are of unique origin. Typically, PCR duplicates are identified as sequence reads that align to the same genomic coordinates using reference-based alignment. However, identical molecules can be independently generated during library preparation. Misidentification of these molecules as PCR duplicates can introduce unforeseen biases during analyses. Here, we developed a cost-effective sequencing adapter design by modifying Illumina TruSeq adapters to incorporate a unique molecular identifier (UMI) while maintaining the capacity to undertake multiplexed, single-index sequencing. Incorporation of UMIs into TruSeq adapters (TrUMIseq adapters) enables identification of bona fide PCR duplicates as identically mapped reads with identical UMIs. Using TrUMIseq adapters, we show that accurate removal of PCR duplicates results in improved accuracy of both allele frequency (AF) estimation in heterogeneous populations using DNA sequencing and gene expression quantification using RNA-Seq.

  9. Generator exchange is associated with an increased rate of Sprint Fidelis lead failure.

    Science.gov (United States)

    Lovelock, Joshua D; Patel, Ayesha; Mengistu, Andenet; Hoskins, Michael; El-Chami, Mikhael; Lloyd, Michael S; Leon, Angel; DeLurgio, David; Langberg, Jonathan J

    2012-10-01

    The Medtronic Sprint Fidelis defibrillator lead is at an increased risk for failure and was recalled in October 2007. Approximately 268,000 leads were implanted, and more than 100,000 patients still have active Fidelis leads. A number of studies have examined the rate and clinical predictors of lead failure, but none has addressed the effect of an implantable cardioverter-defibrillator generator exchange on subsequent lead failure. Although the manufacturer asserts that "Sprint Fidelis performance after device change-out is similar to lead performance without device change-out," published data are lacking. To assess the effect of implantable cardioverter-defibrillator generator exchange on the rate of Fidelis lead failure. A chart review was conducted in patients who underwent implantation of a Fidelis lead. Patients with a functioning Fidelis lead at generator exchange were compared with controls with leads implanted for a comparable amount of time not undergoing ICD replacement. A total of 1366 patients received a Fidelis lead prior to the recall, of which 479 were still actively followed. Seventy-two patients with a functioning lead underwent generator exchange without lead replacement. Following generator replacement, 15 leads failed. Sixty percent of the Fidelis leads failed within 3 months. Generator exchange increased the rate of lead failure compared with matched controls (20.8% vs 2.54%; P exchange is associated with a higher than expected rate of Fidelis lead failure, often within 3 months. The risk-benefit ratio of Fidelis lead replacement at the time of generator exchange may be greater than appreciated. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  10. Travelling wave solutions of the generalized Benjamin-Bona-Mahony equation

    International Nuclear Information System (INIS)

    Estevez, P.G.; Kuru, S.; Negro, J.; Nieto, L.M.

    2009-01-01

    A class of particular travelling wave solutions of the generalized Benjamin-Bona-Mahony equation is studied systematically using the factorization technique. Then, the general travelling wave solutions of Benjamin-Bona-Mahony equation, and of its modified version, are also recovered.

  11. 48 CFR 225.7303-4 - Contingent fees.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Contingent fees. 225.7303....7303-4 Contingent fees. (a) Except as provided in paragraph (b) of this subsection, contingent fees are generally allowable under DoD contracts, provided— (1) The fees are paid to a bona fide employee or a bona...

  12. Somatic chromosomal engineering identifies BCAN-NTRK1 as a potent glioma driver and therapeutic target.

    Science.gov (United States)

    Cook, Peter J; Thomas, Rozario; Kannan, Ram; de Leon, Esther Sanchez; Drilon, Alexander; Rosenblum, Marc K; Scaltriti, Maurizio; Benezra, Robert; Ventura, Andrea

    2017-07-11

    The widespread application of high-throughput sequencing methods is resulting in the identification of a rapidly growing number of novel gene fusions caused by tumour-specific chromosomal rearrangements, whose oncogenic potential remains unknown. Here we describe a strategy that builds upon recent advances in genome editing and combines ex vivo and in vivo chromosomal engineering to rapidly and effectively interrogate the oncogenic potential of genomic rearrangements identified in human brain cancers. We show that one such rearrangement, an microdeletion resulting in a fusion between Brevican (BCAN) and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), is a potent oncogenic driver of high-grade gliomas and confers sensitivity to the experimental TRK inhibitor entrectinib. This work demonstrates that BCAN-NTRK1 is a bona fide human glioma driver and describes a general strategy to define the oncogenic potential of novel glioma-associated genomic rearrangements and to generate accurate preclinical models of this lethal human cancer.

  13. A protein interaction mechanism for suppressing the mechanosensitive Piezo channels

    OpenAIRE

    Zhang, Tingxin; Chi, Shaopeng; Jiang, Fan; Zhao, Qiancheng; Xiao, Bailong

    2017-01-01

    Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca2+ ATPase (SERCA), including the widely expres...

  14. 29 CFR 553.32 - Other FLSA exemptions.

    Science.gov (United States)

    2010-07-01

    ... a bona fide executive, administrative, professional, or outside sales capacity, as these terms are... helpers, loaders, and mechanics employed by a common carrier whose activities directly affect the safety...

  15. 27 CFR 6.101 - Merchandise.

    Science.gov (United States)

    2010-04-01

    ... member, who is also in business as a bona fide producer or vendor of other merchandise (for example..., fixtures, signs, glassware, supplies, services, and advertising specialties to retailers does not...

  16. 29 CFR 1625.8 - Bona fide seniority systems.

    Science.gov (United States)

    2010-07-01

    ... equitable allocation of available employment opportunities and prerogatives among younger and older workers. (b) Adoption of a purported seniority system which gives those with longer service lesser rights, and... upon the circumstances, be a “subterfuge to evade the purposes” of the Act. (c) Unless the essential...

  17. Protein Correlation Profiles Identify Lipid Droplet Proteins with High Confidence*

    Science.gov (United States)

    Krahmer, Natalie; Hilger, Maximiliane; Kory, Nora; Wilfling, Florian; Stoehr, Gabriele; Mann, Matthias; Farese, Robert V.; Walther, Tobias C.

    2013-01-01

    Lipid droplets (LDs) are important organelles in energy metabolism and lipid storage. Their cores are composed of neutral lipids that form a hydrophobic phase and are surrounded by a phospholipid monolayer that harbors specific proteins. Most well-established LD proteins perform important functions, particularly in cellular lipid metabolism. Morphological studies show LDs in close proximity to and interacting with membrane-bound cellular organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and endosomes. Because of these close associations, it is difficult to purify LDs to homogeneity. Consequently, the confident identification of bona fide LD proteins via proteomics has been challenging. Here, we report a methodology for LD protein identification based on mass spectrometry and protein correlation profiles. Using LD purification and quantitative, high-resolution mass spectrometry, we identified LD proteins by correlating their purification profiles to those of known LD proteins. Application of the protein correlation profile strategy to LDs isolated from Drosophila S2 cells led to the identification of 111 LD proteins in a cellular LD fraction in which 1481 proteins were detected. LD localization was confirmed in a subset of identified proteins via microscopy of the expressed proteins, thereby validating the approach. Among the identified LD proteins were both well-characterized LD proteins and proteins not previously known to be localized to LDs. Our method provides a high-confidence LD proteome of Drosophila cells and a novel approach that can be applied to identify LD proteins of other cell types and tissues. PMID:23319140

  18. 48 CFR 809.406-4 - Period of debarment.

    Science.gov (United States)

    2010-10-01

    ... indicated after the DSPE reviews documentary evidence submitted by or on behalf of the contractor setting... evidence, reversal of a conviction, bona fide change of ownership or management, elimination of the cause...

  19. 15 CFR 315.2 - Definitions.

    Science.gov (United States)

    2010-01-01

    ..., part 6, schedule 6, of the Tariff Schedules of the United States (excluding an electric trolley bus and a three-wheeled vehicle) or an automotive truck tractor. (d) Bona fide motor-vehicle manufacturer...

  20. 18 CFR 366.1 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... NATURAL GAS ACT BOOKS AND RECORDS Definitions and Provisions Under PUHCA 2005, the Federal Power Act and... with the bona fide intention of effecting distribution within 12 months of the specific securities so...

  1. 20 CFR 655.736 - What are H-1B-dependent employers and willful violators?

    Science.gov (United States)

    2010-04-01

    ... Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in... not include bona fide consultants and independent contractors. For purposes of this section, the...

  2. 20 CFR 655.22 - Obligations of H-2B employers.

    Science.gov (United States)

    2010-04-01

    ..., salary, or benefits), kickbacks, bribes, tributes, in kind payments, and free labor. (k) If the employer... makes a written bona fide inquiry as to whether the other employer has displaced or intends to displace...

  3. Soil as a Sustainable Resource for the Bioeconomy - BonaRes

    Science.gov (United States)

    Wollschläger, Ute; Amelung, Wulf; Brüggemann, Nicolas; Brunotte, Joachim; Gebbers, Robin; Grosch, Rita; Heinrich, Uwe; Helming, Katharina; Kiese, Ralf; Leinweber, Peter; Reinhold-Hurek, Barbara; Veldkamp, Edzo; Vogel, Hans-Jörg; Winkelmann, Traud

    2017-04-01

    Fertile soils are a fundamental resource for the production of biomass and provision of food and energy. A growing world population and latest climate targets lead to an increasing demand for bio-based products which require preserving and - ideally - improving the long-term productivity of soils as a bio-economic resource. At the same time, other soil functions and ecosystem services need to be maintained: filter for clean water, carbon sequestration, provision and recycling of nutrients, and habitat for biological activity. All these soil functions result from the interaction of a multitude of physical, chemical and biological processes which are insufficiently understood. In addition, we lack understanding about the interplay between the socio-economic system and the soil system and how soil functions benefit human wellbeing, including SDGs. However, a solid and integrated assessment of soil quality requires the consideration of the ensemble of soil functions and its relation to soil management. To make soil management sustainable, we need to establish a scientific knowledge base of complex soil system processes that allows for developing models and tools to quantitatively predict the impact of a multitude of management measures on soil functions. This will finally allow for the provision of options for a site-specific, sustainable soil management. To face this challenge, the German Federal Ministry of Education and Research (BMBF) recently launched the funding program "Soil as a Sustainable Resource for the Bioeconomy - BonaRes". In a joint effort, ten collaborative projects and the coordinating BonaRes Centre are engaged to close existing knowledge gaps for a profound and systemic assessment and understanding of soil functions and their sensitivity to soil management. In BonaRes, the complete process chain of sustainable soil use in the context of a sustainable bio-economy is being addressed: from understanding of soil processes using state-of the art and

  4. Secretome Analysis of Lipid-Induced Insulin Resistance in Skeletal Muscle Cells by a Combined Experimental and Bioinformatics Workflow

    DEFF Research Database (Denmark)

    Deshmukh, Atul S; Cox, Juergen; Jensen, Lars Juhl

    2015-01-01

    , in principle, allows an unbiased and comprehensive analysis of cellular secretomes; however, the distinction of bona fide secreted proteins from proteins released upon lysis of a small fraction of dying cells remains challenging. Here we applied highly sensitive MS and streamlined bioinformatics to analyze......-resistant conditions. Our study demonstrates an efficient combined experimental and bioinformatics workflow to identify putative secreted proteins from insulin-resistant skeletal muscle cells, which could easily be adapted to other cellular models....

  5. 41 CFR 60-20.2 - Recruitment and advertisement.

    Science.gov (United States)

    2010-07-01

    ... engaged in recruiting activity must recruit employees of both sexes for all jobs unless sex is a bona fide... advertisement in columns headed “Male” or “Female” will be considered an expression of a preference, limitation...

  6. 对物权法草案的不同意见及建议%Some opinions and suggestions on the draft of real property law

    Institute of Scientific and Technical Information of China (English)

    梁慧星

    2007-01-01

    It is suggested in the article that exclusivity should be added to the definition of the real property right; the following clauses should be revised: the definition of the real property right, the competency of evidence of the register of immovables, the effectiveness of the bona fide protection of real property registration, the tort liabilities of the registration authority, possession reformula- tion, state ownership of water resources and wildlife resources and public utilities, bona fide acquisition, transfer of contracting and operational rights, and mortgage. The following provisions should be added: the ownership of religious property, the acquisitive prescription, and the pledge on business. It is also suggested that the provisions on claims in rem prescribed in Article 39 and Article 42 be deleted, and the provision on dwelling rights, that is, Chapter XV, also be deleted.

  7. Toward Development of Pluripotent Porcine Stem Cells by Road Mapping Early Embryonic Development

    DEFF Research Database (Denmark)

    Petkov, Stoyan; Freude, Kristine; Mashayekhi-Nezamabadi, Kaveh

    2017-01-01

    The lack in production of bona fide porcine pluripotent stem cells has definitely been hampered by a lack of research into porcine embryo development. Embryonic development in mammals is the extraordinary transition of a single-celled fertilized zygote into a complex fetus, which occurs...... in the uterus of the maternal adult during the early stages of gestation. Biomedical pig models could serve as genetic backgrounds for establishment of embryonic stem cells (ESCs) or other pluripotent stem cells (such as iPSC), which may be used to model and study diseases in vitro. This chapter provides...... insight into the current knowledge of pluripotent states in the developing pig embryo and the current status in establishment of bona fide porcine ESC (pESC) and piPSCs. It reflects the potential causes underlying the difficulty in establishing pluripotent stem cells and reviews recent data on global...

  8. Educating for Professional Identity Development

    NARCIS (Netherlands)

    C.P. Tan (Chin Peil)

    2014-01-01

    markdownabstract__Abstract__ In preparing students for their role in their respective communities, vocational and professional education should provide for learning experiences that acculturate them to become the new and bona fide practitioners. In addition to acquiring pre-requisite knowledge

  9. Economics | Page 12 | IDRC - International Development Research ...

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

    The book is a bona fide crystal ball. It will be a must read for the next decade. David Bloom, Clarence James Gamble Professor of Economics and Demography and ... of Global Health and Population, Harvard School of Public Health, USA.

  10. Population Aging and the Generational Economy: A Global ...

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

    31 oct. 2011 ... The book is a bona fide crystal ball. It will be a must read for the next decade. David Bloom, Clarence James Gamble Professor of Economics and ... of Global Health and Population, Harvard School of Public Health, USA.

  11. 42 CFR 3.20 - Definitions.

    Science.gov (United States)

    2010-10-01

    ..., clinical laboratory, or health center; or (ii) A physician, physician assistant, registered nurse, nurse practitioner, clinical nurse specialist, certified registered nurse anesthetist, certified nurse midwife... the Secretary, which issues decisions in panels of three. Bona fide contract means: (1) A written...

  12. Bona Fide Thermodynamic Temperature in Nonequilibrium Kinetic Ising Models

    OpenAIRE

    Sastre, Francisco; Dornic, Ivan; Chaté, Hugues

    2003-01-01

    We show that a nominal temperature can be consistently and uniquely defined everywhere in the phase diagram of large classes of nonequilibrium kinetic Ising spin models. In addition, we confirm the recent proposal that, at critical points, the large-time ``fluctuation-dissipation ratio'' $X_\\infty$ is a universal amplitude ratio and find in particular $X_\\infty \\approx 0.33(2)$ and $X_\\infty = 1/2$ for the magnetization in, respectively, the two-dimensional Ising and voter universality classes.

  13. The Benjamin-Bona-Mahony equation with dissipative memory

    Czech Academy of Sciences Publication Activity Database

    Dell'Oro, Filippo; Mammeri, Y.; Pata, V.

    2015-01-01

    Roč. 22, č. 4 (2015), s. 899-910 ISSN 1021-9722 Institutional support: RVO:67985840 Keywords : Benjamin-Bona-Mahony equation * dissipative memory * exponential stability * nonlinear contraction semigroup Subject RIV: BA - General Mathematics Impact factor: 0.797, year: 2015 http://link.springer.com/article/10.1007%2Fs00030-014-0308-8

  14. 29 CFR 541.0 - Introductory statement.

    Science.gov (United States)

    2010-07-01

    ... DELIMITING THE EXEMPTIONS FOR EXECUTIVE, ADMINISTRATIVE, PROFESSIONAL, COMPUTER AND OUTSIDE SALES EMPLOYEES... employee employed in a bona fide executive, administrative, or professional capacity (including any... secondary schools), or in the capacity of an outside sales employee, as such terms are defined and delimited...

  15. Long-term Field Experiments as Important Source of Knowledge - Aims of the BonaRes Data Centre

    Science.gov (United States)

    Grosse, Meike; Hierold, Wilfried

    2017-04-01

    BonaRes is short for "soil as a sustainable resource for the bioeconomy". It is funded by the German Federal Ministry of Education and Research (BMBF) under the umbrella of the National Research Strategy BioEconomy 2030. BonaRes consists of ten interdisciplinary research project consortia and the 'BonaRes - Centre for Soil Research' (see also Wollschläger et al 2016). It is one task of the BonaRes Data Centre as part of the 'BonaRes - Centre for Soil Research', to collect data and meta-data of agricultural long-term field experiments (LTFE) in Germany. The definition of LTFE in the context of BonaRes is a minimum duration of twenty years and a static design. LTFE are essential research infrastructures for agricultural sciences and soil sciences amongst other disciplines. Some LTFE run since a very long time; the start of the oldest one in Germany was 1878. Therefore, in many cases valuable time series exist. Data sets of LTFE shall be compiled and made publicly available by the BonaRes Data Centre. The public availability together with an easy access will lead to an enhanced usability of the data. This probably makes the LTFE itself more valuable through an improved visibility and may also help to maintain the LTFE. Beyond the data compilation there is the possibility for every data owner to make a data publication, which offers an additional value for the data owner after his first right of use. A first step towards a joint database is a compilation of all existing LTFE in Germany with meta information to each trial. This information is shown in an interactive web map, what is completely new in that context. Besides the exact position of the LTFE the following metadata are shown: name of the LTFE, website (if available), institution, land use category, participation in existing networks, research theme, start (and maybe end) of the trial, and research parameters. Details on the meta information will be presented in the speech. Literature Wollschläger, U; Helming

  16. 26 CFR 1.911-7 - Procedural rules.

    Science.gov (United States)

    2010-04-01

    ... effective; (v) The exclusion or exclusions the individual is electing; (vi) The foreign country or countries...) The status (either bona fide residence or physical presence) under which the individual claims the exclusion; (viii) The individual's qualifying period of residence or presence; (ix) The individual's foreign...

  17. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H266

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Tubsuwan, Alisa; Schmid, Benjamin

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell...

  18. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H271

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell...

  19. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H196

    DEFF Research Database (Denmark)

    Marthaler, Adele Gabriele; Schmid, Benjamin; Tubsuwan, Alisa

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell...

  20. 29 CFR 5.2 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... mental or managerial. The term laborer or mechanic includes apprentices, trainees, helpers, and, in the..., rather than manual. Persons employed in a bona fide executive, administrative, or professional capacity... apprentice, trainee, and helper are defined as follows: (1) Apprentice means (i) a person employed and...

  1. 75 FR 475 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-01-05

    ... such member's financial condition as disclosed in its most recent balance sheet prepared either in... satisfying the requirement that members make balance sheet information available to bona fide regular... most recent balance sheet . * * *'' FINRA is proposing to provide members with the option of delivering...

  2. 76 FR 48887 - Liddy's Pharmacy, L.L.C. Denial of Application

    Science.gov (United States)

    2011-08-09

    ... doctors who did not appear to have valid physician-patient relationships with the recipients of the... prescriptions pursuant to a legitimate doctor-patient relationship. \\5\\ He also issued eight prescriptions to... persons and established bona fide doctor-patient relationships with them. Here again, Respondent clearly...

  3. 75 FR 65663 - Gilbert Eugene Johnson, M.D.; Revocation of Registration

    Science.gov (United States)

    2010-10-26

    ... doctor-patient relationship and a legitimate medical need for the prescription) and directed the employee... practitioner must establish a bona fide doctor-patient relationship in order to act `in the usual course of... patient relationship''; (2) Respondent ``engaged in indiscriminate or excessive prescribing, dispensing or...

  4. 75 FR 4529 - Circular Welded Carbon Steel Pipes and Tubes From Thailand: Final Results of Antidumping Duty New...

    Science.gov (United States)

    2010-01-28

    ... Compliance Analyst, Office 6, Verification of the Sales Response of Pacific Pipe Public Company, Limited in... Pipe Public Company, Limited, dated August 24, 2009 (Bona Fides Preliminary Memorandum). The Department... Circular Welded Carbon Steel Pipes and Tubes from Thailand: Pacific Pipe Public Company, Limited, dated...

  5. Good faith limitations on protected investments and corporate structuring

    NARCIS (Netherlands)

    Schill, S.W.; Bray, H.L.; Mitchell, A.D.; Sornarajah, M.; Voon, T.

    2015-01-01

    On numerous occasions, investment treaty tribunals have relied—and in some cases refused to rely—on the principle of good faith to ensure that only bona fide investments and investors are protected under the relevant investment treaty. This chapter reviews the jurisprudence on illegal investments

  6. Structure of the DNA-bound BRCA1 C-terminal region from human replication factor C p140 and model of the protein-DNA complex

    NARCIS (Netherlands)

    Kobayashi, M.; AB, E.; Bonvin, A.M.J.J.; Siegal, G.

    2010-01-01

    BRCA1 C-terminal domain (BRCT)-containing proteins are found widely throughout the animal and bacteria kingdoms where they are exclusively involved in cell cycle regulation and DNA metabolism. Whereas most BRCT domains are involved in protein-protein interactions, a small subset has bona fide DNA

  7. 22 CFR 61.5 - Authentication procedures-Imports.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication procedures-Imports. 61.5 Section... AUDIO-VISUAL MATERIALS § 61.5 Authentication procedures—Imports. (a) Applicants seeking Department authentication of foreign produced audio-visual materials shall submit to the Department a bona fide foreign...

  8. 75 FR 66138 - George Mathew, M.D.; Denial of Application

    Science.gov (United States)

    2010-10-27

    ... controlled substances to Internet customers despite never establishing a genuine doctor-patient relationship...'' and thus did not establish ``a valid doctor- patient relationship.'' Id. at 29. Based on an undercover... be a bona fide doctor/patient relationship.'' Id. at 21182. The Agency further noted that ``many...

  9. 26 CFR 1.410(b)-4 - Nondiscriminatory classification test.

    Science.gov (United States)

    2010-04-01

    ..., nature of compensation (i.e., salaried or hourly), geographic location, and similar bona fide business... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.410(b)-4 Nondiscriminatory classification test. (a) In general. A plan satisfies the nondiscriminatory classification test of...

  10. Sphingomyelin synthase-related protein SMSr is a suppressor of ceramide-induced mitochondrial apoptosis

    DEFF Research Database (Denmark)

    Tafesse, Fikadu G.; Vacaru, Ana M.; Bosma, Elleke Fenna

    2014-01-01

    ceramide-induced cell death and that SMSr-mediated ceramide homeostasis requires the N-terminal sterile a-motif, or SAM domain, of the enzyme. These results define ER ceramides as bona fide transducers of mitochondrial apoptosis and indicate a primary role of SMSr in monitoring ER ceramide levels...

  11. 77 FR 25136 - Seamless Refined Copper Pipe and Tube From Mexico: Preliminary Results of Antidumping Duty New...

    Science.gov (United States)

    2012-04-27

    ... for convenience and customs purposes, the written description of the scope of the order is dispositive... business proprietary, see ``Bona Fides Analysis Memorandum'' dated April 23, 2012, for a detailed... appropriate, from the starting price for international freight, inland insurance, U.S. warehouse expenses, U.S...

  12. 12 CFR 563b.530 - What other requirements apply after I convert?

    Science.gov (United States)

    2010-01-01

    ... quotations for the security in a recognized inter-dealer quotation system; (2) Furnishes bona fide competitive bid and offer quotations for the security on request; or (3) May effect transactions for the... Securities Dealers Automated Quotation system. (d) File all post-conversion reports that OTS requires...

  13. 78 FR 69823 - Atlantic Highly Migratory Species; Exempted Fishing, Scientific Research, Display, and Chartering...

    Science.gov (United States)

    2013-11-21

    ... display and educational activities with respect to Atlantic HMS. Since the Magnuson-Stevens Act does not... during that research, NMFS may consider those vessels as bona fide research platforms while conducting..., NMFS review of public comments received on this notice, an applicant's reporting history on past...

  14. The Impossibility of Capitalist Markets in Higher Education

    Science.gov (United States)

    Marginson, Simon

    2013-01-01

    For more than two decades, governments around the world, led by the English-speaking polities, have moved higher education systems closer to the forms of textbook economic markets. Reforms include corporatisation, competitive funding, student charges, output formats and performance reporting. But, no country has established a bona fide economic…

  15. 26 CFR 1.170-2 - Charitable deductions by individuals; limitations (before amendment by Tax Reform Act of 1969).

    Science.gov (United States)

    2010-04-01

    ... community in which the organization operates or if it makes a bona fide dissemination of a brochure... charitable purposes by a single impartial committee. The M Organization, by distribution of pamphlets to the... a brochure containing a financial statement of its operations including a list of all receipts and...

  16. Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor Cells

    NARCIS (Netherlands)

    Maldonado, Paloma P; Angulo, María Cecilia

    The surprising discovery of bona fide synapses between neurons and oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as real partners of neurons in the CNS. The role of these synapses has not been established yet, but a main hypothesis is that neuron-OPC synaptic activity

  17. 48 CFR 52.203-5 - Covenant Against Contingent Fees.

    Science.gov (United States)

    2010-10-01

    ... REGULATION (CONTINUED) CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and... employed or retained to solicit or obtain this contract upon an agreement or understanding for a contingent fee, except a bona fide employee or agency. For breach or violation of this warranty, the Government...

  18. 77 FR 79 - Honey From the People's Republic of China: Preliminary Rescission of the Administrative Review

    Science.gov (United States)

    2012-01-03

    ... dispositive. Bona Fide Analysis In this administrative review, Petitioners alleged that the sales of Dongtai... these sales the Department undertook that analysis in this review. Where all of the sales in a review... whether a sale in a review is unrepresentative or extremely distortive, and therefore excludable as non...

  19. β-Peptoid Foldamers at Last

    DEFF Research Database (Denmark)

    Laursen, Jonas S; Engel-Andreasen, Jens; Olsen, Christian A

    2015-01-01

    in this journal in the late 1990s. Oligomers of N-alkylated 3-aminopropionic acid residues have been called β-peptoids due to their structural similarity to β-peptides and peptoids (N-alkylglycines), respectively. Because bona fide foldamer behavior has been demonstrated for both parent architectures, we wondered...

  20. 16 CFR 238.1 - Bait advertisement.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Bait advertisement. 238.1 Section 238.1 Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES AGAINST BAIT ADVERTISING... when the offer is not a bona fide effort to sell the advertised product. [Guide 1] ...

  1. 24 CFR 3500.15 - Affiliated business arrangements.

    Science.gov (United States)

    2010-04-01

    ... § 3500.14(g) is a return on an ownership interest or franchise relationship. (i) In an affiliated... interest or franchise relationship, between entities in an affiliate relationship, are permissible; and (B... franchise agreement, will determine whether it is a bona fide return on an ownership interest or franchise...

  2. DSS1/Sem1, a multifunctional and intrinsically disordered protein

    DEFF Research Database (Denmark)

    Kragelund, Birthe Brandt; Schenstrøm, Signe Marie; Rebula, Caio A.

    2016-01-01

    DSS1/Sem1 is a versatile intrinsically disordered protein. Besides being a bona fide subunit of the 26S proteasome, DSS1 associates with other protein complexes, including BRCA2-RPA, involved in homologous recombination; the Csn12-Thp3 complex, involved in RNA splicing; the integrator, involved...

  3. 75 FR 28068 - Christopher Henry Lister, P.A.; Revocation of Registration

    Science.gov (United States)

    2010-05-19

    ... that a practitioner must establish and maintain a bonafide doctor-patient relationship in order to act... prescription requirement * * * ensures patients use controlled substances under the supervision of a doctor so... generally looks to state law to determine whether a doctor and patient have established a bona fide doctor...

  4. Knowledge at work: learning and transferring expert reasoning through storytelling

    NARCIS (Netherlands)

    Hernandez-Serrano, J.; Stefanou, S.E.

    2009-01-01

    There is plenty of evidence in many fields of knowledge that storytelling is a bona fide human activity for problem-solving. We believe that a storytelling model for problem-solving can be constructed to organize this discourse. To that end, we carried out a qualitative study using the Grounded

  5. 7 CFR 27.100 - Administration.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Administration. 27.100 Section 27.100 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Administration. The details of the method of carrying out the provisions of this subpart in each bona fide spot...

  6. 36 CFR 5.4 - Commercial passenger-carrying motor vehicles.

    Science.gov (United States)

    2010-07-01

    ... chartered or rented in good faith to the operator, by the owner, for general use at a charge based upon time... initiated, organized, and directed by an established bona fide school or college, institution, society or... group that arranges for the transportation, assumes responsibility for financial risk and management...

  7. RNA/DNA co-analysis from human menstrual blood and vaginal secretion stains

    DEFF Research Database (Denmark)

    Haas, Claus; Hanson, E; Anjos, M J

    2014-01-01

    housekeeping genes for their suitability as reference genes. Six menstrual blood and six vaginal secretion stains, two dilution series (1/4-1/64 pieces of a menstrual blood/vaginal swab) and, optionally, bona fide or mock casework samples of human or non-human origin were analyzed by 24 participating...

  8. When Graduate Degrees Prostitute the Educational Process: Degrees Gone Wild

    Science.gov (United States)

    Lumadue, Richard T.

    2006-01-01

    Graduate degrees prostitute the educational process when they are sold to consumers by unaccredited degree/diploma mills as being equivalent to legitimate, bona-fide degrees awarded by accredited graduate schools. This article carefully analyzes the serious problems of bogus degrees and their association with the religious higher education…

  9. Confirming LBV Candidates Through Variability: A Photometric and Spectroscopic Monitoring Study

    Science.gov (United States)

    Stringfellow, Guy; Gvaramadze, Vasilii

    2013-02-01

    Luminous Blue Variable (LBV) stars represent an extremely rare class of luminous massive stars with high mass loss rates. The paucity ( 12) of confirmed Galactic LBV precludes determining a solid evolutionary connection between LBV and other intermediate (e.g. Ofpe/WN9, WNL) phases in the life of very massive stars. We've been conducting an optical/near-IR spectral survey of a large subset of central stars residing within newly discovered it Spitzer nebulae and have identified over two dozen new candidate LBVs (cLBVs) based on spectral similarity alone; confirming them as bona fide LBVs requires demonstrating 1-3 mag photometric and spectroscopic variability. This marks a significant advancement in the study of massive stars, far outweighing the return from many studies searching for LBVs and WRs the past several decades. Monitoring from semesters 2011B-2012A already has confirmed one new cLBV as a bona fide LBV. We propose to continue optical-IR photometric monitoring of these cLBVS with the 1.3m. Chiron, replacing the RC spectrograph on the 1.5m, now allows high-resolution optical spectroscopic monitoring of bright cLBVs, 11 of which are proposed herein. Spectra are important for understanding the physics driving photometric variability, properties of the wind, and allow analysis of line profiles.

  10. pVHL's kryptonite: E2-EPF UCP.

    Science.gov (United States)

    Ohh, Michael

    2006-08-01

    E2-EPF ubiquitin carrier protein (UCP) is a member of an E2 family of enzymes that catalyzes the ligation of ubiquitin to proteins targeted for destruction by the proteasome. UCP is overexpressed in common human cancers, suggesting its involvement in oncogenesis, but a physiologic target of UCP has not been identified. In a recent report published in Nature Medicine, Jung et al. identified von Hippel-Lindau (VHL) tumor suppressor protein, which targets the alpha subunit of hypoxia-inducible factor (HIF) for ubiquitin-mediated destruction, as a bona fide substrate of UCP and demonstrated a potential pVHL-HIF pathway-dependent role for UCP in cancer development.

  11. 17 CFR 150.3 - Exemptions.

    Science.gov (United States)

    2010-04-01

    ... this part may be exceeded to the extent such position are: (1) Bona fide hedging transactions as defined in § 1.3(z) of this chapter; (2) [Reserved] (3) Spread or arbitrage positions between single... month, in the same crop year; provided however, That such spread or arbitrage positions, when combined...

  12. 17 CFR 150.5 - Exchange-set speculative position limits.

    Science.gov (United States)

    2010-04-01

    ..., straddles, or arbitrage,” of from fixing limits which apply to such positions which are different from... opportunity for arbitrage between the futures market and the cash market in the commodity underlying the... pursuant to this section shall apply to bona fide hedging positions as defined by a contract market in...

  13. 77 FR 32522 - Tapered Roller Bearings and Parts Thereof, Finished and Unfinished From the People's Republic of...

    Science.gov (United States)

    2012-06-01

    ... is renumbered as 8708.99.8180; see Id. Bona Fides Sale Analysis For this review, consistent with the... POR. In evaluating whether or not a sale in a new shipper review is commercially reasonable, and... Shipper Review, 67 FR 11283 (March 13, 2002)). The Department preliminarily finds that the sales of...

  14. 26 CFR 1.132-5 - Working condition fringes.

    Science.gov (United States)

    2010-04-01

    ... exist unless the employee's employer establishes to the satisfaction of the Commissioner that an overall... example, threats are made on the life of an employee), the bona fide business-oriented security concern is... condition fringe. A “working condition fringe” is any property or service provided to an employee of an...

  15. 76 FR 78062 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2011-12-15

    ... Commission (``Commission'') the proposed rule change as described in Items I, II, and III below, which Items... Fees and Cancellation Fees if one or more ATP Firms or the Exchange experiences a bona fide systems... Excessive Bandwidth Utilization Fees and Cancellation Fees if one or more ATP Firms or the Exchange...

  16. 26 CFR 1.409A-1 - Definitions and covered plans.

    Science.gov (United States)

    2010-04-01

    ... short-term deferral rule set forth in paragraph (b)(4) of this section, the inclusion in income of an... plan provides bona fide vacation leave, sick leave, compensatory time, disability pay, or death benefits. For these purposes, the terms “disability pay” and “death benefits” have the same meanings as...

  17. 12 CFR Appendix A to Part 3 - Risk-Based Capital Guidelines

    Science.gov (United States)

    2010-01-01

    ... (as defined in section 2 of this appendix A) by its risk-weighted assets (as calculated pursuant to... customer at the time of the extension or renewal and upon a new, bona fide credit analysis utilizing... organizations that were taken in satisfaction of debts previously contracted, provided that the reporting...

  18. 7 CFR 27.95 - Spot markets to conform to Act and regulations.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Spot markets to conform to Act and regulations. 27.95 Section 27.95 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE... and Differences § 27.95 Spot markets to conform to Act and regulations. Every bona fide spot market...

  19. 18 CFR 367.1 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... company. (6) Book cost means the amount at which property is recorded in these accounts without deduction... with the bona fide intention of effecting distribution within 12 months of the specific securities so... notes or by book accounts only, with respect to which it is mutually agreed or intended between the...

  20. 38 CFR 11.116 - Death of veteran before final settlement.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Death of veteran before... Death of veteran before final settlement. If the veteran dies after making application under the... considered valid if found to bear the bona-fide signature of the applicant, discloses an intention to claim...

  1. 27 CFR 22.102 - Prohibited uses.

    Science.gov (United States)

    2010-04-01

    ...-free alcohol. A separate charge may be made by a hospital, sanitarium or clinic for medicines... and 22.106. Hospitals may not furnish tax-free alcohol for use of physicians in their private practice....106, clinics operated for charity and not for profit may compound bona fide medicines with tax-free...

  2. RNA/DNA co-analysis from blood stains--Results of a second collaborative EDNAP exercise

    DEFF Research Database (Denmark)

    Haas, C.; Hanson, E.; Anjos, M.J.

    2012-01-01

    A second collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling was organized by the European DNA Profiling Group (EDNAP). Six human blood stains, two blood dilution series (5-0.001 [mu]l blood) and, optionally, bona fide or mock casework samples of human or...

  3. 42 CFR 413.85 - Cost of approved nursing and allied health education activities.

    Science.gov (United States)

    2010-10-01

    ... education activities. (a) Statutory basis. This section implements section 1861(v)(1)(A) of the Act and... registered nurse anesthetist (CRNA) education programs that are determined on a reasonable cost basis are... subchapter. They include: (1) Orientation and on-the-job training. (2) Part-time education for bona fide full...

  4. 17 CFR 19.00 - General provisions.

    Science.gov (United States)

    2010-04-01

    ... and derivation of such conversion factors. (Approved by the Office of Management and Budget under... to the following: (1) Excluding products or byproducts of the cash commodity hedged. If the regular... cash positions for bona fide hedging (as defined in § 1.3(z) of this chapter), the same shall be...

  5. 29 CFR 779.401 - Statutory provision.

    Science.gov (United States)

    2010-07-01

    ... elementary or secondary schools), or in the capacity of outside salesman (as such terms are defined and... definition of employee employed in a bona fide executive or administrative capacity because of the number of hours in his workweek which he devotes to activities not directly or closely related to the performance...

  6. A GALEX-BASED SEARCH FOR THE SPARSE YOUNG STELLAR POPULATION IN THE TAURUS-AURIGAE STAR FORMING REGION

    International Nuclear Information System (INIS)

    Gómez de Castro, Ana I.; Lopez-Santiago, Javier; López-Martínez, Fatima; Sánchez, Néstor; Sestito, Paola; Gestoso, Javier Yañez; De Castro, Elisa; Cornide, Manuel

    2015-01-01

    In this work, we identify 63 bona fide new candidates to T Tauri stars (TTSs) in the Taurus-Auriga region, using its ultraviolet excess as our baseline. The initial data set was defined from the GALEX all sky survey (AIS). The GALEX satellite obtained images in the near-ultraviolet (NUV) and far-ultraviolet (FUV) bands where TTSs show a prominent excess compared with main-sequence or giants stars. GALEX AIS surveyed the Taurus-Auriga molecular complex, as well as a fraction of the California Nebula and the Perseus complex; bright sources and dark clouds were avoided. The properties of TTSs in the ultraviolet (GALEX), optical (UCAC4), and infrared (2MASS) have been defined using the TTSs observed with the International Ultraviolet Explorer reference sample. The candidates were identified by means of a mixed ultraviolet-optical-infrared excess set of colors; we found that the FUV-NUV versus J–K color-color diagram is ideally suited for this purpose. From an initial sample of 163,313 bona fide NUV sources, a final list of 63 new candidates to TTSs in the region was produced. The search procedure has been validated by its ability to detect all known TTSs in the area surveyed: 31 TTSs. Also, we show that the weak-lined TTSs are located in a well-defined stripe in the FUV-NUV versus J–K diagram. Moreover, in this work, we provide a list of TTSs photometric standards for future GALEX-based studies of the young stellar population in star forming regions

  7. A GALEX-BASED SEARCH FOR THE SPARSE YOUNG STELLAR POPULATION IN THE TAURUS-AURIGAE STAR FORMING REGION

    Energy Technology Data Exchange (ETDEWEB)

    Gómez de Castro, Ana I.; Lopez-Santiago, Javier; López-Martínez, Fatima; Sánchez, Néstor; Sestito, Paola; Gestoso, Javier Yañez [AEGORA Research Group, Universidad Complutense de Madrid, Plaza de Ciencias 3, E-28040 Madrid (Spain); De Castro, Elisa; Cornide, Manuel [Fac. de CC. Físicas, Universidad Complutense de Madrid, Plaza de Ciencias 1, E-28040 Madrid (Spain)

    2015-02-01

    In this work, we identify 63 bona fide new candidates to T Tauri stars (TTSs) in the Taurus-Auriga region, using its ultraviolet excess as our baseline. The initial data set was defined from the GALEX all sky survey (AIS). The GALEX satellite obtained images in the near-ultraviolet (NUV) and far-ultraviolet (FUV) bands where TTSs show a prominent excess compared with main-sequence or giants stars. GALEX AIS surveyed the Taurus-Auriga molecular complex, as well as a fraction of the California Nebula and the Perseus complex; bright sources and dark clouds were avoided. The properties of TTSs in the ultraviolet (GALEX), optical (UCAC4), and infrared (2MASS) have been defined using the TTSs observed with the International Ultraviolet Explorer reference sample. The candidates were identified by means of a mixed ultraviolet-optical-infrared excess set of colors; we found that the FUV-NUV versus J–K color-color diagram is ideally suited for this purpose. From an initial sample of 163,313 bona fide NUV sources, a final list of 63 new candidates to TTSs in the region was produced. The search procedure has been validated by its ability to detect all known TTSs in the area surveyed: 31 TTSs. Also, we show that the weak-lined TTSs are located in a well-defined stripe in the FUV-NUV versus J–K diagram. Moreover, in this work, we provide a list of TTSs photometric standards for future GALEX-based studies of the young stellar population in star forming regions.

  8. Discriminating strength: a bona fide measure of non-classical correlations

    Science.gov (United States)

    Farace, A.; De Pasquale, A.; Rigovacca, L.; Giovannetti, V.

    2014-07-01

    A new measure of non-classical correlations is introduced and characterized. It tests the ability of using a state ρ of a composite system AB as a probe for a quantum illumination task (e.g. see Lloyd 2008 Science 321 1463), in which one is asked to remotely discriminate between the two following scenarios: (i) either nothing happens to the probe, or (ii) the subsystem A is transformed via a local unitary {{R}_{A}} whose properties are partially unspecified when producing ρ. This new measure can be seen as the discrete version of the recently introduced interferometric power measure (Girolami et al 2013 e-print arXiv:1309.1472) and, at least for the case in which A is a qubit, it is shown to coincide (up to an irrelevant scaling factor) with the local quantum uncertainty measure of Girolami, Tufarelli and Adesso (2013 Phys. Rev. Lett. 110 240402). Analytical expressions are derived which allow us to formally prove that, within the set of separable configurations, the maximum value of our non-classicality measure is achieved over the set of quantum-classical states (i.e. states ρ which admit a statistical unravelling where each element of the associated ensemble is distinguishable via local measures on B).

  9. Peaceful Uses Bona Fides: Criteria for Evaluation and Case Studies

    Energy Technology Data Exchange (ETDEWEB)

    Ajemian, Chris K.; Hazel, Mike; Kessler, Carol E.; Mathews, Carrie E.; Morris, Fred A.; Seward, Amy M.; Peterson, Danielle J.; Smith, Brian W.

    2007-06-06

    This study applies a set of indicators to assess the peaceful nature of a state’s nuclear program. Evaluation of a country’s nuclear program relative to these indicators can help the international community to take appropriate actions to ensure that the growth of the global nuclear energy industry proceeds peacefully and to minimize nuclear proliferation risks.

  10. Discriminating strength: a bona fide measure of non-classical correlations

    Energy Technology Data Exchange (ETDEWEB)

    Farace, A; De Pasquale, A; Giovannetti, V [NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, I-56126 Pisa (Italy); Rigovacca, L [Scuola Normale Superiore, I-56126 Pisa (Italy)

    2014-07-01

    A new measure of non-classical correlations is introduced and characterized. It tests the ability of using a state ρ of a composite system AB as a probe for a quantum illumination task (e.g. see Lloyd 2008 Science 321 1463), in which one is asked to remotely discriminate between the two following scenarios: (i) either nothing happens to the probe, or (ii) the subsystem A is transformed via a local unitary R{sub A} whose properties are partially unspecified when producing ρ. This new measure can be seen as the discrete version of the recently introduced interferometric power measure (Girolami et al 2013 e-print arXiv:1309.1472) and, at least for the case in which A is a qubit, it is shown to coincide (up to an irrelevant scaling factor) with the local quantum uncertainty measure of Girolami, Tufarelli and Adesso (2013 Phys. Rev. Lett. 110 240402). Analytical expressions are derived which allow us to formally prove that, within the set of separable configurations, the maximum value of our non-classicality measure is achieved over the set of quantum-classical states (i.e. states ρ which admit a statistical unravelling where each element of the associated ensemble is distinguishable via local measures on B). (paper)

  11. Discriminating strength: a bona fide measure of non-classical correlations

    International Nuclear Information System (INIS)

    Farace, A; De Pasquale, A; Giovannetti, V; Rigovacca, L

    2014-01-01

    A new measure of non-classical correlations is introduced and characterized. It tests the ability of using a state ρ of a composite system AB as a probe for a quantum illumination task (e.g. see Lloyd 2008 Science 321 1463), in which one is asked to remotely discriminate between the two following scenarios: (i) either nothing happens to the probe, or (ii) the subsystem A is transformed via a local unitary R A whose properties are partially unspecified when producing ρ. This new measure can be seen as the discrete version of the recently introduced interferometric power measure (Girolami et al 2013 e-print arXiv:1309.1472) and, at least for the case in which A is a qubit, it is shown to coincide (up to an irrelevant scaling factor) with the local quantum uncertainty measure of Girolami, Tufarelli and Adesso (2013 Phys. Rev. Lett. 110 240402). Analytical expressions are derived which allow us to formally prove that, within the set of separable configurations, the maximum value of our non-classicality measure is achieved over the set of quantum-classical states (i.e. states ρ which admit a statistical unravelling where each element of the associated ensemble is distinguishable via local measures on B). (paper)

  12. A bona fide baby boom for the Baltics / Aleksei Gunter

    Index Scriptorium Estoniae

    Gunter, Aleksei, 1979-

    2004-01-01

    Seoses jaanuaris alanud vanemahüvitise programmiga ennustatakse sel aastal sündide arvu tõusu. Rahvastikuminister Paul-Eerik Rummo kommentaare. Tabel: Eesti rahvastikuandmed aprill 2003 - aprill 2004

  13. 26 CFR 1.933-1 - Exclusion of certain income from sources within Puerto Rico.

    Science.gov (United States)

    2010-04-01

    ... Puerto Rico. 1.933-1 Section 1.933-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Exclusion of certain income from sources within Puerto Rico. (a) General rule. (1) An individual (whether a United States citizen or an alien), who is a bona fide resident of Puerto Rico during the entire taxable...

  14. Salivary agglutinin/DMBT1SAG expression is up-regulated in the presence of salivary gland tumors

    DEFF Research Database (Denmark)

    Bikker, F J; van der Wal, J E; Ligtenberg, A J M

    2004-01-01

    Salivary agglutinin (SAG) is encoded by the gene Deleted in Malignant Brain Tumors 1 (DMBT1) and represents the salivary variant of DMBT1 (DMBT1(SAG)). While SAG is a bona fide anti-caries factor, DMBT1 was proposed as a candidate tumor-suppressor for brain, digestive tract, and lung cancer. Thou...

  15. 5 CFR 551.432 - Sleep time.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Sleep time. 551.432 Section 551.432... FAIR LABOR STANDARDS ACT Hours of Work Special Situations § 551.432 Sleep time. (a) Except as provided in paragraph (b) of this section, bona fide sleep time that fulfills the following conditions shall...

  16. 29 CFR 541.101 - Business owner.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Business owner. 541.101 Section 541.101 Labor Regulations... Executive Employees § 541.101 Business owner. The term “employee employed in a bona fide executive capacity... equity interest in the enterprise in which the employee is employed, regardless of whether the business...

  17. 75 FR 81677 - Pendency of Request for Exemption From the Bond/Escrow Requirement Relating to the Sale of Assets...

    Science.gov (United States)

    2010-12-28

    ... Requirement Relating to the Sale of Assets by an Employer Who Contributes to a Multiemployer Plan: Rangers... for the five-plan-year period beginning after the sale. PBGC is authorized to grant individual and... Plan Amendments Act of 1980 (``ERISA'' or the ``Act''), provides that a bona fide arm's length sale of...

  18. Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Persson, Morten; Haldager, L

    2011-01-01

    PA-mediated plasminogen activation at the cell surface, which is accomplished by its high-affinity interaction with the growth factor-like domain of uPA. Detailed insights into the molecular basis underlying the interactions between uPAR and its two bona fide ligands, uPA and vitronectin, have been obtained recently by X...

  19. 16 CFR 308.3 - Advertising of pay-per-call services.

    Science.gov (United States)

    2010-01-01

    ... services to children under the age of 12, unless the service is a bona fide educational service. (2) For...-prepared video directed to children under 12, or preceding a movie directed to children under 12 shown in a movie theater; (vi) Whether the advertisement or promotion appears on product packaging directed to...

  20. 29 CFR 778.327 - Temporary or sporadic reduction in schedule.

    Science.gov (United States)

    2010-07-01

    ... rate at $6 per hour for all workweeks in which the employee worked 40 hours or less, approximately $5... at a bona fide $6 rate usually working 50 hours and taking home $330 as total straight time and... Section 778.327 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF...

  1. 77 FR 26175 - Section 42 Qualified Contract Provisions

    Science.gov (United States)

    2012-05-03

    ... indebtedness under general principles of Federal income tax law, and (3) upon the sale of the building, are... building for sale to the general public at the determined qualified contract price upon receipt of a... because of variations under State laws concerning the terms of a bona fide contract and methods for...

  2. Truancy Reduction: Keeping Students in School. Juvenile Justice Bulletin.

    Science.gov (United States)

    Baker, Myriam L.; Sigmon, Jane Nady; Nugent, M. Elaine

    Each school day, hundreds of thousands of students are missing from their classrooms--many without a bona fide excuse. Left unchecked, truancy is a risk factor for serious juvenile delinquency. Truancy's impact also extends into the adult years where it has been linked to numerous negative outcomes. Consequently, it is critical to identify…

  3. Derivation of quantum statistics from Gauss's principle and the second law

    International Nuclear Information System (INIS)

    Lavenda, B.H.

    1988-01-01

    Quantum statistical laws are derived from bona fide stationary probability distributions of physical stochastic processes. These distributions are shown to be the laws of error for which the average occupation numbers are the most probable values. They determine uniquely the statistical entropy functions and the second law gives the quantum statistical distributions

  4. Simpson's Paradox and Confounding Factors in University Rankings: A Demonstration Using QS 2011-12 Data

    Science.gov (United States)

    Soh, Kay Cheng

    2012-01-01

    University ranking has become ritualistic in higher education. Ranking results are taken as bona fide by rank users. Ranking systems usually use large data sets from highly heterogeneous universities of varied backgrounds. This poses the problem of Simpson's Paradox and the lurking variables causing it. Using QS 2011-2012 Ranking data, the dual…

  5. 78 FR 27953 - Reorganization of Foreign-Trade Zone 147 Under Alternative Site Framework Reading, Pennsylvania

    Science.gov (United States)

    2013-05-13

    ... terminate authority for Sites 20-22 if no foreign-status merchandise is admitted for a bona fide customs... Zone 147 Under Alternative Site Framework Reading, Pennsylvania Pursuant to its authority under the... application to the Board (FTZ Docket B-79-2012, docketed 11-1-2012) for authority to reorganize under the ASF...

  6. Structural analysis of the active site architecture of the VapC toxin from Shigella flexneri

    DEFF Research Database (Denmark)

    Xu, Kehan; Dedic, Emil; Brodersen, Ditlev Egeskov

    2016-01-01

    The VapC toxin from the Shigella flexneri 2a virulence plasmid pMYSH6000 belongs to the PIN domain protein family, which is characterized by a conserved fold with low amino acid sequence conservation. The toxin is a bona fide Mg2+-dependent ribonuclease and has been shown to target initiator t...

  7. 17 CFR 242.505 - Exclusion for news media.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exclusion for news media. 242...-Analyst Certification § 242.505 Exclusion for news media. No provision of this Regulation AC shall apply to any person who: (a) Is the publisher of any bona fide newspaper, news magazine or business or...

  8. 26 CFR 20.2056A-4 - Procedures for conforming marital trusts and nontrust marital transfers to the requirements of a...

    Science.gov (United States)

    2010-04-01

    ... that, to the best of my knowledge and belief, the information reported in this Information Statement is... revoked. For example, if a protective assignment is made because a bona fide question exists as to the... payable monthly, quarterly, or at some other interval, and a description of any scheduled changes in the...

  9. 19 CFR Appendix B to Part 171 - Customs Regulations, Guidelines for the Imposition and Mitigation of Penalties for Violations of...

    Science.gov (United States)

    2010-04-01

    ... prior to liquidation. In addition, a potential loss of duty exists where Customs discovers the violation... statement or omission that is based on a bona fide erroneous belief as to the facts, so long as the belief... that do not change the admissibility or entry status of merchandise or its appraised value or...

  10. Fides: Lightweight Authenticated Cipher with Side-Channel Resistance for Constrained Hardware

    DEFF Research Database (Denmark)

    Bilgin, Begul; Bogdanov, Andrey; Knezevic, Miroslav

    2013-01-01

    In this paper, we present a novel lightweight authenticated cipher optimized for hardware implementations called Fides. It is an online nonce-based authenticated encryption scheme with authenticated data whose area requirements are as low as 793 GE and 1001 GE for 80-bit and 96-bit security...

  11. 19 CFR 148.13 - Written declarations.

    Science.gov (United States)

    2010-04-01

    ...) When required. Unless an oral declaration is accepted under § 148.12, the declaration required of a..., HTSUS, for articles to be disposed of as bona fide gifts; or subheading 9804.00.40, HTSUS, for articles... passenger shall state either: (1) The price actually paid for the article in the currency of purchase, or...

  12. 26 CFR 1.141-12 - Remedial actions.

    Science.gov (United States)

    2010-04-01

    ...) Reasonable expectations test met. The issuer reasonably expected on the issue date that the issue would meet... tests or the private loan financing test are bona fide and arm's-length, and the new user pays fair..., is sufficient to pay all the principal of, and interest and call premium on, bonds from the date the...

  13. 76 FR 28242 - Proposed Extension of the Approval of Information Collection Requirements

    Science.gov (United States)

    2011-05-16

    ... Reduction Act of 1995 (PRA95). 44 U.S.C. 3056(c)(2)(A). This program helps to ensure that requested data can..., collection instruments are clearly understood, and the impact of collection requirements on respondents can... part 549, Requirements of a ``Bona Fide Profit-Sharing Plan or Trust''. A copy of the proposed...

  14. 29 CFR 778.407 - The nature of the section 7(f) contract.

    Science.gov (United States)

    2010-07-01

    ... it is not in written form. Furthermore, the contract must be “bona fide.” This implies that both the making of the contract and the settlement of its terms were done in good faith. ... 29 Labor 3 2010-07-01 2010-07-01 false The nature of the section 7(f) contract. 778.407 Section...

  15. 26 CFR 31.3402(f)(2)-1 - Withholding exemption certificates.

    Science.gov (United States)

    2010-04-01

    ... specifies the marital status for Employee C. Employee C began a 4-month unpaid maternity leave of absence... maternity leave ends, Employer W must withhold based on the notice. Example 4. Employer X receives a notice... is on a bona fide leave of absence if the period of such leave does not exceed twelve months or the...

  16. Coaching for ADHD

    Science.gov (United States)

    Murphy, Kevin; Ratey, Nancy; Maynard, Sandy; Sussman, Susan; Wright, Sarah D.

    2010-01-01

    Despite limited scientific study on ADHD coaching as an intervention for adults with ADHD, the field of ADHD coaching has grown significantly and gained popularity in recent years. ADHD coaching is becoming a bona fide profession where one must advance through a rigorous training process, in order to be certified as a professional ADHD coach.…

  17. 19 CFR 148.44 - Gifts.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Gifts. 148.44 Section 148.44 Customs Duties U.S...) PERSONAL DECLARATIONS AND EXEMPTIONS Exemptions for Nonresidents § 148.44 Gifts. (a) Exemption. An arriving... and are to be disposed of by him as bona fide gifts. See § 148.43(b) for limitations on cigars under...

  18. Planck early results. XXVI. Detection with Planck and confirmation by XMM-Newton of PLCK G266.6-27.3, an exceptionally X-ray luminous and massive galaxy cluster at z ~ 1

    DEFF Research Database (Denmark)

    Lähteenmäki, A.; Poutanen, T.; Natoli, P.

    2011-01-01

    We present first results on PLCKG266.6-27.3, a galaxy cluster candidate detected at a signal-to-noise ratio of 5 in the Planck All Sky survey. An XMM-Newton validation observation has allowed us to confirm that the candidate isa bona fide galaxy cluster. With these X-ray data we measure an accurate...

  19. The Characteristics of an Abstract System for the Transfer of ...

    African Journals Online (AJOL)

    The mutual intention to transfer and to receive real rights is not construed as an independent real agreement as it is contained in the obligatory agreement. In a causal system the transferor finds himself in a favourable position in relation to other parties while bona fide third parties undoubtedly get the worst of the deal since ...

  20. 77 FR 42737 - Patient Safety Organizations: Delisting for Cause for The Steward Group PSO

    Science.gov (United States)

    2012-07-20

    ... good faith effort to correct the deficiency. Accordingly, AHRQ has revoked the listing of The Steward... The Patient Safety Act, Public Law 109-41, 42 U.S.C. 299b-21--b-26, provides for the formation of PSOs... 24-month period following the PSO's date of initial listing, at least two bona fide contracts with...

  1. Yet Another Call for a Greater Role for Good Faith in the South ...

    African Journals Online (AJOL)

    This article examines the current approach of the South African courts to the role of good faith or bona fides in contracts, as well as the courts' stated reasons for this approach. The article specifically examines how arguments based on good faith have fared in the Constitutional Court to date, and the prospects for law reform ...

  2. 29 CFR 785.19 - Meal.

    Science.gov (United States)

    2010-07-01

    .... For example, an office employee who is required to eat at his desk or a factory worker who is required to be at his machine is working while eating. (Culkin v. Glenn L. Martin, Nebraska Co., 97 F. Supp... enough for a bona fide meal period. A shorter period may be long enough under special conditions. The...

  3. Semper Fidelis: Some Values of The Marine Retiree Group

    Directory of Open Access Journals (Sweden)

    Virienia Puspita

    2016-01-01

    Full Text Available This research tried to reveal the group values of Marine retiree Depok, which has done by using symbolic convergence theory as the main theory. The aims of this research were to find and identify fantasy themes, rhetorical vision and group values of Marine retiree group in Depok. This study was based on a foundation of interpretative paradigm with qualitative research methods to find a fantasy theme that emerged in the group through the method of analysis of fantasy by Bormann. The results of the this study indicate the stories of Marine retiree in Depok are the bridge of experience of Marine retiree in the past with present time. Besides that, it is the formation of behavior in forms of values, culture and communication behavior of them. From the analysis theme shows that the group values of Marine retiree in Depok has manifested by universal's idealism value of Marines Semper Fidelis (loyalty, sacrifice, dedication, pride and self esteem. The group rhetorical visions are pride of the group, desire for being accepted and close to their group's identity. 

  4. 29 CFR 549.3 - Distinction between plan and trust.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Distinction between plan and trust. 549.3 Section 549.3 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS REQUIREMENTS OF A âBONA FIDE PROFIT-SHARING PLAN OR TRUSTâ § 549.3 Distinction between plan and trust. As used in this part: (a) Profit-sharing plan...

  5. Regulatory Fit and Equal Opportunity/Diversity: Implications for DEOMI

    Science.gov (United States)

    2013-01-01

    sustains regulatory fit (Lee & Aaker , 2004), and greater psychological value is ascribed to expected outcomes when outcomes are pursued in a manner...groups and women. In the military, policy also delineates bona fide occupational qualifications (BFOQs) that specify the personal characteristics...that fails to create regulatory fit (Cesario, Grant, & Higgins, 2004; Cesario, Higgins, & Scholer, 2008; Lee & Aaker , 2004). Training EOA

  6. Sex Discrimination in Employment: What to Know About It, What to Do About It. Second Edition.

    Science.gov (United States)

    National Organization for Women, Boston, MA. Eastern Massachusetts Chapter.

    The opening question in this document is: Have you ever been confronted with sex discrimination? If you can answer yes to any of 42 more specific questions on discriminatory acts, you have a bona fide complaint. From this point the document serves as a guide on what evidence is needed in a complaint, where the complaint is to be filed, and sources…

  7. 29 CFR 1604.2 - Sex as a bona fide occupational qualification.

    Science.gov (United States)

    2010-07-01

    ... narrowly. Label—“Men's jobs” and “Women's jobs”—tend to deny employment opportunities unnecessarily to one... example, the assumption that the turnover rate among women is higher than among men. (ii) The refusal to hire an individual based on stereotyped characterizations of the sexes. Such stereotypes include, for...

  8. 26 CFR 1.937-1 - Bona fide residency in a possession.

    Science.gov (United States)

    2010-04-01

    ... time during the day. Notwithstanding the preceding sentence, the following days will not count as days... organizations in State C. Z receives mail in State C, including brokerage statements, credit card bills, and...

  9. In the arbitration under Chapter 11 of the North American Free Trade Agreement and the UNCITRAL arbitration rules between Methanex Corp, claimant/investor and United States of America, respondent/party : joint post-hearing submission by AMICI to the Tribunal

    Energy Technology Data Exchange (ETDEWEB)

    Mann, H.; Wagner, M.

    2004-06-29

    Canada-based Methanex Corporation is a major producer of methanol, a key component of methyl tertiary butyl ether (MTBE) which is used in unleaded gasoline. Methanex launched an international arbitration against the United States in response to California's ban of MTBE. California argues that MTBE poses a significant risk to human health and safety and the environment. Methanex claims that the the ban is an expropriation of the company's investment and a violation of Chapter 11 of the North American Free Trade Agreement. Methanex is seeking financial compensation under NAFTA's Article 1110. This document represents the International Institute for Sustainable Development (IISD) in its intervention in the Methanex versus United States dispute. IISD was granted Amicus status (friend of the court) in the Tribunal hearing. As such, IISD represents public interest and builds confidence in the dispute settlement system. This post hearing submission addresses the legal consequences of California's measure to ban MTBE as a bona fide (non-health) environmental issue or as a bona fide public heath measure, and determines whether such measures constitute a violation of NAFTA's Article 1110. 1 ref.

  10. A MOOC for Introductory Physics

    Science.gov (United States)

    Schatz, Michael

    2014-03-01

    We describe an effort to develop and to implement a college-level introductory physics (mechanics) MOOC that offers bona fide laboratory experiences. We also discuss efforts to use MOOC curricular materials to ``flip'' the classroom in a large lecture introductory physics course offered on-campus at Georgia Tech. Preliminary results of assessments and surveys from both MOOC and on-campus students will be presented.

  11. Level up Book Club

    Science.gov (United States)

    LaGarde, Jennifer; Winner, Matthew C.

    2012-01-01

    Like all great ideas, Level Up Book Club grew out of a genuine need, the spontaneous firing of a few brain sparks, and the kind of luck that comes from being "in the right place at the right time." By mid-June 2011 the authors were already "bona fide" wonder twins--two educators who, although they'd never met, had stumbled upon each other through…

  12. Our Energy For The Country Project Started Our Via Bona

    International Nuclear Information System (INIS)

    Anon

    2014-01-01

    Slovenske Elektrarne received the main Via Bona award for its complex and extraordinary approach to responsible business. Non-profit fund Pontis has been granting this award since 1998 to companies voluntarily contributing to the mitigation of negative trends and the improvement of positive business aspects beyond legislative requirements. We won with our Energy for the Country programme. The award was given to Paolo Ruzzini, SE CEO and Chairman of the Board of Directors by Andrej Kiska, the new Slovak President.

  13. Influenza-associated thrombotic microangiopathies.

    Science.gov (United States)

    Bitzan, Martin; Zieg, Jakub

    2017-09-07

    Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP). This review explores the role of the influenza virus as trigger of HUS or TTP. We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data. We identified 25 cases of influenza-associated TMA. Five additional cases were linked to influenza vaccination and analyzed separately. Influenza A was found in 83%, 10 out of 25 during the 2009 A(H1N1) pandemic. Two patients had bona fide TTP with ADAMTS13 activity rational treatment approaches.

  14. Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.

    Science.gov (United States)

    Jackson, Belinda M; Abete-Luzi, Patricia; Krause, Michael W; Eisenmann, David M

    2014-04-16

    The Wnt signaling pathway plays a fundamental role during metazoan development, where it regulates diverse processes, including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin-dependent/canonical Wnt pathway up-regulates expression of Wnt target genes to mediate a cellular response. In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway regulates several processes during larval development; however, few target genes of this pathway have been identified. To address this deficit, we used a novel approach of conditionally activated Wnt signaling during a defined stage of larval life by overexpressing an activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared with control animals. We identified 166 differentially expressed genes, of which 104 were up-regulated. A subset of the up-regulated genes was shown to have altered expression in mutants with decreased or increased Wnt signaling; we consider these genes to be bona fide C. elegans Wnt pathway targets. Among these was a group of six genes, including the cuticular collagen genes, bli-1 col-38, col-49, and col-71. These genes show a peak of expression in the mid L4 stage during normal development, suggesting a role in adult cuticle formation. Consistent with this finding, reduction of function for several of the genes causes phenotypes suggestive of defects in cuticle function or integrity. Therefore, this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.

  15. Impossible Certainty: Cost Risk Analysis for Air Force Systems

    Science.gov (United States)

    2006-01-01

    activities remain separate so that a risk assessment is not Introduction 5 tailored (intentionally or even subconsciously ) to fit a predetermined...set- ting aside risk funding was desirable. Under current PPBS and con- gressional rules, some minor reprogramming of funds during the Decisionmaker...available in a timely manner to programs with a bona fide need, without the delays or risks associ- ated with reprogramming . This could encourage program

  16. Identification of SUMO conjugation sites in the budding yeast proteome

    Directory of Open Access Journals (Sweden)

    Miguel Esteras

    2017-10-01

    Full Text Available Post-translational modification by the small ubiquitin-like modifier (SUMO is an important mechanism regulating protein function. Identification of SUMO conjugation sites on substrates is a challenging task. Here we employed a proteomic method to map SUMO acceptor lysines in budding yeast proteins. We report the identification of 257 lysine residues where SUMO is potentially attached. Amongst the hits, we identified already known SUMO substrates and sites, confirming the success of the approach. In addition, we tested several of the novel substrates using SUMO immunoprecipitation analysis and confirmed that the SUMO acceptor lysines identified in these proteins are indeed bona fide SUMOylation sites. We believe that the collection of SUMO sites presented here is an important resource for future functional studies of SUMOylation in yeast.

  17. miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria

    KAUST Repository

    Liew, Yi Jin

    2016-02-12

    MicroRNAs (miRNAs) are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera) are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively). Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae.

  18. miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria

    KAUST Repository

    Liew, Yi Jin; Ryu, Tae Woo; Aranda, Manuel; Ravasi, Timothy

    2016-01-01

    MicroRNAs (miRNAs) are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera) are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively). Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae.

  19. Management of functional Sprint Fidelis leads at cardiac resynchronization therapy-defibrillator generator replacement: a novel option for preventing inappropriate shocks from lead failure in fragile patients with high risk of sudden death.

    Science.gov (United States)

    Zhu, Dennis W X; Chu, Matthew M; House, Chad M

    2017-12-01

    In patients with a functional Sprint Fidelis lead at generator replacement, the manufacturer recommended to either continue to use the existing lead or replace it with a new lead. For those patients who continue to use a functional Fidelis lead, the risk of inappropriate shocks remains present if the lead fails in the future. We evaluated the feasibility of an alternative approach at the time of cardiac resynchronization therapy-defibrillator (CRT-D) generator replacement in patients with a functional bipolar left ventricular (LV) lead for prevention of inappropriate shocks from future Fidelis lead failure. During the procedure, the pace/sense IS-1 connection pin of the functional Fidelis lead was intentionally inserted into the LV port of the new CRT-D generator, while the existing bipolar LV lead IS-1 connection pin was inserted into the right ventricular (RV) pace/sense port. After such switching, the existing bipolar LV lead was used for functional LV pacing/sensing, while the Fidelis lead was used for functional RV pacing and high voltage shock only and could no longer be used for the purpose of sensing and detecting. This approach precluded oversensing and inappropriate shocks should the functional Fidelis lead fail in the future. Six fragile patients, who were not considered suitable candidates for lead replacement, underwent the alternative approach. During a follow-up of 35 ± 23 months, the CRT-D system functioned normally in five patients. The Fidelis lead fractured in one patient 7 months after generator replacement. The malfunction was detected promptly and the defected lead was replaced. No inappropriate detections or shock was triggered. In CRT-D patients with a functional Fidelis lead and a bipolar LV lead, switching of the Fidelis lead pace/sense IS-1 pin with the bipolar LV lead IS-1 pin at generator replacement did not affect normal system function. This novel approach may be valuable in fragile patients with high risk of sudden death for

  20. 78 FR 25181 - Revision of Regulations Defining Bona Fide Cotton Spot Markets

    Science.gov (United States)

    2013-04-30

    ...;Prices of new books are listed in the first FEDERAL REGISTER issue of each #0;week. #0; #0; #0; #0;#0... amending references to the ``New York Cotton Exchange'' to read the ``Intercontinental Exchange.'' DATES...), AMS has considered the economic impact of this action on small entities and has determined that its...

  1. Expression proteomics of UPF1 knockdown in HeLa cells reveals autoregulation of hnRNP A2/B1 mediated by alternative splicing resulting in nonsense-mediated mRNA decay

    Directory of Open Access Journals (Sweden)

    Zavolan Mihaela

    2010-10-01

    Full Text Available Abstract Background In addition to acting as an RNA quality control pathway, nonsense-mediated mRNA decay (NMD plays roles in regulating normal gene expression. In particular, the extent to which alternative splicing is coupled to NMD and the roles of NMD in regulating uORF containing transcripts have been a matter of debate. Results In order to achieve a greater understanding of NMD regulated gene expression we used 2D-DiGE proteomics technology to examine the changes in protein expression induced in HeLa cells by UPF1 knockdown. QPCR based validation of the corresponding mRNAs, in response to both UPF1 knockdown and cycloheximide treatment, identified 17 bona fide NMD targets. Most of these were associated with bioinformatically predicted NMD activating features, predominantly upstream open reading frames (uORFs. Strikingly, however, the majority of transcripts up-regulated by UPF1 knockdown were either insensitive to, or even down-regulated by, cycloheximide treatment. Furthermore, the mRNA abundance of several down-regulated proteins failed to change upon UPF1 knockdown, indicating that UPF1's role in regulating mRNA and protein abundance is more complex than previously appreciated. Among the bona fide NMD targets, we identified a highly conserved AS-NMD event within the 3' UTR of the HNRNPA2B1 gene. Overexpression of GFP tagged hnRNP A2 resulted in a decrease in endogenous hnRNP A2 and B1 mRNA with a concurrent increase in the NMD sensitive isoforms. Conclusions Despite the large number of changes in protein expression upon UPF1 knockdown, a relatively small fraction of them can be directly attributed to the action of NMD on the corresponding mRNA. From amongst these we have identified a conserved AS-NMD event within HNRNPA2B1 that appears to mediate autoregulation of HNRNPA2B1 expression levels.

  2. Human rights, public health and medicinal cannabis use

    OpenAIRE

    Bone, Melissa; Seddon, Toby

    2015-01-01

    This paper explores the interplay between the human rights and drug control frameworks, and critiques case law on medicinal cannabis use to demonstrate that a bona fide human rights perspective allows for a broader conception of ‘health’. This broad conception, encompassing both medicalised and social constructionist definitions, can inform public health policies relating to medicinal cannabis use. The paper also demonstrates how a human rights lens can alleviate a core tension between the St...

  3. Do all psychological treatments really work the same in posttraumatic stress disorder?

    OpenAIRE

    Ehlers, Anke; Bisson, Jonathan; Clark, David M.; Creamer, Mark; Pilling, Steven; Richards, David; Schnurr, Paula P.; Turner, Stuart; Yule, William

    2010-01-01

    A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746–758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not f...

  4. I-DIRT, a general method for distinguishing between specific and nonspecific protein interactions.

    Science.gov (United States)

    Tackett, Alan J; DeGrasse, Jeffrey A; Sekedat, Matthew D; Oeffinger, Marlene; Rout, Michael P; Chait, Brian T

    2005-01-01

    Isolation of protein complexes via affinity-tagged proteins provides a powerful tool for studying biological systems, but the technique is often compromised by co-enrichment of nonspecifically interacting proteins. We describe a new technique (I-DIRT) that distinguishes contaminants from bona fide interactors in immunopurifications, overcoming this most challenging problem in defining protein complexes. I-DIRT will be of broad value for studying protein complexes in biological systems that can be metabolically labeled.

  5. Nuclear terrorism and reality

    International Nuclear Information System (INIS)

    St Sauver, J.E.

    1983-01-01

    Unlike conventional terrorist violence, bona-fide nuclear terrorism is a self-publicizing phenomenon. It is a public event by the very scope of its impact. Apocalyptic and catastrophically destructive, a nuclear explosion is the ideal instrument of mass terror. Rational nuclear insurgents would not inform authorities that a nuclear device is about to be detonated. Advance warning of an impending nuclear explosion would reduce the maximum potential effectiveness of any response to such an event

  6. The Fate of a Healing Goddess: Ocular Pathologies, the Antonine Plague, and the Ancient Roman Cult of Bona Dea

    Directory of Open Access Journals (Sweden)

    Leonardo Ambasciano

    2016-05-01

    Full Text Available The aim of this article is to offer a diachronic and dynamic contextualisation of the ancient Roman cult of Bona Dea, connecting its cognitive underpinnings with its healing dimension. Special attention is devoted to the ocular concerns attested in the epigraphic inventory. The decline of the presence of Bona Dea on the religious scene, attested by the 3rd century CE, is considered to be the multi-causal result of the long-lasting, ocular side-effects of smallpox in the aftermath of the so-called Antonine Plague, which interacted with the correlated and prolonged lack of positive reinforcement concerning symptom relief and cognitive feedback.

  7. Fides et ratio: An early enlightenment defence of non-confessional religion by poiret and his circle

    NARCIS (Netherlands)

    H.A. Krop (Henri)

    2010-01-01

    textabstractIn 1707 an anonymous collection of treatises Fides et ratio was published in Amsterdam. The voluminous work of several authors contains a fierce critique of Locke's notion of faith and the moderate Enlightenment's conception of a reasonable Christianity. The sympathiser with mystic

  8. Critical string from non-Abelian vortex in four dimensions

    Directory of Open Access Journals (Sweden)

    M. Shifman

    2015-11-01

    Full Text Available In a class of non-Abelian solitonic vortex strings supported in certain N=2 super-Yang–Mills theories we search for the vortex which can behave as a critical fundamental string. We use the Polchinski–Strominger criterion of the ultraviolet completeness. We identify an appropriate four-dimensional bulk theory: it has the U(2 gauge group, the Fayet–Iliopoulos term and four flavor hypermultiplets. It supports semilocal vortices with the world-sheet theory for orientational (size moduli described by the weighted CP(2,2 model. The latter is superconformal. Its target space is six-dimensional. The overall Virasoro central charge is critical. We show that the world-sheet theory on the vortex supported in this bulk model is the bona fide critical string.

  9. Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes.

    Directory of Open Access Journals (Sweden)

    Kevin P Keegan

    2007-11-01

    Full Text Available Five independent groups have reported microarray studies that identify dozens of rhythmically expressed genes in the fruit fly Drosophila melanogaster. Limited overlap among the lists of discovered genes makes it difficult to determine which, if any, exhibit truly rhythmic patterns of expression. We reanalyzed data from all five reports and found two sources for the observed discrepancies, the use of different expression pattern detection algorithms and underlying variation among the datasets. To improve upon the methods originally employed, we developed a new analysis that involves compilation of all existing data, application of identical transformation and standardization procedures followed by ANOVA-based statistical prescreening, and three separate classes of post hoc analysis: cross-correlation to various cycling waveforms, autocorrelation, and a previously described fast Fourier transform-based technique. Permutation-based statistical tests were used to derive significance measures for all post hoc tests. We find application of our method, most significantly the ANOVA prescreening procedure, significantly reduces the false discovery rate relative to that observed among the results of the original five reports while maintaining desirable statistical power. We identify a set of 81 cycling transcripts previously found in one or more of the original reports as well as a novel set of 133 transcripts not found in any of the original studies. We introduce a novel analysis method that compensates for variability observed among the original five Drosophila circadian array reports. Based on the statistical fidelity of our meta-analysis results, and the results of our initial validation experiments (quantitative RT-PCR, we predict many of our newly found genes to be bona fide cyclers, and suggest that they may lead to new insights into the pathways through which clock mechanisms regulate behavioral rhythms.

  10. Polycythemia vera among participants of a nuclear weapons test

    International Nuclear Information System (INIS)

    Sobell, J.L.; Codd, M.B.; Silverstein, M.N.; Kurland, L.T.

    1987-01-01

    Three letters-to-the-editors discuss the finding of a statistically significant excess of polycythemia vera cases among participants in the Smoky detonation. Had population-based incidence rates from Rochester been used to derive an expected incidence, and had only bona fide polycythemia vera cases been considered, as is the rule in most epidemiologic studies, the observed frequency of polycythemia vera among participants in the Smoky test would have been found to be well within chance expectations

  11. Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies

    OpenAIRE

    TARDIVEL , Meryem; Bégard , Séverine; Bousset , Luc; Dujardin , Simon; Coens , Audrey; Melki , Ronald; Buée , Luc; Colin , Morvane

    2016-01-01

    A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer?s disease, is a bona fide constituent of TNTs. This i...

  12. BANYAN. III. Radial velocity, rotation, and X-ray emission of low-mass star candidates in nearby young kinematic groups

    Energy Technology Data Exchange (ETDEWEB)

    Malo, Lison; Artigau, Étienne; Doyon, René; Lafrenière, David; Albert, Loïc; Gagné, Jonathan, E-mail: malo@astro.umontreal.ca, E-mail: doyon@astro.umontreal.ca [Département de physique and Observatoire du Mont-Mégantic, Université de Montréal, Montréal, QC H3C 3J7 (Canada)

    2014-06-10

    Based on high-resolution spectra obtained with PHOENIX at Gemini-South, CRIRES at VLT-UT1, and ESPaDOnS at the Canada-France-Hawaii Telescope, we present new measurements of the radial and projected rotational velocities of 219 low-mass stars. The target likely membership was initially established using the Bayesian analysis tool recently presented in Malo et al., taking into account only the position, proper motion, and photometry of the stars to assess their membership probability. In the present study, we include radial velocity as an additional input to our analysis, and in doing so we confirm the high membership probability for 130 candidates: 27 in β Pictoris, 22 in Tucana-Horologium, 25 in Columba, 7 in Carina, 18 in Argus and 18 in AB Doradus, and 13 with an ambiguous membership. Our analysis also confirms the membership of 57 stars proposed in the literature. A subsample of 16 candidates was observed at 3 or more epochs, allowing us to discover 6 new spectroscopic binaries. The fraction of binaries in our sample is 25%, consistent with values in the literature. Of the stars in our sample, 20% show projected rotational velocities (vsin i) higher than 30 km s{sup –1} and therefore are considered as fast rotators. A parallax and other youth indicators are still needed to fully confirm the 130 highly probable candidates identified here as new bona fide members. Finally, based on the X-ray emission of bona fide and highly probable group members, we show that for low-mass stars in the 12-120 Myr age range, the X-ray luminosity is an excellent indicator of youth and better than the more traditionally used R {sub X} parameter, the ratio of X-ray to bolometric luminosity.

  13. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells.

    Science.gov (United States)

    Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

    2009-08-11

    The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFbeta, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP- cells. Remarkably, CD25+GARP- T cells expanded in culture contained 3-5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25-GARP- cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) -infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation.

  14. Nuclear hazard/fire hazard: an elusive and important linkage

    International Nuclear Information System (INIS)

    Mariani, L.P.

    1977-01-01

    The Brown's Ferry Fire signaled a yellow alert for nuclear safety related fire protection and showed that fire protection engineering must be regarded as a bona fide nuclear discipline. A single-failure design criteria violation resulted in fire damage to plant systems and plant instrumentation. Localized damage lead to significant consequences. Although the linkage between fire and nuclear hazard is termed subtle, effective standards and criteria development must be aimed to future plants. Combined fire protection and nuclear engineering inspections are planned

  15. A novel Erm monomethyltransferase in antibiotic-resistant isolates of Mannheimia haemolytica and Pasteurella multocida

    DEFF Research Database (Denmark)

    Desmolaize, Benoit; Rose, Simon; Warrass, Ralf

    2011-01-01

    Mannheimia haemolytica and Pasteurella multocida are aetiological agents commonly associated with respiratory tract infections in cattle. Recent isolates of these pathogens have been shown to be resistant to macrolides and other ribosome-targeting antibiotics. Direct analysis of the 23S r...... without any dimethyltransferase activity. Erm(42) is a novel addition to the Erm family: it is phylogenetically distant from the other Erm family members and it is unique in being a bona fide monomethyltransferase that is disseminated between bacterial pathogens....

  16. MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1

    DEFF Research Database (Denmark)

    Vishnubalaji, Radhakrishnan; Hamam, Rimi; Yue, Shijun

    2016-01-01

    gene targets for the miR-320 family. Inverse correlation between the expression of miR-320 members with SOX4, FOXM1, and FOXQ1 was observed in primary CRC patients' specimens, suggesting that these genes are likely bona fide targets for the miR-320 family. Interestingly, interrogation of the expression...... for the miR-320/SOX4/FOXM1/FOXQ1 axes in promoting CRC development and progression and suggest targeting those networks as potential therapeutic strategy for CRC....

  17. Nuclear power: Yes or no

    International Nuclear Information System (INIS)

    Strotmann, A.

    1979-01-01

    The author deals with the problems of nuclear energy by drawing many comparisons to other fields of engineering and causes of dangers and he does it in a way that the laity can understand him and is informed. Advocates and opponents would act bona fide: the ones were not in fear and would believe in the realization of nuclear energy; the others were in fear for themselves and their environment. So the layman too could either believe or not believe. (HSCH) [de

  18. Promising markers for the detection of premature senescence tumor cells induced by ionizing radiation: Cathepsin D and eukaryotic translation elongation factor 1

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hae-Ok; Han, Na-Kyung; Lee, Jae-Seon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-05-15

    Recently, it has been proved that induction of senescence could be a promising way of tumor treatment. Senescence was originally described in normal human cells undergoing a finite number of divisions before permanent growth arrest. It has now become regarded more broadly as a general biological program of terminal growth arrest. A variety of stresses such as ionizing radiation (IR), oxidative stress, oncogenic transformation, DNA damaging agents triggers stress-induced premature senescence, i.e. rapid and permanent cell growth arrest. Therefore, premature senescence is bona fide barrier to tumorigenesis and hallmark of premalignant tumors. However, there is lack of obvious markers for senescent tumor cells. To identify useful premature senescence markers for tumor cells, we monitored the changes of protein expression profile in IR-induced premature senescence MCF7 human breast cancer cells. We identified biomarkers which evidently changed their expression levels in ionizing radiation-induced senescenct tumor cells.

  19. Promising markers for the detection of premature senescence tumor cells induced by ionizing radiation: Cathepsin D and eukaryotic translation elongation factor 1

    International Nuclear Information System (INIS)

    Byun, Hae-Ok; Han, Na-Kyung; Lee, Jae-Seon

    2008-01-01

    Recently, it has been proved that induction of senescence could be a promising way of tumor treatment. Senescence was originally described in normal human cells undergoing a finite number of divisions before permanent growth arrest. It has now become regarded more broadly as a general biological program of terminal growth arrest. A variety of stresses such as ionizing radiation (IR), oxidative stress, oncogenic transformation, DNA damaging agents triggers stress-induced premature senescence, i.e. rapid and permanent cell growth arrest. Therefore, premature senescence is bona fide barrier to tumorigenesis and hallmark of premalignant tumors. However, there is lack of obvious markers for senescent tumor cells. To identify useful premature senescence markers for tumor cells, we monitored the changes of protein expression profile in IR-induced premature senescence MCF7 human breast cancer cells. We identified biomarkers which evidently changed their expression levels in ionizing radiation-induced senescenct tumor cells

  20. Restricted intra-embryonic origin of bona fide hematopoietic stem cells in the chicken

    NARCIS (Netherlands)

    Yvernogeau, Laurent; Robin, Catherine

    2017-01-01

    Hematopoietic stem cells (HSCs), which are responsible for blood cell production, are generated during embryonic development. Human and chicken embryos share features that position the chicken as a reliable and accessible alternative model to study developmental hematopoiesis. However, the existence

  1. IC 3639 - A new bona fide Compton thick AGN unveiled by NuSTAR

    DEFF Research Database (Denmark)

    Boorman, Peter G.; Gandhi, P.; Alexander, D.

    2016-01-01

    We analyse high-quality NuSTAR observations of the local (z = 0.011) Seyfert 2 active galactic nucleus (AGN) IC 3639, in conjunction with archival Suzaku and Chandra data. This provides the first broadband X-ray spectral analysis of the source, spanning nearly two decades in energy (0.5 -30 keV)....

  2. Keck Spectroscopy of Globular Clusters in the Elliptical Galaxy NGC 3610

    OpenAIRE

    Strader, Jay; Brodie, Jean P.; Schweizer, Francois; Larsen, Soeren S.; Seitzer, Patrick

    2002-01-01

    We present moderate-resolution Keck spectra of nine candidate globular clusters in the possible merger-remnant elliptical galaxy NGC 3610. Eight of the objects appear to be bona fide globular clusters of NGC 3610. We find that two of the clusters belong to an old metal-poor population, five to an old metal-rich population, and only one to an intermediate-age metal-rich population. The estimated age of the intermediate-age cluster is 1-5 Gyr, which is in agreement with earlier estimates of the...

  3. Comment on 'Correlative amplitude-operational phase entanglement embodied by the EPR-pair eigenstate ({eta})'[42.50.Dv Nonclassical states of the electromagnetic field, including entangled photon states; quantum state engineering and measurements; 03.65.Ud Entanglement and quantum nonlocality (e.g. EPR paradox, Bell's inequalities, GHZ states, etc.);

    Energy Technology Data Exchange (ETDEWEB)

    Luis, Alfredo [Departamento de Optica, Facultad de Ciencias Fisicas, Universidad Complutense, 28040 Madrid (Spain)

    2003-01-10

    In a recent paper in this journal Fan (Fan H 2002 J. Phys. A: Math. Gen.35 1007) discards the possibility of using a genuine phase-difference operator to investigate number-phase entanglement because of the lack of unitarity of the Susskind-Glogower phase operators. However, Fan overlooked the existence of a bona fide unitary operator exponential of the phase difference. Here we find the amplitude-phase maximally entangled states as the simultaneous eigenstates of the total number and the phase-difference operators. (comment)

  4. Comment on "Correlative amplitude-operational phase entanglement embodied by the EPR-pair eigenstate |eta) 42.50.Dv Nonclassical states of the electromagnetic field, including entangled photon states; quantum state engineering and measurements; 03.65.Ud Entanglement and quantum nonlocality (e.g. EPR paradox, Bell's inequalities, GHZ states, etc.)"

    CERN Document Server

    Luis, A

    2003-01-01

    In a recent paper in this journal Fan (Fan H 2002 J. Phys. A: Math. Gen.35 1007) discards the possibility of using a genuine phase-difference operator to investigate number-phase entanglement because of the lack of unitarity of the Susskind-Glogower phase operators. However, Fan overlooked the existence of a bona fide unitary operator exponential of the phase difference. Here we find the amplitude-phase maximally entangled states as the simultaneous eigenstates of the total number and the phase-difference operators. (comment)

  5. Joint Force Quarterly. Issue 62, 3rd Quarter, July 2011

    Science.gov (United States)

    2011-07-01

    Dividends: White Lobster on the Mosquito Coast,” Time, April 14, 2011. 10 “ El narcotráfico, una amenaza para FF.AA,” El Comercio , January 13, 2011...the same professional organization as bona fide member U.S . A rm y (M ic ha el L . C as te el ) Army senior NCO directs Soldiers from landing...generous appreciation of the valid ele - ments in the practices and institutions of other nations though they deviate from our own.21 And what of American

  6. Shakespeare in the Head for Health: A Reality Orientation Option for Alzheimer’s Worriers

    OpenAIRE

    Robert Oliphant

    2009-01-01

    By way of bona fides: As with many Americans, my own extended family has over the years given me plenty of direct contact with senile dementia, the general label for Alzheimer’s disease. In addition, a longish stay in a VA hospital (I’m a WWII vet) brought me into contact with the “reality orientation” anti-Alzheimer’s program developed some years back by Dr. Joseph Folsom, Dr. Arthur Cherkin, and others. On the basis of this experience I subsequently wrote a fictionalized case study about...

  7. Pengaruh Sosial Demografi terhadap Produktivitas Tenaga Kerja Perempuan Pengrajin Lontar di Desa Bona, Gianyar

    OpenAIRE

    Andari, Ni Putu Uti; Aswitari, Luh Putu

    2012-01-01

    Bali has many center of home industry. The development of home industry is expected to increase local entrepreneurs income and salary of employee. In palm leaf handicrafts, activities done by women. This study aims to determine the factors that impacted to women labour productivity. This research was conducted in the Bona Village Gianyar Regency. The number of sample is 93 which taken purposively. This study uses multiple linear regression analysis. Results showed that the factors that affect...

  8. A cost-effectiveness analysis of a proactive management strategy for the Sprint Fidelis recall: a probabilistic decision analysis model.

    Science.gov (United States)

    Bashir, Jamil; Cowan, Simone; Raymakers, Adam; Yamashita, Michael; Danter, Matthew; Krahn, Andrew; Lynd, Larry D

    2013-12-01

    The management of the recall is complicated by the competing risks of lead failure and complications that can occur with lead revision. Many of these patients are currently undergoing an elective generator change--an ideal time to consider lead revision. To determine the cost-effectiveness of a proactive management strategy for the Sprint Fidelis recall. We obtained detailed clinical outcomes and costing data from a retrospective analysis of 341 patients who received the Sprint Fidelis lead in British Columbia, where patients younger than 60 years were offered lead extraction when undergoing generator replacement. These population-based data were used to construct and populate a probabilistic Markov model in which a proactive management strategy was compared to a conservative strategy to determine the incremental cost per lead failure avoided. In our population, elective lead revisions were half the cost of emergent revisions and had a lower complication rate. In the model, the incremental cost-effectiveness ratio of proactive lead revision versus a recommended monitoring strategy was $12,779 per lead failure avoided. The proactive strategy resulted in 21 fewer failures per 100 patients treated and reduced the chance of an additional complication from an unexpected surgery. Cost-effectiveness analysis suggests that prospective lead revision should be considered when patients with a Sprint Fidelis lead present for pulse generator change. Elective revision of the lead is justified even when 25% of the population is operated on per year, and in some scenarios, it is both less costly and provides a better outcome. © 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.

  9. Spontaneous Vesicle Recycling in the Synaptic Bouton

    Directory of Open Access Journals (Sweden)

    Sven eTruckenbrodt

    2014-12-01

    Full Text Available The trigger for synaptic vesicle exocytosis is Ca2+, which enters the synaptic bouton following action potential stimulation. However, spontaneous release of neurotransmitter also occurs in the absence of stimulation in virtually all synaptic boutons. It has long been thought that this represents exocytosis driven by fluctuations in local Ca2+ levels. The vesicles responding to these fluctuations are thought to be the same ones that release upon stimulation, albeit potentially triggered by different Ca2+ sensors. This view has been challenged by several recent works, which have suggested that spontaneous release is driven by a separate pool of synaptic vesicles. Numerous articles appeared during the last few years in support of each of these hypotheses, and it has been challenging to bring them into accord. We speculate here on the origins of this controversy, and propose a solution that is related to developmental effects. Constitutive membrane traffic, needed for the biogenesis of vesicles and synapses, is responsible for high levels of spontaneous membrane fusion in young neurons, probably independent of Ca2+. The vesicles releasing spontaneously in such neurons are not related to other synaptic vesicle pools and may represent constitutively releasing vesicles (CRVs rather than bona fide synaptic vesicles. In mature neurons, constitutive traffic is much dampened, and the few remaining spontaneous release events probably represent bona fide spontaneously releasing synaptic vesicles (SRSVs responding to Ca2+ fluctuations, along with a handful of CRVs that participate in synaptic vesicle turnover.

  10. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: Implications for replication and genome packaging

    International Nuclear Information System (INIS)

    Chaturvedi, Sonali; Rao, A.L.N.

    2014-01-01

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein–protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. - Highlights: • YFP fusion proteins of BMV p1a and p2a are biologically active. • Self-interaction was observed for p1a, p2a and CP. • CP interacts with p2a but not p1a. • Majority of reconstituted YFP resulting from bona fide fusion protein partners localized on ER

  11. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: Implications for replication and genome packaging

    Energy Technology Data Exchange (ETDEWEB)

    Chaturvedi, Sonali; Rao, A.L.N., E-mail: arao@ucr.edu

    2014-09-15

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein–protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. - Highlights: • YFP fusion proteins of BMV p1a and p2a are biologically active. • Self-interaction was observed for p1a, p2a and CP. • CP interacts with p2a but not p1a. • Majority of reconstituted YFP resulting from bona fide fusion protein partners localized on ER.

  12. MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Mets, E; Van der Meulen, J; Van Peer, G; Boice, M; Mestdagh, P; Van de Walle, I; Lammens, T; Goossens, S; De Moerloose, B; Benoit, Y; Van Roy, N; Clappier, E; Poppe, B; Vandesompele, J; Wendel, H-G; Taghon, T; Rondou, P; Soulier, J; Van Vlierberghe, P; Speleman, F

    2015-04-01

    The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3'untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL.

  13. A Single Aplysia Neurotrophin Mediates Synaptic Facilitation via Differentially Processed Isoforms Secreted as Mature or Precursor Forms

    Science.gov (United States)

    Kassabov, Stefan R.; Choi, Yun-Beom; Karl, Kevin A.; Vishwasrao, Harshad D.; Bailey, Craig H.; Kandel, Eric R.

    2014-01-01

    Summary Neurotrophins control the development and adult plasticity of the vertebrate nervous system. Failure to identify invertebrate neurotrophin orthologs, however, has precluded studies in invertebrate models, limiting understanding of fundamental aspects of neurotrophin biology and function. We identified a neurotrophin (ApNT) and Trk receptor (ApTrk) in the mollusk Aplysia and find they play a central role in learning related synaptic plasticity. ApNT increases the magnitude and lowers the threshold for induction of long-term facilitation and initiates the growth of new synaptic varicosities at the monosynaptic connection between sensory and motor neurons of the gill-withdrawal reflex. Unlike vertebrate neurotrophins, ApNT has multiple coding exons and exerts distinct synaptic effects through differentially processed and secreted splice isoforms. Our findings demonstrate the existence of bona-fide neurotrophin signaling in invertebrates and reveal a novel, post-transcriptional mechanism, regulating neurotrophin processing and the release of pro- and mature neurotrophins which differentially modulate synaptic plasticity. PMID:23562154

  14. Records, record linkage, and the identification of long term environmental hazards

    Energy Technology Data Exchange (ETDEWEB)

    Acheson, E. D.

    1978-11-15

    Long-term effects of toxic substances in man which have been recognized so far have been noticed because they have involved gross relative risks, or bizarre effects, or have been stumbled upon by chance or because of special circumstances. These facts and some recent epidemiological evidence together suggest that a systematic approach with more precise methods and data would almost certainly reveal the effects of many more toxic substances, particularly in workers exposed in manufacturing industry. Additional ways are suggested in which record linkage techniques might be used to identify substances with long-term toxic effects. Obstacles to further progress in the field of monitoring for long-term hazards in man are: lack of a public policy dealing with confidentiality and informed consent in the use of identifiable personal records, which balances the needs of bona fide research workers with proper safeguards for the privacy of the individual, and lack of resources to improve the quality, accessibility and organization of the appropriate data. (PCS)

  15. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells

    Science.gov (United States)

    Kim, Kitai; Zhao, Rui; Doi, Akiko; Ng, Kitwa; Unternaehrer, Juli; Cahan, Patrick; Hongguang, Huo; Loh, Yuin-Han; Aryee, Martin J.; Lensch, M. William; Li, Hu; Collins, James J.; Feinberg, Andrew P.; Daley, George Q.

    2012-01-01

    We compared bona-fide human induced pluripotent stem cells (iPSC) derived from umbilical cord blood (CB) and neonatal keratinocytes (K). As a consequence of both incomplete erasure of tissue-specific methylation and aberrant de novo methylation, CB-iPSC and K-iPSC are distinct in genome-wide DNA methylation profiles and differentiation potential. Extended passage of some iPSC clones in culture didn't improve their epigenetic resemblance to ESC, implying that some human iPSC retain a residual “epigenetic memory” of their tissue of origin. PMID:22119740

  16. Archaeal origin of tubulin

    Directory of Open Access Journals (Sweden)

    Yutin Natalya

    2012-03-01

    Full Text Available Abstract Tubulins are a family of GTPases that are key components of the cytoskeleton in all eukaryotes and are distantly related to the FtsZ GTPase that is involved in cell division in most bacteria and many archaea. Among prokaryotes, bona fide tubulins have been identified only in bacteria of the genus Prosthecobacter. These bacterial tubulin genes appear to have been horizontally transferred from eukaryotes. Here we describe tubulins encoded in the genomes of thaumarchaeota of the genus Nitrosoarchaeum that we denote artubulins Phylogenetic analysis results are compatible with the origin of eukaryotic tubulins from artubulins. These findings expand the emerging picture of the origin of key components of eukaryotic functional systems from ancestral forms that are scattered among the extant archaea. Reviewers This article was reviewed by Gáspár Jékely and J. Peter Gogarten.

  17. Crystal structure of the C-terminal domain of the RAP74 subunit of human transcription factor IIF

    Energy Technology Data Exchange (ETDEWEB)

    Kamada, Katsuhiko; De Angelis, Jacqueline; Roeder, Robert G.; Burley, Stephen K. (Rockefeller)

    2012-12-13

    The x-ray structure of a C-terminal fragment of the RAP74 subunit of human transcription factor (TF) IIF has been determined at 1.02-{angstrom} resolution. The {alpha}/{beta} structure is strikingly similar to the globular domain of linker histone H5 and the DNA-binding domain of hepatocyte nuclear factor 3{gamma} (HNF-3{gamma}), making it a winged-helix protein. The surface electrostatic properties of this compact domain differ significantly from those of bona fide winged-helix transcription factors (HNF-3{gamma} and RFX1) and from the winged-helix domains found within the RAP30 subunit of TFIIF and the {beta} subunit of TFIIE. RAP74 has been shown to interact with the TFIIF-associated C-terminal domain phosphatase FCP1, and a putative phosphatase binding site has been identified within the RAP74 winged-helix domain.

  18. The BonaRes Centre - A virtual institute for soil research in the context of a sustainable bio-economy

    Science.gov (United States)

    Wollschläger, Ute; Helming, Katharina; Heinrich, Uwe; Bartke, Stephan; Kögel-Knabner, Ingrid; Russell, David; Eberhardt, Einar; Vogel, Hans-Jörg

    2016-04-01

    Fertile soils are central resources for the production of biomass and provision of food and energy. A growing world population and latest climate targets lead to an increasing demand for both, food and bio-energy, which require preserving and improving the long-term productivity of soils as a bio-economic resource. At the same time, other soil functions and ecosystem services need to be maintained. To render soil management sustainable, we need to establish a scientific knowledge base about complex soil system processes that allows for the development of model tools to quantitatively predict the impact of a multitude of management measures on soil functions. This, finally, will allow for the provision of site-specific options for sustainable soil management. To face this challenge, the German Federal Ministry of Education and Research recently launched the funding program "Soil as a Natural Resource for the Bio-Economy - BonaRes". In a joint effort, ten collaborative projects and the coordinating BonaRes Centre are engaged to close existing knowledge gaps for a profound and systemic understanding of soil functions and their sensitivity to soil management. This presentation provides an overview of the concept of the BonaRes Centre which is responsible for i) setting up a comprehensive data base for soil-related information, ii) the development of model tools aiming to estimate the impact of different management measures on soil functions, and iii) establishing a web-based portal providing decision support tools for a sustainable soil management. A specific focus of the presentation will be laid on the so-called "knowledge-portal" providing the infrastructure for a community effort towards a comprehensive meta-analysis on soil functions as a basis for future model developments.

  19. Improved decay rates for solutions for a multidimensional generalized Benjamin-Bona-Mahony equation

    KAUST Repository

    Said-Houari, Belkacem

    2014-01-01

    In this paper, we study the decay rates of solutions for the generalized Benjamin-Bona-Mahony equation in multi-dimensional space. For initial data in some L1-weighted spaces, we prove faster decay rates of the solutions. More precisely, using the Fourier transform and the energy method, we show the global existence and the convergence rates of the solutions under the smallness assumption on the initial data and we give better decay rates of the solutions. This result improves early works in J. Differential Equations 158(2) (1999), 314-340 and Nonlinear Anal. 75(7) (2012), 3385-3392. © 2014-IOS Press.

  20. BANYAN. XI. The BANYAN Σ Multivariate Bayesian Algorithm to Identify Members of Young Associations with 150 pc

    Science.gov (United States)

    Gagné, Jonathan; Mamajek, Eric E.; Malo, Lison; Riedel, Adric; Rodriguez, David; Lafrenière, David; Faherty, Jacqueline K.; Roy-Loubier, Olivier; Pueyo, Laurent; Robin, Annie C.; Doyon, René

    2018-03-01

    BANYAN Σ is a new Bayesian algorithm to identify members of young stellar associations within 150 pc of the Sun. It includes 27 young associations with ages in the range ∼1–800 Myr, modeled with multivariate Gaussians in six-dimensional (6D) XYZUVW space. It is the first such multi-association classification tool to include the nearest sub-groups of the Sco-Cen OB star-forming region, the IC 2602, IC 2391, Pleiades and Platais 8 clusters, and the ρ Ophiuchi, Corona Australis, and Taurus star formation regions. A model of field stars is built from a mixture of multivariate Gaussians based on the Besançon Galactic model. The algorithm can derive membership probabilities for objects with only sky coordinates and proper motion, but can also include parallax and radial velocity measurements, as well as spectrophotometric distance constraints from sequences in color–magnitude or spectral type–magnitude diagrams. BANYAN Σ benefits from an analytical solution to the Bayesian marginalization integrals over unknown radial velocities and distances that makes it more accurate and significantly faster than its predecessor BANYAN II. A contamination versus hit rate analysis is presented and demonstrates that BANYAN Σ achieves a better classification performance than other moving group tools available in the literature, especially in terms of cross-contamination between young associations. An updated list of bona fide members in the 27 young associations, augmented by the Gaia-DR1 release, as well as all parameters for the 6D multivariate Gaussian models for each association and the Galactic field neighborhood within 300 pc are presented. This new tool will make it possible to analyze large data sets such as the upcoming Gaia-DR2 to identify new young stars. IDL and Python versions of BANYAN Σ are made available with this publication, and a more limited online web tool is available at http://www.exoplanetes.umontreal.ca/banyan/banyansigma.php.

  1. Identifying novel genes in C. elegans using SAGE tags

    Directory of Open Access Journals (Sweden)

    Chen Nansheng

    2010-12-01

    Full Text Available Abstract Background Despite extensive efforts devoted to predicting protein-coding genes in genome sequences, many bona fide genes have not been found and many existing gene models are not accurate in all sequenced eukaryote genomes. This situation is partly explained by the fact that gene prediction programs have been developed based on our incomplete understanding of gene feature information such as splicing and promoter characteristics. Additionally, full-length cDNAs of many genes and their isoforms are hard to obtain due to their low level or rare expression. In order to obtain full-length sequences of all protein-coding genes, alternative approaches are required. Results In this project, we have developed a method of reconstructing full-length cDNA sequences based on short expressed sequence tags which is called sequence tag-based amplification of cDNA ends (STACE. Expressed tags are used as anchors for retrieving full-length transcripts in two rounds of PCR amplification. We have demonstrated the application of STACE in reconstructing full-length cDNA sequences using expressed tags mined in an array of serial analysis of gene expression (SAGE of C. elegans cDNA libraries. We have successfully applied STACE to recover sequence information for 12 genes, for two of which we found isoforms. STACE was used to successfully recover full-length cDNA sequences for seven of these genes. Conclusions The STACE method can be used to effectively reconstruct full-length cDNA sequences of genes that are under-represented in cDNA sequencing projects and have been missed by existing gene prediction methods, but their existence has been suggested by short sequence tags such as SAGE tags.

  2. La Graeca fides e la falsità moscovitanel discorso polacco premoderno. Storia di un topos ["Graeca fides and the Perfidy of the Muscovites in the Polish Early Modern Discourse. History of a Topos "

    Directory of Open Access Journals (Sweden)

    Roman Krzywy

    2015-12-01

    Full Text Available "The article discusses the usage of the classical topos Graeca fides to describe the citizens of the Grand Duchy of Moscow in early modern Polish literature (chronicles, diaries, journalistic writings, diplomatic reports etc.. This way of speaking was justified by the identification of the Eastern Orthodox Church with the Greek Byzantine Rite. The formula was used to deprecate Russians and became part of a negative stereotype. The author demonstrates, with diverse examples, how this formula became a constant topos in statements about a country considered hostile in Poland since the 16th century, and in which contexts it was developed."

  3. Do all psychological treatments really work the same in posttraumatic stress disorder?

    Science.gov (United States)

    Ehlers, Anke; Bisson, Jonathan; Clark, David M; Creamer, Mark; Pilling, Steven; Richards, David; Schnurr, Paula P; Turner, Stuart; Yule, William

    2010-03-01

    A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746-758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not focus on the patients' trauma memories or their meanings are either less effective or not yet sufficiently studied. International treatment guidelines therefore recommend trauma-focused psychological treatments as first-line treatments for PTSD. We examine possible reasons for the discrepant conclusions and argue that (1) the selection procedure of the available evidence used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis and conclusions fail to take into account the need to demonstrate that treatments for PTSD are more effective than natural recovery. Furthermore, significant increases in effect sizes of trauma-focused cognitive behavior therapies over the past two decades contradict the conclusion that content of treatment does not matter. To advance understanding of the optimal treatment for PTSD, we recommend further research into the active mechanisms of therapeutic change, including treatment elements commonly considered to be non-specific. We also recommend transparency in reporting exclusions in meta-analyses and suggest that bona fide treatments should be defined on empirical and theoretical grounds rather than by judgments of the investigators' intent. Copyright 2009 Elsevier Ltd. All rights reserved.

  4. Do all psychological treatments really work the same in posttraumatic stress disorder?

    Science.gov (United States)

    Ehlers, Anke; Bisson, Jonathan; Clark, David M.; Creamer, Mark; Pilling, Steven; Richards, David; Schnurr, Paula P.; Turner, Stuart; Yule, William

    2010-01-01

    A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746–758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not focus on the patients' trauma memories or their meanings are either less effective or not yet sufficiently studied. International treatment guidelines therefore recommend trauma-focused psychological treatments as first-line treatments for PTSD. We examine possible reasons for the discrepant conclusions and argue that (1) the selection procedure of the available evidence used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis and conclusions fail to take into account the need to demonstrate that treatments for PTSD are more effective than natural recovery. Furthermore, significant increases in effect sizes of trauma-focused cognitive behavior therapies over the past two decades contradict the conclusion that content of treatment does not matter. To advance understanding of the optimal treatment for PTSD, we recommend further research into the active mechanisms of therapeutic change, including treatment elements commonly considered to be non-specific. We also recommend transparency in reporting exclusions in meta-analyses and suggest that bona fide treatments should be defined on empirical and theoretical grounds rather than by judgments of the investigators' intent. PMID:20051310

  5. Examining the process of de novo gene birth: an educational primer on "integration of new genes into cellular networks, and their structural maturation".

    Science.gov (United States)

    Frietze, Seth; Leatherman, Judith

    2014-03-01

    New genes that arise from modification of the noncoding portion of a genome rather than being duplicated from parent genes are called de novo genes. These genes, identified by their brief evolution and lack of parent genes, provide an opportunity to study the timeframe in which emerging genes integrate into cellular networks, and how the characteristics of these genes change as they mature into bona fide genes. An article by G. Abrusán provides an opportunity to introduce students to fundamental concepts in evolutionary and comparative genetics and to provide a technical background by which to discuss systems biology approaches when studying the evolutionary process of gene birth. Basic background needed to understand the Abrusán study and details on comparative genomic concepts tailored for a classroom discussion are provided, including discussion questions and a supplemental exercise on navigating a genome database.

  6. Plasma effects on subcellular structures

    International Nuclear Information System (INIS)

    Gweon, Bomi; Kim, Dan Bee; Jung, Heesoo; Choe, Wonho; Kim, Daeyeon; Shin, Jennifer H.

    2010-01-01

    Atmospheric pressure helium plasma treated human hepatocytes exhibit distinctive zones of necrotic and live cells separated by a void. We propose that plasma induced necrosis is attributed to plasma species such as oxygen radicals, charged particles, metastables and/or severe disruption of charged cytoskeletal proteins. Interestingly, uncharged cytoskeletal intermediate filaments are only minimally disturbed by plasma, elucidating the possibility of plasma induced electrostatic effects selectively destroying charged proteins. These bona fide plasma effects, which inflict alterations in specific subcellular structures leading to necrosis and cellular detachment, were not observed by application of helium flow or electric field alone.

  7. The phase diagram of high temperature QCD with three flavors of improved staggered quarks

    International Nuclear Information System (INIS)

    Bernard, C.; Burch, T.; DeTar, C.E.; Gottlieb, Steven; Gregory, E.B.; Heller, U.M.; Hetrick, J.E.; Sugar, R.L.; Toussaint, D.

    2004-01-01

    We report on progress in our study of high temperature QCD with three flavors of improved staggered quarks. Simulations are being carried out with three degenerate quarks with masses less than or equal to the strange quark mass, m s , and with degenerate up and down quarks with masses in the range 0.1 m s ≤ m u,d ≤ 0.6 m s , and the strange quark mass fixed near its physical value. For the quark masses studied to date we find rapid crossovers, which sharpen as the quark mass is reduced, rather than bona fide phase transitions

  8. In silico prediction of xenobiotic metabolism in humans

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Fangping [Los Alamos National Laboratory

    2009-01-01

    Xenobiotic metabolism in humans is catalyzed by a few enzymes with broad substrate specificities, which provide the overall broad chemical specificity for nearly all xenobiotics that humans encounter. Xenobiotic metabolism are classified into functional group biotransformations. Based on bona fide reactions and negative examples for each reaction class, support vector machine (SVM) classifiers are built. The input to SVM is a set of atomic and molecular features to define the electrostatic, steric, energetic, geometrical and topological environment of the atoms in the reaction center under the molecule. Results show that the overall sensitivity and specificity of classifiers is around 87%.

  9. TAF9b (Formerly TAF9L) Is a Bona Fide TAF That Has Unique and Overlapping Roles with TAF9

    OpenAIRE

    Frontini, Mattia; Soutoglou, Evi; Argentini, Manuela; Bole-Feysot, Christine; Jost, Bernard; Scheer, Elisabeth; Tora, Làszlò

    2005-01-01

    TFIID plays a key role in transcription initiation of RNA polymerase II preinitiation complex assembly. TFIID is comprised of the TATA box binding protein (TBP) and 14 TBP-associated factors (TAFs). A second set of transcriptional regulatory multiprotein complexes containing TAFs has been described (called SAGA, TFTC, STAGA, and PCAF/GCN5). Using matrix-assisted laser desorption ionization mass spectrometry, we identified a novel TFTC subunit, human TAF9Like, encoded by a TAF9 paralogue gene....

  10. A protein interaction mechanism for suppressing the mechanosensitive Piezo channels.

    Science.gov (United States)

    Zhang, Tingxin; Chi, Shaopeng; Jiang, Fan; Zhao, Qiancheng; Xiao, Bailong

    2017-11-27

    Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca 2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins. SERCA2 strategically suppresses Piezo1 via acting on a 14-residue-constituted intracellular linker connecting the pore-module and mechanotransduction-module. Mutating the linker impairs mechanogating and SERCA2-mediated modulation of Piezo1. Furthermore, the synthetic linker-peptide disrupts the modulatory effects of SERCA2, demonstrating the key role of the linker in mechanogating and regulation. Importantly, the SERCA2-mediated regulation affects Piezo1-dependent migration of endothelial cells. Collectively, we identify SERCA-mediated regulation of Piezos and the functional significance of the linker, providing important insights into the mechanogating and regulation mechanisms of Piezo channels.

  11. Tug of War between Survival and Death: Exploring ATM Function in Cancer

    Science.gov (United States)

    Stagni, Venturina; Oropallo, Veronica; Fianco, Giulia; Antonelli, Martina; Cinà, Irene; Barilà, Daniela

    2014-01-01

    Ataxia-telangiectasia mutated (ATM) kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR). The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer. PMID:24681585

  12. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Science.gov (United States)

    Jurgeit, Andreas; McDowell, Robert; Moese, Stefan; Meldrum, Eric; Schwendener, Reto; Greber, Urs F

    2012-01-01

    Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

  13. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Directory of Open Access Journals (Sweden)

    Andreas Jurgeit

    Full Text Available Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

  14. Tug of War between Survival and Death: Exploring ATM Function in Cancer

    Directory of Open Access Journals (Sweden)

    Venturina Stagni

    2014-03-01

    Full Text Available Ataxia-telangiectasia mutated (ATM kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR. The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer.

  15. Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Courtney M. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Hu, Jianxin [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Thomas, Reuben [Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Gainous, T. Blair [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Celona, Barbara [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Sinha, Tanvi [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Dickel, Diane E. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; Heidt, Analeah B. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Xu, Shan-Mei [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Bruneau, Benoit G. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Pollard, Katherine S. [Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Pennacchio, Len A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; Black, Brian L. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Univ. of California, San Francisco, CA (United States). Dept. of

    2017-03-28

    Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here in this paper, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by the SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo. Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.

  16. Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs

    DEFF Research Database (Denmark)

    Jacobsen, Mette Juul; Cirera Salicio, Susanna; Joller, David

    2011-01-01

    by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes. FINDINGS: The coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence...... polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac...... of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might...

  17. Phosphorylation of ARD1 by IKKβ contributes to its destabilization and degradation

    International Nuclear Information System (INIS)

    Kuo, Hsu-Ping; Lee, Dung-Fang; Xia, Weiya; Lai, Chien-Chen; Li, Long-Yuan; Hung, Mien-Chie

    2009-01-01

    IκB kinase β (IKKβ), a major kinase downstream of various proinflammatory signals, mediates multiple cellular functions through phosphorylation and regulation of its substrates. On the basis of protein sequence analysis, we identified arrest-defective protein 1 (ARD1), a protein involved in apoptosis and cell proliferation processes in many human cancer cells, as a new IKKβ substrate. We provided evidence showing that ARD1 is indeed a bona fide substrate of IKKβ. IKKβ physically associated with ARD1 and phosphorylated it at Ser209. Phosphorylation by IKKβ destabilized ARD1 and induced its proteasome-mediated degradation. Impaired growth suppression was observed in ARD1 phosphorylation-mimic mutant (S209E)-transfected cells as compared with ARD1 non-phosphorylatable mutant (S209A)-transfected cells. Our findings of molecular interactions between ARD1 and IKKβ may enable further understanding of the upstream regulation mechanisms of ARD1 and of the diverse functions of IKKβ.

  18. Epithelial cell proliferation arrest induced by lactate and acetate from Lactobacillus casei and Bifidobacterium breve.

    Directory of Open Access Journals (Sweden)

    Takahiro Matsuki

    Full Text Available In an attempt to identify and characterize how symbiotic bacteria of the gut microbiota affect the molecular and cellular mechanisms of epithelial homeostasis, intestinal epithelial cells were co-cultured with either Lactobacillus or Bifidobacterium as bona fide symbionts to examine potential gene modulations. In addition to genes involved in the innate immune response, genes encoding check-point molecules controlling the cell cycle were among the most modulated in the course of these interactions. In the m-ICcl2 murine cell line, genes encoding cyclin E1 and cyclin D1 were strongly down regulated by L. casei and B. breve respectively. Cell proliferation arrest was accordingly confirmed. Short chain fatty acids (SCFA were the effectors of this modulation, alone or in conjunction with the acidic pH they generated. These results demonstrate that the production of SCFAs, a characteristic of these symbiotic microorganisms, is potentially an essential regulatory effector of epithelial proliferation in the gut.

  19. Nucleon form factors and hidden symmetry in holographic QCD

    International Nuclear Information System (INIS)

    Hong, D.K.; Rho, M.; Yee, H.-U.; Yi, P.

    2007-10-01

    The vector dominance of the electromagnetic (EM) form factors both for mesons and baryons arises naturally in holographic QCD, where both the number of colors and the 't Hooft coupling are taken to be very large, offering a bona-fide derivation of the notion of vector dominance. The crucial ingredient for this is the infinite tower of vector mesons in the approximations made which share features that are characteristic of the quenched approximation in lattice QCD. We approximate the infinite sum by contributions from the lowest four vector mesons of the tower which turn out to saturate the charge and magnetic moment sum rules within a few % and compute them totally free of unknown parameters for momentum transfers Q 2 approx.= 1 GeV 2 . We identify certain observables that can be reliably computed within the approximations and others that are not, and discuss how the improvement of the latter can enable one to bring holographic QCD closer to QCD proper. (author)

  20. Ion Permeation and Mechanotransduction Mechanisms of Mechanosensitive Piezo Channels.

    Science.gov (United States)

    Zhao, Qiancheng; Wu, Kun; Geng, Jie; Chi, Shaopeng; Wang, Yanfeng; Zhi, Peng; Zhang, Mingmin; Xiao, Bailong

    2016-03-16

    Piezo proteins have been proposed as the long-sought-after mechanosensitive cation channels in mammals that play critical roles in various mechanotransduction processes. However, the molecular bases that underlie their ion permeation and mechanotransduction have remained functionally undefined. Here we report our finding of the miniature pore-forming module of Piezo1 that resembles the pore architecture of other trimeric channels and encodes the essential pore properties. We further identified specific residues within the pore module that determine unitary conductance, pore blockage and ion selectivity for divalent and monovalent cations and anions. The non-pore-containing region of Piezo1 confers mechanosensitivity to mechano-insensitive trimeric acid-sensing ion channels, demonstrating that Piezo1 channels possess intrinsic mechanotransduction modules separate from their pore modules. In conclusion, this is the first report on the bona fide pore module and mechanotransduction components of Piezo channels, which define their ion-conducting properties and gating by mechanical stimuli, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Confirming the least massive members of the Pleiades star cluster

    Science.gov (United States)

    Zapatero Osorio, M. R.; Béjar, V. J. S.; Lodieu, N.; Manjavacas, E.

    2018-03-01

    We present optical photometry (i and Z band) and low-resolution spectroscopy (640-1015 nm) of very faint candidate members (J = 20.2-21.2 mag) of the Pleiades star cluster (120 Myr). The main goal is to address their cluster membership via photometric, astrometric, and spectroscopic studies, and to determine the properties of the least massive population of the cluster through the comparison of the data with younger and older spectral counterparts and state-of-the art model atmospheres. We confirm three bona fide Pleiades members that have extremely red optical and infrared colours, effective temperatures of ≈1150 and ≈1350 K, and masses in the interval 11-20 MJup, and one additional likely member that shares the same motion as the cluster but does not appear to be as red as the other members with similar brightness. This latter object requires further near-infrared spectroscopy to fully address its membership in the Pleiades. The optical spectra of two bona fide members were classified as L6-L7 and show features of K I, a tentative detection of Cs I, hydrides, and water vapour with an intensity similar to high-gravity dwarfs of related classification despite their young age. The properties of the Pleiades L6-L7 members clearly indicate that very red colours of L dwarfs are not a direct evidence of ages younger than ≈100 Myr. We also report on the determination of the bolometric corrections for the coolest Pleiades members. These data can be used to interpret the observations of the atmospheres of exoplanets orbiting stars.

  2. Catalytic activity of a novel serine/threonine protein phosphatase PP5 from Leishmania major

    Directory of Open Access Journals (Sweden)

    Norris-Mullins Brianna

    2014-01-01

    Full Text Available Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania. Our knowledge of protein phosphatases (PPs and their implication in signaling events is very limited. Here we report the expression, characterization and mutagenesis analysis of a novel protein phosphatase 5 (PP5 in Leishmania major. Recombinant PP5 is a bona fide phosphatase and is enzymatically active. Site-directed mutagenesis revealed auto-inhibitory roles of the N-terminal region. This is a rational first approach to understand the role of PP5 in the biology of the parasite better as well as its potential future applicability to anti-parasitic intervention.

  3. Functions of the Drosophila JAK-STAT pathway

    Science.gov (United States)

    Amoyel, Marc; Bach, Erika A.

    2012-01-01

    JAK-STAT signaling has been proposed to act in numerous stem cells in a variety of organisms. Here we provide an overview of its roles in three well characterized stem cell populations in Drosophila, in the intestine, lymph gland and testis. In flies, there is a single JAK and a single STAT, which has made the genetic dissection of pathway function considerably easier and facilitated the analysis of communication between stem cells, their niches and offspring. Studies in flies have revealed roles for this pathway as diverse as regulating bona fide intrinsic self-renewal, integrating response to environmental cues that control quiescence and promoting mitogenic responses to stress. PMID:24058767

  4. The Role of PAS Kinase in PASsing the Glucose Signal

    Directory of Open Access Journals (Sweden)

    Julianne H. Grose

    2010-06-01

    Full Text Available PAS kinase is an evolutionarily conserved nutrient responsive protein kinase that regulates glucose homeostasis. Mammalian PAS kinase is activated by glucose in pancreatic beta cells, and knockout mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet. Yeast PAS kinase is regulated by both carbon source and cell integrity stress and stimulates the partitioning of glucose toward structural carbohydrate biosynthesis. In our current model for PAS kinase regulation, a small molecule metabolite binds the sensory PAS domain and activates the enzyme. Although bona fide PAS kinase substrates are scarce, in vitro substrate searches provide putative targets for exploration.

  5. What should we mean by empirical validation in hypnotherapy: evidence-based practice in clinical hypnosis.

    Science.gov (United States)

    Alladin, Assen; Sabatini, Linda; Amundson, Jon K

    2007-04-01

    This paper briefly surveys the trend of and controversy surrounding empirical validation in psychotherapy. Empirical validation of hypnotherapy has paralleled the practice of validation in psychotherapy and the professionalization of clinical psychology, in general. This evolution in determining what counts as evidence for bona fide clinical practice has gone from theory-driven clinical approaches in the 1960s and 1970s through critical attempts at categorization of empirically supported therapies in the 1990s on to the concept of evidence-based practice in 2006. Implications of this progression in professional psychology are discussed in the light of hypnosis's current quest for validation and empirical accreditation.

  6. A CENSUS OF ROTATION AND VARIABILITY IN L1495: A UNIFORM ANALYSIS OF TRANS-ATLANTIC EXOPLANET SURVEY LIGHT CURVES FOR PRE-MAIN-SEQUENCE STARS IN TAURUS

    International Nuclear Information System (INIS)

    Xiao Hongyu; Covey, Kevin R.; Lloyd, James P.; Rebull, Luisa; Charbonneau, David; Mandushev, Georgi; O'Donovan, Francis; Slesnick, Catherine

    2012-01-01

    We analyze light curves obtained by the Trans-atlantic Exoplanet Survey (TrES) for a field centered on the L1495 dark cloud in Taurus. The Spitzer Taurus Legacy Survey catalog identifies 179 bona fide Taurus members within the TrES field; 48 of the known Taurus members are detected by TrES, as well as 26 candidate members identified by the Spitzer Legacy team. We quantify the variability of each star in our sample using the ratio of the standard deviation of the original light curve (σ orig. ) to the standard deviation of a light curve that has been smoothed by 9 or 1001 epochs (σ 9 and σ 1001 , respectively). Known Taurus members typically demonstrate (σ orig. /σ 9 ) orig. /σ 1001 ) orig. /σ 9 ) ∼ 3.0 and (σ orig. /σ 1001 ) ∼ 10, as expected for light curves dominated by unstructured white noise. Of the 74 Taurus members/candidates with TrES light curves, we detect significant variability in 49 sources. Adapting a quantitative metric originally developed to assess the reliability of transit detections, we measure the amount of red and white noise in each light curve and identify 18 known or candidate Taurus members with highly significant period measurements. These appear to be the first periods measured for four of these sources (HD 282276, CX Tau, FP Tau, TrES J042423+265008), and in two other cases, the first non-aliased periods (LkCa 21 and DK Tau AB). For the remainder, the TrES measurements typically agree very well (δP < 1%) with previously reported values. Including periods measured at lower confidence for 15 additional sources, we report periods for 11 objects where no previous periods were found, including 8 confirmed Taurus members. We also identify 10 of the 26 candidate Taurus members that demonstrate variability levels consistent with being bona fide T Tauri stars. A Kolomgorov-Smirnov (K-S) test confirms that these new periods confirm the distinction between the rotation period distributions of stars with and without circumstellar

  7. The Stem Cell Marker Lgr5 Defines a Subset of Postmitotic Neurons in the Olfactory Bulb.

    Science.gov (United States)

    Yu, Yiqun; Moberly, Andrew H; Bhattarai, Janardhan P; Duan, Chen; Zheng, Qian; Li, Fangqi; Huang, Hugh; Olson, William; Luo, Wenqin; Wen, Tieqiao; Yu, Hongmeng; Ma, Minghong

    2017-09-27

    Lgr5, leucine-rich repeat-containing G-protein coupled receptor 5, is a bona fide biomarker for stem cells in multiple tissues. Lgr5 is also expressed in the brain, but the identities and properties of these Lgr5 + cells are still elusive. Using an Lgr5-EGFP reporter mouse line, we found that, from early development to adulthood, Lgr5 is highly expressed in the olfactory bulb (OB), an area with ongoing neurogenesis. Immunostaining with stem cell, glial, and neuronal markers reveals that Lgr5 does not label stem cells in the OB but instead labels a heterogeneous population of neurons with preference in certain subtypes. Patch-clamp recordings in OB slices reveal that Lgr5-EGFP + cells fire action potentials and display spontaneous excitatory postsynaptic events, indicating that these neurons are integrated into OB circuits. Interestingly, R-spondin 3, a potential ligand of Lgr5, is also expressed in the adult OB. Collectively, our data indicate that Lgr5-expressing cells in the OB are fully differentiated neurons and imply distinct roles of Lgr5 and its ligand in postmitotic cells. SIGNIFICANCE STATEMENT Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) is a bona fide stem cell marker in many body organs. Here we report that Lgr5 is also highly expressed in the olfactory bulb (OB), the first relay station in the brain for processing odor information and one of the few neural structures that undergo continuous neurogenesis. Surprisingly, Lgr5 is not expressed in the OB stem cells, but instead in a few subtypes of terminally differentiated neurons, which are incorporated into the OB circuit. This study reveals that Lgr5 + cells in the brain represent a nonstem cell lineage, implying distinct roles of Lgr5 in postmitotic neurons. Copyright © 2017 the authors 0270-6474/17/379403-12$15.00/0.

  8. A common pathway for charge transport through voltage-sensing domains.

    Science.gov (United States)

    Chanda, Baron; Bezanilla, Francisco

    2008-02-07

    Voltage-gated ion channels derive their voltage sensitivity from the movement of specific charged residues in response to a change in transmembrane potential. Several studies on mechanisms of voltage sensing in ion channels support the idea that these gating charges move through a well-defined permeation pathway. This gating pathway in a voltage-gated ion channel can also be mutated to transport free cations, including protons. The recent discovery of proton channels with sequence homology to the voltage-sensing domains suggests that evolution has perhaps exploited the same gating pathway to generate a bona fide voltage-dependent proton transporter. Here we will discuss implications of these findings on the mechanisms underlying charge (and ion) transport by voltage-sensing domains.

  9. Regulation of the Bioavailability of TGF-β and TGF-β-Related Proteins

    Science.gov (United States)

    Robertson, Ian B.; Rifkin, Daniel B.

    2016-01-01

    The bioavailability of members of the transforming growth factor β (TGF-β) family is controlled by a number of mechanisms. Bona fide TGF-β is sequestered into the matrix in a latent state and must be activated before it can bind to its receptors. Here, we review the molecules and mechanisms that regulate the bioavailability of TGF-β and compare these mechanisms with those used to regulate other TGF-β family members. We also assess the physiological significance of various latent TGF-β activators, as well as other extracellular modulators of TGF-β family signaling, by examining the available in vivo data from knockout mouse models and other biological systems. PMID:27252363

  10. Limitations of the government budget constraint: Users vs. issuers of the currency

    Directory of Open Access Journals (Sweden)

    Kelton Stephanie

    2011-01-01

    Full Text Available The financial crisis and ensuing economic meltdown has led to sharp increases in the deficits and debt levels of many advanced economies. The run-up in public sector indebtedness helped to restore private sector balance sheets, laying the foundation for economic recovery in these regions. But the so-called “sovereign” debt crisis in the Eurozone has undermined the fiscal resolve that has, thus far, kept truly sovereign governments from slipping into a bona fide depression. Fearful of becoming the next Greece, governments that could allow an unlimited fiscal adjustment to restore full employment, are methodically weakening their fiscal support mechanisms and setting themselves on a path to becoming the next Japan.

  11. A Gaia DR2 Confirmation that 2MASS J12074836–3900043 is a Member of the TW HYA Association

    Science.gov (United States)

    Gagné, Jonathan; Gonzales, Eileen C.; Faherty, Jacqueline K.

    2018-05-01

    We use new data from Gaia DR2 to confirm that the young L1 $\\gamma$ candidate member of the TW Hya association (TWA) is now a bona fide member with a model-dependent mass estimate of ~15 $M_{Jup}$. The ambiguous M9 $\\gamma$ candidate member 2MASS J12474428---3816464 also gets a higher Bayesian membership probability for TWA membership as a result of Gaia DR2 data and a new radial velocity measurement, but it remains unclear whether it is a true member of TWA or if it is an unrelated young interloper, because it is separated by 4.6 km/s from the locus of TWA members in UVW space.

  12. Theologies, ideologies and evolutionary biology.

    Science.gov (United States)

    Scudo, Francesco M

    2010-01-01

    Since a century evolution has mostly been interpreted by two simple, "opposite" kinds of "theories" — i.e. as due either to fitness differences among genotypes or to some other simple mechanism — while bona fide, more complex theories were less popular throughout. In particular by far the most complete theories ever produced were suddenly, almost universally abandoned just after World War II, though not as a consequence of major breakthroughs. The causes of this situation are examined by analogy with much earlier developments and their demise by Cartesianism. The down to earth solutions these "complete" theories provide to the problems of "speciation" and the origins of cells are contrasted with the "miraculous" approaches by systemic neo-Darwinists.

  13. Dispute resolutions from the field of economy via contracting competence through Arbitration in the republic of Kosovo

    Directory of Open Access Journals (Sweden)

    Krenare Vokshi

    2016-03-01

    Full Text Available In terms of globalized economy, the integration trade cooperation process between state institutions, international organizations, and business entities are being followed by a dynamism regarding creation, modification, and termination of relations through the contracts which are now more standardized. Good business practices offered a good experience in terms of solving disputes on business transactions, local or international, security, efficiency and speed of trailing are enforced only if this issue is foreseen and contracted with special courts of arbitration. The role of arbitration on international trade is not only the solution of disputes. The arbitration has as its mission before the building of a fair trade and legal practice such as bona fides.

  14. Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics.

    Science.gov (United States)

    Garg, Abhishek D; More, Sanket; Rufo, Nicole; Mece, Odeta; Sassano, Maria Livia; Agostinis, Patrizia; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2017-01-01

    The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

  15. Integrin-linked kinase: a Scaffold protein unique among its ilk.

    Science.gov (United States)

    Dagnino, Lina

    2011-06-01

    Integrin-linked kinase (ILK) is a scaffolding protein with central roles in tissue development and homeostasis. Much debate has focused on whether ILK is a bona fide or a pseudo- kinase. This aspect of ILK function has been complicated by the large volumes of conflicting observations obtained from a wide variety of experimental approaches, from in vitro models, to analyses in invertebrates and in mammals. Key findings in support or against the notion that ILK is catalytically active are summarized. The importance of ILK as an adaptor protein is well established, and defining its role as a signaling hub will be the next key step to understand its distinct biological roles across tissues and species.

  16. The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology

    Science.gov (United States)

    Mallet, François; Bouton, Olivier; Prudhomme, Sarah; Cheynet, Valérie; Oriol, Guy; Bonnaud, Bertrand; Lucotte, Gérard; Duret, Laurent; Mandrand, Bernard

    2004-01-01

    The definitive demonstration of a role for a recently acquired gene is a difficult task, requiring exhaustive genetic investigations and functional analysis. The situation is indeed much more complicated when facing multicopy gene families, because most or portions of the gene are conserved among the hundred copies of the family. This is the case for the ERVWE1 locus of the human endogenous retrovirus W family (HERV-W), which encodes an envelope glycoprotein (syncytin) likely involved in trophoblast differentiation. Here we describe, in 155 individuals, the positional conservation of this locus and the preservation of the envelope ORF. Sequencing of the critical elements of the ERVWE1 provirus showed a striking conservation among the 48 alleles of 24 individuals, including the LTR elements involved in the transcriptional machinery, the splice sites involved in the maturation of subgenomic Env mRNA, and the Env ORF. The functionality and tissue specificity of the 5′ LTR were demonstrated, as well as the fusogenic activity of the envelope polymorphic variants. Such functions were also shown to be preserved in the orthologous loci isolated from chimpanzee, gorilla, orangutan, and gibbon. This functional preservation among humans and during evolution strongly argued for the involvement of this recently acquired retroviral envelope glycoprotein in hominoid placental physiology. PMID:14757826

  17. In silico ionomics segregates parasitic from free-living eukaryotes.

    Science.gov (United States)

    Greganova, Eva; Steinmann, Michael; Mäser, Pascal; Fankhauser, Niklaus

    2013-01-01

    Ion transporters are fundamental to life. Due to their ancient origin and conservation in sequence, ion transporters are also particularly well suited for comparative genomics of distantly related species. Here, we perform genome-wide ion transporter profiling as a basis for comparative genomics of eukaryotes. From a given predicted proteome, we identify all bona fide ion channels, ion porters, and ion pumps. Concentrating on unicellular eukaryotes (n = 37), we demonstrate that clustering of species according to their repertoire of ion transporters segregates obligate endoparasites (n = 23) on the one hand, from free-living species and facultative parasites (n = 14) on the other hand. This surprising finding indicates strong convergent evolution of the parasites regarding the acquisition and homeostasis of inorganic ions. Random forest classification identifies transporters of ammonia, plus transporters of iron and other transition metals, as the most informative for distinguishing the obligate parasites. Thus, in silico ionomics further underscores the importance of iron in infection biology and suggests access to host sources of nitrogen and transition metals to be selective forces in the evolution of parasitism. This finding is in agreement with the phenomenon of iron withholding as a primordial antimicrobial strategy of infected mammals.

  18. A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence.

    Science.gov (United States)

    de Souza, Camila Ferreira; Sabedot, Thais S; Malta, Tathiane M; Stetson, Lindsay; Morozova, Olena; Sokolov, Artem; Laird, Peter W; Wiznerowicz, Maciej; Iavarone, Antonio; Snyder, James; deCarvalho, Ana; Sanborn, Zachary; McDonald, Kerrie L; Friedman, William A; Tirapelli, Daniela; Poisson, Laila; Mikkelsen, Tom; Carlotti, Carlos G; Kalkanis, Steven; Zenklusen, Jean; Salama, Sofie R; Barnholtz-Sloan, Jill S; Noushmehr, Houtan

    2018-04-10

    Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal analysis of diffuse gliomas from 77 patients (200 tumors) to enlighten the epigenome-based malignant transformation of initially lower-grade gliomas. Intra-subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify predictive biomarkers for assessing the risk of malignant recurrence at early stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic phenotype, and genomic instability. Molecular abnormalities of longitudinal G-CIMP offer possibilities to defy glioblastoma progression. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Probing the Topology of Density Matrices

    Directory of Open Access Journals (Sweden)

    Charles-Edouard Bardyn

    2018-02-01

    Full Text Available The mixedness of a quantum state is usually seen as an adversary to topological quantization of observables. For example, exact quantization of the charge transported in a so-called Thouless adiabatic pump is lifted at any finite temperature in symmetry-protected topological insulators. Here, we show that certain directly observable many-body correlators preserve the integrity of topological invariants for mixed Gaussian quantum states in one dimension. Our approach relies on the expectation value of the many-body momentum-translation operator and leads to a physical observable—the “ensemble geometric phase” (EGP—which represents a bona fide geometric phase for mixed quantum states, in the thermodynamic limit. In cyclic protocols, the EGP provides a topologically quantized observable that detects encircled spectral singularities (“purity-gap” closing points of density matrices. While we identify the many-body nature of the EGP as a key ingredient, we propose a conceptually simple, interferometric setup to directly measure the latter in experiments with mesoscopic ensembles of ultracold atoms.

  20. Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae.

    Science.gov (United States)

    Uthe, Henriette; Vanselow, Jens T; Schlosser, Andreas

    2017-02-27

    Here we present the most comprehensive analysis of the yeast Mediator complex interactome to date. Particularly gentle cell lysis and co-immunopurification conditions allowed us to preserve even transient protein-protein interactions and to comprehensively probe the molecular environment of the Mediator complex in the cell. Metabolic 15 N-labeling thereby enabled stringent discrimination between bona fide interaction partners and nonspecifically captured proteins. Our data indicates a functional role for Mediator beyond transcription initiation. We identified a large number of Mediator-interacting proteins and protein complexes, such as RNA polymerase II, general transcription factors, a large number of transcriptional activators, the SAGA complex, chromatin remodeling complexes, histone chaperones, highly acetylated histones, as well as proteins playing a role in co-transcriptional processes, such as splicing, mRNA decapping and mRNA decay. Moreover, our data provides clear evidence, that the Mediator complex interacts not only with RNA polymerase II, but also with RNA polymerases I and III, and indicates a functional role of the Mediator complex in rRNA processing and ribosome biogenesis.

  1. Tissue-specific RNA expression marks distant-acting developmental enhancers.

    Directory of Open Access Journals (Sweden)

    Han Wu

    2014-09-01

    Full Text Available Short non-coding transcripts can be transcribed from distant-acting transcriptional enhancer loci, but the prevalence of such enhancer RNAs (eRNAs within the transcriptome, and the association of eRNA expression with tissue-specific enhancer activity in vivo remain poorly understood. Here, we investigated the expression dynamics of tissue-specific non-coding RNAs in embryonic mouse tissues via deep RNA sequencing. Overall, approximately 80% of validated in vivo enhancers show tissue-specific RNA expression that correlates with tissue-specific enhancer activity. Globally, we identified thousands of tissue-specifically transcribed non-coding regions (TSTRs displaying various genomic hallmarks of bona fide enhancers. In transgenic mouse reporter assays, over half of tested TSTRs functioned as enhancers with reproducible activity in the predicted tissue. Together, our results demonstrate that tissue-specific eRNA expression is a common feature of in vivo enhancers, as well as a major source of extragenic transcription, and that eRNA expression signatures can be used to predict tissue-specific enhancers independent of known epigenomic enhancer marks.

  2. New N-Acetyltransferase Fold in the Structure and Mechanism of the Phosphonate Biosynthetic Enzyme FrbF

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Brian; Cobb, Ryan E.; DeSieno, Matthew A.; Zhao, Huimin; Nair, Satish K. (UIUC)

    2015-10-15

    The enzyme FrbF from Streptomyces rubellomurinus has attracted significant attention due to its role in the biosynthesis of the antimalarial phosphonate FR-900098. The enzyme catalyzes acetyl transfer onto the hydroxamate of the FR-900098 precursors cytidine 5'-monophosphate-3-aminopropylphosphonate and cytidine 5'-monophosphate-N-hydroxy-3-aminopropylphosphonate. Despite the established function as a bona fide N-acetyltransferase, FrbF shows no sequence similarity to any member of the GCN5-like N-acetyltransferase (GNAT) superfamily. Here, we present the 2.0 {angstrom} resolution crystal structure of FrbF in complex with acetyl-CoA, which demonstrates a unique architecture that is distinct from those of canonical GNAT-like acetyltransferases. We also utilized the co-crystal structure to guide structure-function studies that identified the roles of putative active site residues in the acetyltransferase mechanism. The combined biochemical and structural analyses of FrbF provide insights into this previously uncharacterized family of N-acetyltransferases and also provide a molecular framework toward the production of novel N-acyl derivatives of FR-900098.

  3. MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1

    DEFF Research Database (Denmark)

    Vishnubalaji, Radhakrishnan; Hamam, Rimi; Shijun, Yue

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer causing high mortality rates world-wide. Delineating the molecular mechanisms leading to CRC development and progression, including the role of microRNAs (miRNAs), are currently being unravelled at a rapid rate. Here, we report frequent down...... for the miR-320/SOX4/FOXM1/FOXQ1 axes in promoting CRC development and progression and suggest targeting those networks as potential therapeutic strategy for CRC....... mice. Global gene expression analysis in CRC cells over-expressing miR-320c, combined with in silico prediction identified 84 clinically-relevant potential gene targets for miR-320 in CRC. Using a series of biochemical assays and functional validation, SOX4, FOXM1, and FOXQ1 were validated as novel...... gene targets for the miR-320 family. Inverse correlation between the expression of miR-320 members with SOX4, FOXM1, and FOXQ1 was observed in primary CRC patients' specimens, suggesting that these genes are likely bona fide targets for the miR-320 family. Interestingly, interrogation of the expression...

  4. Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2.

    Science.gov (United States)

    Rabadán, M Angeles; Herrera, Antonio; Fanlo, Lucia; Usieto, Susana; Carmona-Fontaine, Carlos; Barriga, Elias H; Mayor, Roberto; Pons, Sebastián; Martí, Elisa

    2016-06-15

    Delamination of neural crest (NC) cells is a bona fide physiological model of epithelial-to-mesenchymal transition (EMT), a process that is influenced by Wnt/β-catenin signalling. Using two in vivo models, we show that Wnt/β-catenin signalling is transiently inhibited at the time of NC delamination. In attempting to define the mechanism underlying this inhibition, we found that the scaffold proteins Dact1 and Dact2, which are expressed in pre-migratory NC cells, are required for NC delamination in Xenopus and chick embryos, whereas they do not affect the motile properties of migratory NC cells. Dact1/2 inhibit Wnt/β-catenin signalling upstream of the transcriptional activity of T cell factor (TCF), which is required for EMT to proceed. Dact1/2 regulate the subcellular distribution of β-catenin, preventing β-catenin from acting as a transcriptional co-activator to TCF, yet without affecting its stability. Together, these data identify a novel yet important regulatory element that inhibits β-catenin signalling, which then affects NC delamination. © 2016. Published by The Company of Biologists Ltd.

  5. Discovery of novel small molecule activators of β-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Folkert Verkaar

    Full Text Available Wnt/β-catenin signaling plays a major role in embryonic development and adult stem cell maintenance. Reduced activation of the Wnt/β-catenin pathway underlies neurodegenerative disorders and aberrations in bone formation. Screening of a small molecule compound library with a β-galactosidase fragment complementation assay measuring β-catenin nuclear entry revealed bona fide activators of β-catenin signaling. The compounds stabilized cytoplasmic β-catenin and activated β-catenin-dependent reporter gene activity. Although the mechanism through which the compounds activate β-catenin signaling has yet to be determined, several key regulators of Wnt/β-catenin signaling, including glycogen synthase kinase 3 and Frizzled receptors, were excluded as the molecular target. The compounds displayed remarkable selectivity, as they only induced β-catenin signaling in a human osteosarcoma U2OS cell line and not in a variety of other cell lines examined. Our data indicate that differences in cellular Wnt/β-catenin signaling machinery can be exploited to identify cell type-specific activators of Wnt/β-catenin signaling.

  6. Nonlocal Symmetries, Conservation Laws and Interaction Solutions of the Generalised Dispersive Modified Benjamin-Bona-Mahony Equation

    Science.gov (United States)

    Yan, Xue-Wei; Tian, Shou-Fu; Dong, Min-Jie; Wang, Xiu-Bin; Zhang, Tian-Tian

    2018-05-01

    We consider the generalised dispersive modified Benjamin-Bona-Mahony equation, which describes an approximation status for long surface wave existed in the non-linear dispersive media. By employing the truncated Painlevé expansion method, we derive its non-local symmetry and Bäcklund transformation. The non-local symmetry is localised by a new variable, which provides the corresponding non-local symmetry group and similarity reductions. Moreover, a direct method can be provided to construct a kind of finite symmetry transformation via the classic Lie point symmetry of the normal prolonged system. Finally, we find that the equation is a consistent Riccati expansion solvable system. With the help of the Jacobi elliptic function, we get its interaction solutions between solitary waves and cnoidal periodic waves.

  7. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  8. Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.

    Science.gov (United States)

    Hu, Wen-Yang; Hu, Dan-Ping; Xie, Lishi; Li, Ye; Majumdar, Shyama; Nonn, Larisa; Hu, Hong; Shioda, Toshi; Prins, Gail S

    2017-08-01

    Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution

    Directory of Open Access Journals (Sweden)

    Wen-Yang Hu

    2017-08-01

    Full Text Available Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland.

  10. 1500 Years of Annual Climate and Environmental Variability as Recorded in Bona-Churchill (Alaska) Ice Cores

    Science.gov (United States)

    Thompson, L. G.; Mosley-Thompson, E. S.; Zagorodnov, V.; Davis, M. E.; Mashiotta, T. A.; Lin, P.

    2004-12-01

    In 2003, six ice cores measuring 10.5, 11.5, 11.8, 12.4, 114 and 460 meters were recovered from the col between Mount Bona and Mount Churchill (61° 24'N; 141° 42'W; 4420 m asl). These cores have been analyzed for stable isotopic ratios, insoluble dust content and concentrations of major chemical species. Total Beta radioactivity was measured in the upper sections. The 460-meter core, extending to bedrock, captured the entire depositional record at this site where ice temperatures ranged from -24° C at 10 meters to -19.8° C at the ice/bedrock contact. The shallow cores allow assessment of surface processes under modern meteorological conditions while the deep core offers a ˜1500-year climate and environmental perspective. The average annual net balance is ˜~1000 mm of water equivalent and distinct annual signals in dust and calcium concentrations along with δ 18O allow annual resolution over most of the core. The excess sulfate record reflects many known large volcanic eruptions such as Katmai, Krakatau, Tambora, and Laki which allow validation of the time scale in the upper part of the core. The lower part of the core yields a history of earlier volcanic events. The 460-m Bona-Churchill ice core provides a detailed history of the `Little Ice Age' and medieval warm periods for southeastern Alaska. The source of the White River Ash will be discussed in light of the evidence from this core. The 460-m core also provides a long-term history of the dust fall that originates in north-central China. The annual ice core-derived climate records from southeastern Alaska will facilitate an investigation of the likelihood that the high resolution 1500-year record from the tropical Quelccaya Ice Cap (Peru) preserves a history of the variability of both the PDO and the Aleutian Low.

  11. MicroRNA-27a Is Induced by Leucine and Contributes to Leucine-Induced Proliferation Promotion in C2C12 Cells

    Directory of Open Access Journals (Sweden)

    Guangmang Liu

    2013-07-01

    Full Text Available Leucine, a branched chain amino acid, is well known to stimulate protein synthesis in skeletal muscle. However, the role of leucine in myoblast proliferation remains unclear. In this study, we found that leucine could promote proliferation of C2C12 cells. Moreover, expressions of miR-27a and myostatin (a bona fide target of miR-27a were upregulated and downregulated, respectively, following leucine treatment. We also found that miR-27a loss-of-function by transfection of a miR-27a inhibitor suppressed the promotion of myoblast proliferation caused by leucine. Our results suggest that miR-27a is induced by leucine and contributes to leucine-induced proliferation promotion of myoblast.

  12. Metabolic engineering with plants for a sustainable biobased economy.

    Science.gov (United States)

    Yoon, Jong Moon; Zhao, Le; Shanks, Jacqueline V

    2013-01-01

    Plants are bona fide sustainable organisms because they accumulate carbon and synthesize beneficial metabolites from photosynthesis. To meet the challenges to food security and health threatened by increasing population growth and depletion of nonrenewable natural resources, recent metabolic engineering efforts have shifted from single pathways to holistic approaches with multiple genes owing to integration of omics technologies. Successful engineering of plants results in the high yield of biomass components for primary food sources and biofuel feedstocks, pharmaceuticals, and platform chemicals through synthetic biology and systems biology strategies. Further discovery of undefined biosynthesis pathways in plants, integrative analysis of discrete omics data, and diversified process developments for production of platform chemicals are essential to overcome the hurdles for sustainable production of value-added biomolecules from plants.

  13. Nuclear-industry employee protection provisions of federal law

    International Nuclear Information System (INIS)

    Fidell, E.R.; Marcoux, W.C.

    1982-01-01

    Legislation enacted by Congress in 1978 to provide protection for those employed in the construction or operation of civil nuclear projects who express concerns to employers or others about the propriety of procedures in their places of employment from the standpoint of safety is summarized. The authors describe some recent and anticipated developments in the implementation of the law and offer practical suggestions for the avoidance of particular problems under the law. They counsel that the prudent utility company or other firm involved with nuclear energy will see the statute as another reason for facilitating the flow of bona fide safety concerns rather than as a vehicle for the expression of generalized complaints by malcontents and a convenient shield for substandard performers in the work force

  14. Bona fide colour: DNA prediction of human eye and hair colour from ancient and contemporary skeletal remains

    NARCIS (Netherlands)

    J. Draus-Barini (Jolanta); S. Walsh (Susan); E. Pośpiech (Ewelina); T. Kupiec (Tomasz); H. Głab (Henryk); W. Branicki (Wojciech); M.H. Kayser (Manfred)

    2013-01-01

    textabstractBackground: DNA analysis of ancient skeletal remains is invaluable in evolutionary biology for exploring the history of species, including humans. Contemporary human bones and teeth, however, are relevant in forensic DNA analyses that deal with the identification of perpetrators, missing

  15. Properties of optically selected BL Lacertae candidates from the SDSS

    Science.gov (United States)

    Kügler, S. D.; Nilsson, K.; Heidt, J.; Esser, J.; Schultz, T.

    2014-09-01

    Context. Deep optical surveys open the avenue for finding large numbers of BL Lac objects that are hard to identify because they lack the unique properties classifying them as such. While radio or X-ray surveys typically reveal dozens of sources, recent compilations based on optical criteria alone have increased the number of BL Lac candidates considerably. However, these compilations are subject to biases and may contain a substantial number of contaminating sources. Aims: In this paper we extend our analysis of 182 optically selected BL Lac object candidates from the SDSS with respect to an earlier study. The main goal is to determine the number of bona fide BL Lac objects in this sample. Methods: We examine their variability characteristics, determine their broad-band radio-UV spectral energy distributions (SEDs), and search for the presence of a host galaxy. In addition we present new optical spectra for 27 targets with improved signal-to-noise ratio with respect to the SDSS spectra. Results: At least 59% of our targets have shown variability between SDSS DR2 and our observations by more than 0.1-0.27 mag depending on the telescope used. A host galaxy was detected in 36% of our targets. The host galaxy type and luminosities are consistent with earlier studies of BL Lac host galaxies. Simple fits to broad-band SEDs for 104 targets of our sample derived synchrotron peak frequencies between 13.5 ≤ log 10(νpeak) ≤ 16 with a peak at log 10 ~ 14.5. Our new optical spectra do not reveal any new redshift for any of our objects. Thus the sample contains a large number of bona fide BL Lac objects and seems to contain a substantial fraction of intermediate-frequency peaked BL Lacs. Based on observations collected with the NTT on La Silla (Chile) operated by the European Southern Observatory under proposal 082.B-0133.Based on observations collected at the Centro Astronómico Hispano Alemán (CAHA), operated jointly by the Max-Planck-Institut für Astronomie and the

  16. The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans development.

    Science.gov (United States)

    Kostrouchová, Markéta; Kostrouch, David; Chughtai, Ahmed A; Kaššák, Filip; Novotný, Jan P; Kostrouchová, Veronika; Benda, Aleš; Krause, Michael W; Saudek, Vladimír; Kostrouchová, Marta; Kostrouch, Zdeněk

    2017-01-01

    The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in Caenorhabditis elegans. Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other Metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development. F28F8.5 is a vital gene and its null mutants have severely malformed gonads and do not reproduce. F28F8.5 interacts on the protein level with the Mediator subunits MDT-6 and MDT-30. Our results indicate that F28F8.5 is an orthologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode orthologues.

  17. A sequence-based survey of the complex structural organization of tumor genomes

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Colin; Raphael, Benjamin J.; Volik, Stanislav; Yu, Peng; Wu, Chunxiao; Huang, Guiqing; Linardopoulou, Elena V.; Trask, Barbara J.; Waldman, Frederic; Costello, Joseph; Pienta, Kenneth J.; Mills, Gordon B.; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela; Tao, Quanzhou; Aerni, Sarah J.; Brown, Raymond P.; Bashir, Ali; Gray, Joe W.; Cheng, Jan-Fang; de Jong, Pieter; Nefedov, Mikhail; Ried, Thomas; Padilla-Nash, Hesed M.; Collins, Colin C.

    2008-04-03

    The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization (FISH) confirmed translocations and complex tumor genome structures that include coamplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

  18. High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the Identification of PPIs Antagonists.

    Science.gov (United States)

    Wu, Bainan; Barile, Elisa; De, Surya K; Wei, Jun; Purves, Angela; Pellecchia, Maurizio

    2015-01-01

    In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications.

  19. ARID1B is a specific vulnerability in ARID1A-mutant cancers.

    Science.gov (United States)

    Helming, Katherine C; Wang, Xiaofeng; Wilson, Boris G; Vazquez, Francisca; Haswell, Jeffrey R; Manchester, Haley E; Kim, Youngha; Kryukov, Gregory V; Ghandi, Mahmoud; Aguirre, Andrew J; Jagani, Zainab; Wang, Zhong; Garraway, Levi A; Hahn, William C; Roberts, Charles W M

    2014-03-01

    Recent studies have revealed that ARID1A, encoding AT-rich interactive domain 1A (SWI-like), is frequently mutated across a variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, an ARID1A homolog whose gene product is mutually exclusive with ARID1A in SWI/SNF complexes, as the number 1 gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation in both cancer cells and primary cells. We also find that ARID1A and ARID1B are frequently co-mutated in cancer but that ARID1A-deficient cancers retain at least one functional ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers.

  20. Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities.

    Science.gov (United States)

    Soll, Jennifer M; Sobol, Robert W; Mosammaparast, Nima

    2017-03-01

    Alkylation chemotherapy is one of the most widely used systemic therapies for cancer. While somewhat effective, clinical responses and toxicities of these agents are highly variable. A major contributing factor for this variability is the numerous distinct lesions that are created upon alkylation damage. These adducts activate multiple repair pathways. There is mounting evidence that the individual pathways function cooperatively, suggesting that coordinated regulation of alkylation repair is critical to prevent toxicity. Furthermore, some alkylating agents produce adducts that overlap with newly discovered methylation marks, making it difficult to distinguish between bona fide damaged bases and so-called 'epigenetic' adducts. Here, we discuss new efforts aimed at deciphering the mechanisms that regulate these repair pathways, emphasizing their implications for cancer chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Temporal repression of endogenous pluripotency genes during reprogramming of porcine induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane; Christensen, Marianne; Rasmussen, Mikkel Aabech

    2012-01-01

    Porcine induced pluripotent stem cells (piPSCs) have the capacity to differentiate in vitro and in vivo and form chimeras. However, the lack of transgene silencing of exogenous DNA integrated into the genome and the inability of cells to proliferate in the absence of transgene expression...... pluripotency in the pig. This may help to explain the difficulties in producing stable piPSCs and bona fide embryonic stem cell lines in this species....... transgenes on the expression of the porcine endogenous pluripotency machinery. Endogenous and exogenous gene expression of OCT4, NANOG, SOX2, KLF4, and cMYC was determined at passages 5, 10, 15, and 20, both in cells cultured at 1¿µg/mL doxycycline or 4¿µg/mL doxycycline. Our results revealed that endogenous...

  2. Experience of action depends on intention, not body movement

    DEFF Research Database (Denmark)

    Jensen, Mads; Vagnoni, Eleonora; Overgaard, Morten

    2014-01-01

    in memory. We found that recall of a voluntary action was unaffected by an incongruent involuntary movement. In contrast, recall of an involuntary movement was strongly influenced by an incongruent voluntary action. Our results demonstrate an “intentional capture” of body movement by voluntary actions......, in support of intentional theories of agency, but contrary to reconstructive theories. When asked to recall both actions and movements, people's responses are shaped by memory of what they intended to do, rather than by how their body moved....... effects that they produce. Intentions would then be mere confabulations, and not bona fide experiences. Previous work on voluntary action has focused on immediate experiences of authorship, and few studies have considered memory for voluntary actions. We devised an experiment in which both voluntary...

  3. Mimivirus inaugurated in the 21st century the beginning of a reclassification of viruses.

    Science.gov (United States)

    Sharma, Vikas; Colson, Philippe; Pontarotti, Pierre; Raoult, Didier

    2016-06-01

    Mimivirus and other giant viruses are visible by light microscopy and bona fide microbes that differ from other viruses and from cells that have a ribosome. They can be defined by: giant virion and genome sizes; their complexity, with the presence of DNA and mRNAs and dozens or hundreds of proteins in virions; the presence of translation-associated components; a mobilome including (pro)virophages (and a defence mechanism, named MIMIVIRE, against them) and transpovirons; their monophyly; the presence of the most archaic protein motifs they share with cellular organisms but not other viruses; a broader host range than other viruses. These features show that giant viruses are specific, autonomous, biological entities that warrant the creation of a new branch of microbes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Characterization of dry globular proteins and protein fibrils by synchrotron radiation vacuum UV circular dichroism

    DEFF Research Database (Denmark)

    Nesgaard, Lise W.; Hoffmann, Søren Vrønning; Andersen, Christian Beyschau

    2008-01-01

    Circular dichroism using synchrotron radiation (SRCD) can extend the spectral range down to approximately 130 nm for dry proteins, potentially providing new structural information. Using a selection of dried model proteins, including alpha-helical, beta-sheet, and mixed-structure proteins, we...... with previously published theoretical calculations related to pi-orbital transitions. We also show that drying does not lead to large changes in the secondary structure and does not induce orientational artifacts. In combination with principal component analysis, our SRCD data allow us to distinguish between two...... different types of protein fibrils, highlighting that bona fide fibrils formed by lysozyme are structurally more similar to the nonclassical fibrillar aggregates formed by the SerADan peptide than with the amyloid formed by alpha-synuclein. Thus, despite the lack of direct structural conclusions...

  5. Validation of Kepler's multiple planet candidates. II. Refined statistical framework and descriptions of systems of special interest

    International Nuclear Information System (INIS)

    Lissauer, Jack J.; Bryson, Stephen T.; Rowe, Jason F.; Jontof-Hutter, Daniel; Borucki, William J.; Marcy, Geoffrey W.; Kolbl, Rea; Agol, Eric; Carter, Joshua A.; Torres, Guillermo; Ford, Eric B.; Gilliland, Ronald L.; Star, Kimberly M.; Steffen, Jason H.

    2014-01-01

    We extend the statistical analysis performed by Lissauer et al. in 2012, which demonstrates that the overwhelming majority of Kepler candidate multiple transiting systems (multis) represents true transiting planets, and we develop therefrom a procedure to validate large numbers of planet candidates in multis as bona fide exoplanets. We show that this statistical framework correctly estimates the abundance of false positives already identified around Kepler targets with multiple sets of transit-like signatures based on their abundance around targets with single sets of transit-like signatures. We estimate the number of multis that represent split systems of one or more planets orbiting each component of a binary star system. We use the high reliability rate for multis to validate more than one dozen particularly interesting multi-planet systems herein. Hundreds of additional multi-planet systems are validated in a companion paper by Rowe et al. We note that few very short period (P < 1.6 days) planets orbit within multiple transiting planet systems and discuss possible reasons for their absence. There also appears to be a shortage of planets with periods exceeding a few months in multis.

  6. Regulation of mIκBNS stability through PEST-mediated degradation by proteasome

    Energy Technology Data Exchange (ETDEWEB)

    Park, Koog Chan; Jeong, Jiyeong; Kim, Keun Il, E-mail: kikim@sookmyung.ac.kr

    2014-01-24

    Highlights: • mIκBNS is degraded rapidly by proteasome without ubiquitylation. • N-terminal PEST sequence is responsible for the unstable nature of mIκBNS. • PEST sequence is not critical for nuclear localization of mIκBNS. • There is single bona fide NLS at the C-terminus of mIκBNS. - Abstract: Negative regulatory proteins in a cytokine signaling play a critical role in restricting unwanted excess activation of the signaling pathway. At the same time, negative regulatory proteins need to be removed rapidly from cells to respond properly to the next incoming signal. A nuclear IκB protein called IκBNS is known to inhibit a subset of NF-κB target genes upon its expression by NF-κB activation. Here, we show a mechanism to control the stability of mIκBNS which might be important for cells to prepare the next round signaling. We found that mIκBNS is a short-lived protein of which the stability is controlled by proteasome, independent of ubiquitylation process. We identified that the N-terminal PEST sequence in mIκBNS was critical for the regulation of stability.

  7. Validation of Kepler's multiple planet candidates. II. Refined statistical framework and descriptions of systems of special interest

    Energy Technology Data Exchange (ETDEWEB)

    Lissauer, Jack J.; Bryson, Stephen T.; Rowe, Jason F.; Jontof-Hutter, Daniel; Borucki, William J. [NASA Ames Research Center, Moffett Field, CA 94035 (United States); Marcy, Geoffrey W.; Kolbl, Rea [Astronomy Department, University of California, Berkeley, CA 94720 (United States); Agol, Eric [Department of Astronomy, Box 351580, University of Washington, Seattle, WA 98195 (United States); Carter, Joshua A.; Torres, Guillermo [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Ford, Eric B.; Gilliland, Ronald L.; Star, Kimberly M. [Department of Astronomy and Astrophysics, 525 Davey Laboratory, The Pennsylvania State University, University Park, PA 16802 (United States); Steffen, Jason H., E-mail: Jack.Lissauer@nasa.gov [Department of Physics and Astronomy/CIERA, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208 (United States)

    2014-03-20

    We extend the statistical analysis performed by Lissauer et al. in 2012, which demonstrates that the overwhelming majority of Kepler candidate multiple transiting systems (multis) represents true transiting planets, and we develop therefrom a procedure to validate large numbers of planet candidates in multis as bona fide exoplanets. We show that this statistical framework correctly estimates the abundance of false positives already identified around Kepler targets with multiple sets of transit-like signatures based on their abundance around targets with single sets of transit-like signatures. We estimate the number of multis that represent split systems of one or more planets orbiting each component of a binary star system. We use the high reliability rate for multis to validate more than one dozen particularly interesting multi-planet systems herein. Hundreds of additional multi-planet systems are validated in a companion paper by Rowe et al. We note that few very short period (P < 1.6 days) planets orbit within multiple transiting planet systems and discuss possible reasons for their absence. There also appears to be a shortage of planets with periods exceeding a few months in multis.

  8. To treat or not to treat with testosterone replacement therapy: a contemporary review of management of late-onset hypogonadism and critical issues related to prostate cancer.

    Science.gov (United States)

    Kava, Bruce R

    2014-07-01

    Over the last 10 years there has been a dramatic increase in the number of patients identified and treated with testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH). By virtue of age, race, and family history, many of these patients are concurrently at risk for harboring indolent prostate cancer. Other men are at increased risk for prostate cancer as a result of an elevated serum PSA level or having had a prior prostate biopsy showing prostatic intraepithelial neoplasia (PIN) or atypical small acinar proliferation (ASAP). The clinician is often challenged with the decision whether to initiate TRT in these patients. This review presents a contemporary overview of the rationale for TRT, as well as the relationship between testosterone (endogenous and exogenous) and premalignant and malignant lesions of the prostate. We will discuss preliminary data from several recent series demonstrating that TRT may be safely administered in select patients with certain premalignant and bona fide malignant tumors of the prostate. In the absence of a large randomized clinical trial with long-term outcome data evaluating TRT, we hope that this overview will provide clinicians with an evidence-based approach to managing these anxiety-provoking - and often frustrating - clinical scenarios.

  9. Ferritin associates with marginal band microtubules

    International Nuclear Information System (INIS)

    Infante, Anthony A.; Infante, Dzintra; Chan, M.-C.; How, P.-C.; Kutschera, Waltraud; Linhartova, Irena; Muellner, Ernst W.; Wiche, Gerhard; Propst, Friedrich

    2007-01-01

    We characterized chicken erythrocyte and human platelet ferritin by biochemical studies and immunofluorescence. Erythrocyte ferritin was found to be a homopolymer of H-ferritin subunits, resistant to proteinase K digestion, heat stable, and contained iron. In mature chicken erythrocytes and human platelets, ferritin was localized at the marginal band, a ring-shaped peripheral microtubule bundle, and displayed properties of bona fide microtubule-associated proteins such as tau. Red blood cell ferritin association with the marginal band was confirmed by temperature-induced disassembly-reassembly of microtubules. During erythrocyte differentiation, ferritin co-localized with coalescing microtubules during marginal band formation. In addition, ferritin was found in the nuclei of mature erythrocytes, but was not detectable in those of bone marrow erythrocyte precursors. These results suggest that ferritin has a function in marginal band formation and possibly in protection of the marginal band from damaging effects of reactive oxygen species by sequestering iron in the mature erythrocyte. Moreover, our data suggest that ferritin and syncolin, a previously identified erythrocyte microtubule-associated protein, are identical. Nuclear ferritin might contribute to transcriptional silencing or, alternatively, constitute a ferritin reservoir

  10. The genus Shewanella: from the briny depths below to human pathogen.

    Science.gov (United States)

    Janda, J Michael; Abbott, Sharon L

    2014-11-01

    The genus Shewanella is currently composed of more than 50 species that inhabit a range of marine environs and ecosystems. Several members of this genus, including S. oneidensis, have been identified that could potentially play key roles in environmental processes such as bioremediation of toxic elements and heavy metals and serving as microbial fuel cells. In contrast to this beneficial role, shewanellae are increasingly being implicated as human pathogens in persons exposed through occupational or recreational activities to marine niches containing shewanellae. Documented illnesses linked to Shewanella include skin and soft tissue infections, bacteremia, and otitis media. At present, it is unclear exactly how many Shewanella species are truly bona fide human pathogens. Recent advances in the taxonomy and phylogenetic relatedness of members of this genus, however, support the concept that most human infections are caused by a single species, S. algae. Some phylogenetic data further suggest that some current members of the genus are not true Shewanella species sensu stricto. The current review summarizes our present knowledge of the distribution, epidemiology, disease spectrum, and identification of microbial species focusing on a clinical perspective.

  11. A Historical Perspective on the Identification of Cell Types in Pancreatic Islets of Langerhans by Staining and Histochemical Techniques.

    Science.gov (United States)

    Baskin, Denis G

    2015-08-01

    Before the middle of the previous century, cell types of the pancreatic islets of Langerhans were identified primarily on the basis of their color reactions with histological dyes. At that time, the chemical basis for the staining properties of islet cells in relation to the identity, chemistry and structure of their hormones was not fully understood. Nevertheless, the definitive islet cell types that secrete glucagon, insulin, and somatostatin (A, B, and D cells, respectively) could reliably be differentiated from each other with staining protocols that involved variations of one or more tinctorial techniques, such as the Mallory-Heidenhain azan trichrome, chromium hematoxylin and phloxine, aldehyde fuchsin, and silver impregnation methods, which were popularly used until supplanted by immunohistochemical techniques. Before antibody-based staining methods, the most bona fide histochemical techniques for the identification of islet B cells were based on the detection of sulfhydryl and disulfide groups of insulin. The application of the classical islet tinctorial staining methods for pathophysiological studies and physiological experiments was fundamental to our understanding of islet architecture and the physiological roles of A and B cells in glucose regulation and diabetes. © The Author(s) 2015.

  12. Resonant behavior of the generalized Langevin system with tempered Mittag–Leffler memory kernel

    Science.gov (United States)

    Chen, Yao; Wang, Xudong; Deng, Weihua

    2018-05-01

    The generalized Langevin equation describes anomalous dynamics. Noise is not only the origin of uncertainty but also plays a positive role in helping to detect signals with information, termed stochastic resonance (SR). This paper analyzes the anomalous resonant behaviors of the generalized Langevin system with a multiplicative dichotomous noise and an internal tempered Mittag–Leffler noise. For a system with a fluctuating harmonic potential, we obtain the exact expressions of several types of SR such as the first moment, the amplitude and autocorrelation function for the output signal as well as the signal–noise ratio. We analyze the influence of the tempering parameter and memory exponent on the bona fide SR and the general SR. Moreover, it is detected that the critical memory exponent changes regularly with the increase of the tempering parameter. Almost all the theoretical results are validated by numerical simulations.

  13. Documentation and localization of force-mediated filamin A domain perturbations in moving cells

    Science.gov (United States)

    Nakamura, Fumihiko; Song, Mia; Hartwig, John H.; Stossel, Thomas P.

    2014-08-01

    Endogenously and externally generated mechanical forces influence diverse cellular activities, a phenomenon defined as mechanotransduction. Deformation of protein domains by application of stress, previously documented to alter macromolecular interactions in vitro, could mediate these effects. We engineered a photon-emitting system responsive to unfolding of two repeat domains of the actin filament (F-actin) crosslinker protein filamin A (FLNA) that binds multiple partners involved in cell signalling reactions and validated the system using F-actin networks subjected to myosin-based contraction. Expressed in cultured cells, the sensor-containing FLNA construct reproducibly reported FLNA domain unfolding strikingly localized to dynamic, actively protruding, leading cell edges. The unfolding signal depends upon coherence of F-actin-FLNA networks and is enhanced by stimulating cell contractility. The results establish protein domain distortion as a bona fide mechanism for mechanotransduction in vivo.

  14. Initial embryology and pluripotent stem cells in the pig - the quest for establishing the pig as a model for cell therapy

    DEFF Research Database (Denmark)

    Secher, Jan; Callesen, Henrik; Freude, Karla Kristine

    2016-01-01

    genetically modified pigs emerged. Over the past years, renewed interest in porcine PSCs has sparked activities in deriving in particular porcine induced pluripotent stem cells to develop the pig as a faithful model for studying the potentials and risks associated with induced pluripotent stem cell......The quest for porcine pluripotent stem cells (PSCs) was initiated in the early 90s. Initially, it was the intention to benefit from these cells for production of genetically modified pigs using homologous recombination followed by derivation of chimeric offspring; a technology that has been used...... to produce genetically modified mice since the mid-80s. However, no convincing reports on the generation of bona fide porcine embryonic stem cells or embryonic germ cells resulted from these activities, and with the advent of somatic cell nuclear transfer during the late 90s, alternative methods for creating...

  15. A variational approach to niche construction.

    Science.gov (United States)

    Constant, Axel; Ramstead, Maxwell J D; Veissière, Samuel P L; Campbell, John O; Friston, Karl J

    2018-04-01

    In evolutionary biology, niche construction is sometimes described as a genuine evolutionary process whereby organisms, through their activities and regulatory mechanisms, modify their environment such as to steer their own evolutionary trajectory, and that of other species. There is ongoing debate, however, on the extent to which niche construction ought to be considered a bona fide evolutionary force, on a par with natural selection. Recent formulations of the variational free-energy principle as applied to the life sciences describe the properties of living systems, and their selection in evolution, in terms of variational inference. We argue that niche construction can be described using a variational approach. We propose new arguments to support the niche construction perspective, and to extend the variational approach to niche construction to current perspectives in various scientific fields. © 2018 The Authors.

  16. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  17. Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg2

    DEFF Research Database (Denmark)

    Ueda, Takeshi; Nagamachi, Akiko; Takubo, Keiyo

    2015-01-01

    We previously reported deficiency for Samd9L, which was cloned as a candidate gene for -7/7q- syndrome, accelerated leukemia cooperatively with enhanced expression of a histone demethylase F-box and leucine-rich repeat protein 10 (Fbxl10, also known as Jhdm1b, Kdm2b, and Ndy1). To further...... with a normal G0 to G1 entry, resulting in pleiotropic progenitor cell expansion. Fbxl10 Tg HSCs displayed enhanced expression of neuron specific gene family member 2 (Nsg2) and forced expression of Nsg2 in primary bone marrow cells resulted in expansion of immature cells. In addition, the genes involved....... These findings define Fbxl10 as a bona fide oncogene, whose deregulated expression contributes to the development of leukemia involving metabolic proliferative advantage and Nsg2-mediated impaired differentiation....

  18. Assessing the physical nature of near-Earth asteroids through their dynamical histories

    Science.gov (United States)

    Fernández, Julio A.; Sosa, Andrea; Gallardo, Tabaré; Gutiérrez, Jorge N.

    2014-08-01

    We analyze a sample of 139 near-Earth asteroids (NEAs), defined as those that reach perihelion distances q4.8 au), having Tisserand parameters 2family comets (JFCs) in near-Earth orbits, i.e. with q4.8 au of cometary origin, but it could be even lower if the NEAs in unstable orbits listed before turn out to be bona fide asteroids from the main belt. This study strengthens the idea that NEAs and comets essentially are two distinct populations, and that periods of dormancy in comets must be rare. Most likely, active comets in near-Earth orbits go through a continuous erosion process in successive perihelion passages until disintegration into meteoritic dust and fragments of different sizes. In this scenario, 289P/Blanpain might be a near-devolatized fragment from a by now disintegrated parent comet.

  19. Shouldering the load: A review of Joan Stevenson's work on occupational lifting and design evaluation of load carriage equipment.

    Science.gov (United States)

    Costigan, Patrick A; Morin, Evelyn L; Reid, Susan A

    2014-01-01

    In this paper, Dr. Joan Stevenson's work on assessment of the effects of lifting, supporting and transporting loads is reviewed. A defining attribute of this work is the use of objective, biomechanical measures as the basis from which a fuller understanding of all factors affecting worker performance can be obtained, and how such performance should be measured and evaluated. The central objectives and conclusions of Dr. Stevenson's research programs spanning the years from 1985 through 2012 are summarized and discussed in terms of an overall research trajectory. The guiding principle of Dr. Stevenson's work is to reduce the potential harm to which workers are exposed through the development of bona fide occupational standards, a better understanding of risk factors leading to low back pain, and the establishment of an enhanced objective design process for functional load-bearing clothing and equipment.

  20. 21st International Conference on Few-Body Problems in Physics

    CERN Document Server

    2015-01-01

    The 21st International Conference on Few-Body Problems in Physics (FB21) will take place at the Crowne Plaza Chicago Metro Downtown Hotel in the West Loop area of Chicago, Illinois, USA, from May 18th to 22nd, 2015. The first conference of this series took place in London in 1959 and subsequent meetings were held in Brela (1967), Birmingham (1969), Budapest (1971), Los Angeles (1972), Laval (1974), Delhi (1976), Graz (1978), Eugene (1980), Karlsruhe (1983), Sendai (1986), Vancouver (1989), Adelaide (1992), Williamsburg (1994), Groningen (1997), Taipei (2000), Durham (2003),Santos (2006),Bonn (2009),and Fukuoka (2012) see also "History". FB21 will be conducted with the principles passed by the General Assembly in 2008. In particular, no bona fide scientist will be excluded from participation on the grounds of national origin, nationality, or political considerations unrelated to science.

  1. Generation, genome edition and characterization of iPSC lines from a patient with coenzyme Q10 deficiency harboring a heterozygous mutation in COQ4 gene

    Directory of Open Access Journals (Sweden)

    Damià Romero-Moya

    2017-10-01

    Full Text Available We report the generation, CRISPR/Cas9-edition and characterization of induced pluripotent stem cell (iPSC lines from a patient with coenzyme Q10 deficiency harboring the heterozygous mutation c.483G > C in the COQ4 gene. iPSCs were generated using non-integrative Sendai Viruses containing the reprogramming factors OCT4, SOX2, KLF4 and C-MYC. The iPSC lines carried the c.483G > C COQ4 mutation, silenced the OKSM expression and were mycoplasma-free. They were bona fide pluripotent cells as characterized by morphology, immunophenotype/gene expression for pluripotent-associated markers/genes, NANOG and OCT4 promoter demethylation, karyotype and teratoma formation. The COQ4 mutation was CRISPR/Cas9 edited resulting in isogenic, diploid and off-target free COQ4-corrected iPSCs.

  2. The rare fluorinated natural products and biotechnological prospects for fluorine enzymology.

    Science.gov (United States)

    Chan, K K Jason; O'Hagan, David

    2012-01-01

    Nature has hardly evolved a biochemistry of fluorine although there is a low-level occurrence of fluoroacetate found in selected tropical and subtropical plants. This compound, which is generally produced in low concentrations, has been identified in the plants due to its high toxicity, although to date the biosynthesis of fluoroacetate in plants remains unknown. After that, fluorinated entities in nature are extremely rare, and despite increasingly sophisticated screening and analytical methods applied to natural product extraction, it has been 25 years since the last bona fide fluorinated natural product was identified from an organism. This was the reported isolation of the antibiotic 4-fluorothreonine and the toxin fluoroacetate in 1986 from Streptomyces cattleya. This bacterium has proven amenable to biochemical investigation, the fluorination enzyme (fluorinase) has been isolated and characterized, and the biosynthetic pathway to these bacterial metabolites has been elucidated. Also the fluorinase gene has been cloned into a host bacterium (Salinispora tropica), and this has enabled the de novo production of a bioactive fluorinated metabolite from fluoride ion, by genetic engineering. Biotechnological manipulation of the fluorinase offers the prospects for the assembly of novel fluorinated metabolites by fermentation technology. This is particularly attractive, given the backdrop that about 15-20% of pharmaceuticals licensed each year (new chemical entities) contain a fluorine atom. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator of C. elegans development

    Directory of Open Access Journals (Sweden)

    Markéta Kostrouchová

    2017-06-01

    Full Text Available The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously in Caenorhabditis elegans. Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other Metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development. F28F8.5 is a vital gene and its null mutants have severely malformed gonads and do not reproduce. F28F8.5 interacts on the protein level with the Mediator subunits MDT-6 and MDT-30. Our results indicate that F28F8.5 is an orthologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode orthologues.

  4. Data for a comprehensive map and functional annotation of the human cerebrospinal fluid proteome

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2015-06-01

    Full Text Available Knowledge about the normal human cerebrospinal fluid (CSF proteome serves as a baseline reference for CSF biomarker discovery and provides insight into CSF physiology. In this study, high-pH reverse-phase liquid chromatography (hp-RPLC was first integrated with a TripleTOF 5600 mass spectrometer to comprehensively profile the normal CSF proteome. A total of 49,836 unique peptides and 3256 non-redundant proteins were identified. To obtain high-confidence results, 2513 proteins with at least 2 unique peptides were further selected as bona fide CSF proteins. Nearly 30% of the identified CSF proteins have not been previously reported in the normal CSF proteome. More than 25% of the CSF proteins were components of CNS cell microenvironments, and network analyses indicated their roles in the pathogenesis of neurological diseases. The top canonical pathway in which the CSF proteins participated was axon guidance signaling. More than one-third of the CSF proteins (788 proteins were related to neurological diseases, and these proteins constitute potential CSF biomarker candidates. The mapping results can be freely downloaded at http://122.70.220.102:8088/csf/, which can be used to navigate the CSF proteome. For more information about the data, please refer to the related original article [1], which has been recently accepted by Journal of Proteomics.

  5. Aminoacyl-tRNA-charged eukaryotic elongation factor 1A is a bona fide substrate for Legionelle pneumophila effector glucosyltransferases

    DEFF Research Database (Denmark)

    Tzivelekidis, Tina; Jank, Thomas; Pohl, Corinna

    2011-01-01

    Legionella pneumophila, which is the causative organism of Legionnaires disease, translocates numerous effector proteins into the host cell cytosol by a type IV secretion system during infection. Among the most potent effector proteins of Legionella are glucosyltransferases (Lgt’s), which...

  6. 23rd June 2010 - IATA Director-General and CEO G. Bisignani signing the guest book with Research and Computing Director S. Bertolucci; visiting the LHC superconducting magnet test hall with L. Bottura; throughout accompanied by Adviser for International relations M. Bona.

    CERN Multimedia

    Maximilien Brice

    2010-01-01

    23rd June 2010 - IATA Director-General and CEO G. Bisignani signing the guest book with Research and Computing Director S. Bertolucci; visiting the LHC superconducting magnet test hall with L. Bottura; throughout accompanied by Adviser for International relations M. Bona.

  7. Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor Cells.

    Science.gov (United States)

    Maldonado, Paloma P; Angulo, María Cecilia

    2015-06-01

    The surprising discovery of bona fide synapses between neurons and oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as real partners of neurons in the CNS. The role of these synapses has not been established yet, but a main hypothesis is that neuron-OPC synaptic activity is a signaling pathway controlling OPC proliferation/differentiation, influencing the myelination process. However, new evidences describing non-synaptic mechanisms of communication between neurons and OPCs have revealed that neuron-OPC interactions are more complex than expected. The activation of extrasynaptic receptors by ambient neurotransmitter or local spillover and the ability of OPCs to sense neuronal activity through a potassium channel suggest that distinct modes of communication mediate different functions of OPCs in the CNS. This review discusses different mechanisms used by OPCs to interact with neurons and their potential roles during postnatal development and in brain disorders. © The Author(s) 2014.

  8. A case of misconstrued Rock Military Style

    DEFF Research Database (Denmark)

    Langkjær, Michael Alexander

    2012-01-01

    The motives behind the bona fide uniform derivation represented by The Rolling Stones lead, Mick Jagger, in his white 'frock-dress' worn in 1969 are complex. Jagger wore the white voile, Michael Fish-designed frock at the July 5 memorial concert in Hyde Park, just 48 hours after the death of fellow...... about Jagger's motivations in thus 'cross-dressing'. A notable British precedent for wearing the fustanella, viz. that of Lord Byron back in the 1820s in the Greek War of Independence, which, although a myth (since Byron never actualy wore the fustanella apart from an 1814 London portrait-sitting of him...... Richard, Mick Jagger and Brian Jones back in 1967), Jagger's wearing the costume on the occasion of a memorial concert for Jones was also meant to be symbolic, drawing on English romanticism in a special pleading on behalf of the rock star as a persecuted artist....

  9. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500...

  10. Imaging hydrated microbial extracellular polymers: Comparative analysis by electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Dohnalkova, A.C.; Marshall, M. J.; Arey, B. W.; Williams, K. H.; Buck, E. C.; Fredrickson, J. K.

    2011-01-01

    Microbe-mineral and -metal interactions represent a major intersection between the biosphere and geosphere but require high-resolution imaging and analytical tools for investigating microscale associations. Electron microscopy has been used extensively for geomicrobial investigations and although used bona fide, the traditional methods of sample preparation do not preserve the native morphology of microbiological components, especially extracellular polymers. Herein, we present a direct comparative analysis of microbial interactions using conventional electron microscopy approaches of imaging at room temperature and a suite of cryogenic electron microscopy methods providing imaging in the close-to-natural hydrated state. In situ, we observed an irreversible transformation of the hydrated bacterial extracellular polymers during the traditional dehydration-based sample preparation that resulted in their collapse into filamentous structures. Dehydration-induced polymer collapse can lead to inaccurate spatial relationships and hence could subsequently affect conclusions regarding nature of interactions between microbial extracellular polymers and their environment.

  11. High Precision Renormalization Group Study of the Roughening Transition

    CERN Document Server

    Hasenbusch, M; Pinn, K

    1994-01-01

    We confirm the Kosterlitz-Thouless scenario of the roughening transition for three different Solid-On-Solid models: the Discrete Gaussian model, the Absolute-Value-Solid-On-Solid model and the dual transform of the XY model with standard (cosine) action. The method is based on a matching of the renormalization group flow of the candidate models with the flow of a bona fide KT model, the exactly solvable BCSOS model. The Monte Carlo simulations are performed using efficient cluster algorithms. We obtain high precision estimates for the critical couplings and other non-universal quantities. For the XY model with cosine action our critical coupling estimate is $\\beta_R^{XY}=1.1197(5)$. For the roughening coupling of the Discrete Gaussian and the Absolute-Value-Solid-On-Solid model we find $K_R^{DG}=0.6645(6)$ and $K_R^{ASOS}=0.8061(3)$, respectively.

  12. A role for the transcription factor HEY1 in glioblastoma

    DEFF Research Database (Denmark)

    Hulleman, Esther; Quarto, Micaela; Vernell, Richard

    2009-01-01

    Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes......, such as the Notch and Ras signalling pathways, seem to play an important role in the formation of GBM. In the present study, we show by in situ hybridization on primary tumour material that the transcription factor HEY1, a target of the Notch signalling pathway, is specifically upregulated in glioma...... and that expression of HEY1 in GBM correlates with tumour-grade and survival. In addition, we show by chromatin immunoprecipitations, luciferase assays and Northern blot experiments that HEY1 is a bona fide target of the E2F family of transcription factors, connecting the Ras and Notch signalling pathways. Finally...

  13. The first optical spectra of Wolf-Rayet stars in M101 revealed with Gemini/GMOS

    Science.gov (United States)

    Pledger, J. L.; Shara, M. M.; Wilde, M.; Crowther, P. A.; Long, K. S.; Zurek, D.; Moffat, A. F. J.

    2018-01-01

    Deep narrow-band Hubble Space Telescope (HST) imaging of the iconic spiral galaxy M101 has revealed over a thousand new Wolf-Rayet (WR) candidates. We report spectrographic confirmation of 10 He II-emission line sources hosting 15 WR stars. We find WR stars present at both sub- and super-solar metallicities with WC stars favouring more metal-rich regions compared to WN stars. We investigate the association of WR stars with H II regions using archival HST imaging and conclude that the majority of WR stars are in or associated with H II regions. Of the 10 emission lines sources, only one appears to be unassociated with a star-forming region. Our spectroscopic survey provides confidence that our narrow-band photometric candidates are in fact bona fide WR stars, which will allow us to characterize the progenitors of any core-collapse supernovae that erupt in the future in M101.

  14. Functional genomics of probiotic Escherichia coli Nissle 1917 and 83972, and UPEC strain CFT073: comparison of transcriptomes, growth and biofilm formation

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Vejborg, Rebecca Munk; Klemm, Per

    2010-01-01

    Strain CFT073 is a bona fide uropathogen, whereas strains 83972 and Nissle 1917 are harmless probiotic strains of urinary tract and faecal origin, respectively. Despite their different environmental origins and dispositions the three strains are very closely related and the ancestors of 83972...... of the three strains are closely related. The data demonstrate that the distance from a pathogen to a probiotic strain can be surprisingly short. We demonstrate that Nissle 1917, in spite of its intestinal niche origin, grows well in urine, and is a good biofilm former in this medium in which it also out...... accounting for the impaired biofilm formation. Although the three strains have very different strategies vis-à-vis the human host their functional gene profiles are surprisingly similar. It is also interesting to note that the only two Escherichia coli strains used as probiotics are in fact deconstructed...

  15. Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy.

    Science.gov (United States)

    Pol, Jonathan; Vacchelli, Erika; Aranda, Fernando; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Sautès-Fridman, Catherine; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2015-04-01

    The term "immunogenic cell death" (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers.

  16. Electronic relaxation processes in polyatomic molecules. Progress report, October 1, 1975--September 30, 1976

    International Nuclear Information System (INIS)

    Lim, E.C.

    1976-09-01

    Excitation energy dependence of radiationless decay rate under collision-free conditions was utilized as a probe of intramolecular vibrational relaxation in tetracene and pentacene. The results give evidence of vibrational relaxation which competes with electronic relaxation. The substitution dependence of T 1 (nπ*) → S 0 radiationless transition in monocyclic diazines and the temperature dependence of S 1 non-radiative decay rate in alcoholic solutions of polycyclic monoazines indicate that the vibronic interaction between the lowest energy nπ* and ππ* states leads to a rapid radiationless deactivation of the lower of the two electronic states. Finally, a photon-counting spectrofluorometer of very high sensitivity was constructed, and it was used to record T 2 → T 1 fluorescence in bromoanthracenes and S 2 → S 1 fluorescence in azulene. These spectra represent the first bona-fide, or the most convincing, observation of fluorescence between excited electronic states

  17. Quasiadiabatic modes from viscous inhomogeneities

    CERN Document Server

    Giovannini, Massimo

    2016-04-20

    The viscous inhomogeneities of a relativistic plasma determine a further class of entropic modes whose amplitude must be sufficiently small since curvature perturbations are observed to be predominantly adiabatic and Gaussian over large scales. When the viscous coefficients only depend on the energy density of the fluid the corresponding curvature fluctuations are shown to be almost adiabatic. After addressing the problem in a gauge-invariant perturbative expansion, the same analysis is repeated at a non-perturbative level by investigating the nonlinear curvature inhomogeneities induced by the spatial variation of the viscous coefficients. It is demonstrated that the quasiadiabatic modes are suppressed in comparison with a bona fide adiabatic solution. Because of its anomalously large tensor to scalar ratio the quasiadiabatic mode cannot be a substitute for the conventional adiabatic paradigm so that, ultimately, the present findings seems to exclude the possibility of a successful accelerated dynamics solely...

  18. Characterization of scientific studies usually cited as evidence of adverse effects of GM food/feed.

    Science.gov (United States)

    Sánchez, Miguel A; Parrott, Wayne A

    2017-10-01

    GM crops are the most studied crops in history. Approximately 5% of the safety studies on them show adverse effects that are a cause for concern and tend to be featured in media reports. Although these reports are based on just a handful of GM events, they are used to cast doubt on all GM crops. Furthermore, they tend to come from just a few laboratories and are published in less important journals. Importantly, a close examination of these reports invariably shows methodological flaws that invalidate any conclusions of adverse effects. Twenty years after commercial cultivation of GM crops began, a bona fide report of an adverse health effect due to a commercialized modification in a crop has yet to be reported. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  19. Structural basis and functions of abscisic acid receptors PYLs

    Science.gov (United States)

    Zhang, Xing L.; Jiang, Lun; Xin, Qi; Liu, Yang; Tan, Jian X.; Chen, Zhong Z.

    2015-01-01

    Abscisic acid (ABA) plays a key role in many developmental processes and responses to adaptive stresses in plants. Recently, a new family of nucleocytoplasmic PYR/PYL/RCAR (PYLs) has been identified as bona fide ABA receptors. PYLs together with protein phosphatases type-2C (PP2Cs), Snf1 (Sucrose-non-fermentation 1)-related kinases subfamily 2 (SnRK2s) and downstream substrates constitute the core ABA signaling network. Generally, PP2Cs inactivate SnRK2s kinases by physical interaction and direct dephosphorylation. Upon ABA binding, PYLs change their conformations and then contact and inhibit PP2Cs, thus activating SnRK2s. Here, we reviewed the recent progress in research regarding the structures of the core signaling pathways of ABA, including the (+)-ABA, (−)-ABA and ABA analogs pyrabactin as well as 6AS perception by PYLs, SnRK2s mimicking PYLs in binding PP2Cs. PYLs inhibited PP2Cs in both the presence and absence of ABA and activated SnRK2s. The present review elucidates multiple ABA signal perception and transduction by PYLs, which might shed light on how to design small chemical compounds for improving plant performance in the future. PMID:25745428

  20. STarlight Absorption Reduction through a Survey of Multiple Occulting Galaxies (STARSMOG)

    Science.gov (United States)

    Holwerda, Benne

    2014-10-01

    Dust absorption remains the poorest constrained parameter in both Cosmological distances and multi-wavelength studies of galaxy populations. A galaxy's dust distribution can be measured to great accuracy in the case of an overlapping pair of galaxies, i.e., when a foreground spiral galaxy accidentally overlaps a more distant, preferably elliptical galaxy. We have identified over 300 bona-fide overlapping pairs --well separated in redshift but close on the sky-- in the GAMA spectroscopic survey, taking advantage of its high completeness (98%) on small scales. We propose to map the fine-scale (~50pc) dust structure in these occulting galaxies, using HST/WFC3 SNAP observations. The resulting dust maps will (1) serve as an extinction probability for supernova lightcurve fits in similar type host galaxies, (2) strongly constrain the role of ISM structure in Spectral Energy Distribution models of spiral galaxies, and (3) map the level of ISM turbulence (through the spatial power-spectrum). We ask for SNAP observations with a parent list of 355 targets to ensure a complete and comprehensive coverage of each foreground galaxy mass, radius and inclination. The resulting extinction maps will serve as a library for SNIa measurements, galaxy SED modelling and ISM turbulence measurements.

  1. A conserved tad pilus promotes Vibrio vulnificus oyster colonization.

    Science.gov (United States)

    Pu, Meng; Duriez, Patrick; Arazi, Mattan; Rowe-Magnus, Dean A

    2018-02-01

    Vibrio vulnificus has the highest death rate (>35%) and per-case economic burden ($3.3 million) of any foodborne pathogen in the United States. Infections occur via open wounds or following ingestion of contaminated seafood, most infamously oysters. We isolated a 1000th generation descendant, designated NT that exhibited increased biofilm and aggregate formation relative to its parent. We identified two significant causal changes underlying these phenotypes. First, the entire 24-kb capsular polysaccharide biosynthesis locus, which is essential for virulence but inhibits biofilm formation, had been purged from the genome. However, NT formed more extensive biofilms and aggregates than a defined cps mutant, suggesting that additional factor(s) contributed to its phenotypes. Second, the expression of a tight adherence (tad) pilus locus was elevated in NT. Deletion of the associated pilin (flp) decreased NT biofilm and aggregate formation. Furthermore, NTΔflp strains were deficient relative to NT in an oyster colonization model, demonstrating a positive correlation between the biofilm and aggregation phenotypes associated with Tad pilus production and efficient bacterial retention by feeding oysters. Despite being widely distributed in the Vibrionaceae, this is the first demonstration of a bona fide physiological role for a Tad pilus in this bacterial family. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  2. Faith-adapted psychological therapies for depression and anxiety: Systematic review and meta-analysis.

    Science.gov (United States)

    Anderson, Naomi; Heywood-Everett, Suzanne; Siddiqi, Najma; Wright, Judy; Meredith, Jodi; McMillan, Dean

    2015-05-01

    Incorporating faith (religious or spiritual) perspectives into psychological treatments has attracted significant interest in recent years. However, previous suggestion that good psychiatric care should include spiritual components has provoked controversy. To try to address ongoing uncertainty in this field we present a systematic review and meta-analysis to assess the efficacy of faith-based adaptations of bona fide psychological therapies for depression or anxiety. A systematic review and meta-analysis of randomised controlled trials were performed. The literature search yielded 2274 citations of which 16 studies were eligible for inclusion. All studies used cognitive or cognitive behavioural models as the basis for their faith-adapted treatment (F-CBT). We identified statistically significant benefits of using F-CBT. However, quality assessment using the Cochrane risk of bias tool revealed methodological limitations that reduce the apparent strength of these findings. Whilst the effect sizes identified here were statistically significant, there were relatively a few relevant RCTs available, and those included were typically small and susceptible to significant biases. Biases associated with researcher or therapist allegiance were identified as a particular concern. Despite some suggestion that faith-adapted CBT may out-perform both standard CBT and control conditions (waiting list or "treatment as usual"), the effect sizes identified in this meta-analysis must be considered in the light of the substantial methodological limitations that affect the primary research data. Before firm recommendations about the value of faith-adapted treatments can be made, further large-scale, rigorously performed trials are required. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. 15 February 2012 - Geneva United Nations Office Director-General K.-J. Tokayev in the LHC tunnel with Adviser for Relations with international organisations M. Bona and Technology Department Head F. Bordry.

    CERN Multimedia

    Jean-claude Gadmer

    2012-01-01

    Kassym-Jomart Tokayev, director-general of the United Nations Office at Geneva, (centre picture 02), visited CERN on 15 February. He toured the LHC tunnel with Maurizio Bona, CERN’s adviser to the director-general, relations with international organizations, left, and Frédérick Bordry, CERN’s technology department head. He also visited the ATLAS underground experimental area, as well as the exhibition at the Globe of Science and Innovation.

  4. THE TAURUS SPITZER SURVEY: NEW CANDIDATE TAURUS MEMBERS SELECTED USING SENSITIVE MID-INFRARED PHOTOMETRY

    International Nuclear Information System (INIS)

    Rebull, L. M.; Padgett, D. L.; McCabe, C.-E.; Noriega-Crespo, A.; Carey, S. J.; Brooke, T.; Hillenbrand, L. A.; Stapelfeldt, K. R.; Angione, J. R.; Huard, T.; Terebey, S.; Audard, M.; Baldovin-Saavedra, C.; Monin, J.-L.; Menard, F.; Bouvier, J.; Fukagawa, M.; Guedel, M.; Knapp, G. R.; Allen, L. E.

    2010-01-01

    We report on the properties of pre-main-sequence objects in the Taurus molecular clouds as observed in seven mid- and far-infrared bands with the Spitzer Space Telescope. There are 215 previously identified members of the Taurus star-forming region in our ∼44 deg 2 map; these members exhibit a range of Spitzer colors that we take to define young stars still surrounded by circumstellar dust (noting that ∼20% of the bona fide Taurus members exhibit no detectable dust excesses). We looked for new objects in the survey field with similar Spitzer properties, aided by extensive optical, X-ray, and ultraviolet imaging, and found 148 new candidate members of Taurus. We have obtained follow-up spectroscopy for about half the candidate sample, thus far confirming 34 new members, three probable new members, and 10 possible new members, an increase of 15%-20% in Taurus members. Of the objects for which we have spectroscopy, seven are now confirmed extragalactic objects, and one is a background Be star. The remaining 93 candidate objects await additional analysis and/or data to be confirmed or rejected as Taurus members. Most of the new members are Class II M stars and are located along the same cloud filaments as the previously identified Taurus members. Among non-members with Spitzer colors similar to young, dusty stars are evolved Be stars, planetary nebulae, carbon stars, galaxies, and active galactic nuclei.

  5. Autoradiographic detection of diphtheria toxin resistant mutants in human diploid fibroblasts

    International Nuclear Information System (INIS)

    Gupta, R.S.; Singh, B.

    1985-01-01

    An autoradiographic procedure for the detection of diphtheria toxin (DT) resistant (Dip/sub R/) mutants in human diploid fibroblast (HDF) cells has been developed. The assay is based on the observation that when HDFs from confluent cultures are seeded in medium containing 0.01 flocculating units/ml or higher concentration of DT, protein synthesis in sensitive cells is severely inhibited by 4-6 hr. If at this or later time, a radiolabeled protein precursor (eg, 3 H-leucine) is added to the culture, it is almost exclusively incorporated into the resistant cells, which are then readily identified by autoradiography. These studies provide strong evidence that the labeled cells identified by autoradiography are bona fide Dip/sub R/ mutants. The detection of Dip/sub R/ cells by autoradiography is apparently not affected by the presence of the sensitive cells in the mixtures. The spontaneous frequency of Dip/sub R/ cells in HDFs has been found to be in the range of 1-5 x 10 -6 , and this increases in a dose dependent manner upon treatment with the mutagen ethyl methanesulfonate. These results indicate that the autoradiographic assay could be used for quantitative mutagenesis. Since the autoradiographic assay does not depend on cell division, it may prove useful in estimating the incidence of pre-existing mutations in cell populations that either do not divide or have very limited growth potential (eg, lymphocytes, muscle cells, neurons, senescent fibroblasts, etc.)

  6. Photometric Determination of the Mass Accretion Rates of Pre-main-sequence Stars. V. Recent Star Formation in the 30 Dor Nebula

    Science.gov (United States)

    De Marchi, Guido; Panagia, Nino; Beccari, Giacomo

    2017-09-01

    We report on the properties of the low-mass stars that recently formed in the central ˜ 2\\buildrel{ \\prime}\\over{.} 7× 2\\buildrel{ \\prime}\\over{.} 7 of 30 Dor, including the R136 cluster. Using the photometric catalog of De Marchi et al., based on observations with the Hubble Space Telescope, and the most recent extinction law for this field, we identify 1035 bona fide pre-main-sequence (PMS) stars showing {{H}}α excess emission at the 4σ level with an {{H}}α equivalent width of 20 Å or more. We find a wide spread in age spanning the range ˜ 0.1{--}50 {Myr}. We also find that the older PMS objects are placed in front of the R136 cluster and are separated from it by a conspicuous amount of absorbing material, indicating that star formation has proceeded from the periphery into the interior of the region. We derive physical parameters for all PMS stars, including masses m, ages t, and mass accretion rates {\\dot{M}}{acc}. To identify reliable correlations between these parameters, which are intertwined, we use a multivariate linear regression fit of the type {log}{\\dot{M}}{acc}=a× {log}t+b× {log}m+c. The values of a and b for 30 Dor are compatible with those found in NGC 346 and NGC 602. We extend the fit to a uniform sample of 1307 PMS stars with 0.5contract NAS5-26555.

  7. New Insights into the Role of the Immune Microenvironment in Breast Carcinoma

    Science.gov (United States)

    de la Cruz-Merino, Luis; Barco-Sánchez, Antonio; Henao Carrasco, Fernando; Nogales Fernández, Esteban; Vallejo Benítez, Ana; Brugal Molina, Javier; Martínez Peinado, Antonio; Grueso López, Ana; Ruiz Borrego, Manuel; Codes Manuel de Villena, Manuel; Sánchez-Margalet, Víctor; Nieto-García, Adoración; Alba Conejo, Emilio; Casares Lagar, Noelia; Ibáñez Martínez, José

    2013-01-01

    Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future. PMID:23861693

  8. A novel expansin protein from the white-rot fungus Schizophyllum commune.

    Directory of Open Access Journals (Sweden)

    Omar Eduardo Tovar-Herrera

    Full Text Available A novel expansin protein (ScExlx1 was found, cloned and expressed from the Basidiomycete fungus Schizophylum commune. This protein showed the canonical features of plant expansins. ScExlx1 showed the ability to form "bubbles" in cotton fibers, reduce the size of avicel particles and enhance reducing sugar liberation from cotton fibers pretreated with the protein and then treated with cellulases. ScExlx1 was able to bind cellulose, birchwood xylan and chitin and this property was not affected by different sodium chloride concentrations. A novel property of ScExlx1 is its capacity to enhance reducing sugars (N-acetyl glucosamine liberation from pretreated chitin and further added with chitinase, which has not been reported for any expansin or expansin-like protein. To the best of our knowledge, this is the first report of a bona fide fungal expansin found in a basidiomycete and we could express the bioactive protein in Pichia pastoris.

  9. The HectoMAP Cluster Survey. I. redMaPPer Clusters

    Science.gov (United States)

    Sohn, Jubee; Geller, Margaret J.; Rines, Kenneth J.; Hwang, Ho Seong; Utsumi, Yousuke; Diaferio, Antonaldo

    2018-04-01

    We use the dense HectoMAP redshift survey to explore the properties of 104 redMaPPer cluster candidates. The redMaPPer systems in HectoMAP cover the full range of richness and redshift (0.08 systems included in the Subaru/Hyper Suprime-Cam public data release are bona fide clusters. The median number of spectroscopic members per cluster is ∼20. We include redshifts of 3547 member candidates listed in the redMaPPer catalog whether they are cluster members or not. We evaluate the redMaPPer membership probability spectroscopically. The purity (number of real systems) in redMaPPer exceeds 90% even at the lowest richness. Three massive galaxy clusters (M ∼ 2 × 1013 M ⊙) associated with X-ray emission in the HectoMAP region are not included in the public redMaPPer catalog with λ rich > 20, because they lie outside the cuts for this catalog.

  10. Yet another call for a greater Role for good Faith in the South African Law of Contract: Can we banish the Law of the Jungle, while avoiding the Elephant in the Room?

    Directory of Open Access Journals (Sweden)

    Andre M Louw

    2013-12-01

    Full Text Available This article examines the current approach of the South African courts to the role of good faith or bona fides in contracts, as well as the courts’ stated reasons for this approach. The article specifically examines how arguments based on good faith have fared in the Constitutional Court to date, and the prospects for law reform to emanate from that court in the near future. The author suggests an understanding of good faith which he believes is in line with the Constitution of the Republic of South Africa, 1996 and argues that in terms of such an understanding of a robust good faith doctrine the legal fraternity or the courts can avoid some of the dangers that the judges of the Supreme Court of Appeal have warned about in this context in recent years. The author shares some concluding thoughts on the pressing need for law reform with respect to the role and presence of good faith in contracts.

  11. Cell cloning-on-the-spot by using an attachable silicone cylinder.

    Science.gov (United States)

    Park, Hong Bum; Son, Wonseok; Chae, Dong Han; Lee, Jisu; Kim, Il-Woung; Yang, Woomi; Sung, Jae Kyu; Lim, Kyu; Lee, Jun Hee; Kim, Kyung-Hee; Park, Jong-Il

    2016-06-10

    Cell cloning is a laboratory routine to isolate and keep particular properties of cultured cells. Transfected or other genetically modified cells can be selected by the traditional microbiological cloning. In addition, common laboratory cell lines are prone to genotypic drift during their continual culture, so that supplementary cloning steps are often required to maintain correct lineage phenotypes. Here, we designed a silicone-made attachable cloning cylinder, which facilitated an easy and bona fide cloning of interested cells. This silicone cylinder was easy to make, showed competent stickiness to laboratory plastics including culture dishes, and hence enabled secure isolation and culture for days of selected single cells, especially, on the spots of preceding cell-plating dishes under microscopic examination of visible cellular phenotypes. We tested the silicone cylinder in the monoclonal subcloning from a heterogeneous population of a breast cancer cell line, MDA-MB-231, and readily established independent MDA-MB-231 subclones showing different sublineage phenotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. B Cell Help by CD1d-Rectricted NKT Cells

    Directory of Open Access Journals (Sweden)

    Livia Clerici

    2015-10-01

    Full Text Available B cell activation and antibody production against foreign antigens is a central step of host defense. This is achieved via highly regulated multi-phase processes that involve a variety of cells of both innate and adaptive arms of the immune system. MHC class II-restricted CD4+ T cells specific for peptide antigens, which acquire professional follicular B cell helper functions, have been long recognized as key players in this process. Recent data, however, challenge this paradigm by showing the existence of other helper cell types. CD1d restricted NKT cells specific for lipid antigens are one such new player and can coopt bona fide follicular helper phenotypes. Their role in helping antigen-specific B cell response to protein antigens, as well as to the so called “help-less” antigens that cannot be recognized by T follicular helper cells, is being increasingly elucidated, highlighting their potential pathophysiological impact on the immune response, as well as on the design of improved vaccine formulations.

  13. Abscisic acid perception and signaling: structural mechanisms and applications

    Science.gov (United States)

    Ng, Ley Moy; Melcher, Karsten; Teh, Bin Tean; Xu, H Eric

    2014-01-01

    Adverse environmental conditions are a threat to agricultural yield and therefore exert a global effect on livelihood, health and the economy. Abscisic acid (ABA) is a vital plant hormone that regulates abiotic stress tolerance, thereby allowing plants to cope with environmental stresses. Previously, attempts to develop a complete understanding of the mechanisms underlying ABA signaling have been hindered by difficulties in the identification of bona fide ABA receptors. The discovery of the PYR/PYL/RCAR family of ABA receptors therefore represented a major milestone in the effort to overcome these roadblocks; since then, many structural and functional studies have provided detailed insights into processes ranging from ABA perception to the activation of ABA-responsive gene transcription. This understanding of the mechanisms of ABA perception and signaling has served as the basis for recent, preliminary developments in the genetic engineering of stress-resistant crops as well as in the design of new synthetic ABA agonists, which hold great promise for the agricultural enhancement of stress tolerance. PMID:24786231

  14. 235Cf anti ν discrepancy and the sulfur discrepancy

    International Nuclear Information System (INIS)

    Smith, J.R.

    1979-01-01

    The cantankerous discrepancy among measured values of anti ν for 235 Cf appears at last to be nearing a final resolution. A recent review has summarized the progress that has been achieved through revaluation upward by 0.5% of two manganese bath values anti ν and the performance of a new liquid scintillator measurement. A new manganese bath measurement at INEL is in reasonably good agreement with previous manganese bath values of 235 Cf anti ν. It now appears that the manganese bath values could still be systematically low by as much as 0.4% because the BNL-325 thermal absorption cross section for sulfur may be as much as 10% low. There is a bona fide discrepancy between measurements of the sulfur cross section by pile oscillators and the values derived from transmission measurements. The resolution of this discrepancy is a prerequisite to the final resolution of the 235 Cf anti ν discrepancy. 22 references

  15. Ultimately short ballistic vertical graphene Josephson junctions

    Science.gov (United States)

    Lee, Gil-Ho; Kim, Sol; Jhi, Seung-Hoon; Lee, Hu-Jong

    2015-01-01

    Much efforts have been made for the realization of hybrid Josephson junctions incorporating various materials for the fundamental studies of exotic physical phenomena as well as the applications to superconducting quantum devices. Nonetheless, the efforts have been hindered by the diffusive nature of the conducting channels and interfaces. To overcome the obstacles, we vertically sandwiched a cleaved graphene monoatomic layer as the normal-conducting spacer between superconducting electrodes. The atomically thin single-crystalline graphene layer serves as an ultimately short conducting channel, with highly transparent interfaces with superconductors. In particular, we show the strong Josephson coupling reaching the theoretical limit, the convex-shaped temperature dependence of the Josephson critical current and the exceptionally skewed phase dependence of the Josephson current; all demonstrate the bona fide short and ballistic Josephson nature. This vertical stacking scheme for extremely thin transparent spacers would open a new pathway for exploring the exotic coherence phenomena occurring on an atomic scale. PMID:25635386

  16. Giant Viruses of Amoebae: A Journey Through Innovative Research and Paradigm Changes.

    Science.gov (United States)

    Colson, Philippe; La Scola, Bernard; Raoult, Didier

    2017-09-29

    Giant viruses of amoebae were discovered serendipitously in 2003; they are visible via optical microscopy, making them bona fide microbes. Their lifestyle, structure, and genomes break the mold of classical viruses. Giant viruses of amoebae are complex microorganisms. Their genomes harbor between 444 and 2,544 genes, including many that are unique to viruses, and encode translation components; their virions contain >100 proteins as well as mRNAs. Mimiviruses have a specific mobilome, including virophages, provirophages, and transpovirons, and can resist virophages through a system known as MIMIVIRE (mimivirus virophage resistance element). Giant viruses of amoebae bring upheaval to the definition of viruses and tend to separate the current virosphere into two categories: very simple viruses and viruses with complexity similar to that of other microbes. This new paradigm is propitious for enhanced detection and characterization of giant viruses of amoebae, and a particular focus on their role in humans is warranted.

  17. CK2—An Emerging Target for Neurological and Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Julia Castello

    2017-01-01

    Full Text Available Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses. Full and conditional CK2 knockout mice have further elucidated the importance of CK2 in brain development, neuronal activity, and behavior. This review will discuss recent advances in the field that point to CK2 as a regulator of neuronal functions and as a potential novel target to treat neurological and psychiatric disorders.

  18. Separate and Unequal: Judicial Culture, Employment Qualifications and Muslim Headscarf Debates

    Directory of Open Access Journals (Sweden)

    Joyce Marie Mushaben

    2013-09-01

    Full Text Available Few European lawmakers have analyzed the implications of Muslim headscarf bans for equal employment opportunity. EU anti-discrimination directives suggest that contradictory member-state approaches will eventually invoke a judicial Community response at national expense. Drawing on the bona fide occupational qualification (BFOQ standard, this study compares the “judicial cultures” of the U.S. Supreme Court, the German Constitutional Court, the European Court of Human Rights (ECHR and the European Court of Justice (ECJ. It argues that while the ECJ initially invoked Roman law precepts shared by a majority of its member-states through the 1980s, it has come to embrace Anglo-American norms stressing individual freedoms over state interests. Given their strong support for equal treatment and social inclusion, EU justices will be more likely than member-state or ECHR judges to overturn existing bans on hejab at the workplace, once such a case makes its way onto the ECJ docket.

  19. Human rights, public health and medicinal cannabis use.

    Science.gov (United States)

    Bone, Melissa; Seddon, Toby

    2016-01-01

    This paper explores the interplay between the human rights and drug control frameworks and critiques case law on medicinal cannabis use to demonstrate that a bona fide human rights perspective allows for a broader conception of 'health'. This broad conception, encompassing both medicalised and social constructionist definitions, can inform public health policies relating to medicinal cannabis use. The paper also demonstrates how a human rights lens can alleviate a core tension between the State and the individual within the drug policy field. The leading medicinal cannabis case in the UK highlights the judiciary's failure to engage with an individual's human right to health as they adopt an arbitrary, externalist view, focussing on the legality of cannabis to the exclusion of other concerns. Drawing on some international comparisons, the paper considers how a human rights perspective can lead to an approach to medicinal cannabis use which facilitates a holistic understanding of public health.

  20. Autologous blood cell therapies from pluripotent stem cells

    Science.gov (United States)

    Lengerke, Claudia; Daley, George Q.

    2010-01-01

    Summary The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.g. without the use of oncoproteins and gene transfer based on viruses inserting randomly into the genome), a major challenge in the field remains how to efficiently differentiate PSCs to specific lineages and how to select for cells that will function normally upon transplantation in adults. In this review, we analyse the in vitro differentiation potential of PSCs to the hematopoietic lineage discussing blood cell types that can be currently obtained, limitations in derivation of adult-type HSCs and prospects for clinical application of PSCs-derived blood cells. PMID:19910091

  1. Direct Genesis of Functional Rodent and Human Schwann Cells from Skin Mesenchymal Precursors

    Directory of Open Access Journals (Sweden)

    Matthew P. Krause

    2014-07-01

    Full Text Available Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs, a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought.

  2. Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies.

    Science.gov (United States)

    Tardivel, Meryem; Bégard, Séverine; Bousset, Luc; Dujardin, Simon; Coens, Audrey; Melki, Ronald; Buée, Luc; Colin, Morvane

    2016-11-04

    A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer's disease, is a bona fide constituent of TNTs. This is important because Tau appears beside filamentous actin and myosin 10 as a specific marker of these fine protrusions of membranes and cytosol that are difficult to visualize. Furthermore, we observed that exogenous Tau species increase the number of TNTs established between primary neurons, thereby facilitating the intercellular transfer of Tau fibrils. In conclusion, Tau may contribute to the formation and function of the highly dynamic TNTs that may be involved in the prion-like propagation of Tau assemblies.

  3. Semi-supervised Learning Predicts Approximately One Third of the Alternative Splicing Isoforms as Functional Proteins

    Directory of Open Access Journals (Sweden)

    Yanqi Hao

    2015-07-01

    Full Text Available Alternative splicing acts on transcripts from almost all human multi-exon genes. Notwithstanding its ubiquity, fundamental ramifications of splicing on protein expression remain unresolved. The number and identity of spliced transcripts that form stably folded proteins remain the sources of considerable debate, due largely to low coverage of experimental methods and the resulting absence of negative data. We circumvent this issue by developing a semi-supervised learning algorithm, positive unlabeled learning for splicing elucidation (PULSE; http://www.kimlab.org/software/pulse, which uses 48 features spanning various categories. We validated its accuracy on sets of bona fide protein isoforms and directly on mass spectrometry (MS spectra for an overall AU-ROC of 0.85. We predict that around 32% of “exon skipping” alternative splicing events produce stable proteins, suggesting that the process engenders a significant number of previously uncharacterized proteins. We also provide insights into the distribution of positive isoforms in various functional classes and into the structural effects of alternative splicing.

  4. Myxoma virus M130R is a novel virulence factor required for lethal myxomatosis in rabbits.

    Science.gov (United States)

    Barrett, John W; Werden, Steven J; Wang, Fuan; McKillop, William M; Jimenez, June; Villeneuve, Danielle; McFadden, Grant; Dekaban, Gregory A

    2009-09-01

    Myxoma virus (MV) is a highly lethal, rabbit-specific poxvirus that induces a disease called myxomatosis in European rabbits. In an effort to understand the function of predicted immunomodulatory genes we have deleted various viral genes from MV and tested the ability of these knockout viruses to induce lethal myxomatosis. MV encodes a unique 15 kD cytoplasmic protein (M130R) that is expressed late (12h post infection) during infection. M130R is a non-essential gene for MV replication in rabbit, monkey or human cell lines. Construction of a targeted gene knockout virus (vMyx130KO) and infection of susceptible rabbits demonstrate that the M130R knockout virus is attenuated and that loss of M130R expression allows the rabbit host immune system to effectively respond to and control the lethal effects of MV. M130R expression is a bona fide poxviral virulence factor necessary for full and lethal development of myxomatosis.

  5. Towards Holography via Quantum Source-Channel Codes

    Science.gov (United States)

    Pastawski, Fernando; Eisert, Jens; Wilming, Henrik

    2017-07-01

    While originally motivated by quantum computation, quantum error correction (QEC) is currently providing valuable insights into many-body quantum physics, such as topological phases of matter. Furthermore, mounting evidence originating from holography research (AdS/CFT) indicates that QEC should also be pertinent for conformal field theories. With this motivation in mind, we introduce quantum source-channel codes, which combine features of lossy compression and approximate quantum error correction, both of which are predicted in holography. Through a recent construction for approximate recovery maps, we derive guarantees on its erasure decoding performance from calculations of an entropic quantity called conditional mutual information. As an example, we consider Gibbs states of the transverse field Ising model at criticality and provide evidence that they exhibit nontrivial protection from local erasure. This gives rise to the first concrete interpretation of a bona fide conformal field theory as a quantum error correcting code. We argue that quantum source-channel codes are of independent interest beyond holography.

  6. Qualitative Methods in Patient-Centered Outcomes Research.

    Science.gov (United States)

    Vandermause, Roxanne; Barg, Frances K; Esmail, Laura; Edmundson, Lauren; Girard, Samantha; Perfetti, A Ross

    2017-02-01

    The Patient-Centered Outcomes Research Institute (PCORI), created to fund research guided by patients, caregivers, and the broader health care community, offers a new research venue. Many (41 of 50) first funded projects involved qualitative research methods. This study was completed to examine the current state of the science of qualitative methodologies used in PCORI-funded research. Principal investigators participated in phenomenological interviews to learn (a) how do researchers using qualitative methods experience seeking funding for, implementing and disseminating their work; and (b) how may qualitative methods advance the quality and relevance of evidence for patients? Results showed the experience of doing qualitative research in the current research climate as "Being a bona fide qualitative researcher: Staying true to research aims while negotiating challenges," with overlapping patterns: (a) researching the elemental, (b) expecting surprise, and (c) pushing boundaries. The nature of qualitative work today was explicitly described and is rendered in this article.

  7. RNA/DNA co-analysis from human saliva and semen stains--results of a third collaborative EDNAP exercise

    DEFF Research Database (Denmark)

    Haas, Claus; Hanson, E; Anjos, M J

    2013-01-01

    samples of human or non-human origin were analyzed by 20 participating laboratories using an RNA extraction or RNA/DNA co-extraction method. Two novel mRNA multiplexes were used: a saliva triplex (HTN3, STATH and MUC7) and a semen pentaplex (PRM1, PRM2, PSA, SEMG1 and TGM4). The laboratories used......A third collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling was organized by the European DNA Profiling Group (EDNAP). Twenty saliva and semen stains, four dilution series (10-0.01 µl saliva, 5-0.01 µl semen) and, optionally, bona fide or mock casework...... different chemistries and instrumentation and a majority (16/20) were able to successfully isolate and detect mRNA in dried stains. The simultaneous extraction of RNA and DNA from individual stains not only permitted a confirmation of the presence of saliva/semen (i.e. tissue/fluid source of origin...

  8. Subversion of inflammasome activation and pyroptosis by pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Larissa D Cunha

    2013-11-01

    Full Text Available Activation of the inflammasome occurs in response to a notably high number of pathogenic microbes and is a broad innate immune response that effectively contributes to restriction of pathogen replication and generation of adaptive immunity. Activation of these platforms leads to caspase-1- and/or caspase-11-dependent secretion of proteins, including cytokines, and induction of a specific form of cell death called pyroptosis, which directly or indirectly contribute for restriction of pathogen replication. Not surprisingly, bona fide intracellular pathogens developed strategies for manipulation of cell death to guarantee intracellular replication. In this sense, the remarkable advances in the knowledge of the inflammasome field have been accompanied by several reports characterizing the inhibition of this platform by several pathogenic bacteria. Herein, we review some processes used by pathogenic bacteria, including Yersinia spp., Pseudomonas aeruginosa, Vibrio parahaemolyticus, Chlamydia trachomatis, Francisella tularensis, Shigella flexneri, Legionella pneumophila and Coxiella burnetii to evade the activation of the inflammasome and the induction of pyroptosis.

  9. An Annotation Agnostic Algorithm for Detecting Nascent RNA Transcripts in GRO-Seq.

    Science.gov (United States)

    Azofeifa, Joseph G; Allen, Mary A; Lladser, Manuel E; Dowell, Robin D

    2017-01-01

    We present a fast and simple algorithm to detect nascent RNA transcription in global nuclear run-on sequencing (GRO-seq). GRO-seq is a relatively new protocol that captures nascent transcripts from actively engaged polymerase, providing a direct read-out on bona fide transcription. Most traditional assays, such as RNA-seq, measure steady state RNA levels which are affected by transcription, post-transcriptional processing, and RNA stability. GRO-seq data, however, presents unique analysis challenges that are only beginning to be addressed. Here, we describe a new algorithm, Fast Read Stitcher (FStitch), that takes advantage of two popular machine-learning techniques, hidden Markov models and logistic regression, to classify which regions of the genome are transcribed. Given a small user-defined training set, our algorithm is accurate, robust to varying read depth, annotation agnostic, and fast. Analysis of GRO-seq data without a priori need for annotation uncovers surprising new insights into several aspects of the transcription process.

  10. Pore-forming activity of pestivirus p7 in a minimal model system supports genus-specific viroporin function.

    Science.gov (United States)

    Largo, Eneko; Gladue, Douglas P; Huarte, Nerea; Borca, Manuel V; Nieva, José L

    2014-01-01

    Viroporins are small integral membrane proteins functional in viral assembly and egress by promoting permeabilization. Blocking of viroporin function therefore constitutes a target for antiviral development. Classical swine fever virus (CSFV) protein p7 has been recently regarded as a class II viroporin. Here, we sought to establish the determinants of the CSFV p7 permeabilizing activity in a minimal model system. Assessment of an overlapping peptide library mapped the porating domain to the C-terminal hydrophobic stretch (residues 39-67). Pore-opening dependence on pH or sensitivity to channel blockers observed for the full protein required the inclusion of a preceding polar sequence (residues 33-38). Effects of lipid composition and structural data further support that the resulting peptide (residues 33-67), may comprise a bona fide surrogate to assay p7 activity in model membranes. Our observations imply that CSFV p7 relies on genus-specific structures-mechanisms to perform its viroporin function. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence

    Directory of Open Access Journals (Sweden)

    Camila Ferreira de Souza

    2018-04-01

    Full Text Available Summary: Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal analysis of diffuse gliomas from 77 patients (200 tumors to enlighten the epigenome-based malignant transformation of initially lower-grade gliomas. Intra-subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify predictive biomarkers for assessing the risk of malignant recurrence at early stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic phenotype, and genomic instability. Molecular abnormalities of longitudinal G-CIMP offer possibilities to defy glioblastoma progression. : IDH-mutant lower-grade glioma glioblastoma often progresses to a more aggressive phenotype upon recurrence. de Souza et al. examines the intra-subtype heterogeneity of initial G-CIMP-high and use this information to identify predictive biomarkers for assessing the risk of recurrence and malignant transformation. Keywords: longitudinal gliomas, DNA methylation, IDH mutation, G-CIMP-high, intra-subtype heterogeneity, malignant transformation and recurrence, G-CIMP-low, stem cell-like glioblastoma, predictive biomarkers

  12. Ewing's Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue.

    Science.gov (United States)

    Parafioriti, Antonina; Bason, Caterina; Armiraglio, Elisabetta; Calciano, Lucia; Daolio, Primo Andrea; Berardocco, Martina; Di Bernardo, Andrea; Colosimo, Alessia; Luksch, Roberto; Berardi, Anna C

    2016-04-30

    The molecular mechanism responsible for Ewing's Sarcoma (ES) remains largely unknown. MicroRNAs (miRNAs), a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs) by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis.

  13. 26th August 2010 - World Meteorological Organization Secretary-General M. Jarraud signing the guest book with CERN Director-General R. Heuer and visiting the LHC superconducting magnet test hall with Technology Department Head F. Bordry; throughout accompanied by M. Bona, CERN Relations with International Organisations

    CERN Multimedia

    Maximilien Brice

    2010-01-01

    26th August 2010 - World Meteorological Organization Secretary-General M. Jarraud signing the guest book with CERN Director-General R. Heuer and visiting the LHC superconducting magnet test hall with Technology Department Head F. Bordry; throughout accompanied by M. Bona, CERN Relations with International Organisations

  14. Protection of Fundamental Rights Post-Lisbon:The Interaction between the EU Charter of Fundamental Rights, the European Convention on Human Rights (ECHR) and National Constitutions (FIDE National Report for the United Kingdom)

    OpenAIRE

    Lock, Tobias; Layden, Patrick

    2011-01-01

    This is the United Kingdom national report for the FIDE XXV Congress on the 'Protection of Fundamental Rights Post-Lisbon'. The national report consist of answers from a UK perspective to questions posed by the general rapporteur on the following general topics: Nature and scope of fundamental rights protected; Horizontal Effect and Collision of rights; Consequences of the entry into force of the EU Charter of Fundamental Rights; Consequences of the accession of the EU to the ECHR; The future...

  15. Heterozygous mutations of FREM1 are associated with an increased risk of isolated metopic craniosynostosis in humans and mice.

    Directory of Open Access Journals (Sweden)

    Lisenka E L M Vissers

    2011-09-01

    Full Text Available The premature fusion of the paired frontal bones results in metopic craniosynostosis (MC and gives rise to the clinical phenotype of trigonocephaly. Deletions of chromosome 9p22.3 are well described as a cause of MC with variably penetrant midface hypoplasia. In order to identify the gene responsible for the trigonocephaly component of the 9p22.3 syndrome, a cohort of 109 patients were assessed by high-resolution arrays and MLPA for copy number variations (CNVs involving 9p22. Five CNVs involving FREM1, all of which were de novo variants, were identified by array-based analyses. The remaining 104 patients with MC were then subjected to targeted FREM1 gene re-sequencing, which identified 3 further mutant alleles, one of which was de novo. Consistent with a pathogenic role, mouse Frem1 mRNA and protein expression was demonstrated in the metopic suture as well as in the pericranium and dura mater. Micro-computed tomography based analyses of the mouse posterior frontal (PF suture, the human metopic suture equivalent, revealed advanced fusion in all mice homozygous for either of two different Frem1 mutant alleles, while heterozygotes exhibited variably penetrant PF suture anomalies. Gene dosage-related penetrance of midfacial hypoplasia was also evident in the Frem1 mutants. These data suggest that CNVs and mutations involving FREM1 can be identified in a significant percentage of people with MC with or without midface hypoplasia. Furthermore, we present Frem1 mutant mice as the first bona fide mouse model of human metopic craniosynostosis and a new model for midfacial hypoplasia.

  16. Prognostic classification of MDS is improved by the inclusion of FISH panel testing with conventional cytogenetics.

    Science.gov (United States)

    Kokate, Prajakta; Dalvi, Rupa; Koppaka, Neeraja; Mandava, Swarna

    2017-10-01

    Cytogenetics is a critical independent prognostic factor in myelodysplastic syndromes (MDS). Conventional cytogenetics (CC) and Fluorescence in situ hybridization (FISH) Panel Testing are extensively used for the prognostic stratification of MDS, although the FISH test is not yet a bona fide component of the International Prognostic Scoring System (IPSS). The present study compares the utility of CC and FISH to detect chromosomal anomalies and in prognostic categorization. GTG-Banding and FISH Panel Testing specifically for -5/-5q, -7/-7q, +8 and -20q was performed on whole blood or bone marrow samples from 136 patients with MDS. Chromosomal anomalies were found in 40 cases by CC, including three novel translocations. FISH identified at least one anomaly in 54/136 (39.7%) cases. More than one anomaly was found in 18/54 (33.3%) cases, therefore, overall FISH identified 75 anomalies of which 32 (42.6%) were undetected by CC. FISH provided additional information in cases with CC failure and in cases with a normal karyotype. Further, in ten cases with an abnormal karyotype, FISH could identify additional anomalies, increasing the number of abnormalities per patient. Although CC is the gold standard in the cytogenetic profiling of MDS, FISH has proven to be an asset in identifying additional abnormalities. The number of anomalies per patient can predict the prognosis in MDS and hence, FISH contributed towards prognostic re-categorization. The FISH Panel testing should be used as an adjunct to CC, irrespective of the adequacy of the number of metaphases in CC, as it improves the prognostic classification of MDS. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Arabidopsis SUMO protease ASP1 positively regulates flowering time partially through regulating FLC stability 

    KAUST Repository

    Kong, Xiangxiong; Luo, Xi; Qu, Gao Ping; Liu, Peng; Jin, Jing Bo

    2016-01-01

    The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C (FLC), a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1 (ASP1) resulted in a strong late-flowering phenotype under long-days, but to a lesser extent under short-days. ASP1 localizes in the nucleus and exhibited a SUMO protease activity in vitro and in vivo. The conserved Cys-577 in ASP1 is critical for its enzymatic activity, as well as its physiological function in the regulation of flowering time. Genetic and gene expression analyses demonstrated that ASP1 promotes transcription of positive regulators of flowering, such as FT, SOC1 and FD, and may function in both CO-dependent photoperiod pathway and FLC-dependent pathways. Although the transcription level of FLC was not affected in the loss-of-function asp1 mutant, the protein stability of FLC was increased in the asp1 mutant. Taken together, this study identified a novel bona fide SUMO protease, ASP1, which positively regulates transition to flowering at least partly by repressing FLC protein stability.

  18. Functional characterisation of parvulin-type peptidyl prolyl cis-trans isomerase, PinA in Dictyostelium discoideum

    International Nuclear Information System (INIS)

    Haokip, Nemneineng; Naorem, Aruna

    2017-01-01

    Pin1-type parvulins are unique among PPIases that can catalyse an otherwise slow cis-trans isomerisation of phosphorylated peptide bond preceding proline in target proteins. This prolyl isomerisation process can regulate activity, stability and localisation of target proteins and thus control cellular processes like eukaryotic cell proliferation, cell cycle progression and gene regulation. Towards understanding the function of Pin1-type prolyl isomerisation in Dictyostelium discoideum, a slime mould with distinct growth and developmental phases, we identified PinA as a novel Pin1-type parvulin by its ability to complement the temperature sensitivity phenotype associated with a mutation in ESS1 in S. cerevisiae. In D. discoideum, pinA is temporally and spatially regulated during growth and development. PinA is both nuclear as well as cytoplasmic in the growing cells. We further show that loss of pinA (pinA − ) leads to decreased growth rate, reduced spore formation and abnormal prespore-prestalk patterning. We conclude that PinA is required for normal growth as well as development in D. discoideum. - Highlights: • PinA is a bona fide homologue of S. cerevisiae Ess1. • PinA is required for normal cell proliferation of D. discoideum. • PinA is spatially localised in developmental structures. • PinA is important for cell differentiation and patterning.

  19. Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation.

    Science.gov (United States)

    Marsolier, J; Perichon, M; DeBarry, J D; Villoutreix, B O; Chluba, J; Lopez, T; Garrido, C; Zhou, X Z; Lu, K P; Fritsch, L; Ait-Si-Ali, S; Mhadhbi, M; Medjkane, S; Weitzman, J B

    2015-04-16

    Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PIN1 in T. annulata (TaPIN1) that is secreted into the host cell and modulates oncogenic signalling pathways. Here we show that TaPIN1 is a bona fide prolyl isomerase and that it interacts with the host ubiquitin ligase FBW7, leading to its degradation and subsequent stabilization of c-JUN, which promotes transformation. We performed in vitro and in silico analysis and in vivo zebrafish xenograft experiments to demonstrate that TaPIN1 is directly inhibited by the anti-parasite drug buparvaquone (and other known PIN1 inhibitors) and is mutated in a drug-resistant strain. Prolyl isomerization is thus a conserved mechanism that is important in cancer and is used by Theileria parasites to manipulate host oncogenic signalling.

  20. Unfolded Protein Response (UPR Regulator Cib1 Controls Expression of Genes Encoding Secreted Virulence Factors in Ustilago maydis.

    Directory of Open Access Journals (Sweden)

    Martin Hampel

    Full Text Available The unfolded protein response (UPR, a conserved eukaryotic signaling pathway to ensure protein homeostasis in the endoplasmic reticulum (ER, coordinates biotrophic development in the corn smut fungus Ustilago maydis. Exact timing of UPR activation is required for virulence and presumably connected to the elevated expression of secreted effector proteins during infection of the host plant Zea mays. In the baker's yeast Saccharomyces cerevisiae, expression of UPR target genes is induced upon binding of the central regulator Hac1 to unfolded protein response elements (UPREs in their promoters. While a role of the UPR in effector secretion has been described previously, we investigated a potential UPR-dependent regulation of genes encoding secreted effector proteins. In silico prediction of UPREs in promoter regions identified the previously characterized effector genes pit2 and tin1-1, as bona fide UPR target genes. Furthermore, direct binding of the Hac1-homolog Cib1 to the UPRE containing promoter fragments of both genes was confirmed by quantitative chromatin immunoprecipitation (qChIP analysis. Targeted deletion of the UPRE abolished Cib1-dependent expression of pit2 and significantly affected virulence. Furthermore, ER stress strongly increased Pit2 expression and secretion. This study expands the role of the UPR as a signal hub in fungal virulence and illustrates, how biotrophic fungi can coordinate cellular physiology, development and regulation of secreted virulence factors.

  1. Recruitment of the major vault protein by InlK: a Listeria monocytogenes strategy to avoid autophagy.

    Directory of Open Access Journals (Sweden)

    Laurent Dortet

    2011-08-01

    Full Text Available L. monocytogenes is a facultative intracellular bacterium responsible for listeriosis. It is able to invade, survive and replicate in phagocytic and non-phagocytic cells. The infectious process at the cellular level has been extensively studied and many virulence factors have been identified. Yet, the role of InlK, a member of the internalin family specific to L. monocytogenes, remains unknown. Here, we first show using deletion analysis and in vivo infection, that InlK is a bona fide virulence factor, poorly expressed in vitro and well expressed in vivo, and that it is anchored to the bacterial surface by sortase A. We then demonstrate by a yeast two hybrid screen using InlK as a bait, validated by pulldown experiments and immunofluorescence analysis that intracytosolic bacteria via an interaction with the protein InlK interact with the Major Vault Protein (MVP, the main component of cytoplasmic ribonucleoproteic particules named vaults. Although vaults have been implicated in several cellular processes, their role has remained elusive. Our analysis demonstrates that MVP recruitment disguises intracytosolic bacteria from autophagic recognition, leading to an increased survival rate of InlK over-expressing bacteria compared to InlK(- bacteria. Together these results reveal that MVP is hijacked by L. monocytogenes in order to counteract the autophagy process, a finding that could have major implications in deciphering the cellular role of vault particles.

  2. RaftProt: mammalian lipid raft proteome database.

    Science.gov (United States)

    Shah, Anup; Chen, David; Boda, Akash R; Foster, Leonard J; Davis, Melissa J; Hill, Michelle M

    2015-01-01

    RaftProt (http://lipid-raft-database.di.uq.edu.au/) is a database of mammalian lipid raft-associated proteins as reported in high-throughput mass spectrometry studies. Lipid rafts are specialized membrane microdomains enriched in cholesterol and sphingolipids thought to act as dynamic signalling and sorting platforms. Given their fundamental roles in cellular regulation, there is a plethora of information on the size, composition and regulation of these membrane microdomains, including a large number of proteomics studies. To facilitate the mining and analysis of published lipid raft proteomics studies, we have developed a searchable database RaftProt. In addition to browsing the studies, performing basic queries by protein and gene names, searching experiments by cell, tissue and organisms; we have implemented several advanced features to facilitate data mining. To address the issue of potential bias due to biochemical preparation procedures used, we have captured the lipid raft preparation methods and implemented advanced search option for methodology and sample treatment conditions, such as cholesterol depletion. Furthermore, we have identified a list of high confidence proteins, and enabled searching only from this list of likely bona fide lipid raft proteins. Given the apparent biological importance of lipid raft and their associated proteins, this database would constitute a key resource for the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Cancer immunogenomic approach to neoantigen discovery in a checkpoint blockade responsive murine model of oral cavity squamous cell carcinoma

    Science.gov (United States)

    Zolkind, Paul; Przybylski, Dariusz; Marjanovic, Nemanja; Nguyen, Lan; Lin, Tianxiang; Johanns, Tanner; Alexandrov, Anton; Zhou, Liye; Allen, Clint T.; Miceli, Alexander P.; Schreiber, Robert D.; Artyomov, Maxim; Dunn, Gavin P.; Uppaluri, Ravindra

    2018-01-01

    Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines. Here, we aimed to define a platform for checkpoint and other immunotherapy studies using syngeneic HNSCC cell line models (MOC2 and MOC22), and evaluated the association between mutation burden, predicted neoantigen landscape, infiltrating T cell populations and responsiveness of tumors to anti-PD1 therapy. We defined dramatic hematopoietic cell transcriptomic alterations in the MOC22 anti-PD1 responsive model in both tumor and draining lymph nodes. Using a cancer immunogenomics pipeline and validation with ELISPOT and tetramer analysis, we identified the H-2Kb-restricted ICAM1P315L (mICAM1) as a neoantigen in MOC22. Finally, we demonstrated that mICAM1 vaccination was able to protect against MOC22 tumor development defining mICAM1 as a bona fide neoantigen. Together these data define a pre-clinical HNSCC model system that provides a foundation for future investigations into combination and novel therapeutics. PMID:29423108

  4. Arabidopsis SUMO protease ASP1 positively regulates flowering time partially through regulating FLC stability 

    KAUST Repository

    Kong, Xiangxiong

    2016-12-07

    The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C (FLC), a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1 (ASP1) resulted in a strong late-flowering phenotype under long-days, but to a lesser extent under short-days. ASP1 localizes in the nucleus and exhibited a SUMO protease activity in vitro and in vivo. The conserved Cys-577 in ASP1 is critical for its enzymatic activity, as well as its physiological function in the regulation of flowering time. Genetic and gene expression analyses demonstrated that ASP1 promotes transcription of positive regulators of flowering, such as FT, SOC1 and FD, and may function in both CO-dependent photoperiod pathway and FLC-dependent pathways. Although the transcription level of FLC was not affected in the loss-of-function asp1 mutant, the protein stability of FLC was increased in the asp1 mutant. Taken together, this study identified a novel bona fide SUMO protease, ASP1, which positively regulates transition to flowering at least partly by repressing FLC protein stability.

  5. Regulatory T-cells in autoimmune diseases: challenges, controversies and--yet--unanswered questions.

    Science.gov (United States)

    Grant, Charlotte R; Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego; Longhi, Maria Serena

    2015-02-01

    Regulatory T cells (Tregs) are central to the maintenance of self-tolerance and tissue homeostasis. Markers commonly used to define human Tregs in the research setting include high expression of CD25, FOXP3 positivity and low expression/negativity for CD127. Many other markers have been proposed, but none unequivocally identifies bona fide Tregs. Tregs are equipped with an array of mechanisms of suppression, including the modulation of antigen presenting cell maturation and function, the killing of target cells, the disruption of metabolic pathways and the production of anti-inflammatory cytokines. Treg impairment has been reported in a number of human autoimmune conditions and includes Treg numerical and functional defects and conversion into effector cells in response to inflammation. In addition to intrinsic Treg impairment, resistance of effector T cells to Treg control has been described. Discrepancies in the literature are common, reflecting differences in the choice of study participants and the technical challenges associated with investigating this cell population. Studies differ in terms of the methodology used to define and isolate putative regulatory cells and to assess their suppressive function. In this review we outline studies describing Treg frequency and suppressive function in systemic and organ specific autoimmune diseases, with a specific focus on the challenges faced when investigating Tregs in these conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. The putative Leishmania telomerase RNA (LeishTER undergoes trans-splicing and contains a conserved template sequence.

    Directory of Open Access Journals (Sweden)

    Elton J R Vasconcelos

    Full Text Available Telomerase RNAs (TERs are highly divergent between species, varying in size and sequence composition. Here, we identify a candidate for the telomerase RNA component of Leishmania genus, which includes species that cause leishmaniasis, a neglected tropical disease. Merging a thorough computational screening combined with RNA-seq evidence, we mapped a non-coding RNA gene localized in a syntenic locus on chromosome 25 of five Leishmania species that shares partial synteny with both Trypanosoma brucei TER locus and a putative TER candidate-containing locus of Crithidia fasciculata. Using target-driven molecular biology approaches, we detected a ∼2,100 nt transcript (LeishTER that contains a 5' spliced leader (SL cap, a putative 3' polyA tail and a predicted C/D box snoRNA domain. LeishTER is expressed at similar levels in the logarithmic and stationary growth phases of promastigote forms. A 5'SL capped LeishTER co-immunoprecipitated and co-localized with the telomerase protein component (TERT in a cell cycle-dependent manner. Prediction of its secondary structure strongly suggests the existence of a bona fide single-stranded template sequence and a conserved C[U/C]GUCA motif-containing helix II, representing the template boundary element. This study paves the way for further investigations on the biogenesis of parasite TERT ribonucleoproteins (RNPs and its role in parasite telomere biology.

  7. Location analysis for the estrogen receptor-α reveals binding to diverse ERE sequences and widespread binding within repetitive DNA elements

    Science.gov (United States)

    Mason, Christopher E.; Shu, Feng-Jue; Wang, Cheng; Session, Ryan M.; Kallen, Roland G.; Sidell, Neil; Yu, Tianwei; Liu, Mei Hui; Cheung, Edwin; Kallen, Caleb B.

    2010-01-01

    Location analysis for estrogen receptor-α (ERα)-bound cis-regulatory elements was determined in MCF7 cells using chromatin immunoprecipitation (ChIP)-on-chip. Here, we present the estrogen response element (ERE) sequences that were identified at ERα-bound loci and quantify the incidence of ERE sequences under two stringencies of detection: ERE sequence. We demonstrate that ∼50% of all ERα-bound loci do not have a discernable ERE and show that most ERα-bound EREs are not perfect consensus EREs. Approximately one-third of all ERα-bound ERE sequences reside within repetitive DNA sequences, most commonly of the AluS family. In addition, the 3-bp spacer between the inverted ERE half-sites, rather than being random nucleotides, is C(A/T)G-enriched at bona fide receptor targets. Diverse ERα-bound loci were validated using electrophoretic mobility shift assay and ChIP-polymerase chain reaction (PCR). The functional significance of receptor-bound loci was demonstrated using luciferase reporter assays which proved that repetitive element ERE sequences contribute to enhancer function. ChIP-PCR demonstrated estrogen-dependent recruitment of the coactivator SRC3 to these loci in vivo. Our data demonstrate that ERα binds to widely variant EREs with less sequence specificity than had previously been suspected and that binding at repetitive and nonrepetitive genomic targets is favored by specific trinucleotide spacers. PMID:20047966

  8. Location analysis for the estrogen receptor-alpha reveals binding to diverse ERE sequences and widespread binding within repetitive DNA elements.

    Science.gov (United States)

    Mason, Christopher E; Shu, Feng-Jue; Wang, Cheng; Session, Ryan M; Kallen, Roland G; Sidell, Neil; Yu, Tianwei; Liu, Mei Hui; Cheung, Edwin; Kallen, Caleb B

    2010-04-01

    Location analysis for estrogen receptor-alpha (ERalpha)-bound cis-regulatory elements was determined in MCF7 cells using chromatin immunoprecipitation (ChIP)-on-chip. Here, we present the estrogen response element (ERE) sequences that were identified at ERalpha-bound loci and quantify the incidence of ERE sequences under two stringencies of detection: ERE sequence. We demonstrate that approximately 50% of all ERalpha-bound loci do not have a discernable ERE and show that most ERalpha-bound EREs are not perfect consensus EREs. Approximately one-third of all ERalpha-bound ERE sequences reside within repetitive DNA sequences, most commonly of the AluS family. In addition, the 3-bp spacer between the inverted ERE half-sites, rather than being random nucleotides, is C(A/T)G-enriched at bona fide receptor targets. Diverse ERalpha-bound loci were validated using electrophoretic mobility shift assay and ChIP-polymerase chain reaction (PCR). The functional significance of receptor-bound loci was demonstrated using luciferase reporter assays which proved that repetitive element ERE sequences contribute to enhancer function. ChIP-PCR demonstrated estrogen-dependent recruitment of the coactivator SRC3 to these loci in vivo. Our data demonstrate that ERalpha binds to widely variant EREs with less sequence specificity than had previously been suspected and that binding at repetitive and nonrepetitive genomic targets is favored by specific trinucleotide spacers.

  9. Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

    Science.gov (United States)

    Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

    2010-01-01

    Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

  10. The β Pictoris association low-mass members: Membership assessment, rotation period distribution, and dependence on multiplicity

    Science.gov (United States)

    Messina, S.; Lanzafame, A. C.; Malo, L.; Desidera, S.; Buccino, A.; Zhang, L.; Artemenko, S.; Millward, M.; Hambsch, F.-J.

    2017-10-01

    Context. Low-mass members of young loose stellar associations and open clusters exhibit a wide spread of rotation periods. Such a spread originates from the distributions of masses and initial rotation periods. However, multiplicity can also play a significant role. Aims: We aim to investigate the role played by physical companions in multiple systems in shortening the primordial disk lifetime, anticipating the rotation spin up with respect to single stars. Methods: We have compiled the most extensive list to date of low-mass bona fide and candidate members of the young 25-Myr β Pictoris association. We have measured from our own photometric time series or from archival time series the rotation periods of almost all members. In a few cases the rotation periods were retrieved from the literature. We used updated UVWXYZ components to assess the membership of the whole stellar sample. Thanks to the known basic properties of most members we built the rotation period distribution distinguishing between bona fide members and candidate members and according to their multiplicity status. Results: We find that single stars and components of multiple systems in wide orbits (>80 AU) have rotation periods that exhibit a well defined sequence arising from mass distribution with some level of spread likely arising from initial rotation period distribution. All components of multiple systems in close orbits (Pleiades shows that whereas the evolution of F-G stars is well reproduced by angular momentum evolution models, this is not the case for the slow K and early-M stars. Finally, we find that the amplitude of their light curves is correlated neither with rotation nor with mass. Conclusions: Once single stars and wide components of multiple systems are separated from close components of multiple systems, the rotation period distributions exhibit a well defined dependence on mass that allows us to make a meaningful comparison with similar distributions of either younger or older

  11. ‘Ekhaya: Human displacement and the yearning for familial homecoming. From Throne (Cathedra to Home (Oikos in a grassroots ecclesiology of place and space: Fides Quaerens Domum et Locum [Faith Seeking Home and Space

    Directory of Open Access Journals (Sweden)

    Daniel J. Louw

    2017-04-01

    Full Text Available The classical definition of theology is ‘faith-seeking understanding’ (fides quaerens intellectum. The focus is on the understanding/interpretation of the object of Christian faith: God. There is another root for the quest for understanding, namely the praxis situation of faith. People live in particular historical contexts that have their own distinctive problems and possibilities; thus, the focus on place and space in a theology of home. A praxis approach is to learn life and the gospel from below, thus the emphasis on a grassroots ecclesiology that is structured like an oikos, a familial dwelling place. This understanding of the dynamics of the fellowship of believers as  oikodomein is captured by the Zulu notion for the yearning for home (home sickness: Ekhaya. It is argued that Ekhaya thinking is an alternative route for an operative ecclesiology that caters for the need of marginalised, oppressed, displaced and homeless people. Practical theology is thus described as fides  quaerens domum et locum [faith-seeking home and place], namely to inhabit. An Ekhaya approach to practical theological ecclesiology is about critical reflection through the eyes of those who are weak and who don’t count for much by the standards of successful people and institutions.

  12. Cellular repressor of E1A-stimulated genes is a bona fide lysosomal protein which undergoes proteolytic maturation during its biosynthesis

    International Nuclear Information System (INIS)

    Schaehs, Philipp; Weidinger, Petra; Probst, Olivia C.; Svoboda, Barbara; Stadlmann, Johannes; Beug, Hartmut; Waerner, Thomas; Mach, Lukas

    2008-01-01

    Cellular repressor of E1A-stimulated genes (CREG) has been reported to be a secretory glycoprotein implicated in cellular growth and differentiation. We now show that CREG is predominantly localized within intracellular compartments. Intracellular CREG was found to lack an N-terminal peptide present in the secreted form of the protein. In contrast to normal cells, CREG is largely secreted by fibroblasts missing both mannose 6-phosphate receptors. This is not observed in cells lacking only one of them. Mass spectrometric analysis of recombinant CREG revealed that the protein contains phosphorylated oligosaccharides at either of its two N-glycosylation sites. Cellular CREG was found to cosediment with lysosomal markers upon subcellular fractionation by density-gradient centrifugation. In fibroblasts expressing a CREG-GFP fusion construct, the heterologous protein was detected in compartments containing lysosomal proteins. Immunolocalization of endogenous CREG confirmed that intracellular CREG is localized in lysosomes. Proteolytic processing of intracellular CREG involves the action of lysosomal cysteine proteinases. These results establish that CREG is a lysosomal protein that undergoes proteolytic maturation in the course of its biosynthesis, carries the mannose 6-phosphate recognition marker and depends on the interaction with mannose 6-phosphate receptors for efficient delivery to lysosomes

  13. Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from Shigella flexneri.

    Science.gov (United States)

    Burgess, Jamie L; Jones, Heather B; Kumar, Prashant; Toth, Ronald T; Middaugh, C Russell; Antony, Edwin; Dickenson, Nicholas E

    2016-05-01

    Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents. © 2016 The Protein Society.

  14. Discord of response

    International Nuclear Information System (INIS)

    Roga, W; Illuminati, F; Giampaolo, S M

    2014-01-01

    The presence of quantum correlations in a quantum state is related to the state's response to local unitary perturbations. Such a response is quantified by the distance between the unperturbed and perturbed states, minimized with respect to suitably identified sets of local unitary operations. In order to be a bona fide measure of quantum correlations, the distance function must be chosen among those that are contractive under completely positive and trace preserving (CPTP) maps. The most relevant instances of such physically well-behaved metrics include the trace, the Bures, and the Hellinger distance. To each of these metrics one can associate the corresponding discord of response, namely the trace, or Hellinger, or Bures minimum distance from the set of unitarily perturbed states. All these three discords of response satisfy the basic axioms for a proper measure of quantum correlations. In the present work we focus in particular on the Bures distance, which enjoys the unique property of being both Riemannian and contractive under CPTP maps, and admits important operational interpretations in terms of state distinguishability. We compute analytically the Bures discord of response for two-qubit states with maximally mixed marginals and we compare it with the corresponding Bures geometric discord, namely the geometric measure of quantum correlations defined as the Bures distance from the set of classical-quantum states. Finally, we investigate and identify the maximally quantum correlated two-qubit states according to the Bures discord of response. These states exhibit a remarkable nonlinear dependence on the global state purity. (paper)

  15. Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor-β/δ (PPARβ/δ.

    Directory of Open Access Journals (Sweden)

    Till Adhikary

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are nuclear receptors with essential functions in lipid, glucose and energy homeostasis, cell differentiation, inflammation and metabolic disorders, and represent important drug targets. PPARs heterodimerize with retinoid X receptors (RXRs and can form transcriptional activator or repressor complexes at specific DNA elements (PPREs. It is believed that the decision between repression and activation is generally governed by a ligand-mediated switch. We have performed genomewide analyses of agonist-treated and PPARβ/δ-depleted human myofibroblasts to test this hypothesis and to identify global principles of PPARβ/δ-mediated gene regulation. Chromatin immunoprecipitation sequencing (ChIP-Seq of PPARβ/δ, H3K4me3 and RNA polymerase II enrichment sites combined with transcriptional profiling enabled the definition of 112 bona fide PPARβ/δ target genes showing either of three distinct types of transcriptional response: (I ligand-independent repression by PPARβ/δ; (II ligand-induced activation and/or derepression by PPARβ/δ; and (III ligand-independent activation by PPARβ/δ. These data identify PPRE-mediated repression as a major mechanism of transcriptional regulation by PPARβ/δ, but, unexpectedly, also show that only a subset of repressed genes are activated by a ligand-mediated switch. Our results also suggest that the type of transcriptional response by a given target gene is connected to the structure of its associated PPRE(s and the biological function of its encoded protein. These observations have important implications for understanding the regulatory PPAR network and PPARβ/δ ligand-based drugs.

  16. Novel carotenoid cleavage dioxygenase catalyzes the first dedicated step in saffron crocin biosynthesis

    KAUST Repository

    Frusciante, Sarah; Diretto, Gianfranco; Bruno, Mark; Ferrante, Paola; Pietrella, Marco; Prado-Cabrero, Alfonso; Rubio-Moraga, Á ngela L.; Beyer, Peter D.; Gó mez-Gó mez, Lourdes; Al-Babili, Salim; Giuliano, Giovanni

    2014-01-01

    Crocus sativus stigmas are the source of the saffron spice and accumulate the apocarotenoids crocetin, crocins, picrocrocin, and safranal, responsible for its color, taste, and aroma. Through deep transcriptome sequencing, we identified a novel dioxygenase, carotenoid cleavage dioxygenase 2 (CCD2), expressed early during stigma development and closely related to, but distinct from, the CCD1 dioxygenase family. CCD2 is the only identified member of a novel CCD clade, presents the structural features of a bona fide CCD, and is able to cleave zeaxanthin, the presumed precursor of saffron apocarotenoids, both in Escherichia coli and in maize endosperm. The cleavage products, identified through high-resolution mass spectrometry and comigration with authentic standards, are crocetin dialdehyde and crocetin, respectively. In vitro assays show that CCD2 cleaves sequentially the 7,8 and 7′,8′ double bonds adjacent to a 3-OH-β-ionone ring and that the conversion of zeaxanthin to crocetin dialdehyde proceeds via the C30 intermediate 3-OH-β-apo-8′-carotenal. In contrast, zeaxanthin cleavage dioxygenase (ZCD), an enzyme previously claimed to mediate crocetin formation, did not cleave zeaxanthin or 3-OH-β-apo-8′-carotenal in the test systems used. Sequence comparison and structure prediction suggest that ZCD is an N-truncated CCD4 form, lacking one blade of the β-propeller structure conserved in all CCDs. These results constitute strong evidence that CCD2 catalyzes the first dedicated step in crocin biosynthesis. Similar to CCD1, CCD2 has a cytoplasmic localization, suggesting that it may cleave carotenoids localized in the chromoplast outer envelope.

  17. Identification of the arabidopsis RAM/MOR signalling network: adding new regulatory players in plant stem cell maintenance and cell polarization

    Science.gov (United States)

    Zermiani, Monica; Begheldo, Maura; Nonis, Alessandro; Palme, Klaus; Mizzi, Luca; Morandini, Piero; Nonis, Alberto; Ruperti, Benedetto

    2015-01-01

    Background and Aims The RAM/MOR signalling network of eukaryotes is a conserved regulatory module involved in co-ordination of stem cell maintenance, cell differentiation and polarity establishment. To date, no such signalling network has been identified in plants. Methods Genes encoding the bona fide core components of the RAM/MOR pathway were identified in Arabidopsis thaliana (arabidopsis) by sequence similarity searches conducted with the known components from other species. The transcriptional network(s) of the arabidopsis RAM/MOR signalling pathway were identified by running in-depth in silico analyses for genes co-regulated with the core components. In situ hybridization was used to confirm tissue-specific expression of selected RAM/MOR genes. Key Results Co-expression data suggested that the arabidopsis RAM/MOR pathway may include genes involved in floral transition, by co-operating with chromatin remodelling and mRNA processing/post-transcriptional gene silencing factors, and genes involved in the regulation of pollen tube polar growth. The RAM/MOR pathway may act upstream of the ROP1 machinery, affecting pollen tube polar growth, based on the co-expression of its components with ROP-GEFs. In silico tissue-specific co-expression data and in situ hybridization experiments suggest that different components of the arabidopsis RAM/MOR are expressed in the shoot apical meristem and inflorescence meristem and may be involved in the fine-tuning of stem cell maintenance and cell differentiation. Conclusions The arabidopsis RAM/MOR pathway may be part of the signalling cascade that converges in pollen tube polarized growth and in fine-tuning stem cell maintenance, differentiation and organ polarity. PMID:26078466

  18. Novel carotenoid cleavage dioxygenase catalyzes the first dedicated step in saffron crocin biosynthesis

    KAUST Repository

    Frusciante, Sarah

    2014-08-05

    Crocus sativus stigmas are the source of the saffron spice and accumulate the apocarotenoids crocetin, crocins, picrocrocin, and safranal, responsible for its color, taste, and aroma. Through deep transcriptome sequencing, we identified a novel dioxygenase, carotenoid cleavage dioxygenase 2 (CCD2), expressed early during stigma development and closely related to, but distinct from, the CCD1 dioxygenase family. CCD2 is the only identified member of a novel CCD clade, presents the structural features of a bona fide CCD, and is able to cleave zeaxanthin, the presumed precursor of saffron apocarotenoids, both in Escherichia coli and in maize endosperm. The cleavage products, identified through high-resolution mass spectrometry and comigration with authentic standards, are crocetin dialdehyde and crocetin, respectively. In vitro assays show that CCD2 cleaves sequentially the 7,8 and 7′,8′ double bonds adjacent to a 3-OH-β-ionone ring and that the conversion of zeaxanthin to crocetin dialdehyde proceeds via the C30 intermediate 3-OH-β-apo-8′-carotenal. In contrast, zeaxanthin cleavage dioxygenase (ZCD), an enzyme previously claimed to mediate crocetin formation, did not cleave zeaxanthin or 3-OH-β-apo-8′-carotenal in the test systems used. Sequence comparison and structure prediction suggest that ZCD is an N-truncated CCD4 form, lacking one blade of the β-propeller structure conserved in all CCDs. These results constitute strong evidence that CCD2 catalyzes the first dedicated step in crocin biosynthesis. Similar to CCD1, CCD2 has a cytoplasmic localization, suggesting that it may cleave carotenoids localized in the chromoplast outer envelope.

  19. Ewing’s Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue

    Directory of Open Access Journals (Sweden)

    Antonina Parafioriti

    2016-04-01

    Full Text Available The molecular mechanism responsible for Ewing’s Sarcoma (ES remains largely unknown. MicroRNAs (miRNAs, a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis.

  20. 15th December 2010 - World Intellectual Property Organization Director-General F. Gurry signing the guest book with CERN Director-General R. Heuer; visiting CMS control room, experimental cavern and LHC tunnel with Collaboration Deputy Spokesperson J. Incandela, accompanied by M. Bona.

    CERN Multimedia

    Maximilien Brice

    2010-01-01

    CERN-HI-1012325 36, from left to right: WIPO Arbitration and Mediation Center, Global Issues Sector Director E. Wilbers; CERN Adviser, Relations with International Organisations, M. Bona; CMS Collaboration Deputy Spokesperson, University of California Santa Barbara J. Incandela; WIPO Deputy Director General, Global Issues Sector J. C. Wichard; WIPO Director-General F. Gurry; WIPO Executive Director and Chief of Staff, Office of the Director General N. Prasad.

  1. Interlopers at the Fringes of Empire: The Procurators of the Propaganda Fide Papal Congregation in Canton and Macao, 1700-1823

    Directory of Open Access Journals (Sweden)

    Eugenio Menegon

    2017-12-01

    Full Text Available The office of the procurator of the papal Sacred Congregation for the Propagation of the Faith (Sacra Congregatio de Propaganda Fide offers a unique case study of noncommercial interloping in the long eighteenth century in the Pearl River Delta, and reveals the complexity and fluidity of life at the intersection of Asian and European maritime environments in that special human ecosystem. The oceanic infrastructure of the Age of Sail and the Sino-Western trade system in Canton sustained the Catholic missionary enterprise in Asia, and the professional figure of the procurator represented its economic and political linchpin. Procurators were agents connected with both European and Qing imperial formations, yet not directly at their service. They utilized existing maritime trade networks to their own advantage without being integral parts of those networks’ economic mechanisms. All the while, they subverted Qing prohibitions against Christianity. Using sources preserved in Rome, this article offers new insights into the global mechanisms of trade, communication, and religious exchange embodied by the procurators-interlopers and their networks, with significant implications for the history of the Sino-Western trade system, Qing policies toward the West and Christianity, and the history of Asian Catholic missions.

  2. Confirmation of the Luminous Blue Variable Status of MWC 930

    Directory of Open Access Journals (Sweden)

    A. S. Miroshnichenko

    2014-01-01

    Full Text Available We present spectroscopic and photometric observations of the emission-line star MWC 930 (V446 Sct during its long-term optical brightening in 2006–2013. Based on our earlier data we suggested that the object has features found in Luminous Blue Variables (LBV, such as a high luminosity (~3 105 L⊙, a low wind terminal velocity (~140 km s−1, and a tendency to show strong brightness variations (~1 mag over 20 years. For the last ~7 years it has been exhibiting a continuous optical and near-IR brightening along with a change of the emission-line spectrum appearance and cooling of the star’s photosphere. We present the object’s V-band light curve, analyze the spectral variations, and compare the observed properties with those of other recognized Galactic LBVs, such as AG Car and HR Car. Overall we conclude the MWC 930 is a bona fide Galactic LBV that is currently in the middle of an S Dor cycle.

  3. From Plant Infectivity to Growth Patterns: The Role of Blue-Light Sensing in the Prokaryotic World

    Directory of Open Access Journals (Sweden)

    Aba Losi

    2014-01-01

    Full Text Available Flavin-based photoreceptor proteins of the LOV (Light, Oxygen, and Voltage and BLUF (Blue Light sensing Using Flavins superfamilies are ubiquitous among the three life domains and are essential blue-light sensing systems, not only in plants and algae, but also in prokaryotes. Here we review their biological roles in the prokaryotic world and their evolution pathways. An unexpected large number of bacterial species possess flavin-based photosensors, amongst which are important human and plant pathogens. Still, few cases are reported where the activity of blue-light sensors could be correlated to infectivity and/or has been shown to be involved in the activation of specific genes, resulting in selective growth patterns. Metagenomics and bio-informatic analysis have only recently been initiated, but signatures are beginning to emerge that allow definition of a bona fide LOV or BLUF domain, aiming at better selection criteria for novel blue-light sensors. We also present here, for the first time, the phylogenetic tree for archaeal LOV domains that have reached a statistically significant number but have not at all been investigated thus far.

  4. Identification and functional analysis of a second RBF-2 binding site within the HIV-1 promoter

    International Nuclear Information System (INIS)

    Dahabieh, Matthew S.; Ooms, Marcel; Malcolm, Tom; Simon, Viviana; Sadowski, Ivan

    2011-01-01

    Transcription from the HIV-1 long terminal repeat (LTR) is mediated by numerous host transcription factors. In this study we characterized an E-box motif (RBE1) within the core promoter that was previously implicated in both transcriptional activation and repression. We show that RBE1 is a binding site for the RBF-2 transcription factor complex (USF1, USF2, and TFII-I), previously shown to bind an upstream viral element, RBE3. The RBE1 and RBE3 elements formed complexes of identical mobility and protein constituents in gel shift assays, both with Jurkat T-cell nuclear extracts and recombinant USF/TFII-I. Furthermore, both elements are regulators of HIV-1 expression; mutations in LTR-luciferase reporters and in HIV-1 molecular clones resulted in decreased transcription, virion production, and proviral expression in infected cells. Collectively, our data indicate that RBE1 is a bona fide RBF-2 binding site and that the RBE1 and RBE3 elements are necessary for mediating proper transcription from the HIV-1 LTR.

  5. Time evolution in quantum cosmology

    International Nuclear Information System (INIS)

    Lawrie, Ian D.

    2011-01-01

    A commonly adopted relational account of time evolution in generally covariant systems, and more specifically in quantum cosmology, is argued to be unsatisfactory, insofar as it describes evolution relative to observed readings of a clock that does not exist as a bona fide observable object. A modified strategy is proposed, in which evolution relative to the proper time that elapses along the worldline of a specific observer can be described through the introduction of a ''test clock,'' regarded as internal to, and hence unobservable by, that observer. This strategy is worked out in detail in the case of a homogeneous cosmology, in the context of both a conventional Schroedinger quantization scheme, and a 'polymer' quantization scheme of the kind inspired by loop quantum gravity. Particular attention is given to limitations placed on the observability of time evolution by the requirement that a test clock should contribute only a negligible energy to the Hamiltonian constraint. It is found that suitable compromises are available, in which the clock energy is reasonably small, while Dirac observables are reasonably sharply defined.

  6. AGN outflows as neutrino sources: an observational test

    Science.gov (United States)

    Padovani, P.; Turcati, A.; Resconi, E.

    2018-04-01

    We test the recently proposed idea that outflows associated with Active Galactic Nuclei (AGN) could be neutrino emitters in two complementary ways. First, we cross-correlate a list of 94 "bona fide" AGN outflows with the most complete and updated repository of IceCube neutrinos currently publicly available, assembled by us for this purpose. It turns out that AGN with outflows matched to an IceCube neutrino have outflow and kinetic energy rates, and bolometric powers larger than those of AGN with outflows not matched to neutrinos. Second, we carry out a statistical analysis on a catalogue of [O III] λ5007 line profiles using a sample of 23,264 AGN at z values (˜6 and 18 per cent respectively, pre-trial) for relatively high velocities and luminosities. Our results are consistent with a scenario where AGN outflows are neutrino emitters but at present do not provide a significant signal. This can be tested with better statistics and source stacking. A predominant role of AGN outflows in explaining the IceCube data appears in any case to be ruled out.

  7. Comments on open-quotes interpretations of quantum mechanics, joint measurement of incompatible observables, and counterfactual definitenessclose quotes

    International Nuclear Information System (INIS)

    Stapp, H.P.

    1994-01-01

    Some seeming logical deficiencies in a recent paper are described. The author responds to the arguments of the work by de Muynck, De Baere, and Martens (MDM), who argue it is widely accepted today that some sort of nonlocal effect is needed to resolve the problems raised by the works of Einstein, Podolsky, and Rosen (EPR) and John Bell. In MBM a variety of arguments are set forth that aim to invalidate the existing purported proofs of nonlocality and to provide, moreover, a local solution to the problems uncovered by EPR and Bell. Much of the argumentation in MBM is based on the idea of introducing 'nonideal' measurements, which, according to MBM, allow one to construct joint probability distributions for incompatible observables. The existence of a bona fide joint probability distribution for the incompatible observables occurring in the EPRB experiments would entail that Bell's inequalities can be satisfied, and hence that the mathematical basis for the nonlocal effects would disappear. This relult would apparently allow one to eliminate the need for nonlocal effects by considering experiments of this new kind

  8. Safeguards Culture: lesson learned

    International Nuclear Information System (INIS)

    Frazar, S.; Mladineo, S.V.

    2010-01-01

    After the discovery of Iraq's clandestine nuclear program in 1991, the international community developed new tools for evaluating and demonstrating states' nuclear intentions. The International Atomic Energy Agency (IAEA) developed a more holistic approach toward international safeguards verification to garner more complete information about states' nuclear activities. This approach manifested itself in State Level Evaluations, using information from a variety of sources, including the implementation of integrated safeguards in Member States, to reach a broader conclusion. Those wishing to exhibit strong nonproliferation postures to a more critical international community took steps to demonstrate their nonproliferation 'bona fides'. As these Member States signed and brought into force the Additional Protocol, submitted United Nations Security Council Resolution 1540 reports and strengthened their export control laws, the international community began to consider the emergence of so-called safeguards cultures. Today, safeguards culture can be a useful tool for measuring nonproliferation postures, but so far its impact on the international safeguards regime has been under appreciated. There is no agreed upon definition for safeguards culture nor agreement on how it should be measured.

  9. Circadian remodeling of neuronal circuits involved in rhythmic behavior.

    Directory of Open Access Journals (Sweden)

    María Paz Fernández

    2008-03-01

    Full Text Available Clock output pathways are central to convey timing information from the circadian clock to a diversity of physiological systems, ranging from cell-autonomous processes to behavior. While the molecular mechanisms that generate and sustain rhythmicity at the cellular level are well understood, it is unclear how this information is further structured to control specific behavioral outputs. Rhythmic release of pigment dispersing factor (PDF has been proposed to propagate the time of day information from core pacemaker cells to downstream targets underlying rhythmic locomotor activity. Indeed, such circadian changes in PDF intensity represent the only known mechanism through which the PDF circuit could communicate with its output. Here we describe a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit, which display higher complexity during the day and significantly lower complexity at nighttime, both under daily cycles and constant conditions. In support to its circadian nature, cycling is lost in bona fide clockless mutants. We propose this clock-controlled structural plasticity as a candidate mechanism contributing to the transmission of the information downstream of pacemaker cells.

  10. Glioblastoma formation from cell population depleted of Prominin1-expressing cells.

    Directory of Open Access Journals (Sweden)

    Kenji Nishide

    2009-08-01

    Full Text Available Prominin1 (Prom1, also known as CD133 in human has been widely used as a marker for cancer stem cells (CSCs, which self-renew and are tumorigenic, in malignant tumors including glioblastoma multiforme (GBM. However, there is other evidence showing that Prom1-negative cancer cells also form tumors in vivo. Thus it remains controversial whether Prom1 is a bona fide marker for CSCs. To verify if Prom1-expressing cells are essential for tumorigenesis, we established a mouse line, whose Prom1-expressing cells can be eliminated conditionally by a Cre-inducible DTA gene on the Prom1 locus together with a tamoxifen-inducible CreER(TM, and generated glioma-initiating cells (GICs-LD by overexpressing both the SV40 Large T antigen and an oncogenic H-Ras(L61 in neural stem cells of the mouse line. We show here that the tamoxifen-treated GICs-LD (GICs-DTA form tumor-spheres in culture and transplantable GBM in vivo. Thus, our studies demonstrate that Prom1-expressing cells are dispensable for gliomagenesis in this mouse model.

  11. Endothelial Progenitor Cells as Shuttle of Anticancer Agents.

    Science.gov (United States)

    Laurenzana, Anna; Margheri, Francesca; Chillà, Anastasia; Biagioni, Alessio; Margheri, Giancarlo; Calorini, Lido; Fibbi, Gabriella; Del Rosso, Mario

    2016-10-01

    Cell therapies are treatments in which stem or progenitor cells are stimulated to differentiate into specialized cells able to home to and repair damaged tissues. After their discovery, endothelial progenitor cells (EPCs) stimulated worldwide interest as possible vehicles to perform autologous cell therapy of tumors. Taking into account the tumor-homing properties of EPCs, two different approaches to control cancer progression have been pursued by combining cell-based therapy with gene therapy or with nanomedicine. The first approach is based on the possibility of engineering EPCs to express different transgenes, and the second is based on the capacity of EPCs to take up nanomaterials. Here we review the most important progress covering the following issues: the characterization of bona fide endothelial progenitor cells, their role in tumor vascularization and metastasis, and preclinical data about their use in cell-based tumor therapy, considering antiangiogenic, suicide, immune-stimulating, and oncolytic virus gene therapy. The mixed approach of EPC cell therapy and nanomedicine is discussed in terms of plasmonic-dependent thermoablation and molecular imaging.

  12. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development.

    Science.gov (United States)

    Ortega-Molina, Ana; Boss, Isaac W; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W; Mottok, Anja; Hother, Christoffer; Liu, Shichong; Cao, Xing-Jun; Tam, Wayne; Shaknovich, Rita; Garcia, Benjamin A; Gascoyne, Randy D; Ge, Kai; Shilatifard, Ali; Elemento, Olivier; Nussenzweig, Andre; Melnick, Ari M; Wendel, Hans-Guido

    2015-10-01

    The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways.

  13. The Number of Neutrinos and the Z Line Shape

    CERN Document Server

    Blondel, Alain

    2016-01-01

    The Standard Theory can fit any number of fermion families, as long as the number of leptons and quark families are the same. At the time of the conception of LEP, the number of such families was unknown, and it was feared that the Z resonance would be washed out by decaying into so many families of neutrinos! It took only a few weeks in the fall of 1989 to determine that the number is three. The next six years (from 1990 to 1995) were largely devoted to the accurate determination of the Z line shape, with a precision that outperformed the most optimistic expectations by a factor of 10. The tale of these measurements is a bona fide mystery novel, the precession of electrons being strangely perturbed by natural phenomena, such as tides, rain, hydroelectric power, fast trains, not to mention vertical electrostatic separators. The number hidden in the loops of this treasure hunt was 179, the first estimate of the mass of the top quark; then, once that was found, where predicted, the next number was close to zero...

  14. A HST/WFC3 Search for Substellar Companions in the Orion Nebula Cluster

    Science.gov (United States)

    Strampelli, Giovanni Maria; Aguilar, Jonathan; Aparicio, Antonio; Piotto, Giampaolo; Pueyo, Laurent; Robberto, Massimo

    2018-01-01

    We present new results relative to the population of substellar binaries in the Orion Nebula Cluster. We reprocessed HST/WFC3 data using an analysis technique developed to detect close companions in the wings of the stellar PSFs, based on the PyKLIP implementation of the KLIP PSF subtraction algorithm. Starting from a sample of ~1200 stars selected over the range J=11-15 mag, we were able to uncover ~80 candidate companions in the magnitude range J=16-23 mag. We use the presence of the 1.4 micron H2O absorption feature in the companion photosphere to discriminate 32 bona-fide substellar candidates from a population of reddened background objects. We derive an estimate of the companion mass assuming a 2Myr isochrone and the reddening of their primary. With 8 stellar companions, 19 brown dwarfs and 5 planetary mass objects, our study provide us with an unbiased sample of companions at the low-mass end of the IMF, probing the transition from binary to planetary systems.

  15. Human ecology, statistical analysis, and the logic of valid correlations DOI:10.5007/2175-7984.2011v10n19p57

    Directory of Open Access Journals (Sweden)

    Fernando Dias de Avila-Pires

    2011-10-01

    Full Text Available Human health ecology is an expanding field of interdisciplinary research, combining knowledge drawn from distinct areas. Human ecology is essentially interdisciplinary. The search for the origin and distribution of diseases demands a combination of theories and methods from both natural and social sciences. There is a limit to the replication and repetition of observations and experiments in scientific research: hence the importance of statistics. As a tool, statistical analyses are usually based upon selected samples and samples must be representative of the whole. Irrelevant, erroneous, false, and misleading, information based on flawed interpretation of statistics has always plagued scientific publications. In some cases, not only professional ethics has been breached, but risks to well-being and health has been fostered. In this article I will not deal with fraud, but with bona fide errors of judgment and the use of erroneous statistical concepts. My objective in this article is to caution against a common practice adopted by researchers while using qualitative as well as quantitative methods of analysis to establish demographic categories.

  16. D-branes in a non-critical superstrings and minimal super Yang-Mills in various dimensions

    International Nuclear Information System (INIS)

    Ashok, S.K.; Murthy, S.; Troost, J.

    2005-11-01

    We construct and analyze D-branes in superstring theories in even dimensions less than ten. The backgrounds under study are supersymmetric R d-1,1 x SL(2,R) k /U(1) where the level of the supercoset is tuned such as to provide bona fide string theory backgrounds. We provide exact boundary states for D-branes that are localized at the tip of the cigar SL(2,R)/U(1) supercoset conformal field theory. We analyze the spectra of open strings on these D-branes and show explicitly that they are consistent with supersymmetry in d = 2,4 and 6. The low energy theory on the world-volume of the D-brane in each case is pure Yang-Mills theory with minimal supersymmetry. In the case with four macroscopic flat directions d = 4, we realize an N = 1 super Yang-Mills theory, and we interpret the backreaction for the dilaton as the running of the gauge coupling, and study the relation between R-symmetry breaking in the gauge theory and the backreaction on the Rr axion. (author)

  17. Evolution and phylogeny of B lymphocytes

    Directory of Open Access Journals (Sweden)

    Fabiola Claudio-Piedras

    2016-05-01

    Full Text Available B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

  18. The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

    Science.gov (United States)

    Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

    2018-01-29

    Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

  19. New Markov Model Approaches to Deciphering Microbial Genome Function and Evolution: Comparative Genomics of Laterally Transferred Genes

    Energy Technology Data Exchange (ETDEWEB)

    Borodovsky, M.

    2013-04-11

    Algorithmic methods for gene prediction have been developed and successfully applied to many different prokaryotic genome sequences. As the set of genes in a particular genome is not homogeneous with respect to DNA sequence composition features, the GeneMark.hmm program utilizes two Markov models representing distinct classes of protein coding genes denoted "typical" and "atypical". Atypical genes are those whose DNA features deviate significantly from those classified as typical and they represent approximately 10% of any given genome. In addition to the inherent interest of more accurately predicting genes, the atypical status of these genes may also reflect their separate evolutionary ancestry from other genes in that genome. We hypothesize that atypical genes are largely comprised of those genes that have been relatively recently acquired through lateral gene transfer (LGT). If so, what fraction of atypical genes are such bona fide LGTs? We have made atypical gene predictions for all fully completed prokaryotic genomes; we have been able to compare these results to other "surrogate" methods of LGT prediction.

  20. INTRIGOSS: A new Library of High Resolution Synthetic Spectra

    Science.gov (United States)

    Franchini, Mariagrazia; Morossi, Carlo; Di Marcancantonio, Paolo; Chavez, Miguel; GES-Builders

    2018-01-01

    INTRIGOSS (INaf Trieste Grid Of Synthetic Spectra) is a new High Resolution (HiRes) synthetic spectral library designed for studying F, G, and K stars. The library is based on atmosphere models computed with specified individual element abundances via ATLAS12 code. Normalized SPectra (NSP) and surface Flux SPectra (FSP), in the 4800-5400 Å wavelength range, were computed by means of the SPECTRUM code. The synthetic spectra are computed with an atomic and bi-atomic molecular line list including "bona fide" Predicted Lines (PLs) built by tuning loggf to reproduce very high SNR Solar spectrum and the UVES-U580 spectra of five cool giants extracted from the Gaia-ESO survey (GES). The astrophysical gf-values were then assessed by using more than 2000 stars with homogenous and accurate atmosphere parameters and detailed chemical composition from GES. The validity and greater accuracy of INTRIGOSS NSPs and FSPs with respect to other available spectral libraries is discussed. INTRIGOSS will be available on the web and will be a valuable tool for both stellar atmospheric parameters and stellar population studies.

  1. Saving money on rig refurbishments through foreign trade zones or duty-drawback

    International Nuclear Information System (INIS)

    Ward, R.J. Jr.

    1997-01-01

    The recent boom in day rates for rigs capable of drilling in deep water and harsh environments has created a frenzy of rig refurbishment activity in shipyards located in US Gulf states. In most instances, the destination for the rigs upon completion is the US Outer Continental Shelf (USOCS) in the Gulf of Mexico. The problem faced by contractors/operators planning to use US shipyards is that this circumstance has caused difficulty in shielding rigs and their foreign-sourced components from US Customs duties. Under US Customs law, a bona fide exportation requires severance from US commerce and joining to the commerce of some foreign country or, in the case of a vessel supply, a qualifying international voyage. The USOCS does not qualify as an exportation, nor do movements to drilling sites located on it qualify as an international voyage. Described here are two possible solutions to this economic dilemma and an example of how the foreign trade zone solution was applied by Global marine in its plans for upgrading some of its semisubmersible drilling rigs for deepwater USOCS work

  2. Extending the Neuroanatomic Territory of Diffuse Midline Glioma, K27M Mutant: Pineal Region Origin.

    Science.gov (United States)

    Gilbert, Andrea R; Zaky, Wafik; Gokden, Murat; Fuller, Christine E; Ocal, Eylem; Leeds, Norman E; Fuller, Gregory N

    2018-01-01

    Diffuse midline glioma, H3-K27M mutant (DMG-K27M) is a newly described, molecularly distinct infiltrative glioma that almost exclusively arises in midline CNS structures, including the brain stem, especially the pons, as well as the thalamus and spinal cord with rare examples seen in the cerebellum, third ventricle, and hypothalamus. To our knowledge, only 1 case of a molecularly confirmed DMG-K27M arising in the pineal region has been previously reported. We present the second occurrence of a tissue-confirmed DMG-K27M of the pineal region, which, to our knowledge, is the first case reported in a child and the first case with documented preoperative MRI. This case, in addition to a prior report described in an adult, defines the lower end of a broad age range of DMG-K27M onset (12-65 years) and establishes the pineal gland as a bona fide site of origin for this newly codified midline glioma. © 2017 S. Karger AG, Basel.

  3. Annotating and quantifying pri-miRNA transcripts using RNA-Seq data of wild type and serrate-1 globular stage embryos of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Daniel Lepe-Soltero

    2017-12-01

    Full Text Available The genome annotation for the model plant Arabidopsis thaliana does not include the primary transcripts from which MIRNAs are processed. Here we present and analyze the raw mRNA sequencing data from wild type and serrate-1 globular stage embryos of A. thaliana, ecotype Columbia. Because SERRATE is required for pri-miRNA processing, these precursors accumulate in serrate-1 mutants, facilitating their detection using standard RNA-Seq protocols. We first use the mapping of the RNA-Seq reads to the reference genome to annotate the potential primary transcripts of MIRNAs expressed in the embryo. We then quantify these pri-miRNAs in wild type and serrate-1 mutants. Finally, we use differential expression analysis to determine which are up-regulated in serrate-1 compared to wild type, to select the best candidates for bona fide pri-miRNAs expressed in the globular stage embryos. In addition, we analyze a previously published RNA-Seq dataset of wild type and dicer-like 1 mutant embryos at the globular stage [1]. Our data are interpreted and discussed in a separate article [2].

  4. Annotating and quantifying pri-miRNA transcripts using RNA-Seq data of wild type and serrate-1 globular stage embryos of Arabidopsis thaliana.

    Science.gov (United States)

    Lepe-Soltero, Daniel; Armenta-Medina, Alma; Xiang, Daoquan; Datla, Raju; Gillmor, C Stewart; Abreu-Goodger, Cei

    2017-12-01

    The genome annotation for the model plant Arabidopsis thaliana does not include the primary transcripts from which MIRNAs are processed. Here we present and analyze the raw mRNA sequencing data from wild type and serrate-1 globular stage embryos of A. thaliana , ecotype Columbia. Because SERRATE is required for pri-miRNA processing, these precursors accumulate in serrate-1 mutants, facilitating their detection using standard RNA-Seq protocols. We first use the mapping of the RNA-Seq reads to the reference genome to annotate the potential primary transcripts of MIRNAs expressed in the embryo. We then quantify these pri-miRNAs in wild type and serrate-1 mutants. Finally, we use differential expression analysis to determine which are up-regulated in serrate-1 compared to wild type, to select the best candidates for bona fide pri-miRNAs expressed in the globular stage embryos. In addition, we analyze a previously published RNA-Seq dataset of wild type and dicer-like 1 mutant embryos at the globular stage [1]. Our data are interpreted and discussed in a separate article [2].

  5. Memorandum Order No. 151, 27 January 1988.

    Science.gov (United States)

    1988-01-01

    This Order creates in the Philippines a National Government Center (NGC) Housing Committee to implement Proclamation No. 137 of 11 August 1987, which set aside 150 acres of land for the development of a housing project. The project is to serve as a prototype for developing land within the framework of the existing urban land reform laws. The Committee has the power to do the following: "b.1) Define the project's concept and strategies of implementation; b.2) formulate policies and guidelines on: b.2.1) land disposition, allocation and distribution of NGC housing site to bona fide residents subject to the provisions of Proclamation No. 137 dated August 11, 1987; b.2.2) population containment within the defined project area; b.2.3) qualified beneficiaries for the project; b.2.4) housing finance for beneficiaries; and b.2.5) project administration and other implementation requirements; b.3) formulate systems and procedures for project implementation; b.4) prepare the project's work program and budget; b.5) identify and mobilize fund resources for project implementation; b.6) monitor and evaluate all phases of project implementation; b.7) make final decisions on all cases and issues affecting project implementation which cannot be resolved at the operations level; b.8) call on any government department or agency for assistance whenever necessary." Further provisions of the order deal with the composition of the Committee, the Project Administrator, support agencies, and funding, among other things. full text

  6. Inhibition of histone deacetylases 1 and 6 enhances cytarabine-induced apoptosis in pediatric acute myeloid leukemia cells.

    Science.gov (United States)

    Xu, Xuelian; Xie, Chengzhi; Edwards, Holly; Zhou, Hui; Buck, Steven A; Ge, Yubin

    2011-02-16

    Pediatric acute myeloid leukemia (AML) remains a challenging disease to treat even with intensified cytarabine-based chemotherapy. Histone deacetylases (HDACs) have been reported to be promising therapeutic targets for treating AML. However, HDAC family members that are involved in chemotherapy sensitivities remain unknown. In this study, we sought to identify members of the HDAC family that are involved in cytarabine sensitivities, and to select the optimal HDACI that is most efficacious when combined with cytarabine for treating children with AML. Expression profiles of classes I, II, and IV HDACs in 4 pediatric AML cell lines were determined by Western blotting. Inhibition of class I HDACs by different HDACIs was measured post immnunoprecipitation. Individual down-regulation of HDACs in pediatric AML cells was performed with lentiviral shRNA. The effects of cytarabine and HDACIs on apoptosis were determined by flow cytometry analysis. Treatments with structurally diverse HDACIs and HDAC shRNA knockdown experiments revealed that down-regulation of both HDACs 1 and 6 is critical in enhancing cytarabine-induced apoptosis in pediatric AML, at least partly mediated by Bim. However, down-regulation of HDAC2 may negatively impact cytarabine sensitivities in the disease. At clinically achievable concentrations, HDACIs that simultaneously inhibited both HDACs 1 and 6 showed the best anti-leukemic activities and significantly enhanced cytarabine-induced apoptosis. Our results further confirm that HDACs are bona fide therapeutic targets for treating pediatric AML and suggest that pan-HDACIs may be more beneficial than isoform-specific drugs.

  7. Characterization of 14-3-3 isoforms expressed in the Echinococcus granulosus pathogenic larval stage.

    Science.gov (United States)

    Teichmann, Aline; Vargas, Daiani M; Monteiro, Karina M; Meneghetti, Bruna V; Dutra, Cristine S; Paredes, Rodolfo; Galanti, Norbel; Zaha, Arnaldo; Ferreira, Henrique B

    2015-04-03

    The 14-3-3 protein family of eukaryotic regulators was studied in Echinococcus granulosus, the causative agent of cystic hydatid disease. These proteins mediate important cellular processes in eukaryotes and are expected to play important roles in parasite biology. Six isoforms of E. granulosus 14-3-3 genes and proteins (Eg14-3-3.1-6) were analyzed, and their phylogenetic relationships were established with bona fide 14-3-3 orthologous proteins from eukaryotic species. Eg14-3-3 isoforms with previous evidence of expression (Eg14-3-3.1-4) in E. granulosus pathogenic larval stage (metacestode) were cloned, and recombinant proteins were used for functional studies. These protein isoforms were detected in different components of E. granulosus metacestode, including interface components with the host. The roles that are played by Eg14-3-3 proteins in parasite biology were inferred from the repertoires of interacting proteins with each isoform, as assessed by gel overlay, cross-linking, and affinity chromatography assays. A total of 95 Eg14-3-3 protein ligands were identified by mass spectrometry. Eg14-3-3 isoforms have shared partners (44 proteins), indicating some overlapping functions; however, they also bind exclusive partners (51 proteins), suggesting Eg14-3-3 functional specialization. These ligand repertoires indicate the involvement of Eg14-3-3 proteins in multiple biochemical pathways in the E. granulosus metacestode and note some degree of isoform specialization.

  8. NSV 11749, AN ELDER SIBLING OF THE BORN-AGAIN STARS V605 Aql AND V4334 Sgr?

    Energy Technology Data Exchange (ETDEWEB)

    Miller Bertolami, M. M.; Althaus, L. G. [Facultad de Ciencias Astronomicas y Geofisicas, Universidad Nacional de La Plata, Paseo del Bosque s/n, 1900 La Plata (Argentina); Rohrmann, R. D. [Instituto de Ciencias Astronomicas, de la Tierra y del Espacio, CONICET, Av. de Espana 1512 (Sur) CC 49, 5400 San Juan (Argentina); Granada, A., E-mail: mmiller@fcaglp.unlp.edu.ar [Observatoire Astronomique de l' Universite de Geneve 51, Chemin des Maillettes, CH-1290, Sauverny (Switzerland)

    2011-12-20

    We argue that NSV 11749, an eruption observed in the early twentieth century, was a rare event known as 'very late thermal pulse' (VLTP). To support our argument we compare the light curve of NSV 11749 with those of the two bona fide VLTP objects known to date, V4334 Sgr and V605 Aql, and with those predicted by state-of-the-art stellar evolution models. Next, we explore the INT Photometric H-Alpha Survey (IPHAS) and Two Micron All Sky Survey (2MASS) catalogs for possible counterparts of the eruption. Our analysis shows that the VLTP scenario outperforms all other proposed scenarios as an explanation of NSV 11749. We identify an IPHAS/2MASS source at the eruption location of NSV 11749. The derived colors suggest that the object is not enshrouded in a thick dust shell as V605 Aql and V4334 Sgr. Also, the absence of an apparent planetary nebula at the eruption location suggests differences with known VLTP objects which might be linked to the intensity of the eruption and the mass of the object. Further exploration of this source and scenario seems desirable. If NSV 11749 was a born-again star, it would be the third event of its kind to have been observed and will strongly help us to increase our understanding of the later stages of stellar evolution and violent reactive convective burning.

  9. Networking in autism: leveraging genetic, biomarker and model system findings in the search for new treatments.

    Science.gov (United States)

    Veenstra-VanderWeele, Jeremy; Blakely, Randy D

    2012-01-01

    Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder affecting approximately 1% of children. ASD is defined by core symptoms in two domains: negative symptoms of impairment in social and communication function, and positive symptoms of restricted and repetitive behaviors. Available treatments are inadequate for treating both core symptoms and associated conditions. Twin studies indicate that ASD susceptibility has a large heritable component. Genetic studies have identified promising leads, with converging insights emerging from single-gene disorders that bear ASD features, with particular interest in mammalian target of rapamycin (mTOR)-linked synaptic plasticity mechanisms. Mouse models of these disorders are revealing not only opportunities to model behavioral perturbations across species, but also evidence of postnatal rescue of brain and behavioral phenotypes. An intense search for ASD biomarkers has consistently pointed to elevated platelet serotonin (5-HT) levels and a surge in brain growth in the first 2 years of life. Following a review of the diversity of ASD phenotypes and its genetic origins and biomarkers, we discuss opportunities for translation of these findings into novel ASD treatments, focusing on mTor- and 5-HT-signaling pathways, and their possible intersection. Paralleling the progress made in understanding the root causes of rare genetic syndromes that affect cognitive development, we anticipate progress in models systems using bona fide ASD-associated molecular changes that have the potential to accelerate the development of ASD diagnostics and therapeutics.

  10. Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells

    Directory of Open Access Journals (Sweden)

    Xiang Y. Kong

    2014-03-01

    Full Text Available Human kidney predominant protein, NCU-G1, is a highly conserved protein with an unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no detectable expression of this gene were created using a gene-trap strategy, and Ncu-g1gt/gt mice were successfully characterized. Lysosomal disorders are mainly caused by lack of or malfunctioning of proteins in the endosomal-lysosomal pathway. The clinical symptoms vary, but often include liver dysfunction. Persistent liver damage activates fibrogenesis and, if unremedied, eventually leads to liver fibrosis/cirrhosis and death. We demonstrate that the disruption of Ncu-g1 results in spontaneous liver fibrosis in mice as the predominant phenotype. Evidence for an increased rate of hepatic cell death, oxidative stress and active fibrogenesis were detected in Ncu-g1gt/gt liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1gt/gt Kupffer cells. Because only a few transgenic mouse models have been identified with chronic liver injury and spontaneous liver fibrosis development, we propose that the Ncu-g1gt/gt mouse could be a valuable new tool in the development of novel treatments for the attenuation of fibrosis due to chronic liver damage.

  11. The four serotypes of dengue recognize the same putative receptors in Aedes aegypti midgut and Ae. albopictus cells

    Directory of Open Access Journals (Sweden)

    Camacho-Nuez Minerva

    2006-10-01

    Full Text Available Abstract Background Dengue viruses (DENV attach to the host cell surface and subsequently enter the cell by receptor-mediated endocytosis. Several primary and low affinity co-receptors for this flavivirus have been identified. However, the presence of these binding molecules on the cell surface does not necessarily render the cell susceptible to infection. Determination of which of them serve as bona fide receptors for this virus in the vector may be relevant to treating DENV infection and in designing control strategies. Results (1 Overlay protein binding assay showed two proteins with molecular masses of 80 and 67 kDa (R80 and R67. (2 Specific antibodies against these two proteins inhibited cell binding and infection. (3 Both proteins were bound by all four serotypes of dengue virus. (4 R80 and R67 were purified by affinity chromatography from Ae. aegypti mosquito midguts and from Ae albopictus C6/36 cells. (5 In addition, a protein with molecular mass of 57 kDa was purified by affinity chromatography from the midgut extracts. (6 R80 and R67 from radiolabeled surface membrane proteins of C6/36 cells were immunoprecipitated by antibodies against Ae. aegypti midgut. Conclusion Our results strongly suggest that R67 and R80 are receptors for the four serotypes of dengue virus in the midgut cells of Ae. aegypti and in C6/36 Ae. albopictus cells.

  12. NSV 11749, AN ELDER SIBLING OF THE BORN-AGAIN STARS V605 Aql AND V4334 Sgr?

    International Nuclear Information System (INIS)

    Miller Bertolami, M. M.; Althaus, L. G.; Rohrmann, R. D.; Granada, A.

    2011-01-01

    We argue that NSV 11749, an eruption observed in the early twentieth century, was a rare event known as 'very late thermal pulse' (VLTP). To support our argument we compare the light curve of NSV 11749 with those of the two bona fide VLTP objects known to date, V4334 Sgr and V605 Aql, and with those predicted by state-of-the-art stellar evolution models. Next, we explore the INT Photometric H-Alpha Survey (IPHAS) and Two Micron All Sky Survey (2MASS) catalogs for possible counterparts of the eruption. Our analysis shows that the VLTP scenario outperforms all other proposed scenarios as an explanation of NSV 11749. We identify an IPHAS/2MASS source at the eruption location of NSV 11749. The derived colors suggest that the object is not enshrouded in a thick dust shell as V605 Aql and V4334 Sgr. Also, the absence of an apparent planetary nebula at the eruption location suggests differences with known VLTP objects which might be linked to the intensity of the eruption and the mass of the object. Further exploration of this source and scenario seems desirable. If NSV 11749 was a born-again star, it would be the third event of its kind to have been observed and will strongly help us to increase our understanding of the later stages of stellar evolution and violent reactive convective burning.

  13. Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins

    International Nuclear Information System (INIS)

    Corcelle, V.; Stieger, B.; Gjinovci, A.; Wollheim, C.B.; Gauthier, B.R.

    2006-01-01

    Despite extensive studies, the hematopoietic versus hepatic origin of liver progenitor oval cells remains controversial. The aim of this study was to determine the origin of such cells after liver injury and to establish an oval cell line. Rat liver injury was induced by subcutaneous insertion of 2-AAF pellets for 7 days with subsequent injection of CCl 4 . Livers were removed 9 to 13 days post-CCl 4 treatment. Immunohistochemistry was performed using anti-c-kit, OV6, Thy1, CK19, AFP, vWF and Rab3b. Isolated non-parenchymal cells were grown on mouse embryonic fibroblast, and their gene expression profile was characterized by RT-PCR. We identified a subpopulation of OV6/CK19/Rab3b-expressing cells that was activated in the periportal region of traumatized livers. We also characterized a second subpopulation that expressed the HSCs marker c-kit but not Thy1. Although we successfully isolated both cell types, OV6/CK19/Rab3b + cells fail to propagate while c-kit + -HSCs appeared to proliferate for up to 7 weeks. Cells formed clusters which expressed c-kit, Thy1 and albumin. Our results indicate that a bona fide oval progenitor cell population resides within the liver and is distinct from c-kit + -HSCs. Oval cells require the hepatic niche to proliferate, while cells mobilized from the circulation proliferate and transdifferentiate into hepatocytes without evidence of cell fusion

  14. Identification of novel NPRAP/δ-catenin-interacting proteins and the direct association of NPRAP with dynamin 2.

    Directory of Open Access Journals (Sweden)

    Carolina Koutras

    Full Text Available Neural plakophilin-related armadillo protein (NPRAP or δ-catenin is a neuronal-specific protein that is best known for its interaction with presenilin 1 (PS1. Interestingly, the hemizygous loss of NPRAP is associated with severe mental retardation in cri du chat syndrome (CDCS, and mutations in PS1 cause an aggressive, early-onset form of Alzheimer's disease. Until recently, studies on the function of NPRAP have focused on its ability to modulate dendritic protrusion elaboration through its binding to cell adhesion and scaffolding molecules. However, mounting evidence indicates that NPRAP participates in intracellular signaling and exists in the nucleus, where it modulates gene expression. This apparent bifunctional nature suggests an elaborate neuronal role, but how NPRAP came to participate in such distinct subcellular events remains a mystery. To gain insight into this pathway, we immunoprecipitated NPRAP from human SH SY5Y cells and identified several novel interacting proteins by mass spectrometry. These included neurofilament alpha-internexin, interferon regulatory protein 2 binding factors, and dynamins 1 and 2. We further validated dynamin 2/NPRAP colocalization and direct interaction in vivo, confirming their bona fide partnership. Interestingly, dynamin 2 has established roles in endocytosis and actin assembly, and both of these processes have the potential to interface with the cell adhesion and intracellular signaling processes that involve NPRAP. Our data provide new avenues for approaching NPRAP biology and suggest a broader role for this protein than previously thought.

  15. Contribution of CoA Ligases to Benzenoid Biosynthesis in Petunia Flowers[W

    Science.gov (United States)

    Klempien, Antje; Kaminaga, Yasuhisa; Qualley, Anthony; Nagegowda, Dinesh A.; Widhalm, Joshua R.; Orlova, Irina; Shasany, Ajit Kumar; Taguchi, Goro; Kish, Christine M.; Cooper, Bruce R.; D’Auria, John C.; Rhodes, David; Pichersky, Eran; Dudareva, Natalia

    2012-01-01

    Biosynthesis of benzoic acid from Phe requires shortening of the side chain by two carbons, which can occur via the β-oxidative or nonoxidative pathways. The first step in the β-oxidative pathway is cinnamoyl-CoA formation, likely catalyzed by a member of the 4-coumarate:CoA ligase (4CL) family that converts a range of trans-cinnamic acid derivatives into the corresponding CoA thioesters. Using a functional genomics approach, we identified two potential CoA-ligases from petunia (Petunia hybrida) petal-specific cDNA libraries. The cognate proteins share only 25% amino acid identity and are highly expressed in petunia corollas. Biochemical characterization of the recombinant proteins revealed that one of these proteins (Ph-4CL1) has broad substrate specificity and represents a bona fide 4CL, whereas the other is a cinnamate:CoA ligase (Ph-CNL). RNA interference suppression of Ph-4CL1 did not affect the petunia benzenoid scent profile, whereas downregulation of Ph-CNL resulted in a decrease in emission of benzylbenzoate, phenylethylbenzoate, and methylbenzoate. Green fluorescent protein localization studies revealed that the Ph-4CL1 protein is localized in the cytosol, whereas Ph-CNL is in peroxisomes. Our results indicate that subcellular compartmentalization of enzymes affects their involvement in the benzenoid network and provide evidence that cinnamoyl-CoA formation by Ph-CNL in the peroxisomes is the committed step in the β-oxidative pathway. PMID:22649270

  16. Contribution of CoA ligases to benzenoid biosynthesis in petunia flowers.

    Science.gov (United States)

    Klempien, Antje; Kaminaga, Yasuhisa; Qualley, Anthony; Nagegowda, Dinesh A; Widhalm, Joshua R; Orlova, Irina; Shasany, Ajit Kumar; Taguchi, Goro; Kish, Christine M; Cooper, Bruce R; D'Auria, John C; Rhodes, David; Pichersky, Eran; Dudareva, Natalia

    2012-05-01

    Biosynthesis of benzoic acid from Phe requires shortening of the side chain by two carbons, which can occur via the β-oxidative or nonoxidative pathways. The first step in the β-oxidative pathway is cinnamoyl-CoA formation, likely catalyzed by a member of the 4-coumarate:CoA ligase (4CL) family that converts a range of trans-cinnamic acid derivatives into the corresponding CoA thioesters. Using a functional genomics approach, we identified two potential CoA-ligases from petunia (Petunia hybrida) petal-specific cDNA libraries. The cognate proteins share only 25% amino acid identity and are highly expressed in petunia corollas. Biochemical characterization of the recombinant proteins revealed that one of these proteins (Ph-4CL1) has broad substrate specificity and represents a bona fide 4CL, whereas the other is a cinnamate:CoA ligase (Ph-CNL). RNA interference suppression of Ph-4CL1 did not affect the petunia benzenoid scent profile, whereas downregulation of Ph-CNL resulted in a decrease in emission of benzylbenzoate, phenylethylbenzoate, and methylbenzoate. Green fluorescent protein localization studies revealed that the Ph-4CL1 protein is localized in the cytosol, whereas Ph-CNL is in peroxisomes. Our results indicate that subcellular compartmentalization of enzymes affects their involvement in the benzenoid network and provide evidence that cinnamoyl-CoA formation by Ph-CNL in the peroxisomes is the committed step in the β-oxidative pathway.

  17. AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia.

    Science.gov (United States)

    Virts, Elizabeth L; Jankowska, Anna; Mackay, Craig; Glaas, Marcel F; Wiek, Constanze; Kelich, Stephanie L; Lottmann, Nadine; Kennedy, Felicia M; Marchal, Christophe; Lehnert, Erik; Scharf, Rüdiger E; Dufour, Carlo; Lanciotti, Marina; Farruggia, Piero; Santoro, Alessandra; Savasan, Süreyya; Scheckenbach, Kathrin; Schipper, Jörg; Wagenmann, Martin; Lewis, Todd; Leffak, Michael; Farlow, Janice L; Foroud, Tatiana M; Honisch, Ellen; Niederacher, Dieter; Chakraborty, Sujata C; Vance, Gail H; Pruss, Dmitry; Timms, Kirsten M; Lanchbury, Jerry S; Alpi, Arno F; Hanenberg, Helmut

    2015-09-15

    Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2-6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2-6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2-6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene. © The Author 2015. Published by Oxford University Press.

  18. Discovery and annotation of small proteins using genomics, proteomics and computational approaches

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaohan; Tschaplinski, Timothy J.; Hurst, Gregory B.; Jawdy, Sara; Abraham, Paul E.; Lankford, Patricia K.; Adams, Rachel M.; Shah, Manesh B.; Hettich, Robert L.; Lindquist, Erika; Kalluri, Udaya C.; Gunter, Lee E.; Pennacchio, Christa; Tuskan, Gerald A.

    2011-03-02

    Small proteins (10 200 amino acids aa in length) encoded by short open reading frames (sORF) play important regulatory roles in various biological processes, including tumor progression, stress response, flowering, and hormone signaling. However, ab initio discovery of small proteins has been relatively overlooked. Recent advances in deep transcriptome sequencing make it possible to efficiently identify sORFs at the genome level. In this study, we obtained 2.6 million expressed sequence tag (EST) reads from Populus deltoides leaf transcriptome and reconstructed full-length transcripts from the EST sequences. We identified an initial set of 12,852 sORFs encoding proteins of 10 200 aa in length. Three computational approaches were then used to enrich for bona fide protein-coding sORFs from the initial sORF set: (1) codingpotential prediction, (2) evolutionary conservation between P. deltoides and other plant species, and (3) gene family clustering within P. deltoides. As a result, a high-confidence sORF candidate set containing 1469 genes was obtained. Analysis of the protein domains, non-protein-coding RNA motifs, sequence length distribution, and protein mass spectrometry data supported this high-confidence sORF set. In the high-confidence sORF candidate set, known protein domains were identified in 1282 genes (higher-confidence sORF candidate set), out of which 611 genes, designated as highest-confidence candidate sORF set, were supported by proteomics data. Of the 611 highest-confidence candidate sORF genes, 56 were new to the current Populus genome annotation. This study not only demonstrates that there are potential sORF candidates to be annotated in sequenced genomes, but also presents an efficient strategy for discovery of sORFs in species with no genome annotation yet available.

  19. The learning curve for hip arthroscopy: a systematic review.

    Science.gov (United States)

    Hoppe, Daniel J; de Sa, Darren; Simunovic, Nicole; Bhandari, Mohit; Safran, Marc R; Larson, Christopher M; Ayeni, Olufemi R

    2014-03-01

    The learning curve for hip arthroscopy is consistently characterized as "steep." The purpose of this systematic review was to (1) identify the various learning curves reported in the literature, (2) examine the evidence supporting these curves, and (3) determine whether this evidence supports an accepted number of cases needed to achieve proficiency. The electronic databases Embase and Medline were screened for any clinical studies reporting learning curves in hip arthroscopy. Two reviewers conducted a full-text review of eligible studies and a hand search of conference proceedings and reference sections of the included articles. Inclusion/exclusion criteria were applied, and a quality assessment was completed for each included article. Descriptive statistics were compiled. We identified 6 studies with a total of 1,063 patients. Studies grouped surgical cases into "early" versus "late" in a surgeon's experience, with 30 cases being the most common cutoff used. Most of these studies used descriptive statistics and operative time and complication rates as measures of competence. Five of 6 studies showed improvement in these measures between early and late experience, but only one study proposed a bona fide curve. This review shows that when 30 cases was used as the cutoff point to differentiate between early and late cases in a surgeon's experience, there were significant reductions in operative time and complication rates. However, there was insufficient evidence to quantify the learning curve and validate 30, or any number of cases, as the point at which the learning curve plateaus. As a result, this number should be interpreted with caution. Level IV, systematic review of Level IV studies. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  20. Clinical implementation of KRAS testing in metastatic colorectal carcinoma: the pathologist's perspective.

    Science.gov (United States)

    Ross, Jeffrey S

    2012-10-01

    Mutation status of the KRAS gene identifies a distinct disease subtype of metastatic colorectal carcinoma that does not respond to antibody therapeutics targeting the epidermal growth factor receptor. This is currently the only validated marker in metastatic colorectal carcinoma with a clear implication in treatment selection. KRAS testing is widely accepted in clinical practice to guide metastatic colorectal carcinoma therapeutic decisions, and there are many commercially available platforms to perform the test. To evaluate the critical role of pathologists in the full implementation of KRAS testing by optimizing tumor tissue collection and fixation procedures and by choosing testing technologies and reliable Clinical Laboratory Improvement Amendments of 1988-certified laboratories to perform the tests. Prospective clinical trials, retrospective studies, and quality assessment and survey reports were identified in the following databases: PubMed, American Society of Clinical Oncology Proceedings (American Society of Clinical Oncology Annual Meeting and Gastrointestinal Cancer Symposium) and European Society for Medical Oncology Proceedings (Annals of Oncology European Society for Medical Oncology Congress and Annals of Oncology World Congress on Gastrointestinal Cancers). More bona fide standards are needed to address the variety of available test methods, which have different performance characteristics including speed, sensitivity to detect rare mutations, and technical requirements. Refined standards addressing timing of KRAS testing, laboratory performance and accuracy, quality assurance and control, proper tissue collection, and appropriate result reporting would also be greatly beneficial. Pathologists should be aware that the amount of information they need to manage will increase, because future trends and technological advances will enhance the predictive power of diagnostic tests or the scope of the biomarker panels tested routinely across tumor types.

  1. New ultracool subdwarfs identified in large-scale surveys using Virtual Observatory tools. I. UKIDSS LAS DR5 vs. SDSS DR7

    Science.gov (United States)

    Lodieu, N.; Espinoza Contreras, M.; Zapatero Osorio, M. R.; Solano, E.; Aberasturi, M.; Martín, E. L.

    2012-06-01

    Aims: The aim of the project is to improve our knowledge of the low-mass and low-metallicity population to investigate the influence of metallicity on the stellar (and substellar) mass function. Methods: We present the results of a photometric and proper motion search aimed at discovering ultracool subdwarfs in large-scale surveys. We employed and combined the Fifth Data Release (DR5) of the UKIRT Infrared Deep Sky Survey (UKIDSS) Large Area Survey (LAS) and the Sloan Digital Sky Survey (SDSS) Data Release 7 complemented with ancillary data from the Two Micron All-Sky Survey (2MASS), the DEep Near-Infrared Survey (DENIS) and the SuperCOSMOS Sky Surveys (SSS). Results: The SDSS DR7 vs. UKIDSS LAS DR5 search returned a total of 32 ultracool subdwarf candidates, only two of which are recognised as a subdwarf in the literature. Twenty-seven candidates, including the two known ones, were followed-up spectroscopically in the optical between 600 and 1000 nm, thus covering strong spectral features indicative of low metallicity (e.g., CaH), 21 with the Very Large Telescope, one with the Nordic Optical Telescope, and five were extracted from the Sloan spectroscopic database to assess (or refute) their low-metal content. We confirm 20 candidates as subdwarfs, extreme subdwarfs, or ultra-subdwarfs with spectral types later than M5; this represents a success rate of ≥ 60%. Among those 20 new subdwarfs, we identify two early-L subdwarfs that are very likely located within 100 pc, which we propose as templates for future searches because they are the first examples of their subclass. Another seven sources are solar-metallicity M dwarfs with spectral types between M4 and M7 without Hα emission, suggesting that they are old M dwarfs. The remaining five candidates do not have spectroscopic follow-up yet; only one remains as a bona-fide ultracool subdwarf after revision of their proper motions. We assigned spectral types based on the current classification schemes and, when

  2. Наблюдения върху лексикалната вариативност при библейските цитати в Йоан-Екзарховия превод на De Fide Orthodoxa

    Directory of Open Access Journals (Sweden)

    Татяна [Tatiana] Илиева [Ilieva

    2016-10-01

    Full Text Available Observations on the theological terminology in the biblical quotations in John the Exarch’s translation of De Fide Orthodoxa The paper presented here aims at comparing the theological terms as used, on the one hand, in the biblical quotations in John the Exarch’s translation of De fide orthodoxa and, on the other, in the Old Bulgarian (Grigirovich Prophetologion, Codex Marianus, Codex Zographiensis, Sinai Psalter, Enina Apostolos as well as in some Middle Bulgarian (Bologna Psalter, Karpinski Apostolos, Ohridski Apostolos Old Russian (Mstislav Gospels, Yurievski Gospels, Pogodinov Psalter, Chudov Psalter, Tolstoev Apostolos, Hristinopol Apostolos and Old Serbia (Shishatovatski Apostolos, Matich Apostolos monuments. Also taken in consideration are the respective parts in certain theological writings associated with the Preslav Literary Centre.   Uwagi o terminologii teologicznej w cytatach z Biblii w przekładzie De Fide Orthodoxa Jana Egzarchy Celem artykułu jest porównanie terminologii teologicznej w cytatach biblijnych w przekładzie De fide othodoxa Jana Egzarchy, w starobułgarskich zabytkach językowych (Lekcjonarz Grigorowizca, Kodeks Mariański, Kodeks Zografski, Psałterz Synajski, Apostoł Eniński, w wybranych zabytkach średniobułgarskich (Psałterz Boloński, Apostoł Karpinski, Apostoł Ohrydzki, staroruskich (Ewangeliarz Mścisława, Ewangeliarz Jurjewski, Psałterz Pogodina, Psałterz Chłudowa, Apostoł Tołstoja, Apostoł Krystynopolski i staroserbskich (Apostoł Sziszatowacki, Apostoł Maticia. Analizie poddano także poszczególne części wybranych pism teologicznych powstałych w presławskiej szkole piśmienniczej.

  3. Scientific progress and the prospects for culture-bound syndromes.

    Science.gov (United States)

    Blease, Charlotte

    2010-12-01

    This paper aims to show that the classification by the American Psychiatric Association (APA) in the Diagnostic and Statistical Manual of Mental Disorders (DSM) of a distinct listing of disorders known as Culture-Bound Syndromes (CBS) is misguided. I argue that the list of CBS (in Appendix I of the manual) comprises either (a) genuine disorders that should be included within the main body of the DSM; or (b) ersatz-disorders that serve a practical role for psychiatrists dealing with patients from certain cultures but will one day be eliminated or assimilated by bona fide DSM classifications. In support of these views I draw on claims from two key themes in the philosophy of science: (1) the claim that all folk (that is, non-scientific) explanations for phenomena are thoroughly theoretical and therefore fallible; and (2) the occurrence of theoretical elimination in the history of science. I contend that any ersatz-disorders located in the DSM that are judged to be radically false do not differ in kind from eliminated theories in the history of pre-science. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Fourier transform inequalities for phylogenetic trees.

    Science.gov (United States)

    Matsen, Frederick A

    2009-01-01

    Phylogenetic invariants are not the only constraints on site-pattern frequency vectors for phylogenetic trees. A mutation matrix, by its definition, is the exponential of a matrix with non-negative off-diagonal entries; this positivity requirement implies non-trivial constraints on the site-pattern frequency vectors. We call these additional constraints "edge-parameter inequalities". In this paper, we first motivate the edge-parameter inequalities by considering a pathological site-pattern frequency vector corresponding to a quartet tree with a negative internal edge. This site-pattern frequency vector nevertheless satisfies all of the constraints described up to now in the literature. We next describe two complete sets of edge-parameter inequalities for the group-based models; these constraints are square-free monomial inequalities in the Fourier transformed coordinates. These inequalities, along with the phylogenetic invariants, form a complete description of the set of site-pattern frequency vectors corresponding to bona fide trees. Said in mathematical language, this paper explicitly presents two finite lists of inequalities in Fourier coordinates of the form "monomial < or = 1", each list characterizing the phylogenetically relevant semialgebraic subsets of the phylogenetic varieties.

  5. Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: implications for replication and genome packaging.

    Science.gov (United States)

    Chaturvedi, Sonali; Rao, A L N

    2014-09-01

    In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein-protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase. Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Latin American social medicine across borders: South-South cooperation and the making of health solidarity.

    Science.gov (United States)

    Birn, Anne-Emanuelle; Muntaner, Carles

    2018-02-22

    Latin American social medicine efforts are typically understood as national endeavours, involving health workers, policymakers, academics, social movements, unions, and left-wing political parties, among other domestic actors. But Latin America's social medicine trajectory has also encompassed considerable between-country solidarity, building on early twentieth century interchanges among a range of players who shared approaches for improving living and working conditions and instituting protective social policies. Since the 1960s, Cuba's country-to-country solidarity has stood out, comprising medic exchanges, training, and other forms of support for the health and social struggles of oppressed peoples throughout Latin America and around the world, recently via Misión Barrio Adentro in Venezuela. These efforts strive for social justice-oriented health cooperation based on horizontal power relations, shared political values, a commitment to social and economic redistribution, bona fide equity, and an understanding of the societal determination of health that includes, but goes well beyond, public health and medical care. With Latin America's left-wing surge now receding, this article traces the provenance, dynamics, impact, challenges, and legacy of health solidarity across Latin American borders and its prospects for continuity.

  7. Not so sweet refrain: sugar-sweetened beverage taxes, industry opposition and harnessing the lessons learned from tobacco control legal challenges.

    Science.gov (United States)

    George, Anita

    2018-05-21

    As a growing number of countries implement, or announce plans to introduce, a sugar-sweetened beverage (SSB) tax, this paper explores the public health rationale for such a tax and provides an overview of the international normative and policy instruments supporting the introduction of fiscal measures on sugary drinks. After examining parallels between the legal arguments raised by the food and beverage industry in opposition to SSB taxes and those raised by the tobacco industry in response to tobacco control measures, this paper draws four key lessons that will assist countries to design effective and robust SSB tax measures and counter food and beverage industry opposition: regulatory distinctions in tax coverage should be based on bona fide, evidence-based reasoning; evidence-based measures need to be tailored to a country's public health objectives as part of a comprehensive strategy to address unhealthy diet consumption; procedural requirements and due process should be observed in the drafting and implementation of the measure; and regulatory space exists within domestic constitutions, laws and international trade and investment agreements recognising the sovereign right of states to regulate in the interests of public health.

  8. A novel small molecule methyltransferase is important for virulence in Candida albicans.

    Science.gov (United States)

    Lissina, Elena; Weiss, David; Young, Brian; Rella, Antonella; Cheung-Ong, Kahlin; Del Poeta, Maurizio; Clarke, Steven G; Giaever, Guri; Nislow, Corey

    2013-12-20

    Candida albicans is an opportunistic pathogen capable of causing life-threatening infections in immunocompromised individuals. Despite its significant health impact, our understanding of C. albicans pathogenicity is limited, particularly at the molecular level. One of the largely understudied enzyme families in C. albicans are small molecule AdoMet-dependent methyltransferases (smMTases), which are important for maintenance of cellular homeostasis by clearing toxic chemicals, generating novel cellular intermediates, and regulating intra- and interspecies interactions. In this study, we demonstrated that C. albicans Crg1 (CaCrg1) is a bona fide smMTase that interacts with the toxin in vitro and in vivo. We report that CaCrg1 is important for virulence-related processes such as adhesion, hyphal elongation, and membrane trafficking. Biochemical and genetic analyses showed that CaCrg1 plays a role in the complex sphingolipid pathway: it binds to exogenous short-chain ceramides in vitro and interacts genetically with genes of glucosylceramide pathway, and the deletion of CaCRG1 leads to significant changes in the abundance of phytoceramides. Finally we found that this novel lipid-related smMTase is required for virulence in the waxmoth Galleria mellonella, a model of infection.

  9. Oxygen isotopic anomalies in Allende inclusion HAL

    International Nuclear Information System (INIS)

    Lee, T.; Mayeda, T.K.; Clayton, R.N.

    1980-01-01

    The oxygen isotopic composition has been measured on the constituent phases of Allende inclusion HAL, which has unusual mineralogical, chemical, and calcium isotopic compositions. The oxygen in HAL is heterogeneous, with the rim showing more ''normal'' composition and the hibonite core showing large deviation from both the terrestrial material and the usual inclusions. The observed pattern indicates that HAL is a bona fide and more devious member of the rare ''FUN'' family, whose isotopic composition is characterized by correlated nuclear effects and extreme mass fractionation. The data imply that HAL has suffered a large oxygen mass fractionation of 25% 0 per mass unit, followed by exchange with oxygen in a second reservoir. The present experiment supports the identification of two distinct reservoirs from which all refractory inclusions in carbonaceous meteorites derived their oxygen. The required fractionation process seems to operate according to the volatility of various elements and could have been caused by evaporation during a heating event. Nuclear anomalies can be produced in the same heating event if the progenitors of the refractory inclusions were macroscopic aggregates of tiny pre-solar interstellar dust grains and if these grains were destroyed differentially during the evaporation

  10. iPTF14yb: The First Discovery of a Gamma-Ray Burst Afterglow Independent of a High-Energy Trigger

    Science.gov (United States)

    Cenko, S. Bradley; Urban, Alex L.; Perley, Daniel A.; Horesh, Assaf; Corsi, Alessandra; Fox, Derek B.; Cao, Yi; Kasliwal, Mansi M.; Lien, Amy; Arcavi, Iair; hide

    2015-01-01

    We report here the discovery by the Intermediate Palomar Transient Factory (iPTF) of iPTF14yb, a luminous (Mr >> -27.8 mag), cosmological (redshift 1.9733), rapidly fading optical transient. We demonstrate, based on probabilistic arguments and a comparison with the broader population, that iPTF14yb is the optical afterglow of the long-duration gamma-ray burst GRB 140226A. This marks the first unambiguous discovery of a GRB afterglow prior to (and thus entirely independent of) an associated high-energy trigger. We estimate the rate of iPTF14yb-like sources (i.e., cosmologically distant relativistic explosions) based on iPTF observations, inferring an all-sky value of Rrel = 610/yr (68% confidence interval of 110-2000/yr). Our derived rate is consistent (within the large uncertainty) with the all-sky rate of on-axis GRBs derived by the Swift satellite. Finally, we briefly discuss the implications of the nondetection to date of bona fide "orphan" afterglows (i.e., those lacking detectable high-energy emission) on GRB beaming and the degree of baryon loading in these relativistic jets.

  11. Cilia are required for asymmetric nodal induction in the sea urchin embryo.

    Science.gov (United States)

    Tisler, Matthias; Wetzel, Franziska; Mantino, Sabrina; Kremnyov, Stanislav; Thumberger, Thomas; Schweickert, Axel; Blum, Martin; Vick, Philipp

    2016-08-23

    Left-right (LR) organ asymmetries are a common feature of metazoan animals. In many cases, laterality is established by a conserved asymmetric Nodal signaling cascade during embryogenesis. In most vertebrates, asymmetric nodal induction results from a cilia-driven leftward fluid flow at the left-right organizer (LRO), a ciliated epithelium present during gastrula/neurula stages. Conservation of LRO and flow beyond the vertebrates has not been reported yet. Here we study sea urchin embryos, which use nodal to establish larval LR asymmetry as well. Cilia were found in the archenteron of embryos undergoing gastrulation. Expression of foxj1 and dnah9 suggested that archenteron cilia were motile. Cilia were polarized to the posterior pole of cells, a prerequisite of directed flow. High-speed videography revealed rotating cilia in the archenteron slightly before asymmetric nodal induction. Removal of cilia through brief high salt treatments resulted in aberrant patterns of nodal expression. Our data demonstrate that cilia - like in vertebrates - are required for asymmetric nodal induction in sea urchin embryos. Based on these results we argue that the anterior archenteron represents a bona fide LRO and propose that cilia-based symmetry breakage is a synapomorphy of the deuterostomes.

  12. Logical reformulation of quantum mechanics. I. Foundations

    International Nuclear Information System (INIS)

    Omnes, R.

    1988-01-01

    The basic rules of quantum mechanics are reformulated. They deal primarily with individual systems and do not assume that every ket may represent a physical state. The customary kinematic and dynamic rules then allow to construct consistent Boolean logics describing the history of a system, following essentially Griffiths' proposal. Logical implication is defined within these logics, the multiplicity of which reflects the complementary principle. Only one interpretive rule of quantum mechanics is necessary in such a framework. It states that these logics provide bona fide foundations for the description of a quantum system and for reasoning about it. One attempts to build up classical physics, including classical logic, on these quantum foundations. The resulting theory of measurement needs not to state a priori that the eigenvalues of an observable have to be the results of individual measurements nor to assume wave packet reduction. Both these properties can be obtained as consequences of the basic rules. One also needs not to postulate that every observable is measurable, even in principle. A proposition calculus is obtained, allowing in principle the replacement of the discussion of problems concerned with the practical interpretation of experiments by due calculations

  13. Prions, prion-like prionoids, and neurodegenerative disordersVacancy

    Directory of Open Access Journals (Sweden)

    Ashok Verma

    2016-01-01

    Full Text Available Prion diseases or transmissible spongiform encephalopathies are fatal neurodegenerative diseases characterized by the aggregation and deposition of the misfolded prion protein in the brain. α-synuclein (α-syn-associated multiple system atrophy has been recently shown to be caused by a bona fide α-syn prion strain. Several other misfolded native proteins such as β-amyloid, tau and TDP-43 share some aspects of prions although none of them is shown to be transmissible in nature or in experimental animals. However, these prion-like “prionoids” are causal to a variety of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The remarkable recent discovery of at least two new α-syn prion strains and their transmissibility in transgenic mice and in vitro cell models raises a distinct question as to whether some specific strain of other prionoids could have the capability of disease transmission in a manner similar to prions. In this overview, we briefly describe human and other mammalian prion diseases and comment on certain similarities between prion and prionoid and the possibility of prion-like transmissibility of some prionoid strains.

  14. Partial coherence with application to the monotonicity problem of coherence involving skew information

    Science.gov (United States)

    Luo, Shunlong; Sun, Yuan

    2017-08-01

    Quantifications of coherence are intensively studied in the context of completely decoherent operations (i.e., von Neuamnn measurements, or equivalently, orthonormal bases) in recent years. Here we investigate partial coherence (i.e., coherence in the context of partially decoherent operations such as Lüders measurements). A bona fide measure of partial coherence is introduced. As an application, we address the monotonicity problem of K -coherence (a quantifier for coherence in terms of Wigner-Yanase skew information) [Girolami, Phys. Rev. Lett. 113, 170401 (2014), 10.1103/PhysRevLett.113.170401], which is introduced to realize a measure of coherence as axiomatized by Baumgratz, Cramer, and Plenio [Phys. Rev. Lett. 113, 140401 (2014), 10.1103/PhysRevLett.113.140401]. Since K -coherence fails to meet the necessary requirement of monotonicity under incoherent operations, it is desirable to remedy this monotonicity problem. We show that if we modify the original measure by taking skew information with respect to the spectral decomposition of an observable, rather than the observable itself, as a measure of coherence, then the problem disappears, and the resultant coherence measure satisfies the monotonicity. Some concrete examples are discussed and related open issues are indicated.

  15. Flocking with discrete symmetry: The two-dimensional active Ising model.

    Science.gov (United States)

    Solon, A P; Tailleur, J

    2015-10-01

    We study in detail the active Ising model, a stochastic lattice gas where collective motion emerges from the spontaneous breaking of a discrete symmetry. On a two-dimensional lattice, active particles undergo a diffusion biased in one of two possible directions (left and right) and align ferromagnetically their direction of motion, hence yielding a minimal flocking model with discrete rotational symmetry. We show that the transition to collective motion amounts in this model to a bona fide liquid-gas phase transition in the canonical ensemble. The phase diagram in the density-velocity parameter plane has a critical point at zero velocity which belongs to the Ising universality class. In the density-temperature "canonical" ensemble, the usual critical point of the equilibrium liquid-gas transition is sent to infinite density because the different symmetries between liquid and gas phases preclude a supercritical region. We build a continuum theory which reproduces qualitatively the behavior of the microscopic model. In particular, we predict analytically the shapes of the phase diagrams in the vicinity of the critical points, the binodal and spinodal densities at coexistence, and the speeds and shapes of the phase-separated profiles.

  16. Tip60 degradation by adenovirus relieves transcriptional repression of viral transcriptional activator EIA.

    Science.gov (United States)

    Gupta, A; Jha, S; Engel, D A; Ornelles, D A; Dutta, A

    2013-10-17

    Adenoviruses are linear double-stranded DNA viruses that infect human and rodent cell lines, occasionally transform them and cause tumors in animal models. The host cell challenges the virus in multifaceted ways to restrain viral gene expression and DNA replication, and sometimes even eliminates the infected cells by programmed cell death. To combat these challenges, adenoviruses abrogate the cellular DNA damage response pathway. Tip60 is a lysine acetyltransferase that acetylates histones and other proteins to regulate gene expression, DNA damage response, apoptosis and cell cycle regulation. Tip60 is a bona fide tumor suppressor as mice that are haploid for Tip60 are predisposed to tumors. We have discovered that Tip60 is degraded by adenovirus oncoproteins EIB55K and E4orf6 by a proteasome-mediated pathway. Tip60 binds to the immediate early adenovirus promoter and suppresses adenovirus EIA gene expression, which is a master regulator of adenovirus transcription, at least partly through retention of the virally encoded repressor pVII on this promoter. Thus, degradation of Tip60 by the adenoviral early proteins is important for efficient viral early gene transcription and for changes in expression of cellular genes.

  17. Antiplatelet antibody may cause delayed transfusion-related acute lung injury

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    Torii Y

    2011-09-01

    Full Text Available Yoshitaro Torii1, Toshiki Shimizu1, Takashi Yokoi1, Hiroyuki Sugimoto1, Yuichi Katashiba1, Ryotaro Ozasa1, Shinya Fujita1, Yasushi Adachi2, Masahiko Maki3, Shosaku Nomura11The First Department of Internal Medicine, Kansai Medical University, Osaka, 2Department of Clinical Pathology, Toyooka Hospital, Hyogo, 3First Department of Pathology, Kansai Medical University, Osaka, JapanAbstract: A 61-year-old woman with lung cancer developed delayed transfusion-related acute lung injury (TRALI syndrome after transfusion of plasma- and leukoreduced red blood cells (RBCs for gastrointestinal bleeding due to intestinal metastasis. Acute lung injury (ALI recurred 31 days after the first ALI episode. Both ALI episodes occurred 48 hours after transfusion. Laboratory examinations revealed the presence of various antileukocyte antibodies including antiplatelet antibody in the recipient's serum but not in the donors' serum. The authors speculate that antiplatelet antibodies can have an inhibitory effect in the recipient, which can modulate the bona fide procedure of ALI and lead to a delay in the onset of ALI. This case illustrates the crucial role of a recipient's platelets in the development of TRALI.Keywords: delayed TRALI syndrome, recurrence, anti-platelet antibody

  18. Isolation of sphere-forming stem cells from the mouse inner ear.

    Science.gov (United States)

    Oshima, Kazuo; Senn, Pascal; Heller, Stefan

    2009-01-01

    The mammalian inner ear has very limited ability to regenerate lost sensory hair cells. This deficiency becomes apparent when hair cell loss leads to hearing loss as a result of either ototoxic insult or the aging process. Coincidently, with this inability to regenerate lost hair cells, the adult cochlea does not appear to harbor cells with a proliferative capacity that could serve as progenitor cells for lost cells. In contrast, adult mammalian vestibular sensory epithelia display a limited ability for hair cell regeneration, and sphere-forming cells with stem cell features can be isolated from the adult murine vestibular system. The neonatal inner ear, however, does harbor sphere-forming stem cells residing in cochlear and vestibular tissues. Here, we provide protocols to isolate sphere-forming stem cells from neonatal vestibular and cochlear sensory epithelia as well as from the spiral ganglion. We further describe procedures for sphere propagation, cell differentiation, and characterization of inner ear cell types derived from spheres. Sphere-forming stem cells from the mouse inner ear are an important tool for the development of cellular replacement strategies of damaged inner ears and are a bona fide progenitor cell source for transplantation studies.

  19. Bayesian assessment of moving group membership: importance of models and prior knowledge

    Science.gov (United States)

    Lee, Jinhee; Song, Inseok

    2018-04-01

    Young nearby moving groups are important and useful in many fields of astronomy such as studying exoplanets, low-mass stars, and the stellar evolution of the early planetary systems over tens of millions of years, which has led to intensive searches for their members. Identification of members depends on the used models sensitively; therefore, careful examination of the models is required. In this study, we investigate the effects of the models used in moving group membership calculations based on a Bayesian framework (e.g. BANYAN II) focusing on the beta-Pictoris moving group (BPMG). Three improvements for building models are suggested: (1) updating a list of accepted members by re-assessing memberships in terms of position, motion, and age, (2) investigating member distribution functions in XYZ, and (3) exploring field star distribution functions in XYZ and UVW. The effect of each change is investigated, and we suggest using all of these improvements simultaneously in future membership probability calculations. Using this improved MG membership calculation and the careful examination of the age, 57 bona fide members of BPMG are confirmed including 12 new members. We additionally suggest 17 highly probable members.

  20. Intracellular vesicle acidification promotes maturation of infectious poliovirus particles.

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    Alexsia L Richards

    Full Text Available The autophagic pathway acts as part of the immune response against a variety of pathogens. However, several pathogens subvert autophagic signaling to promote their own replication. In many cases it has been demonstrated that these pathogens inhibit or delay the degradative aspect of autophagy. Here, using poliovirus as a model virus, we report for the first time bona fide autophagic degradation occurring during infection with a virus whose replication is promoted by autophagy. We found that this degradation is not required to promote poliovirus replication. However, vesicular acidification, which in the case of autophagy precedes delivery of cargo to lysosomes, is required for normal levels of virus production. We show that blocking autophagosome formation inhibits viral RNA synthesis and subsequent steps in the virus cycle, while inhibiting vesicle acidification only inhibits the final maturation cleavage of virus particles. We suggest that particle assembly, genome encapsidation, and virion maturation may occur in a cellular compartment, and we propose the acidic mature autophagosome as a candidate vesicle. We discuss the implications of our findings in understanding the late stages of poliovirus replication, including the formation and maturation of virions and egress of infectious virus from cells.

  1. Remarks on stable and quasi-stable k-strings at large N

    International Nuclear Information System (INIS)

    Armoni, A.; Shifman, M.

    2003-01-01

    We discuss k-strings in the large-N Yang-Mills theory and its supersymmetric extension. Whereas the tension of the bona fide (stable) QCD string is expected to depend only on the N-ality of the representation, tensions that depend on specific representation R are often reported in the lattice literature. In particular, adjoint strings are discussed and found in certain simulations. We clarify this issue by systematically exploiting the notion of the quasi-stable strings which becomes well-defined at large N. The quasi-stable strings with representation-dependent tensions decay, but the decay rate (per unit length per unit time) is suppressed as Λ 2 F(N) where F(N) falls off as a function of N. It can be determined on the case-by-case basis. The quasi-stable strings eventually decay into stable strings whose tension indeed depends only on the N-ality. We also briefly review large-N arguments showing why the Casimir formula for the string tension cannot be correct, and present additional arguments in favor of the sine formula. Finally, we comment on the relevance of our estimates to Euclidean lattice measurements

  2. LACEwING: A New Moving Group Analysis Code

    Energy Technology Data Exchange (ETDEWEB)

    Riedel, Adric R. [Department of Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Blunt, Sarah C.; Faherty, Jacqueline K. [Department of Astrophysics, American Museum of Natural History, New York, NY 10024 (United States); Lambrides, Erini L. [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States); Rice, Emily L. [Department of Engineering Science and Physics, The College of Staten Island, Staten Island, NY 10314 (United States); Cruz, Kelle L., E-mail: arr@astro.caltech.edu [Department of Physics and Astronomy, Hunter College, New York, NY 10065 (United States)

    2017-03-01

    We present a new nearby young moving group (NYMG) kinematic membership analysis code, LocAting Constituent mEmbers In Nearby Groups (LACEwING), a new Catalog of Suspected Nearby Young Stars, a new list of bona fide members of moving groups, and a kinematic traceback code. LACEwING is a convergence-style algorithm with carefully vetted membership statistics based on a large numerical simulation of the Solar Neighborhood. Given spatial and kinematic information on stars, LACEwING calculates membership probabilities in 13 NYMGs and three open clusters within 100 pc. In addition to describing the inputs, methods, and products of the code, we provide comparisons of LACEwING to other popular kinematic moving group membership identification codes. As a proof of concept, we use LACEwING to reconsider the membership of 930 stellar systems in the Solar Neighborhood (within 100 pc) that have reported measurable lithium equivalent widths. We quantify the evidence in support of a population of young stars not attached to any NYMGs, which is a possible sign of new as-yet-undiscovered groups or of a field population of young stars.

  3. Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes.

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    Christophe M Raynaud

    Full Text Available Mesenchymal progenitors or stromal cells have shown promise as a therapeutic strategy for a range of diseases including heart failure. In this context, we explored the growth and differentiation potential of mesenchymal progenitors (MPs derived in vitro from human embryonic stem cells (hESCs. Similar to MPs isolated from bone marrow, hESC derived MPs (hESC-MPs efficiently differentiated into archetypical mesenchymal derivatives such as chondrocytes and adipocytes. Upon treatment with 5-Azacytidine or TGF-β1, hESC-MPs modified their morphology and up-regulated expression of key cardiac transcription factors such as NKX2-5, MEF2C, HAND2 and MYOCD. Nevertheless, NKX2-5+ hESC-MP derivatives did not form contractile cardiomyocytes, raising questions concerning the suitability of these cells as a platform for cardiomyocyte replacement therapy. Gene profiling experiments revealed that, although hESC-MP derived cells expressed a suite of cardiac related genes, they lacked the complete repertoire of genes associated with bona fide cardiomyocytes. Our results suggest that whilst agents such as TGF-β1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.

  4. Inhibition of histone deacetylases 1 and 6 enhances cytarabine-induced apoptosis in pediatric acute myeloid leukemia cells.

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    Xuelian Xu

    Full Text Available BACKGROUND: Pediatric acute myeloid leukemia (AML remains a challenging disease to treat even with intensified cytarabine-based chemotherapy. Histone deacetylases (HDACs have been reported to be promising therapeutic targets for treating AML. However, HDAC family members that are involved in chemotherapy sensitivities remain unknown. In this study, we sought to identify members of the HDAC family that are involved in cytarabine sensitivities, and to select the optimal HDACI that is most efficacious when combined with cytarabine for treating children with AML. METHODOLOGY: Expression profiles of classes I, II, and IV HDACs in 4 pediatric AML cell lines were determined by Western blotting. Inhibition of class I HDACs by different HDACIs was measured post immnunoprecipitation. Individual down-regulation of HDACs in pediatric AML cells was performed with lentiviral shRNA. The effects of cytarabine and HDACIs on apoptosis were determined by flow cytometry analysis. RESULTS: Treatments with structurally diverse HDACIs and HDAC shRNA knockdown experiments revealed that down-regulation of both HDACs 1 and 6 is critical in enhancing cytarabine-induced apoptosis in pediatric AML, at least partly mediated by Bim. However, down-regulation of HDAC2 may negatively impact cytarabine sensitivities in the disease. At clinically achievable concentrations, HDACIs that simultaneously inhibited both HDACs 1 and 6 showed the best anti-leukemic activities and significantly enhanced cytarabine-induced apoptosis. CONCLUSION: Our results further confirm that HDACs are bona fide therapeutic targets for treating pediatric AML and suggest that pan-HDACIs may be more beneficial than isoform-specific drugs.

  5. Characterization of a Novel Class I Transcription Factor A (CITFA) Subunit That Is Indispensable for Transcription by the Multifunctional RNA Polymerase I of Trypanosoma brucei

    KAUST Repository

    Nguyen, T. N.

    2012-10-26

    Trypanosoma brucei is the only organism known to have evolved a multifunctional RNA polymerase I (pol I) system that is used to express the parasite\\'s ribosomal RNAs, as well as its major cell surface antigens, namely, the variant surface glycoprotein (VSG) and procyclin, which are vital for establishing successful infections in the mammalian host and the tsetse vector, respectively. Thus far, biochemical analyses of the T. brucei RNA pol I transcription machinery have elucidated the subunit structure of the enzyme and identified the class I transcription factor A (CITFA). CITFA binds to RNA pol I promoters, and its CITFA-2 subunit was shown to be absolutely essential for RNA pol I transcription in the parasite. Tandem affinity purification (TAP) of CITFA revealed the subunits CITFA-1 to -6, which are conserved only among kinetoplastid organisms, plus the dynein light chain DYNLL1. Here, by tagging CITFA-6 instead of CITFA-2, a complex was purified that contained all known CITFA subunits, as well as a novel proline-rich protein. Functional studies carried out in vivo and in vitro, as well as a colocalization study, unequivocally demonstrated that this protein is a bona fide CITFA subunit, essential for parasite viability and indispensable for RNA pol I transcription of ribosomal gene units and the active VSG expression site in the mammalian-infective life cycle stage of the parasite. Interestingly, CITFA-7 function appears to be species specific, because expression of an RNA interference (RNAi)-resistant CITFA-7 transgene from Trypanosoma cruzi could not rescue the lethal phenotype of silencing endogenous CITFA-7.

  6. Screen for ISG15-crossreactive deubiquitinases.

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    André Catic

    2007-07-01

    Full Text Available The family of ubiquitin-like molecules (UbLs comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs might exist, capable of recognizing both ubiquitin and ISG15.We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1, USP13 (IsoT3, and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43. USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome.By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice.

  7. Structural analysis of the nurse shark (new) antigen receptor (NAR): molecular convergence of NAR and unusual mammalian immunoglobulins.

    Science.gov (United States)

    Roux, K H; Greenberg, A S; Greene, L; Strelets, L; Avila, D; McKinney, E C; Flajnik, M F

    1998-09-29

    We recently have identified an antigen receptor in sharks called NAR (new or nurse shark antigen receptor) that is secreted by splenocytes but does not associate with Ig light (L) chains. The NAR variable (V) region undergoes high levels of somatic mutation and is equally divergent from both Ig and T cell receptors (TCR). Here we show by electron microscopy that NAR V regions, unlike those of conventional Ig and TCR, do not form dimers but rather are independent, flexible domains. This unusual feature is analogous to bona fide camelid IgG in which modifications of Ig heavy chain V (VH) sequences prevent dimer formation with L chains. NAR also displays a uniquely flexible constant (C) region. Sequence analysis and modeling show that there are only two types of expressed NAR genes, each having different combinations of noncanonical cysteine (Cys) residues in the V domains that likely form disulfide bonds to stabilize the single antigen-recognition unit. In one NAR class, rearrangement events result in mature genes encoding an even number of Cys (two or four) in complementarity-determining region 3 (CDR3), which is analogous to Cys codon expression in an unusual human diversity (D) segment family. The NAR CDR3 Cys generally are encoded by preferred reading frames of rearranging D segments, providing a clear design for use of preferred reading frame in antigen receptor D regions. These unusual characteristics shared by NAR and unconventional mammalian Ig are most likely the result of convergent evolution at the molecular level.

  8. The V protein of Tioman virus is incapable of blocking type I interferon signaling in human cells.

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    Grégory Caignard

    Full Text Available The capacity of a virus to cross species barriers is determined by the development of bona fide interactions with cellular components of new hosts, and in particular its ability to block IFN-α/β antiviral signaling. Tioman virus (TioV, a close relative of mumps virus (MuV, has been isolated in giant fruit bats in Southeast Asia. Nipah and Hendra viruses, which are present in the same bat colonies, are highly pathogenic in human. Despite serological evidences of close contacts between TioV and human populations, whether TioV is associated to some human pathology remains undetermined. Here we show that in contrast to the V protein of MuV, the V protein of TioV (TioV-V hardly interacts with human STAT2, does not degrade STAT1, and cannot block IFN-α/β signaling in human cells. In contrast, TioV-V properly binds to human STAT3 and MDA5, and thus interferes with IL-6 signaling and IFN-β promoter induction in human cells. Because STAT2 binding was previously identified as a host restriction factor for some Paramyxoviridae, we established STAT2 sequence from giant fruit bats, and binding to TioV-V was tested. Surprisingly, TioV-V interaction with STAT2 from giant fruit bats is also extremely weak and barely detectable. Altogether, our observations question the capacity of TioV to appropriately control IFN-α/β signaling in both human and giant fruit bats that are considered as its natural host.

  9. Astrocyte uncoupling as a cause of human temporal lobe epilepsy.

    Science.gov (United States)

    Bedner, Peter; Dupper, Alexander; Hüttmann, Kerstin; Müller, Julia; Herde, Michel K; Dublin, Pavel; Deshpande, Tushar; Schramm, Johannes; Häussler, Ute; Haas, Carola A; Henneberger, Christian; Theis, Martin; Steinhäuser, Christian

    2015-05-01

    Glial cells are now recognized as active communication partners in the central nervous system, and this new perspective has rekindled the question of their role in pathology. In the present study we analysed functional properties of astrocytes in hippocampal specimens from patients with mesial temporal lobe epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp recording, K(+) concentration analysis, electroencephalography/video-monitoring, and fate mapping analysis. We found that the hippocampus of patients with mesial temporal lobe epilepsy with sclerosis is completely devoid of bona fide astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly present in non-sclerotic specimens. To decide whether these glial changes represent cause or effect of mesial temporal lobe epilepsy with sclerosis, we developed a mouse model that reproduced key features of human mesial temporal lobe epilepsy with sclerosis. In this model, uncoupling impaired K(+) buffering and temporally preceded apoptotic neuronal death and the generation of spontaneous seizures. Uncoupling was induced through intraperitoneal injection of lipopolysaccharide, prevented in Toll-like receptor4 knockout mice and reproduced in situ through acute cytokine or lipopolysaccharide incubation. Fate mapping confirmed that in the course of mesial temporal lobe epilepsy with sclerosis, astrocytes acquire an atypical functional phenotype and lose coupling. These data suggest that astrocyte dysfunction might be a prime cause of mesial temporal lobe epilepsy with sclerosis and identify novel targets for anti-epileptogenic therapeutic intervention. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. The PorX response regulator of the Porphyromonas gingivalis PorXY two-component system does not directly regulate the Type IX secretion genes but binds the PorL subunit.

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    Maxence S Vincent

    2016-08-01

    Full Text Available The Type IX secretion system (T9SS is a versatile multi-protein complex restricted to bacteria of the Bacteriodetes phylum and responsible for the secretion of surface attachment of diverse proteins that participate to S-layer formation, gliding motility or pathogenesis. The T9SS is poorly characterized but a number of proteins involved in the assembly of the secretion apparatus in the oral pathogen Porphyromonas gingivalis have been identified based on genome substractive analyses. Among these proteins, PorY and PorX encode typical two-component system (TCS sensor and CheY-like response regulator respectively. Although the porX and porY genes do not localize at the same genetic locus, it has been proposed that PorXY form a bona fide TCS. Deletion of the porX in P. gingivalis causes a slight decrease of the expression of a number of other T9SS genes, including sov, porT, porP, porK, porL, porM, porN and porY. Here, we show that PorX and the soluble cytoplasmic domain of PorY interact. Using electrophoretic mobility shift, DNA-protein co-purification and heterologous host expression assays, we showed that PorX does not bind and does not directly regulate expression of the T9SS genes. Finally, we show that PorX interacts with the cytoplasmic domain of PorL, a component of the T9SS membrane core complex and propose that the CheY-like PorX protein might be involved in the dynamics of the T9SS.

  11. Incomplete Memories: The Natural Suppression of Tissue-Resident Memory CD8 T Cells in the Lung

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    Katie L. Reagin

    2018-01-01

    Full Text Available The yearly, cyclic impact of viruses like influenza on human health and the economy is due to the high rates of mutation of traditional antibody targets, which negate any preexisting humoral immunity. However, the seasonality of influenza infections can equally be attributed to an absent or defective memory CD8 T cell response since the epitopes recognized by these cells are derived from essential virus proteins that mutate infrequently. Experiments in mouse models show that protection from heterologous influenza infection is temporally limited and conferred by a population of tissue-resident memory (TRM cells residing in the lung and lung airways. TRM are elicited by a diverse set of pathogens penetrating mucosal barriers and broadly identified by extravascular staining and expression of the activation and adhesion molecules CD69 and CD103. Interestingly, lung TRM fail to express these molecules, which could limit tissue retention, resulting in airway expulsion or death with concomitant loss of heterologous protection. Here, we make the case that respiratory infections uniquely evoke a form of natural immunosuppression whereby specific cytokines and cell–cell interactions negatively impact memory cell programming and differentiation. Respiratory memory is not only short-lived but most of the memory cells in the lung parenchyma may not be bona fide TRM. Given the quantity of microbes humans inhale over a lifetime, limiting cellular residence could be a mechanism employed by the respiratory tract to preserve organismal vitality. Therefore, successful efforts to improve respiratory immunity must carefully and selectively breach these inherent tissue barriers.

  12. On the Weak-Wind Problem in Massive Stars: X-Ray Spectra Reveal a Massive Hot Wind in mu Columbae

    Science.gov (United States)

    Huenemoerder, David P.; Oskinova, Lidia M.; Ignace, Richard; Waldron, Wayne L.; Todt, Helge; Hamaguchi, Kenji; Kitamoto, Shunji

    2012-01-01

    Mu Columbae is a prototypical weak-wind O star for which we have obtained a high-resolution X-ray spectrum with the Chandra LETG/ACIS instrument and a low-resolution spectrum with Suzaku. This allows us, for the first time, to investigate the role of X-rays on the wind structure in a bona fide weak-wind system and to determine whether there actually is a massive hot wind. The X-ray emission measure indicates that the outflow is an order of magnitude greater than that derived from UV lines and is commensurate with the nominal wind-luminosity relationship for O stars. Therefore, the "weak-wind problem"--identified from cool wind UV/optical spectra--is largely resolved by accounting for the hot wind seen in X-rays. From X-ray line profiles, Doppler shifts, and relative strengths, we find that this weak-wind star is typical of other late O dwarfs. The X-ray spectra do not suggest a magnetically confined plasma-the spectrum is soft and lines are broadened; Suzaku spectra confirm the lack of emission above 2 keV. Nor do the relative line shifts and widths suggest any wind decoupling by ions. The He-like triplets indicate that the bulk of the X-ray emission is formed rather close to the star, within five stellar radii. Our results challenge the idea that some OB stars are "weak-wind" stars that deviate from the standard wind-luminosity relationship. The wind is not weak, but it is hot and its bulk is only detectable in X-rays.

  13. The Role of Pontin and Reptin in Cellular Physiology and Cancer Etiology

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    Yu-Qian Mao

    2017-08-01

    Full Text Available Pontin (RUVBL1, TIP49, TIP49a, Rvb1 and Reptin (RUVBL2, TIP48, TIP49b, Rvb2 are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers. However, their exact functions are still quite unknown as they interact with many molecular complexes with vastly different downstream effectors. Within the nucleus, Pontin and Reptin participate in the TIP60 and INO80 complexes important for chromatin remodeling. Although not transcription factors themselves, Pontin and Reptin modulate the transcriptional activities of bona fide proto-oncogenes such as MYC and β-catenin. They associate with proteins involved in DNA damage repair such as PIKK complexes as well as with the core complex of Fanconi anemia pathway. They have also been shown to be important for cell cycle progression, being involved in assembly of telomerase, mitotic spindle, RNA polymerase II, and snoRNPs. When the two ATPases localize to the cytoplasm, they were reported to promote cancer cell invasion and metastasis. Due to their various roles in carcinogenesis, it is not surprising that Pontin and Reptin are proving to be important biomarkers for diagnosis and prognosis of various cancers. They are also current targets for the development of new therapeutic anticancer drugs.

  14. The GCKIII Kinase Sps1 and the 14-3-3 Isoforms, Bmh1 and Bmh2, Cooperate to Ensure Proper Sporulation in Saccharomyces cerevisiae

    Science.gov (United States)

    Slubowski, Christian J.; Paulissen, Scott M.; Huang, Linda S.

    2014-01-01

    Sporulation in the budding yeast Saccharomyces cerevisiae is a developmental program initiated in response to nutritional deprivation. Sps1, a serine/threonine kinase, is required for sporulation, but relatively little is known about the molecular mechanisms through which it regulates this process. Here we show that SPS1 encodes a bona-fide member of the GCKIII subfamily of STE20 kinases, both through phylogenetic analysis of the kinase domain and examination of its C-terminal regulatory domain. Within the regulatory domain, we find Sps1 contains an invariant ExxxPG region conserved from plant to human GCKIIIs that we call the EPG motif; we show this EPG motif is important for SPS1 function. We also find that Sps1 is phosphorylated near its N-terminus on Threonine 12, and that this phosphorylation is required for the efficient production of spores. In Sps1, Threonine 12 lies within a 14-3-3 consensus binding sequence, and we show that the S. cerevisiae 14-3-3 proteins Bmh1 and Bmh2 bind Sps1 in a Threonine 12-dependent fashion. This interaction is significant, as BMH1 and BMH2 are required during sporulation and genetically interact with SPS1 in sporulating cells. Finally, we observe that Sps1, Bmh1 and Bmh2 are present in both the nucleus and cytoplasm during sporulation. We identify a nuclear localization sequence in Sps1 at amino acids 411–415, and show that this sequence is necessary and sufficient for nuclear localization. Taken together, these data identify regions within Sps1 critical for its function and indicate that SPS1 and 14-3-3s act together to promote proper sporulation in S. cerevisiae. PMID:25409301

  15. BANYAN. II. Very low mass and substellar candidate members to nearby, young kinematic groups with previously known signs of youth

    International Nuclear Information System (INIS)

    Gagné, Jonathan; Lafrenière, David; Doyon, René; Malo, Lison; Artigau, Étienne

    2014-01-01

    We present Bayesian Analysis for Nearby Young AssociatioNs II (BANYAN II), a modified Bayesian analysis for assessing the membership of later-than-M5 objects to any of several Nearby Young Associations (NYAs). In addition to using kinematic information (from sky position and proper motion), this analysis exploits 2MASS-WISE color-magnitude diagrams in which old and young objects follow distinct sequences. As an improvement over our earlier work, the spatial and kinematic distributions for each association are now modeled as ellipsoids whose axes need not be aligned with the Galactic coordinate axes, and we use prior probabilities matching the expected populations of the NYAs considered versus field stars. We present an extensive contamination analysis to characterize the performance of our new method. We find that Bayesian probabilities are generally representative of contamination rates, except when a parallax measurement is considered. In this case contamination rates become significantly smaller and hence Bayesian probabilities for NYA memberships are pessimistic. We apply this new algorithm to a sample of 158 objects from the literature that are either known to display spectroscopic signs of youth or have unusually red near-infrared colors for their spectral type. Based on our analysis, we identify 25 objects as new highly probable candidates to NYAs, including a new M7.5 bona fide member to Tucana-Horologium, making it the latest-type member. In addition, we reveal that a known L2γ dwarf is co-moving with a bright M5 dwarf, and we show for the first time that two of the currently known ultra red L dwarfs are strong candidates to the AB Doradus moving group. Several objects identified here as highly probable members to NYAs could be free-floating planetary-mass objects if their membership is confirmed.

  16. Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.

    Science.gov (United States)

    Ijssennagger, Noortje; Janssen, Aafke W F; Milona, Alexandra; Ramos Pittol, José M; Hollman, Danielle A A; Mokry, Michal; Betzel, Bark; Berends, Frits J; Janssen, Ignace M; van Mil, Saskia W C; Kersten, Sander

    2016-05-01

    The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA alters hepatic expression of many genes. However, no data are available on the effects of OCA in the human liver. Here we generated gene expression profiles in human precision cut liver slices (hPCLS) after treatment with OCA. hPCLS were incubated with OCA for 24 h. Wild-type or FXR(-/-) mice received OCA or vehicle by oral gavage for 7 days. Transcriptomic analysis showed that well-known FXR target genes, including NR0B2 (SHP), ABCB11 (BSEP), SLC51A (OSTα) and SLC51B (OSTβ), and ABCB4 (MDR3) are regulated by OCA in hPCLS. Ingenuity pathway analysis confirmed that 'FXR/RXR activation' is the most significantly changed pathway upon OCA treatment. Comparison of gene expression profiles in hPCLS and mouse livers identified 18 common potential FXR targets. ChIP-sequencing in mouse liver confirmed FXR binding to IR1 sequences of Akap13, Cgnl1, Dyrk3, Pdia5, Ppp1r3b and Tbx6. Our study shows that hPCLS respond to OCA treatment by upregulating well-known FXR target genes, demonstrating its suitability to study FXR-mediated gene regulation. We identified six novel bona-fide FXR target genes in both mouse and human liver. Finally, we discuss a possible explanation for changes in high or low density lipoprotein observed in NASH and primary biliary cholangitis patients treated with OCA based on the genomic expression profile in hPCLS. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  17. Identification of Conserved and Potentially Regulatory Small RNAs in Heterocystous Cyanobacteria

    Directory of Open Access Journals (Sweden)

    Manuel eBrenes-Álvarez

    2016-02-01

    Full Text Available Small RNAs (sRNAs are a growing class of non-protein-coding transcripts that participate in the regulation of virtually every aspect of bacterial physiology. Heterocystous cyanobacteria are a group of photosynthetic organisms that exhibit multicellular behaviour and developmental alternatives involving specific transcriptomes exclusive of a given physiological condition or even a cell type. In the context of our ongoing effort to understand developmental decisions in these organisms we have undertaken an approach to the global identification of sRNAs. Using differential RNA-Seq we have previously identified transcriptional start sites for the model heterocystous cyanobacterium Nostoc sp. PCC 7120. Here we combine this dataset with a prediction of Rho-independent transcriptional terminators and an analysis of phylogenetic conservation of potential sRNAs among 89 available cyanobacterial genomes. In contrast to predictive genome-wide approaches, the use of an experimental dataset comprising all active transcriptional start sites (differential RNA-Seq facilitates the identification of bona fide sRNAs. The output of our approach is a dataset of predicted potential sRNAs in Nostoc sp. PCC 7120, with different degrees of phylogenetic conservation across the 89 cyanobacterial genomes analyzed. Previously described sRNAs appear among the predicted sRNAs, demonstrating the performance of the algorithm. In addition, new predicted sRNAs are now identified that can be involved in regulation of different aspects of cyanobacterial physiology, including adaptation to nitrogen stress, the condition that triggers differentiation of heterocysts (specialized nitrogen-fixing cells. Transcription of several predicted sRNAs that appear exclusively in the genomes of heterocystous cyanobacteria is experimentally verified by Northern blot. Cell-specific transcription of one of these sRNAs, NsiR8 (nitrogen stress-induced RNA 8, in developing heterocysts is also

  18. Computational identification and analysis of novel sugarcane microRNAs

    Directory of Open Access Journals (Sweden)

    Thiebaut Flávia

    2012-07-01

    Full Text Available Abstract Background MicroRNA-regulation of gene expression plays a key role in the development and response to biotic and abiotic stresses. Deep sequencing analyses accelerate the process of small RNA discovery in many plants and expand our understanding of miRNA-regulated processes. We therefore undertook small RNA sequencing of sugarcane miRNAs in order to understand their complexity and to explore their role in sugarcane biology. Results A bioinformatics search was carried out to discover novel miRNAs that can be regulated in sugarcane plants submitted to drought and salt stresses, and under pathogen infection. By means of the presence of miRNA precursors in the related sorghum genome, we identified 623 candidates of new mature miRNAs in sugarcane. Of these, 44 were classified as high confidence miRNAs. The biological function of the new miRNAs candidates was assessed by analyzing their putative targets. The set of bona fide sugarcane miRNA includes those likely targeting serine/threonine kinases, Myb and zinc finger proteins. Additionally, a MADS-box transcription factor and an RPP2B protein, which act in development and disease resistant processes, could be regulated by cleavage (21-nt-species and DNA methylation (24-nt-species, respectively. Conclusions A large scale investigation of sRNA in sugarcane using a computational approach has identified a substantial number of new miRNAs and provides detailed genotype-tissue-culture miRNA expression profiles. Comparative analysis between monocots was valuable to clarify aspects about conservation of miRNA and their targets in a plant whose genome has not yet been sequenced. Our findings contribute to knowledge of miRNA roles in regulatory pathways in the complex, polyploidy sugarcane genome.

  19. The Citrus ABA signalosome: identification and transcriptional regulation during sweet orange fruit ripening and leaf dehydration.

    Science.gov (United States)

    Romero, Paco; Lafuente, María T; Rodrigo, María J

    2012-08-01

    The abscisic acid (ABA) signalling core in plants include the cytosolic ABA receptors (PYR/PYL/RCARs), the clade-A type 2C protein phosphatases (PP2CAs), and the subclass III SNF1-related protein kinases 2 (SnRK2s). The aim of this work was to identify these ABA perception system components in sweet orange and to determine the influence of endogenous ABA on their transcriptional regulation during fruit development and ripening, taking advantage of the comparative analysis between a wild-type and a fruit-specific ABA-deficient mutant. Transcriptional changes in the ABA signalosome during leaf dehydration were also studied. Six PYR/PYL/RCAR, five PP2CA, and two subclass III SnRK2 genes, homologous to those of Arabidopsis, were identified in the Citrus genome. The high degree of homology and conserved motifs for protein folding and for functional activity suggested that these Citrus proteins are bona fide core elements of ABA perception in orange. Opposite expression patterns of CsPYL4 and CsPYL5 and ABA accumulation were found during ripening, although there were few differences between varieties. In contrast, changes in expression of CsPP2CA genes during ripening paralleled those of ABA content and agreeed with the relevant differences between wild-type and mutant fruit transcript accumulation. CsSnRK2 gene expression continuously decreased with ripening and no remarkable differences were found between cultivars. Overall, dehydration had a minor effect on CsPYR/PYL/RCAR and CsSnRK2 expression in vegetative tissue, whereas CsABI1, CsAHG1, and CsAHG3 were highly induced by water stress. The global results suggest that responsiveness to ABA changes during citrus fruit ripening, and leaf dehydration was higher in the CsPP2CA gene negative regulators than in the other ABA signalosome components.

  20. BANYAN. II. Very low mass and substellar candidate members to nearby, young kinematic groups with previously known signs of youth

    Energy Technology Data Exchange (ETDEWEB)

    Gagné, Jonathan; Lafrenière, David; Doyon, René; Malo, Lison; Artigau, Étienne [Département de Physique and Observatoire du Mont-Mégantic, Université de Montréal, C.P. 6128 Succ. Centre-ville, Montréal, Qc H3C 3J7 (Canada)

    2014-03-10

    We present Bayesian Analysis for Nearby Young AssociatioNs II (BANYAN II), a modified Bayesian analysis for assessing the membership of later-than-M5 objects to any of several Nearby Young Associations (NYAs). In addition to using kinematic information (from sky position and proper motion), this analysis exploits 2MASS-WISE color-magnitude diagrams in which old and young objects follow distinct sequences. As an improvement over our earlier work, the spatial and kinematic distributions for each association are now modeled as ellipsoids whose axes need not be aligned with the Galactic coordinate axes, and we use prior probabilities matching the expected populations of the NYAs considered versus field stars. We present an extensive contamination analysis to characterize the performance of our new method. We find that Bayesian probabilities are generally representative of contamination rates, except when a parallax measurement is considered. In this case contamination rates become significantly smaller and hence Bayesian probabilities for NYA memberships are pessimistic. We apply this new algorithm to a sample of 158 objects from the literature that are either known to display spectroscopic signs of youth or have unusually red near-infrared colors for their spectral type. Based on our analysis, we identify 25 objects as new highly probable candidates to NYAs, including a new M7.5 bona fide member to Tucana-Horologium, making it the latest-type member. In addition, we reveal that a known L2γ dwarf is co-moving with a bright M5 dwarf, and we show for the first time that two of the currently known ultra red L dwarfs are strong candidates to the AB Doradus moving group. Several objects identified here as highly probable members to NYAs could be free-floating planetary-mass objects if their membership is confirmed.

  1. The Latin American DILI Registry Experience: A Successful Ongoing Collaborative Strategic Initiative

    Directory of Open Access Journals (Sweden)

    Fernando Bessone

    2016-02-01

    Full Text Available Drug induced liver injury (DILI is a rare but well recognized serious adverse reaction. Pre-marketing studies may not detect liver injury, and DILI becomes very often apparent after the drug is launched to the market. Specific biomarkers for DILI prediction or diagnosis are not available. Toxic liver reactions present with a wide spectrum of phenotypes and severity, and our knowledge on the mechanisms underlying idiosyncratic reactions and individual susceptibility is still limited. To overcome these limitations, country-based registries and multicenter research networks have been created in Europe and North America. Reliable epidemiological data on DILI in Latin America (LA, a region with a large variety of ethnic groups, were however lacking. Fortunately, a LA network of DILI was set up in 2011, with the support of the Spanish DILI Registry from the University of Malaga. The primary aim of the Latin DILI Network (LATINDILIN Registry was to prospectively identify bona fide DILI cases and to collect biological samples to study genetic biomarkers. Physicians involved in the project must complete a structured report form describing the DILI case presentation and follow-up which is submitted to a Coordinator Center in each country, where it is further assessed for completeness. During the last four years, several LA countries (Argentina, Uruguay, Chile, Mexico, Paraguay, Brazil, Ecuador, Peru, Venezuela and Colombia have joined the network and committed with this project. At that point, to identify both our strengths and weaknesses was a very important issue. In this review, we will describe how the LATINDILI Registry was created. The aims and methods to achieve these objectives will be discussed in depth. Additionally, both the difficulties we have faced and the strategies to solve them will be also pinpointed. Finally, we will report on our preliminary results, and discuss ideas to expand and to keep running this network.

  2. Pseudepigraphy and the Petrine school: Spirit and tradition in 1 and 2 Peter and Jude

    Directory of Open Access Journals (Sweden)

    Patrick Chatelion Counet

    2006-09-01

    Full Text Available This article identifies four “patterns of religion” (E P Sanders in the pseudepigraphic letters of Peter and Jude in order to support the hypothesis of a “Petrine school” (J H Elliott. The first pattern that connects the letters is a Geisttradition (K Aland, guaranteeing continuity of tradition. The second is the interrelationship between faith and ethics (fides quae and fides qua. The combination of sanctification and eschatology is a third pattern connecting the three documents. Finally, two florilegia can be identified (one from the Old Testament and apocrypha, and one from the chokmatic tradition, suggesting a fourth pattern: a warning against ungodliness and infidelity. The existence of a Petrine group could represent a preliminary stage of subsequent Early Catholicism.

  3. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

    International Nuclear Information System (INIS)

    Noda, Saori; Takahashi, Atsushi; Hayashi, Takeru; Tanuma, Sei-ichi; Hatakeyama, Masanori

    2016-01-01

    SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

  4. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Saori [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Takahashi, Atsushi; Hayashi, Takeru [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Tanuma, Sei-ichi [Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Hatakeyama, Masanori, E-mail: mhata@m.u-tokyo.ac.jp [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

    2016-01-22

    SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

  5. RNA-Seq analysis during the life cycle of Cryptosporidium parvum reveals significant differential gene expression between proliferating stages in the intestine and infectious sporozoites.

    Science.gov (United States)

    Lippuner, Christoph; Ramakrishnan, Chandra; Basso, Walter U; Schmid, Marc W; Okoniewski, Michal; Smith, Nicholas C; Hässig, Michael; Deplazes, Peter; Hehl, Adrian B

    2018-05-01

    Cryptosporidium parvum is a major cause of diarrhoea in humans and animals. There are no vaccines and few drugs available to control C. parvum. In this study, we used RNA-Seq to compare gene expression in sporozoites and intracellular stages of C. parvum to identify genes likely to be important for successful completion of the parasite's life cycle and, thereby, possible targets for drugs or vaccines. We identified 3774 protein-encoding transcripts in C. parvum. Applying a stringent cut-off of eight fold for determination of differential expression, we identified 173 genes (26 coding for predicted secreted proteins) upregulated in sporozoites. On the other hand, expression of 1259 genes was upregulated in intestinal stages (merozoites/gamonts) with a gene ontology enrichment for 63 biological processes and upregulation of 117 genes in 23 metabolic pathways. There was no clear stage specificity of expression of AP2-domain containing transcription factors, although sporozoites had a relatively small repertoire of these important regulators. Our RNA-Seq analysis revealed a new calcium-dependent protein kinase, bringing the total number of known calcium-dependent protein kinases (CDPKs) in C. parvum to 11. One of these, CDPK1, was expressed in all stages, strengthening the notion that it is a valid drug target. By comparing parasites grown in vivo (which produce bona fide thick-walled oocysts) and in vitro (which are arrested in sexual development prior to oocyst generation) we were able to confirm that genes encoding oocyst wall proteins are expressed in gametocytes and that the proteins are stockpiled rather than generated de novo in zygotes. RNA-Seq analysis of C. parvum revealed genes expressed in a stage-specific manner and others whose expression is required at all stages of development. The functional significance of these can now be addressed through recent advances in transgenics for C. parvum, and may lead to the identification of viable drug and vaccine

  6. Calcineurin Targets Involved in Stress Survival and Fungal Virulence.

    Directory of Open Access Journals (Sweden)

    Hee-Soo Park

    2016-09-01

    Full Text Available Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. Calcineurin is activated by increased Ca2+ levels caused by stress, and transduces signals by dephosphorylating protein substrates. Herein, we identified and characterized calcineurin substrates in C. neoformans by employing phosphoproteomic TiO2 enrichment and quantitative mass spectrometry. The identified targets include the transactivator Crz1 as well as novel substrates whose functions are linked to P-bodies/stress granules (PBs/SGs and mRNA translation and decay, such as Pbp1 and Puf4. We show that Crz1 is a bona fide calcineurin substrate, and Crz1 localization and transcriptional activity are controlled by calcineurin. We previously demonstrated that thermal and other stresses trigger calcineurin localization to PBs/SGs. Several calcineurin targets localized to PBs/SGs, including Puf4 and Pbp1, contribute to stress resistance and virulence individually or in conjunction with Crz1. Moreover, Pbp1 is also required for sexual development. Genetic epistasis analysis revealed that Crz1 and the novel targets Lhp1, Puf4, and Pbp1 function in a branched calcineurin pathway that orchestrates stress survival and virulence. These findings support a model whereby calcineurin controls stress and virulence, at the transcriptional level via Crz1, and post-transcriptionally by localizing to PBs/SGs and acting on targets involved in mRNA metabolism. The calcineurin targets identified in this study share little overlap with known calcineurin substrates, with the exception of Crz1. In particular, the mRNA binding proteins and PBs/SGs residents comprise a cohort of novel calcineurin targets that have not been previously linked to calcineurin in mammals or in Saccharomyces cerevisiae. This study suggests either extensive evolutionary rewiring of the calcineurin pathway, or alternatively that these novel calcineurin targets have yet

  7. A novel Toxoplasma gondii nuclear factor TgNF3 is a dynamic chromatin-associated component, modulator of nucleolar architecture and parasite virulence.

    Directory of Open Access Journals (Sweden)

    Alejandro Olguin-Lamas

    2011-03-01

    Full Text Available In Toxoplasma gondii, cis-acting elements present in promoter sequences of genes that are stage-specifically regulated have been described. However, the nuclear factors that bind to these cis-acting elements and regulate promoter activities have not been identified. In the present study, we performed affinity purification, followed by proteomic analysis, to identify nuclear factors that bind to a stage-specific promoter in T. gondii. This led to the identification of several nuclear factors in T. gondii including a novel factor, designated herein as TgNF3. The N-terminal domain of TgNF3 shares similarities with the N-terminus of yeast nuclear FK506-binding protein (FKBP, known as a histone chaperone regulating gene silencing. Using anti-TgNF3 antibodies, HA-FLAG and YFP-tagged TgNF3, we show that TgNF3 is predominantly a parasite nucleolar, chromatin-associated protein that binds specifically to T. gondii gene promoters in vivo. Genome-wide analysis using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identified promoter occupancies by TgNF3. In addition, TgNF3 has a direct role in transcriptional control of genes involved in parasite metabolism, transcription and translation. The ectopic expression of TgNF3 in the tachyzoites revealed dynamic changes in the size of the nucleolus, leading to a severe attenuation of virulence in vivo. We demonstrate that TgNF3 physically interacts with H3, H4 and H2A/H2B assembled into bona fide core and nucleosome-associated histones. Furthermore, TgNF3 interacts specifically to histones in the context of stage-specific gene silencing of a promoter that lacks active epigenetic acetylated histone marks. In contrast to virulent tachyzoites, which express the majority of TgNF3 in the nucleolus, the protein is exclusively located in the cytoplasm of the avirulent bradyzoites. We propose a model where TgNF3 acts essentially to coordinate nucleolus and nuclear functions by modulating

  8. Action principle for the generalized harmonic formulation of general relativity

    International Nuclear Information System (INIS)

    Brown, J. David

    2011-01-01

    An action principle for the generalized harmonic formulation of general relativity is presented. The action is a functional of the spacetime metric and the gauge source vector. An action principle for the Z4 formulation of general relativity has been proposed recently by Bona, Bona-Casas, and Palenzuela. The relationship between the generalized harmonic action and the Bona, Bona-Casas, and Palenzuela action is discussed in detail.

  9. Molecular Basis for Converting (2S-Methylsuccinyl-CoA Dehydrogenase into an Oxidase

    Directory of Open Access Journals (Sweden)

    Simon Burgener

    2017-12-01

    Full Text Available Although flavoenzymes have been studied in detail, the molecular basis of their dioxygen reactivity is only partially understood. The members of the flavin adenosine dinucleotide (FAD-dependent acyl-CoA dehydrogenase and acyl-CoA oxidase families catalyze similar reactions and share common structural features. However, both enzyme families feature opposing reaction specificities in respect to dioxygen. Dehydrogenases react with electron transfer flavoproteins as terminal electron acceptors and do not show a considerable reactivity with dioxygen, whereas dioxygen serves as a bona fide substrate for oxidases. We recently engineered (2S-methylsuccinyl-CoA dehydrogenase towards oxidase activity by rational mutagenesis. Here we characterized the (2S-methylsuccinyl-CoA dehydrogenase wild-type, as well as the engineered (2S-methylsuccinyl-CoA oxidase, in detail. Using stopped-flow UV-spectroscopy and liquid chromatography-mass spectrometry (LC-MS based assays, we explain the molecular base for dioxygen reactivity in the engineered oxidase and show that the increased oxidase function of the engineered enzyme comes at a decreased dehydrogenase activity. Our findings add to the common notion that an increased activity for a specific substrate is achieved at the expense of reaction promiscuity and provide guidelines for rational engineering efforts of acyl-CoA dehydrogenases and oxidases.

  10. Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast

    International Nuclear Information System (INIS)

    Yang, Hanna; Kwon, Chang Seob; Choi, Yoonjung; Lee, Daeyoup

    2016-01-01

    Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5′ promoter and 3′ termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes. Furthermore, the increase of H3K56Ac and H4K20me1 and antisense RNA production was observed in the absence of the histone H3K36 methyltransferase Set2 and histone deacetylase complex (HDAC) that are involved in the suppression of histone turnover within the coding regions. These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast.

  11. Autonomous rexinoid death signaling is suppressed by converging signaling pathways in immature leukemia cells.

    Science.gov (United States)

    Benoit, G R; Flexor, M; Besançon, F; Altucci, L; Rossin, A; Hillion, J; Balajthy, Z; Legres, L; Ségal-Bendirdjian, E; Gronemeyer, H; Lanotte, M

    2001-07-01

    On their own, retinoid X receptor (RXR)-selective ligands (rexinoids) are silent in retinoic acid receptor (RAR)-RXR heterodimers, and no selective rexinoid program has been described as yet in cellular systems. We report here on the rexinoid signaling capacity that triggers apoptosis of immature promyelocytic NB4 cells as a default pathway in the absence of survival factors. Rexinoid-induced apoptosis displays all features of bona fide programmed cell death and is inhibited by RXR, but not RAR antagonists. Several types of survival signals block rexinoid-induced apoptosis. RARalpha agonists switch the cellular response toward differentiation and induce the expression of antiapoptosis factors. Activation of the protein kinase A pathway in the presence of rexinoid agonists induces maturation and blocks immature cell apoptosis. Addition of nonretinoid serum factors also blocks cell death but does not induce cell differentiation. Rexinoid-induced apoptosis is linked to neither the presence nor stability of the promyelocytic leukemia-RARalpha fusion protein and operates also in non-acute promyelocytic leukemia cells. Together our results support a model according to which rexinoids activate in certain leukemia cells a default death pathway onto which several other signaling paradigms converge. This pathway is entirely distinct from that triggered by RAR agonists, which control cell maturation and postmaturation apoptosis.

  12. How carbon credits could drive the emergence of renewable energies

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, John A. [Macquarie Graduate School of Management, Macquarie University, Sydney, NSW 2109 (Australia)

    2008-10-15

    The shift to renewable energy options and low-carbon technologies, in response to the concerns over energy security and climate change, is proceeding more slowly than many would like. The usual argument against rapid deployment of new technologies is the costs imposed on the economy, commonly interpreted in terms of upfront costs to be borne or involving large cash transfers to fund, for example, efforts to preserve rainforests. In this contribution I argue that such a perspective provides a continuing barrier to taking effective action, whereas a perspective based on creation and use of carbon credits provides a means of avoiding the shock of abrupt industrial change. Carbon credits granted for bona fide carbon load reductions could be created through private initiative, for example by merchant banks, to constitute a market that will complement regulatory-based initiatives such as national emissions trading systems. This is not a novel idea; indeed it is the way that capitalism has funded every major change, including the Industrial Revolution, through the creation of credit. The emergence of a global carbon credit economy is likely to precede a global regulatory system governing climate change and will doubtless help to stimulate the emergence of such a global system. (author)

  13. Controlling the prion propensity of glutamine/asparagine-rich proteins.

    Science.gov (United States)

    Paul, Kacy R; Ross, Eric D

    2015-01-01

    The yeast Saccharomyces cerevisiae can harbor a number of distinct prions. Most of the yeast prion proteins contain a glutamine/asparagine (Q/N) rich region that drives prion formation. Prion-like domains, defined as regions with high compositional similarity to yeast prion domains, are common in eukaryotic proteomes, and mutations in various human proteins containing prion-like domains have been linked to degenerative diseases, including amyotrophic lateral sclerosis. Here, we discuss a recent study in which we utilized two strategies to generate prion activity in non-prion Q/N-rich domains. First, we made targeted mutations in four non-prion Q/N-rich domains, replacing predicted prion-inhibiting amino acids with prion-promoting amino acids. All four mutants formed foci when expressed in yeast, and two acquired bona fide prion activity. Prion activity could be generated with as few as two mutations, suggesting that many non-prion Q/N-rich proteins may be just a small number of mutations from acquiring aggregation or prion activity. Second, we created tandem repeats of short prion-prone segments, and observed length-dependent prion activity. These studies demonstrate the considerable progress that has been made in understanding the sequence basis for aggregation of prion and prion-like domains, and suggest possible mechanisms by which new prion domains could evolve.

  14. The perils of pathogen discovery: origin of a novel parvovirus-like hybrid genome traced to nucleic acid extraction spin columns.

    Science.gov (United States)

    Naccache, Samia N; Greninger, Alexander L; Lee, Deanna; Coffey, Lark L; Phan, Tung; Rein-Weston, Annie; Aronsohn, Andrew; Hackett, John; Delwart, Eric L; Chiu, Charles Y

    2013-11-01

    Next-generation sequencing was used for discovery and de novo assembly of a novel, highly divergent DNA virus at the interface between the Parvoviridae and Circoviridae. The virus, provisionally named parvovirus-like hybrid virus (PHV), is nearly identical by sequence to another DNA virus, NIH-CQV, previously detected in Chinese patients with seronegative (non-A-E) hepatitis. Although we initially detected PHV in a wide range of clinical samples, with all strains sharing ∼99% nucleotide and amino acid identity with each other and with NIH-CQV, the exact origin of the virus was eventually traced to contaminated silica-binding spin columns used for nucleic acid extraction. Definitive confirmation of the origin of PHV, and presumably NIH-CQV, was obtained by in-depth analyses of water eluted through contaminated spin columns. Analysis of environmental metagenome libraries detected PHV sequences in coastal marine waters of North America, suggesting that a potential association between PHV and diatoms (algae) that generate the silica matrix used in the spin columns may have resulted in inadvertent viral contamination during manufacture. The confirmation of PHV/NIH-CQV as laboratory reagent contaminants and not bona fide infectious agents of humans underscores the rigorous approach needed to establish the validity of new viral genomes discovered by next-generation sequencing.

  15. Molecular details of secretory phospholipase A2 from flax (Linum usitatissimum L.) provide insight into its structure and function.

    Science.gov (United States)

    Gupta, Payal; Dash, Prasanta K

    2017-09-11

    Secretory phospholipase A 2 (sPLA 2 ) are low molecular weight proteins (12-18 kDa) involved in a suite of plant cellular processes imparting growth and development. With myriad roles in physiological and biochemical processes in plants, detailed analysis of sPLA 2 in flax/linseed is meagre. The present work, first in flax, embodies cloning, expression, purification and molecular characterisation of two distinct sPLA 2 s (I and II) from flax. PLA 2 activity of the cloned sPLA 2 s were biochemically assayed authenticating them as bona fide phospholipase A 2 . Physiochemical properties of both the sPLA 2 s revealed they are thermostable proteins requiring di-valent cations for optimum activity.While, structural analysis of both the proteins revealed deviations in the amino acid sequence at C- & N-terminal regions; hydropathic study revealed LusPLA 2 I as a hydrophobic protein and LusPLA 2 II as a hydrophilic protein. Structural analysis of flax sPLA 2 s revealed that secondary structure of both the proteins are dominated by α-helix followed by random coils. Modular superimposition of LusPLA 2 isoforms with rice sPLA 2 confirmed monomeric structural preservation among plant phospholipase A 2 and provided insight into structure of folded flax sPLA 2 s.

  16. Pea DNA topoisomerase I is phosphorylated and stimulated by casein kinase 2 and protein kinase C.

    Science.gov (United States)

    Tuteja, Narendra; Reddy, Malireddy Kodandarami; Mudgil, Yashwanti; Yadav, Badam Singh; Chandok, Meena Rani; Sopory, Sudhir Kumar

    2003-08-01

    DNA topoisomerase I catalyzes the relaxation of superhelical DNA tension and is vital for DNA metabolism; therefore, it is essential for growth and development of plants. Here, we have studied the phosphorylation-dependent regulation of topoisomerase I from pea (Pisum sativum). The purified enzyme did not show autophosphorylation but was phosphorylated in an Mg(2+)-dependent manner by endogenous protein kinases present in pea nuclear extracts. This phosphorylation was abolished with calf intestinal alkaline phosphatase and lambda phosphatase. It was also phosphorylated by exogenous casein kinase 2 (CK2), protein kinase C (PKC; from animal sources), and an endogenous pea protein, which was purified using a novel phorbol myristate acetate affinity chromatography method. All of these phosphorylations were inhibited by heparin (inhibitor of CK2) and calphostin (inhibitor of PKC), suggesting that pea topoisomerase I is a bona fide substrate for these kinases. Spermine and spermidine had no effect on the CK2-mediated phosphorylation, suggesting that it is polyamine independent. Phospho-amino acid analysis showed that only serine residues were phosphorylated, which was further confirmed using antiphosphoserine antibody. The topoisomerase I activity increased after phosphorylation with exogenous CK2 and PKC. This study shows that these kinases may contribute to the physiological regulation of DNA topoisomerase I activity and overall DNA metabolism in plants.

  17. Bonding and structure of copper nitrenes.

    Science.gov (United States)

    Cundari, Thomas R; Dinescu, Adriana; Kazi, Abul B

    2008-11-03

    Copper nitrenes are of interest as intermediates in the catalytic aziridination of olefins and the amination of C-H bonds. However, despite advances in the isolation and study of late-transition-metal multiply bonded complexes, a bona fide structurally characterized example of a terminal copper nitrene has, to our knowledge, not been reported. In anticipation of such a report, terminal copper nitrenes are studied from a computational perspective. The nitrene complexes studied here are of the form (beta-diketiminate)Cu(NPh). Density functional theory (DFT), complete active space self-consistent-field (CASSCF) electronic structure techniques, and hybrid quantum mechanical/molecular mechanical (QM/MM) methods are employed to study such species. While DFT methods indicate that a triplet (S = 1) is the ground state, CASSCF calculations indicate that a singlet (S = 0) is the ground state, with only a small energy gap between the singlet and triplet. Moreover, the ground-state (open-shell) singlet copper nitrene is found to be highly multiconfigurational (i.e., biradical) and to possess a bent geometry about the nitrene nitrogen, contrasting with the linear nitrene geometry of the triplet copper nitrenes. CASSCF calculations also reveal the existence of a closed-shell singlet state with some degree of multiple bonding character for the copper-nitrene bond.

  18. Implications of the interstellar object 1I/'Oumuamua for planetary dynamics and planetesimal formation

    Science.gov (United States)

    Raymond, Sean N.; Armitage, Philip J.; Veras, Dimitri; Quintana, Elisa V.; Barclay, Thomas

    2018-05-01

    'Oumuamua, the first bona fide interstellar planetesimal, was discovered passing through our Solar system on a hyperbolic orbit. This object was likely dynamically ejected from an extrasolar planetary system after a series of close encounters with gas giant planets. To account for 'Oumuamua's detection, simple arguments suggest that ˜1 M⊕ of planetesimals are ejected per solar mass of Galactic stars. However, that value assumes mono-sized planetesimals. If the planetesimal mass distribution is instead top-heavy, the inferred mass in interstellar planetesimals increases to an implausibly high value. The tension between theoretical expectations for the planetesimal mass function and the observation of 'Oumuamua can be relieved if a small fraction ({˜ } 0.1-1 {per cent}) of planetesimals are tidally disrupted on the pathway to ejection into 'Oumuamua-sized fragments. Using a large suite of simulations of giant planet dynamics including planetesimals, we confirm that 0.1-1 per cent of planetesimals pass within the tidal disruption radius of a gas giant on their pathway to ejection. 'Oumuamua may thus represent a surviving fragment of a disrupted planetesimal. Finally, we argue that an asteroidal composition is dynamically disfavoured for 'Oumuamua, as asteroidal planetesimals are both less abundant and ejected at a lower efficiency than cometary planetesimals.

  19. Globalization of Craniofacial Plastic Surgery: Foreign Mission Programs for Cleft Lip and Palate

    Science.gov (United States)

    Laub, Donald R.

    2015-01-01

    Abstract International Humanitarian Interchanges are a bona fide component of surgery and medicine. Additionally, these programs also provide substantial benefit both to the doers and the recipients. The foreign mission program is potentially a weapon of foreign policy which is underutilized and underestimated. Physician job dissatisfaction is increasing. However, the happiness and satisfaction of the participants in the short-term multidisciplinary trips, repeated, well-organized and respectful, with rather complete integration of the surgical system of the sister countries (“Plan B”), approaches 100%. The theory of the International Humanitarian Interchanges is based on substance, on medical theory. These trips are particularly successful in interchanges with medium-resourced countries. Furthermore, the academic visiting professor (“Plan A”: hi-resource place to hi-resource place), the One Man Can Save the World model (“Plan C”: to the low-resource place), and the intriguing Horton Peace Plan have possibilities for long-term benefit to the doer, recipient, the field of surgery, and the body of knowledge. In all of these, our country and the family of nations advance. The theoretical basis is not always religious nor the grand strategy plan; both have either proselytizing or political dominance as primary motives, and are mentioned as historically helpful. PMID:26080114

  20. Distinguishing quantum from classical oscillations in a driven phase qubit

    International Nuclear Information System (INIS)

    Shevchenko, S N; Omelyanchouk, A N; Zagoskin, A M; Savel'ev, S; Nori, Franco

    2008-01-01

    Rabi oscillations are coherent transitions in a quantum two-level system under the influence of a resonant drive, with a much lower frequency dependent on the perturbation amplitude. These serve as one of the signatures of quantum coherent evolution in mesoscopic systems. It was shown recently (Groenbech-Jensen N and Cirillo M 2005 Phys. Rev. Lett. 95 067001) that in phase qubits (current-biased Josephson junctions) this effect can be mimicked by classical oscillations arising due to the anharmonicity of the effective potential. Nevertheless, we find qualitative differences between the classical and quantum effects. Firstly, while the quantum Rabi oscillations can be produced by the subharmonics of the resonant frequency ω 10 (multiphoton processes), the classical effect also exists when the system is excited at the overtones, nω 10 . Secondly, the shape of the resonance is, in the classical case, characteristically asymmetric, whereas quantum resonances are described by symmetric Lorentzians. Thirdly, the anharmonicity of the potential results in the negative shift of the resonant frequency in the classical case, in contrast to the positive Bloch-Siegert shift in the quantum case. We show that in the relevant range of parameters these features allow us to distinguish confidently the bona fide Rabi oscillations from their classical Doppelgaenger